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Peter A. Heic hart/ Hans P.

Philipsen
Odontogenic Tumors and Allied Lesions
Odontogenic Tumors
and Allied besions

Prof Dr Peter A. Reichart


H um b o ldt-Univers ity of Berlin
B er lin, Germany

Prof Dr odont Hans P. Philipsen


Guadalm ina A lta, Spain

Quintessence Publishing Co Ltd


London, Berlin, Chicago, Copenhage n, Paris, Milan, Barcelona,
Istanbul, Sao Paulo, Tokyo, New Delhi, Moscow, Prague, Warsaw
Brit ish Library Catalogu ing in Publication Data

Reicha rt, P. (Peter)


Odo ntogenic tumors and allied lesions
1. Odontogenic tumors 2. Od ontogenic cysts 3. Jaws - Canc er
I. Title II. Philipsen, H. P. (Hans P.)

616 .9'923 14

ISBN 18509 70599

Copy right 2004 Quintessence Pub lishing Co. Ltd ., Londo n

Quintessence PUblishing Co. Ltd


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All rig hts reserved. This book or any part thereof may not be reproduc ed,
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ISBN 1-850 97-059-9


Contents

Sectio n Three: Benig n Neo plasms and Tumo r-like Lesions Showing

Odont og enic Epith elium With Odo ntog enic Ecto mesenchy me, With

or Without Dent al Hard Tissue Form ation 117

Introduction to Mixed Odo ntoge nic Tumors 117

Chapter 12 Ameloblastic Fibroma 121

Chapter 13 Ameloblastic Fibrodentinom a 129

Chapter 14 Ameloblastic Fibro-odont oma 133

Chapter 15 Complex Odonto ma 141

Chapter 16 Compound Odontoma 149

Chapter 17 Calcifying Ghost Cell Odontogenic Cysts/ Tumors

(Odontogenic Ghost Cell Lesions) 155

Chapter 18 Odontoameloblastoma 171

Sectio n Four: Benign Neoplasm s and Tumor-like Lesions Showing

Mese nc hyme and/or Ectornesench yrne s s - ; 177

Introductio n 177

Chapter 19 Odontogenic Fibroma 179

Chapter 20 Odontogenic Myxoma or Myxofibroma 189

Chapter 21 Benign Cemento blasto ma 199

Section Five: Maligna nt Epithelial Odo ntoqe nic Neoplasms 205

Introd uction to Odontoge nic Carcinomas 205

Chapter 22 Metastasizing, Malignant Ameloblasto ma 207

Chapter 23 Ameloblastic Carcinoma (Primary, Second ary [Dedifferentiated]

Intraosseous; Secondary [Dedifferentiated] Extraosseous) 215

Chapter 24 Primary Intraosseous Squamous Cell Carcinoma (Solid) 221

Chapter 25 Primary Intraosseous Squamous Cell Carcinoma Derived

from Odo ntog enic Cysts 227

Chapter 26 Primary Intraosseous Squamous Cell Carcinoma Derived

from Keratinizing Cystic Odontogenic Tumor 233

Chapter 27 Clear Cell Odontogenic Carcinoma 239

Chapter 28 Ghost Cell Odontog enic Carcinoma 249

Contents

Section Six: Malig nant Ectom esenc hyma l Odo ntogenic Neoplasms

(Odontog enic Sarcomas) 253

Introd uction to Odontogenic Sarcomas 253

Chapter 29 Ameloblastic Fibrosarcoma 255

Chapter 30 Ameioblastic Fibrodentinosarco ma and Fibro-odontosarcoma 263

Chapter 31 Odontogenic Carcinosarcoma 269

Section Seven: Neop lasms and Other Lesions Occurring in the

Maxillofacial Ske leton 271

Introduction to Neoplastic and Non-neoplastic Osseous Lesions 271

Chapte r 32 Ossifying Fibroma 273

Chapter 33 Fibrous Dysplasia 281

Chapter 34 Focal Cemento-osseous Dysplasia 293

Chapter 35 Florid Cemento-osseous Dysplasia 301

Chapter 36 Cherubism 309

Chapter 37 Central Giant Cell Lesion (Granuloma) 3 19

Section Eight: Pseudocysts of the Jaws 333

Introduction 333

Chapter 38 Aneurysmal Bone Cavity (Aneu rysmal Bone Cyst) 335

Chapter 39 Simp le Bone Cavity (Simp le Bone Cyst) 343

Chapter 40 Lingual Mandibular Bone Depression (Staf ne's Cavity) 351

Chapter 41 Focal Marrow-containing Jaw Cavity (Focal Osteoporotic

Bone Marrow Defect) 359

Secti,on Nine: Nonodontogenic Jaw Tu mor of Neurocrest Orig in 365

Introduction 365

Chapter 42 Melanotic Neuroectodermal Tumo r of Infancy 367

Index 375

Forewo rd

Intheyears since the Second World War, and ified by an international panel of oral and
particularly in the past three decades, there anatomical patho logists appointed by the
have been considerable advanc es in under World Health Organization and chaired by
standing of the natural history, structure and Jens Pind borg . Their recommendations
behaviour of the odontogenic tumors. Prior were pub lished in 197 1 in the work Histo
lothis,there was of course interest inthe sub logical Typing of Odontogenic Tumours, Jaw
ject and attempts were made to classifythem Cysts, and Allied Lesions. These proposals
in a logical manner. As early as 1887, Bland were refined further in 1992 in the Second
Sutton had proposed subd ividing the 'odon Edition of th is WHO series under the simp ler
tomes' into those arising from aberrations of head ing Histological Typing of Odontogenic
the enamel organ , aberrations of the follicle, Tumours. This 1992 classification classified
of the papilla , and aberrations of the whol e both benign and malignant odo ntogenic tu
tooth germ. He also included a fifth group of mors into those of odontogenic epithelium
anomalous odontomes. The report of t he without odontogenic ectomesenchyme,
British Dental Associatio n, pub lished in 1914 those of odontogenic epithe lium with odon
and authored by Gabell, James and Payne, togenic ectomesenchyme, and those of
included both radicu lar and den tigerous odontogen ic ectomesenchyme.
cysts as odontomes, and also grouped the Contemporaneous ly, large numbers of
lesions into t hree categories, those of ep clinicopathological and laboratory studies of
ithelial, composite and connective tissue ori t he range of odontogenic tumors have
gin. been published in peer-reviewed journals,
The 1946 classification published by contribut ing great ly to our unde rstanding of
Thoma and Goldman separated the odon these lesions. Peter Reichart and Hans Pe
togenic tumors into th ose of ectodermal, ter Philipsen, the authors of this book, have
mesode rmal and mixed origin . This was themselves made valuab le cont ribut ions to
widelyaccepted intextbooks and formed the scholarsh ip in this field in a series of meticu
basis of the 1950 classification approved by lously documented reviews and descriptions
the American Academy of Oral Patho locy. of topics such as the amelob lastoma, uni
In 1958, Pindborg and Clausen (Finn Pree cystic ameloblastoma, desmoplastic amelo
torius) proposed a classification that sepa blastoma , adenomatoid odo ntoge nic tumor,
rated the epithelial odontogenic tumors into and most recently a suggestion for revisions
two groups according to whether or not there of the 1992 WHO classification. It is wo rth
were inductive changes in the connective tis record ing here that it was Philipsen who ,with
sue. This concept was developed and mod Birn, introduced the term adenomatoid

9
Preface

We have made an effort to present the chap- as witnessed by a rather steep increase in
tersof this book in a uniform and easy-to-use pub lications on lesions covered by the clas-
format. In some instances, however, we have sification. The purpose of the WHO classifi-
had to deviate from the "beaten track" and cations was clearly expressed by Kramer et
introdu ce an extra parag rap h or sec tion al5 whe n they wrote the following: "The pub-
when appropriate. The terminology of the lications in the series International Histologi-
chapter titles may not imme diately be tarnll- cal Classification of Tumours are not intend-
iar to you. We have a priori chosen the terms ed to serve as textb ook s, but rather to
agreed on tod ay by a majority of investiga- facilitate the adoption of a uniforrn terminol-
tors, and those we, based on the most recent ogy that will fac ilitate and irnprove commu-
suggestions, find the most appropriate. The nication arnong cancer workers. For this rea-
subtitle (in brackets) may, however, be met son literature references have been omitted
with a nod of recognition. and readers should refer to standard wor ks
The reader will app reciate that the tumors for bibliograp hies."
and lesions covered in the text are rare in re- There is no doubt that the pub lication of
lation to the frequency of benign and malig- the WHO classifications intensified the zeal
nant tumors in all locations; Baden 1 gave a for do ing research in the field of odontogenic
conservative estimate of about 0.002 % to tumors and publishing the results, because
0.003% of all surgicals received in large cen- terminology and a d iagn ostic frarnework
ters. If only neop lasms were considered, the were now available. We have, however, gen-
frequency wou id inc rease to about 0.006%. erally been disappointed in trying to trace
Bhaskar? fou nd that odontogenic tu mo rs "standard wo rks for bibliographies." A true
comprise 2.4% of all lesions biopsied in a standard work on odontogenic tumo rs does
dental office. A more recent co mparable fig- not exist, apart from Baden's, which is now
ure from Mexico City" was 2.5%. 30 years old but was comprehensive at the
Odon to genic tu mo rs, neop lasms, and time.
other lesions related to the jawbones have We und ertook to write this book because
for years been recognized as presenting clin- we felt a need to fill this gap by co mpiling the
ical, radiologic, and histopatho log ic chal- increasing amo unt of data within this field.
lenges. The first appearance of World Health What initiated thoug hts of embarking on this
Organization (WHO) Histo log ic Typing of project were both the innumerable times we
Odontogenic Tum ors in 19714 mad e a had to look up passages in the blue WHO
marked impact on the general interest in the boo ks over the years and the fact that we did
study of this particular field of oral pathology, not always agree with the authors. Having

11
Preface

devoted many years of research to this field project. However, we believe that it is very de-
and having coauthored and pub lished a con- sirable to learn more about the lesions de-
siderable number of related articles, we re~ scribed in the present book. It surely can be
garded ourselves as reasonably competent done, provided that financial support can be
to do the job. Now, our readers-sunderqrad- obtained , but it must be app reciated that very
uate and postgraduate studen ts, surgeons, few of these tumors and cond itions oonsti-
radiologists, oral as well as general patholo- tute a public health prob lem.
gists, and anyone d oing research in th is We consider the preparation of this book
field-have to judg e whether we have, not ac- to be a great academic challenge and the fl-
co mp lished, but at least approached th e nal result as a valuable, practical aid in the
task. early diagnosis of odo ntoge nic tumors and
The references in each chapter have been lesions. As readers will see, the number of
selected based on their merit of priority or new entities, additional subvariants of exist-
their inclusion of a recent, thorough review ing lesions, and modified conce pts have in-
of the condition in question. We hope that creased su bstantially d uring t he period
the mention of appro priate literature will stirn- (197 1- 199 2) between the first and second
ulate further studies of the many types of l e~ ed it ions of the WHO classifications. The
sions. The reader will realize that, in the vast amount of new knowledg e accum ulated in
majority of the lesions disc ussed , there is a the field since 1992 is quite astonishing and,
strong need for more case reports and, for already at this stage, there seems to be a
the more common lesions, a need for small- need for a revision of the definitions of odo n-
er or larger series of stud ies. It is our experi- togenic tumors and allied lesions as sug-
ence that for the latter category it is of great gested in chapter 2.
importance to present data in detail, includ- This book includes an extensive number
ing all relevant information for each and every of illustrations, most of whic h have been col-
patient. lected by the authors over more than three
The information presented in this book is decades. As is well known to all those who
taken from previously pub lished cases.Such have dealt with the d iagnosis and treatment
a retrospective app roach suffers from sever- of odontogenic neoplasms, some of these
al disadvantages, including the inconsisten- (such as odo nto mas) are relatively common,
cy of both the data provided in the different while others are exceed ingly rare and one
articles and the classifications used. We re- may see only one or two cases of them du r-
gret to say that this is the best we can do at ing a professional lifetim e. While we were
prese nt. Significant additional knowledge able to illustrate most of the common tumors
about the biologic profile of odontogenic tu- quite well, our material on rare lesions was
mors and other lesions of the jaws wo uld be not always sufficient. So we asked our col-
gained from a large prospective study in leagues around the world to provide us with
which such variables as clinical features, ml- needed examples, includ ing clinical radi-
croscopic diagnosis, treatme nt, and follow- ographs, co mputed tomographs, and mag-
up can be acc urately recorded. To establish netic resonance images, as well as histolog-
a prospective study wou ld, however, be dit- ic slides and photomic rograp hs of particular
fic ult because the rarity of a co nsiderable lesions.
number of lesions would necessitate multi- We would like to express our sincere grat-
institutional co operation if sufficient exam- itude and thanks to all who have helped us
pies are to be obtained. It may seem an in- so generously. The following colleagues pro-
surm ountable task to engage in such a vid ed radiographic illustrations, histologic

12
Preface

slides, or photomicrographs: Prof M. Altini, Finally, we are very grateful to our wives,
Johannesburg , Repu blic of South Africa; Kirsten and Barbara, who supported us dur-
Prof E. Ariji, Japan; Prof A. Eckardt, Han- ing the years it took to finish this book.
nover, Germ any; Prof G. Jundt, Basle ,
Switzerland; Prof C. Opitz, Berlin, Germany; Hans P. Philipsen,
Prof R.J. Radlanski, Berlin, Germany; Prof J. Guadalmina Alta, Spain
Reibel, Copenhagen, Denmark; Prof J.J. Sci-
ubba, Baltimore, USA; Prof I. van der Waal, Peter A. Reichart,
Amsterdam, The Netherlands; Prof W. Wag- Berlin, Germany
ner, Mainz, Germany; Prof J. Wo lf, Berlin, July 2003
Germany.
The photographic docu mentation wou ld
not have been possible without the ded icat-
ed professionalism of photog raphers J. Eck- References
ert and R. Hoey. The graph ic art was done
by W. Lorenz. We express our sincere grati- 1. Bade n E. Odontogenic tum ors. Pathol Annu 197 1;
tude to these three individua ls. 6:475 -568.
Ourth anks also go to Ilona Trettin, our sec- 2. Bhaskar SN. Synopsis of Oral Patholoqy. 3d ed . St.
retary, who never got tired of making yet an- Louis: CV Mosby, 1969:225-226.
other correction and add ition to the text. We 3. Mosq ueda-Taylor A, Ledesma-Montes C, Ca-
arealso grateful for her sk illful preparation of ballero-Sand oval S, et al. Odon togenic tumors in
Mexico. A co llaborative retrospective study of 349
the bar graphs for the individual chapters.
cases. Oral Surg Oral Med Oral Pathol Oral Radio!
Also, we would like to thank Sylvia Kaatz for Ended 1997;84:672- 675.
helping to retrieve references in the different
4. Pindborg JJ, Kramer IRH. Histological Typing of
libraries of Berlin. Odontogenic Tumours, Jaw Cysts, and Allied Le-
In particular, we would like to express our sions. Berlin: Springer-Verlag, 1971.
gratitude to th e publisher of Quintessence, 5. Kram er IRH, Pind borg JJ, Shear M. Histolog ical
Herm Haase, and all his wonderful cowork- Typ ing of Odo ntogen ic Tumo urs. 2d ed . Berlin:
ers who made this project possible. Springe r-Verlag, 1992.

13
Section One

General Introduction: Classification,


Normal Odontogenesis, Radiography

15
Chapter 1

Introduction:
Odontogenic Tumors and Allied Lesions

Odontogenic tumors (OTs) have been a top- o ping d ifferential d iagnoses. An und er-
ic of considerable interest to oral patholo- standing of the biologic behavior of OTs is of
gists, who have stud ied and catalogued fund amental imp ortance to the final diagno-
them for several decades . Odontoge nic tu- sis and to treatment planning .This book aims
mors, the term tumor being used th roughout at giving the reader a thorough insight into
this book in its broadest sense, co nstitute a the field of odon tog enic tumor pathology;
group of heterogenous lesions that range clinical and rad iolog ic data, as we ll as
from hamartomatous or non-neoplastic tis- histop athologic aspects, form an important
sue proliferations to malignant neoplasms part of each chapte r.
with metastatic capabi lities. These lesions The book covers a total of 27 neoplasms,
are of varying rarity with in odon toge nic tis- hamartomatous or tum orlike lesions all aris-
sues, but very rare (and in some cases, ex- ing from the odontog enic apparatus. In ad-
tremely rare) when viewed in the co ntext of dition, it covers 11 distinctivejaw lesions that
the entire human tumor pathology. must be distingu ished from odo ntogen ic tu-
Odontog enic tum ors are lesions derived mors. Some of the tumors included have
from epith elial, ecto mese nchymal, and/or been reported only in recent years.Thus, only
mesench ymal eleme nts that are, o r have prelim inary clinical and histo pathologic
been, part of the tooth-form ing apparatus. characteristic s of such cases can be pre-
These tum ors, therefore, are found exc lu- sented. However, it is hoped that the litera-
sively within the jawbones (intrabony or cen- ture references cited will urge pathologists to
trally located) or in the soft mucosal tissue report more cases in order to increase the
overlying tooth-bearing areas (peripherally detailed knowle dge of these characteristics.
located). The tum ors may be generated at Over the years- in fact, since 1867 when
any stage of an individual's life. t he French physician Broca1 proposed a
The reader is remind ed that correlation of classification oftumors originating from den-
histologic features with complete historical, tal tissues-several histologic classifications
clinical, and radiographic information is not have been devised to help comp rehend this
only help fu l but also, in a conside rabl e complex gro up of lesions. Most of the early
number of instances, essential to ensure an attempts were rather complicated and the
accurate diagnosis of tum or pathology. Di- nom enclature used was inconsistent.
agnoses predi cated o n mi cro scopi c ap- It should be appreciated that it takes con-
pearance alone may prove inconclus ive or siderable time for any center to accum ulate
unreliable. Knowledge of the basic epidem i- representative cases in sufficient numbers,
ological features, such as age, gender, and and with adequate follow-up information, for
location, can be extremely valuable in devel- useful comparative data to emerge. Further,

17
1: Odontogenic Tumors and Allied Lesions

due to the complexity of the tissues involved, views on treatment also are presented .
it is only recently that classification attempts Whereas the WH O c lassification s do not con-
have been successful and applicable. tain references for each chapter, the present
Among the prerequisites for comparative authors have chosen to incl ude a number of
studies of oncol ogy is inte rnatio nal agree- relevant citations. A literature search cover-
ment on histologic c riteria for the defin ition ing all chapte rs was terminated in the first
and classification of tumors types and a stan- months of 2002.
dardized nomenclature.As a result of a 5 year Although it has been only 12 years since
collabo rative effort organized by the World the seco nd edition of Histological Typing of
Health Organization (WHO) and carried out Odontogenic Tumours was pub lished , the
by the International Reference Centre at the amount of new information and accumulat-
Department of Oral Pathology, Royal Dental ed know ledge in this field has already grow n
COllege , Co pe nhagen , Den mark, the firs t co nsiderably. Based on the most recent ad-
co nsensus on taxonomy of odo ntogenic tu- vances in the unde rstanding of th e origins
mors, cysts, and allied lesions was pub lished and interactions of odontogenic tissues in tu-
in 197 1.2 The classification was based on the mor developm ent, as well as on recent re-
conc ept suggeste d by Pind bo rg and ports of hit herto unknow n tum or entities and
Clausen in 19583 that th e characteristic in- variants,the auth ors thought it appropriate to
teractions between epithelial and ecto mes- let these new advances make an impa ct by
enchymal tissue elements occ urring during sugg esting a revised version of the 1992
normal tooth development aiso ope rate to a classificatlon.f
certain extent in the pathogenesis and his- In Marc h 200 3, the authors of this book
tod ifferentiation of odo ntogenic tumo rs. The were invited to participate in Pathology and
WHO effo rt was th e first aut horitat ive and Genetics of Tumours of the Head and Neck,
useful guide to the c lassification of od onto- the fift h volu me of the new WHO Blue Book
genic tumors; an updated second edition ap- series WHO Classification of Tumours, start-
peared in 1992 .4 ed in the year 2000. Tumours of the Head
This c lassificatio n, as we ll as other vo l- and Neck includes a chapte r on the odon to-
umes of the WHO series International Histo- gen ic tumors (c hapte r 6). At the Editor ial and
logical Classification of Tumours (published Co nse nsus Co nfe ren ce in Lyon, France
since 1967), was not intended to serve as a (IARC) in July 2003 , a fi nal class ification
textbook but rather as a guide facilit ating the was develop ed based on the present au-
adoption of a uniform te rminology that will tho rs' revised version of the 1992 WHO c las-
ease communication amo ng onco log ists. AI- slficat lon .> Than ks to the cou rtesy of our
thouq h the WHO c lassification foc uses on publisher, Ou intessenz, at a late stage in the
histology, it also co ntains certain sporadic, production of th is book we were able to in-
sho rt accounts on epidemiological informa- clude the entire new tumor classification (see
tion such as age and gender distribution, lo- chapter 2 of this book) as it will appear in the
cation, and radiologic features pertaining to new WHO vo lume, wh ich is sched uled for
the individ ual tumor entities. publication in spring 2004 .
The scope of the present book covers up- The readerwill note that reference is made
dated information on relevant epidemiologi- to the 1992 WHO classification in the pres-
cal features, rad iologic characte ristics, and ent book (see "Histologic definitions" from
full acc ounts on the histop athology of ind i- chapter 5 on), despite the fact that a new
vidual tu mours. In add ition, recu rrence rates WHO classification is pend ing. This is main-
and-w here app ropr iate-note s on latest ly fo r historical pu rposes.

18
References

References

1. Broca PP. Reche rches sur un nou veau groupe de 4. Krame r IRH, Pindb org JJ , Shear M. Histological
tumeurs d esig nees sous Ie no m d'odontomes. Typing of Odontogenic Tumo urs. 2d eo . Berlin:
Paris 186 7. Springer-Verlag, ' 992.
2. Pindborg JJ . Kramer IRH. Histolo gical Typing of 5. Philipsen HP, Re ichart PA. Revision of the 199 2 ed i-
Odontoge nic Tumours, Jaw Cysts. and Allied Le- tio n of the WHO histological typing of o do ntogen ic
sions. Berlin: Sp ringer-Verlag, 1971. tum ou rs. A suggestion. J Oral Pathol Med 2002;
3. Pindborg JJ, Clausen F. Classification of odonto- 3 1:253 - 258.
genic tumors. A suggestion. Acta Odo nto l Scand
1958:16:293-301.

19
Chapter 2

Classification of Odontogenic Tumors


and Allied Lesions

The following classification was approved at Odontogenic epithelium with odontogenic


the Editor ial and Co nsensus Co nfer en ce ectomesenchyme with or withou t dental hard
held In Lyon, France (WHO/ IARC) in Ju ly tissue formation
2003 in conjunction with the preparation of
the new WHO Blue Book volume Pathology Ameloblastic fibroma
and Genetics of Tumours of the Head and Ameloblastic fibrod entinoma
Neck. The pathology of odo ntog enic tumo rs Ameloblastic fibro-odontoma
is the subject of chapter 6 of that volume. Comp lex odo ntoma
Compo und odo ntoma
Odo ntoameloblastoma
Calcifying cystic odontogenic tu mor
Neoplasms and tum or-like Dentinogen ic ghost ce ll tumor

lesions arising from t he odonto- Mesenchyme and/ or odontogenic ectomes-


genic apparatus enchyme with or without included odonto-
genic epithelium
Benign
Odontogenic flb rorna" (epithelium-poor and
Odontogenic epithelium with mature, fibrous epithelium-rich types)
stroma; odontogenic ectomesenchyme not Odontogenic myxo ma or fib romyxom a
present' Cem entoblastoma

Ameloblastomas'
Solid/multicystic Malignant tu mors (odonto genic carcin o-
Extraosseous/ perlpheral mas)s
Desmoplastic
Unicystic Metastasizing, malignant ameloblastoma
Squamous od ontogenic tumor Ameloblastic carcinoma
Calcifying epithelial odo ntogenic tumor (a) pr imary
Adenomatoid odo ntogenic tu mor (b) seconda ry (dedifferentiated), intra-
Kerati nizing cystic odo ntoge nic tumor" osseous
(c) seco nd ary (d edifferenti ated ), extra-
osseous
Primary intraosse ous squ amous cell carci-
noma (PIOSCC)
21
2: Classification of Odontogenic Tumors and Allied Lesions

(a) PIosee solid type strating epithelial-ectomesenc hymal interac-


(b) PIosee de rived from od ontogenic tions) in contrast to tumors described in Sec-
cysts tion three, chapters 12 to 16 (so-called mixed
(c) PIOSCC derived fro m kerat inizing odontoge nic tumors).
cystic odontogenic tumo r
Clear cell odo ntogenic carcinoma 2 The plural form ("amelob lastomas") under-
Ghost cell odo ntogenic carcinoma sco res what recent advances have clearly
shown, that today it is not sufficient to diag-
nose a tum or merely as an ameloblastoma.
Malig nant tum ors (odo ntogenic sarcomas) There are several variants of this neoplasm
and of utmost significance is that they show
Ameloblastic fibrosarcoma distinct variations in their clinical and demo-
Ameloblastic fibrodentin o- and fibro-odon- graphic aspects as well as in their biologic
tosarcoma behavior. These variants are describ ed in
chapters 5 to 8.

3 As stated in the Preface, odo ntogenic cysts


Neoplasm s a nd othe r lesions
are not addressed in the present book. Re-
occ urring in the maxillofacial cently, a wealth of clinical and molecular (ge-
skeleton netic) evidence has ind icated that the odo n-
togenic keratocyst (OKC) now has to be
Osseous neoplasms regarded as a benign cystic neoplasm. 13 At
Ossifying fibroma the earlier mentioned Editorial and Consen-
sus Confe rence (in July of 2003 ) in associa-
Non-neoplastic lesions tion wit h the preparation of the fort hcom ing
Fibrous dysplasia WHO volume Pathology and Genetics of Tu-
Osseous dysplasia mours of the Head and Neck , there was con-
Central giant cell lesion sensus that the OKC should be included in
Cherubism chapter 6 (odontogenic tumors) under the
Aneurysmal bone cyst term keratin izing cystic odontogenic tumor
Simple bone cyst (KCOT). Because the present book was in
the final stage of proofreading at the time the
conference was being held, it was unfortu-
nately not possible to add a new chapter on
Com me nts on tumor classifica- the KCOT.

tion 4 The odontogenic fibroma represents a rare


and controversial tu mor. At present two vari-
The numbe ring (, .5) refers to the preced ing ants can be distingu ished: the epit helium-
classification. poo r typ e and the epithelium-rich type, for-
merly known as the simp le and complex (or
1 An important aspect associated with the WHO) types, respectively.
definition of this group of tumors lies in the
characteristics of the tumor stroma. The stro- 5 The terminology used to describe malig-
ma is relatively acellular and fibrous (and thus nant ep ithelial odo ntogenic tumors (in par-
presumably has no capability of demo n- tlcular chapters 22 to 26 of th is book) has var-

22
References

ied since th e WHO publ ished the initial Refe renc es


consensus (first edition, 1971) on the taxon-
omyof odontogenic tumors. Minor changes 1. Shear M. The aggressive nature of the odon togenic
keratocyst: Is it a benign cystic neop lasm? Part 1.
were introduced in t he sec o nd ed ition
Clinical and early experimental evidence of agg res-
(1992). It is only in very recent years that sive behaviou r. Oral Onco I 200 2;38:219- 226.
additional knowled ge has accumulated,
2. Shear M. The aggressive nature of the odo ntogenic
prompting Eversole" to refine the classifica- keratocyst: Is it a benign cystic neoplasm? Part 2.
tion of malignant odo ntoge nic tumors. The Proliferation and ge netic studies. Oral Onco l 2002;
WHO-classification shown here is a further 38 :323-33 1.
modification that deviates considerably from 3. Shear M. The aggress ive nature of the odon togenic
that of the WHO 1992 classification. keratocyst: Is t a benign cystic neoplas m? Part 3.
Immunocytochem istry of cytc keratin and other ep-
ithelial cell markers. Oral Oncol 2002 ;38:407-4 15.
The reader should be aware of the fact that
the present book covers more entities than 4. Eversole LA. Maligna nt epithelial odontogenic tu-
the ones included in the above new WHO mors. Sem Diagn PathoI 1999;16:3 17-324.
classification.

23
Chapter 3

Early Normal Odontogenesis with Special


Reference to the Development and Fate of the
Dental Laminae

Inorderto understand and appreciate the ori- Odontogenesis


ginand development of odontogenictumors
and hamartomatous lesions, a knowledge of
certain eariy stages of normal odontogen e- The dental lamina (dental plate)
sisis a basic requirement. This chapter pres-
ents the processes involved in the develop- The first signs of tooth development appear
ment of the dental lamina complex and the du ring the sixth week of gestation. 008 2 ob-
final disintegration and fate of this interesting served the first sign of the dental anlage in
epithelial struct ure. There is presently in- embryo s with a crown-rump (CR) length of 8
creasing evidence that residues of odo nto- to 9 mm. At this stage the primitive oral cav-
genic epithelium play a role in the histogen- ity, or sto mo de um, is lined by ectoderm,
esis of odo ntogen ic tumors, hamartomas, whic h consists of a basal layer of cuboi dal to
and cysts. However, the present authors do low columnar cells and a surface layer of flat-
not agree with McClatchey's 1 claim that the tened squa mous cells. The rich glycoge n
ameloblastic carcinoma,the maxillaryamelo- co ntent of th eir cytoplasm gives them an
blastoma, and the squamo us odo ntogenic empty ("clear cell") app earance. The epithe-
tumor are directly linked to and derived from lium is separated from the underlying neural
the dental lamina. crest- derived ectomesenchyme by a base-
Tooth development involves regional and ment membrane. Certain cells in the basal
temporal patterning of the individual tooth cell layer of the oral epithelium begin to pro-
primordium. Odo ntogenesis comprises initi- liferate at a more rapid rate than do the ad-
ation, morphogenesis, and cytodifferentia- jacent cells. As a result, an epithelial thick-
tion, controlled by sequential and recipro cal ening arises on the mandi bular, maxillary,
epithelial-ecto mesenchyma l interactio ns. and medial nasal processes and is interrupt-
Only certain aspects of the initiation, that is, ed by the nasal pit of the maxilla. This ep-
the earliest stages of the formation of the ithelial thicken ing, or primary epithelial band,
tooth primord ium, will be dealt with here. has often been called the dental lamina but
should co rrectly be termed the dental plate,
analogous to neural plate and nasal plate
(Figs 3-1 and 3-2).

25
3: Early Norm al Odo ntogenesis

" .. ' .".~ '.

\ ::.., :~ '. ~ ':-:,\\:;


Fig 3-1 Photo- Th e d enta l a nd v estibular laminae
. ';~:~
."~ :. micrograph
~ .. , ~ ~
:
show ing th e ini- In e m b ryos w it h 11 to 14 mm of C R le ngt h,
">. , OE;" tial downgrowth t he e p ithe lial t hicken ing begins to p ro liferate
from the primi- into t he ecto mesenc hy me that shows a c o n-
tive oral epitheli- d en sati on of ce lls in fhe im m ed iate vic inity of
um forming the t he d enta l pl ate. T his lead s to the fo mnat io n
dental plate. No- of a n epithe lial sheet t hat form s a horsesh oe-
tic e the cell-rich
shaped structu re in b oth d evelo p ing jaw s .
ectomesench y-
Shortly the reaft e r, in e m bryos w ith 15-m m
me (arrows) ;
(hematoxylin- CR le ng th , t h is s heet d iv id es into tw o
eosin [H&E] p rocess es of w h ich t h e inner (lin g ua l o r
xSO). OE ~ oral palata l) ban d deve lops into the p rimordiu m
epithelium; Ol of the ectoderma l po rtio n of th e teeth or the
= den tal lam ina. d e nta l la m ina (Fig 3-3). Th e f ree margin of the

DE
~

"'~
o "'"
o
o "0 <> -e ; <:1
Q Q c;:. ,," " EM ", Co
(;)0:;:0 c o:>':>
0;) 0 Q
G:>o~
Q 0 Q 0
9 CI Q G>

Fig 3-2 Schematic drawing of the events shown


in Fig 3-1. OE ~ oral epithelium; OP ~ dental plate;
EM = ectomesenchyme with co ndensation of its
cells adjacent to the dental plate (arrow ) (mod i-
fied after Mjar and Fejerskov-).

Fig 3-4 Form ation of an epith elial bud (enamel


organ, EO) at the end of the dental lamina (Dl.),
Not ice the cavitation of the vestib ular lamina (Vl),
Fig 3-3 Schematic d rawing showing the d evel- the first step toward form ation of a vestibule. At
opment of the denta l lamina (Ol) and th e d evel- the bottom of 1I1e Vl there is an initial epithelial
opment of the vestibular lamina (Vl ) on the lin- p roliferat io n lead ing to the fo rmatio n of accesso-
gua l side of the Dl. , OE< o ral epithelium (mod ified ry salivary glands (SAL) (mod ified after Mjar and
after Mjar and Fejerskov") , Fejerskov'),

26
Odo ntogenesis

dental lamina is not linear but possesses a Th e lateral lamina and en am el niche
wavy contour. The outer (buccal or labial)
band-often referred to as the lip-furrow band , With the formation of the tooth ger ms for pri-
the buccog ingival lamina, or the vestibul ar mary teeth on the labial (facial) aspect of th e
lamina (see Fig 3-3)-develops so me w hat de ntal lam ina, some of th e dental lamina is
later than the dental lamina. The vestibular extended labially as an ep ith elial bridge co n-
lamina grow s slowly into the mesenc hyme, necting the differentiating tooth organ with
and at a certain stage the co re cells disinte- the dental lamina. This lateral extension is
grate to produ ce cavitation. The slitlike cavi- called the lateral lamina (Fig 3-5). Occasion-
ty thus formed is the vestibule of the mou th ally, gro wth forces of th e mesen chyme adja-
(Fig 3-4).The epithelium that is retained co n- cent to the latera l lam ina prod uce a cavita-
tributes to the mucosal lining of the vestibu le. tion , called the enamel niche , between the
Later, further epithelial downgrowt hs into lamina and th e dental organ. Neithe r the lat-
the connective tissue fro m the bottom of th e eral lamina nor th e enamel niche is func-
vestibule result in the formation of the minor, tionally important.
accessory salivary gland s. The ecto de rm lin-
ing the labial and buccal wa ll of the vestib ule
demarcates the c hee ks and the lips from the
tooth-bearing regions. Th us, the vestibular
lamina not on ly form s the oral vestibule but,
in Its develop mental path, participates with
the dental lamina in defining t he max illary
and mandibular arc hes into w hic h dental
laminae will proceed in odo ntogenesis.

The ename l organ

At intervalsalong the length olthe dental lam-


ina, small rou nde d epithe lial sw ellings or
buds are form ed sho rtly after estab lishment
of the lamina. Each swel ling is a result of the
rapid proliferation of the epithelial cells and
represents the enamel organ of the decidu-
ousteeth (see Fig 3-4). The first tooth buds
to appear are those of the anterior segment
of the mandibl e (mandibular dec iduous or
primary incisors) and the initiation of the en-
Fig 3-5 Formation of the deciduous tooth germs
tire decid uous dentition occurs d uring the
occurring on the labial aspect of the dental lami-
second month in utero. 00e 2 found that th e
na (DL). An epithelial bridge (lateral lamina, LL)
distance between the maxillary right and left connects the DL with the bell-shapedtooth germ.
deciduous central incisors was greate r than The free tip of the DL proliferates into the ee-
the same distance in th e mandible. He sug- tome senchyme as the successional lamina (SL),
gested that th is difference could be respon- providing the anlage for a permanent tooth. OE ~
sible for the more frequ ent median d iaste ma oral epithelium (modified after Mj6 r and Fejer-
in the maxilla. skov').

27
3: Early Normal Odontogenesis

~D E DL LL SL DE
'"< ,.,.

._._o:".',

M2 M3

Fig 3-6 Schematic presentation of several important features in the (nonchronological) development
of th e dental laminae. The de ntal lam ina (DL) provides tooth ge rms for decid uous t eeth and th rough
the successional lamina (SL) pro vides tooth ge rms for per manent incisors, canines, and premo lars.
Permanent molars (M" M" and M 3 ) devel op from a distal extension of the DL, the accessional lami-
na, which is situated below the oral epithelium (OE). VE = vestibule; VL = vestibular lamina; LL = lat-
erallamin a. Note that all three perm anent molars exhibit a successional lamina that does not develo p
further.

The successional lamina "original" dental lamina which grows back-


ward underneath the oral epithelium (Fig 3-
After the formation of the bell-shaped enam- 6). Th is part of the dental lamina co mplex is
el organ, the free terminal or tip of the dental cal led the accessional lamina (t he parent
lamina begi ns to proliferate lingually (or dental lamina. or lamina for permanent mo-
palatally) into the ecto mesenchyme to the lars). These segments of the de ntal lamina
enamel organ of each dec iduou s tooth; this elongate progressively, keeping pace with
occ urs in the 4th month of fetal growt h. This the iengthening of the arches and maturation
newly established growth center is known as of the maxilla and mandible.The earliest sign
th e successional (succed aneous) lami na of the enamel organ of the first permanent
(see Fig 3-5) and is destined to provide the molar is seen in the 4th fetal month . The sec-
anlage for th e perm anent teeth replacing the ond permanent molar appears sho rtly befo re
primary predecessors, inc isors for incisors, birth and the third molar is initiated when the
canines for canines, and premolars for pri- child is about 4 to 5 years of age. When the
mary molars. The process of prod ucing the too th germ of t he third permanent molar is
first 20 permanent teeth (incisors, canines, well defined, the dental lamina may extend
and prem olars) occurs from the 5th fetal farther distally and give rise to the epithelial
mont h (central incisor) to th e 10th month of primo rdium of a fourth molar- and even a
age (seco nd premolar). fifth .
Proliferative activity may, however, termi-
nate prematur ely so the laminae and the as-
Th e accessional lam ina soc iated to oth germs for the third molars are
not prod uced . This accounts for the possib le
At 3'/, to 4 fetal month s (160-mm CR length) absence of th e permanent third molars in
the permanent molars that do not have de- some individuals. Meyer' and 00e5 among
ciduous predecessors begin to appear.They others have demonstrated that the first, sec-
arise directly from a distal extension of the ond, and third permanent molar anlages all

28
Disintegration of the denta l lamina complex

exhibit a successional lamina (see Fig 3-6) in


the same manner as do th e prim ary tooth
primordia. However,th is lamina does not de-
velop into a successor (0 0e5 called this lam-
ina "an abortive successor") but rather shows
fragmentation into epithelial remnants or dis-
integrates.

Disintegration of the dental


lam ina comp lex

The complex pattern of dental lam inae be-


gins to fragment or disintegrate due to ec-
Fig 3-7 Initial fragmentation of the dental lamina
tomesenchymal invasion shortly after the es-
(OL) starting at the orodental epithelial junction
tablishment of the tooth germs. Thes e (OEJ). Several perforations (POL) have occurred.
processes occur initially in the lamina con- LL = lateral lamina; SL = succ ession al lamina; OE
necting the tooth bud to the overlying oral ep- ~ oral epithelium.
ithelium. From the area known as the oro-
dental epithelial junction (the zone where the
dental lamina joins with the oral epithelium),
disorganization or fragmentation of the den-
tal lamina progresses toward the developing chapte r 5), ad enomatoid od ontogenic tu-
enamel organ (Fig 3-7).Some cells ofthe lam- mors (see chapte r 11), and calcifying ep-
ina persist and tend to agg regate through ithelial odo ntogenic tumors (see chapter 10).
proliferation into nests, known traditionally as
epithelial pearls (Serres pearls).
The successional and accessional lami- Additional odontogenic epit he lial cell
nae also disintegrate and give rise to odo n- residues
togenic epithelial remnants. It is widely held
that th e vast majority of th ese epithelial Rem nants from the dental lamina co mplex
residues persist throughout life as vital, but are not the only epithelial residues persisting
mostly inactive ("resting"), cell clusters. How- after th e co mpletion of the normal odo nto-
ever, some of these ce ll rests- or "waste genesis. When dentin formation has started,
products"-of normal human odo ntogenesis changes occ ur in the epithelial root sheath
seem to be triggered by hitherto unknow n (Her/wig roo t sheath), which consists mainly
mechanisms to proliferation and a resulting of th e inner and outer de ntal epithelium. It
production later in life of well-know n patho- loses its co nti nuity as ectomesenchy mal
logic entities, lik e epithelium-lined cysts ce lls from the surrou ndi ng denta l fo llicl e
(dentigerous cysts, odontogenic kerato- grow betwe en the epithelial cells and the ce-
cysts, ging ival cysts of infancy, and lateral mentoblasts start to produce cementum ma-
periodontal cysts) and epithelial odonto- trix on th e surface of the dentin. The frag-
genic tumors such as amelob lasto mas (see mentation of the root sheath results in the

29
3: Early Normal Odontogenesis

creation of a network of epithe lial cel ls cased even after tooth eX1raction. They con-
around the root. Sim pson ," w ho stud ied the cluded that these structu res appeared to be
fate of th is epithe lial netw or k in th e p eri- identical to those fou nd in t he pteryg o-
odont ium of 95 pr em olars fro m pat ient s man dibular space in a structu re known as
aged 8 '/, to 54 years, found th atthe network t he organ of Ch ievitz. The reason for thi s
in the youn gest spec imens resembled a per- problem may be explained by Hod son' s find-
fo rated sheet rather than a net. With the pas- inqs.?
sage of tim e the amount of ep ithelium di- J Vald erhaug and Nylen 9 sho wed in th eir
minished so that the network beca me a wide electron mic rosco pic stud ies th at th e ep-
mesh and th e strands of ep ithe lium thinned . ithelial islands and strands we re separated
Later the network was seen to break up and from the connect ive period ontal tissue by a
many isolated strands and islands were ob- typical basemen t lamin a. ~e i r study furt her
served . Finally, on ly scattered remnan ts of revealed that the cells co ntained all the nec-
epithelium (rests of Malassez) were present. essary components to meet whatever func-
The author present ed a graph indicating that tional dema nds might be placed on th em
the rests degenerate in a fairly regular man- thro ugh enviro nme nta l alte ratio ns. So, al-
ner over time. The rate is rapid at first but though the te rm ce ll rest must be considered
eventually becomes very slow, and th e au- an apt one, this do es not preclude the pos-
thor co ncluded that it is unlikely th at many sibility that the resting cell can return to a
adult period ontal membranes are complete- mo re active state if appropriately stimulated.
ly free of epithelial residues. "whereas an inflammatory reaction doe s
;-lodson?stud ied the ep ithelial residu es in not seem to playa role in triggering dental
human jaws with special referen ce to eden- laminae residues to prolife ration resulting in
tulous jaw reg ions in 37 autopsi es of subjects odonto ge nic cyst and tumor development,
aged 23 to 87. In edentulous jaws, epithelial inflammation is likely to be a ma in facto r in
nests were found in 58% of the incisor and the proliferative activity of the epithelial rests
14% of the th ird molar regions. They were lo- o f Malasse z that pro d uce s pathologic le-
cated in the "eruption tract " (gube rnacular slons. Some of the lesions believed to origi-
canal), including its extension into the gum. nate from the rests of Ma lassez are periapi -
~ e s i d u e s were fo und up to the age of 87 cal (de ntal or radic ular) cysts and parade ntal
years. Often the odo nto genic remnants were cysts.
embedded intraneurally in the nerve fib er
bund les of the gubern acular canal.
Interestingly, several years later, Eversole Remnants arising from the oute r enamel
and l.eider" reported the case of a 58-year- epithelium
old edentulous man with an anterio r maxil-
lary defect whi ch w as considered to be a Eriguch i lO has produ ced evide nce tor th e ex-
posteX1raction focu s of bone def icie ncy. To istence of yet another source of odo ntoge nic
rule out a path o logic process, a tr eph ine ep ithe lial remna nts not pr eviou sly recog-
bon e biopsy was p erformed. Histolog y nized. During th e bell stage of tooth devel-
showed marro w spaces containing nerve opment, th e outer enamel epithelium co n-
fibers; wit hin th e nerve, sur rounded by pe- sists of a layer of low cu boida l cells. In human
ripheral-or iented axis cylinders, were ovoid embryos of 80-mm CR lengt h, the auth or ob-
clusters of ep ithelial cells. The aut ho rs con- served that some cells of the outer enam el
sidered it highly unlikelythat odontogenic ep- ep ithelium tend to group to get her in small
ithelium wo uld become int raneurally en- epithelial "pearl-lik e" st ructures , similar in

30
Disintegration of the dental lamin a complex

morphology though smaller than those seen 00e5 regarded the first, second, and possi-
developing from the dental lamina. They do bly th ird permanent molars as belonging to
not persist as individual pearls but disapp ear the first dentition.
fairly soon and are not traceable In the latter Although the overall activity of the various
half of embryonic life. These remnants are dental laminae thus covers a cons iderable
not likely to play a role as nid i for develop- period of time (from week 6 of embryonic de-
ment into patholog ic lesions. velopment to the age of 4 years) any partic-
In embryos of 23()"to 26()..mm CR length, ular portion of it only functions for a very short
the author further demonstrated thin epithe- period before differentiation, fragmentation
lial strands (in cross sectio ns com posed of 2 into epithelial rests, or total disintegration.
to 5 polyhedric cells) rad iating from the out-
erenamel epithelium but corresponding only
to the masticatory part of the presumptive The gube rnaculum dentis
crown. The strands tend to proliferate and
mayreach 1.5 to 1.8 mm in length; thus, they Although the success ional teeth-that is, the
almost come in contact with the epithelial permanent inci sors, canines , and premo-
ridges of the overlying oral mucous mem- lars-eventually become isolated in their own
brane epithelium. The strands also show a bony crypts,they maintain conti nuity with the
tendency to join togeth er, forming netlik e connective tissue of the lamina propria of the
configurations. They are often acco mpanied overlying gingiva. This is achieved through
by or intermingled with small blood vessels, the persistence of an intrabony canal or cor-
which should not be mistaken for the ep- ridor called the gub ernaculum demis, or gu-
ithelial strands. The strands later show bernacular canal, which con nects the two."
fragmentation, espec ially close to the oral ep- This canal is occ upied by the gubernacular
ithelium, with the form ation of several spher- cord whic h co mprises mainly fibrous con-
ical epithelial pearls that blend with cor re- nective t issue that co ntains peripheral
sponding remnants from the dental laminae nerves, blood and lymphatic channels, and
located in the connective tissue of the gingi- epithelial cells or cell clusters from the frag-
val lamina propria. These outer enamel ep- mented dental lamina. Thus, the gubernac-
ithelium-derived residues are, in contrast to ular co rd is the connective tissue link be-
the rests mentioned above, likely to act as a tween the crypt (or perifollicular connective
source for the develop ment of patho logic le- tissue) and the oral mucous membrane. It
sions later in life. has been proposed that the gube rnacular
co rd provides the directional path for erup-
tion of the permanent teeth. The gu bernac-
Permanent molars ular canals, whose superficial orifices lie on
the lingual (or palatal) aspect of the crowns
The permanenf molars function throughout of the deciduous teeth , can be recogn ized
life without replace ment so th e question read ily in dried jaws of child ren. The dental
arises of whether they belong to the first den- lami na remnants can t hus be trac ed as
tit.on but have no successors, or to the sec- "pearls on a string" from the gingival iamina
ond dentition but have lost their predeces- propria down to the perifolliculartissue (tooth
sors. Norberg 11 postulated that the seco nd sac) surround ing the developing permanent
permanent molar belongs to the seco nd den- tooth (Fig 3-8).
tition, since he believed it is derived from the Based on these find ings, Philipsen et al ' 3
successional lamina; in co ntrast, Meyer' and sugg ested t hat t he adenomato id odonto-

31
3: Early Normal Odontogenesis

genic tu mor (AOT) (as well as several others)


is derived from rem nants of the de ntal lami-
na co mplex. The AOT (see ch apter 1 1 ) oc-
c urs in both an intrao sseous and an ex-
traosseo us (per iphe ral) var iant, and these
variants all show id entical histology. To con-
ceptualize a un ified source of orig in for the
diverse location s of the AOT , one has to look
to od ont og enic epithelium w ith a wid e-
spread occurrenc e thro ug h the enti re gu -
bernac ular canal. On ly on e candidate match-
es the requireme nts: the epithelial rem nants
of the dental lamina com plex.

References
Fig 3- 8 Epithelial remnants (ER, shown as tiny
1. McC latchey KD. Tumors of the de ntal lam ina: A
selective review. Semin Diagn Pathol 198 7; c irc les ) from the dent al lam ina localized to t he
4:200- 204. gubernacular canal that links the tooth sac (TS)
around the developing permanent tooth bud
2. Ooe T. On the early d evelop ment of human den-
(PTB) with the lingual gingiva. 0 1" deciduous in-
tal lamina. Okajimas Folia An at Jp n 1959:32:
97-108. cisor (drawing modified after Scott and Sy-
mons !" ),
3. Mjar lA, Fejerskov 0, eds. Histology of the Hum an
Tooth. 2d ed. Copenhagen: Mun ksgaard, 1979.
chapter 2.
4. Meyer W. Lehrbuch de r nor malen Histologie un d
Entw icklu ngsges chichte der Zahne des Men-
sc hen. M unich, 193 2:19 5 - 20 8.
5. ooe T. Develop ment of human first and second
permanent mo lar, with special reference to the 10. Eriguchi K. Uber d ie Entstehung und Involution
distal portion of the de nta l lamina. Anat Embryol der aus d er Zah nleist e sowi e aus dem Schme lz-
(Berl) 19 79 ;155:22 1- 240. epit he t herstam mend en Ep ithel perlen. Yo ko-
6. Sim pson HE. The degeneratio n of the rests of
hama Med Bull 1959: 10:352 -373.
Malassez with age as observed by th e apo xestic 11. Norbe rg 0. Studies of the huma n jaw s and teeth
technique. J Periodontal 19 65:3 6:288 - 29 1. during the first years of life. Z Anat Entwicklunqs-
7. Hodson JJ. Epithelial residues of the jaw w ith spe-
gesch 1960 ;122:1- 21.
c ial referenc e to t he edentul ous jaw . J A nat 12 . Hod son JJ . The gubernac ulum d entis . Dent Pract
196 2;96:16 -24. Dent Rec 1971 ;21:4 23-4 28 .
8. Eversole LR, Leider AS. Max illary intraoss eous 13. PhiJipsen HP, Sam man N, Ormiston IW, Wu PC,
neuroepi thelial struct ures resembling th ose see n Reic hart PA. Variants of th e ad enom atoid odon-
in the organ of C hievitz. Oral Surg 1978; 46 :555- togenic tumo r w ith a not e on tumor orig in. J Ora!
558. Pathol Med 199 2;2 1:348 -352.
9. Valde rhaug JP, Nylen MU. Funct ion of epithelial 14 . Scott JH , Symons NBB. Int roduction to Dental
rests as su ggest ed by their ultrastructure. J Peri- Anatomy . 9 t h ed . Edi nb u rgh: Ch urc hill living-
odontal Res 196 6 ;1:69 - 78. ston e, 198 2:107 -108.

32
Chapter 4

Christian Sche ifele


Radiography as an Important Tool in Diagnosing
Odontogenic Tumors and Allied Lesions
of the Maxillofacial Skeleton

1. Introducti on decade, Thi s is particularly relevant when


there are long-term postoperative follow-up
examinations which are necessary for a con-
Radiography is often th e first step in diag- siderable number of odontog enic tum ors,To
nosing an odo ntogenic tumor; a screening keep expos ure to diagnostic radiation to a
radiograph is made and evaluated ,It can also m inimum, th e backgroun d fo r all rad i-
bethe final step before creating a wo rking di- ographic examinations should be based on
agnosis, after a complete history has been th e principle "as low (exposure) as reason-
taken and physical and laboratory examina- ably achievab le (ALARA),'"
tions have been done, In both instances. a
number of co nsiderations have to be made
relating to the application of imaging pro ce-
duresthat are presently available, 2. Summation images
Odontogenic tum ors are co mposed of a
number of different soft and hard structures, 2.1 Intraoral radio grap hs
including co mpo nents der ived from ecto-
derm , ectomesenchyme, and mesenchyme Intraoral dental radiographs are usually the
proper, Pulpal tissue and enamel represent first step in clarifying the nature of suspicious
the extremes in radiographic density and , in findings in pano ramic images, provided the
a number of lesions, may be closely associ- region of interest is attainable, It has been
ated, Therefore, their radiographic app ear- stressed that intraoral imaging is. wh ere ap-
ance may vary from complete radio luce ncy plicab le, an indispensable part of the diag-
to mixed radiolucency/ radiopacity to co m- nostic pro cedur e for odo ntogenic tumo rs,
plete radiopacity (Tab le 4-1), This has especially been shown in the early
For lesions of the jaws, any suitable imag- stages of both adenomat oid odo ntogenic tu-
ing procedure requ ires radiation exposure, mors and odontomas in which it otherwise
except for magnetic reso nance imag ing may be impossible to demonstrate discrete
(MRI) and sonography, While radiation dose foci of calcified deposits,2,3Occ lusal views of
values in dental radiography are co mpara- the jaws provide easy imaging of displaced
tively low. rad iation dose burdens may be teeth in a second plane, In all intraoral and
considerable with comp ute d tomog raphy extraoral projections, the radiographic eval-
(GT), which has been applied extensively in uation may be d isturbed by superimposing
dentomaxillofacial radiology during the last structures,

33
4: Use of Radiography in Diagnosing Odontogenic Tumors and Allied Lesions

Tab le 4-1 Suggested imagin g tech niq ues acc ord ing to odontogenic tumor type

Imaging techn iques

.>,
,
J::
J:: 0. c
0. 0
~
~
Ol
0
Ol
0
ro n
~
<D
<D
.~

'6 E co e ,
0 J::
~ C
-
~<D
0. 0.
~ :J ~
lii
0 0'"
0. o cr
ct:l :..=
Ol
E
~
c
J::
t x
w
~.o
0 f- a:
:2'
0
0 0 (j)

Neoplasms and tumor-like lesions arising from th e odontogen ic app aratus

Benign
Odontogenic epithelium with relatively acellular fibrous stroma, odontogenic ecto mes-
enchyme not present
Ameloblastomas Solidj multicystic (+) + (+)
Extraosseous (peripheral) + (+)
Desmoplastic (+) +
Unicystic + (+) (+)
Squa mous odo ntoge nic tumo rs + +
Calcifying epithelial odontogenic tum or + (+) (+) (+)
Aden omatoid odo nto genic tum or + + (+)

Odontogenic epith elium with odontogenic ectomesenchyme with or without dental hard tis-
sue formation

Ameloblastic fibroma and fibrodentinoma


(neoplastic and non-neoplastic ) (+) +
Complex and co mpo und odontoma (+) +
Amelo blastic fibro-odontoma (+) + (+)
Odontoamelob lastoma (+) +
Ghost cell odo ntogenic tumor (+) + (+) (+)

Odontogenic ectomesenchyme and/or mesenchyme with or without included odontogenic


epithelium

Odontogenic fibroma (+) + (+)


Odontogenic myxom a or myxofibrom a (+) + (+) (+)
Cem entoblastom a (+) + (+)

Malignant
Odontogenic carcinomas and sarco mas + + + (+)

CT == computed tomography; MRI = magnetic resonance imaging; + = first choice; (+) = supplementary.

34
Dental pano ramic radiographs and co nventional to mog rams

2.2 Extraoral special project io ns Iy calcifications and small density d iffer-


ences, as described earlier?
Special projections of t he jaws and skull are
of minor significance tod ay. They are used
for a survey of lesions not substantially ex-
ceedingthe alveolar bone, including those in 3. Dental panorami c
the jaws and fac ial structures. A seco nd ob-
jective is often to demonstrate lesions in a radiograp hs and conventional
second plane. Common special projections tomograms
include the lateral oblique projection of one
half of the mandi ble, the posterior-anterior 3 .1 Dental panoramic radiographs
projection (PA, or Clementschitsch view) of
the mandible, and the lateral (cephalometric) The first descriptions of odo ntoge nic tumors
and PA views of the sku ll. These techniques in dental panoramic radiographs were pub-
are advisable for the demonstration of le- lished in the 19 70s. ' 2 At present , dental
sions if other facilities are not available. panoramic radiog raphs provide the state-of-
the-art view of the jaws and are mandatory
for any scree ning protocol in oral radiolo-
gy.13. 14
2.3 Dig ital imaging in int ra- and Like all tomograms, dental panoramic im-
extraoral projections ages show a somewhat lower resolution (2
to 3 line pairs/ rum) than co mparable plain
Intraoral imaging was one of the first areas film radi ographs, especia lly intrao ral radi-
within radiology where digital methods were ographs (> 30 line pairs/ rnrn). However, the
effectively able to replace the con ventional speed and ease that allow the clinician to ob-
film-based image4 ,5 Due to the small file size tain a complete survey at low exposure dos-
of intraoral dental images, the storag e and es strongly cou nter balance th is disadvan-
exchange of these radiograp hs have never tage.
been a problem. Today, there are two meth-
ods of image acquisition in intraoral dental
radiography: sensors and the imaging plate 3.2 Cross-sectional views in dental
system.5 .6 panoramic units
At present, the spatial resolution of sensor
systems exceeds that of the imaging plate In modern units, the position of t he image lay-
systems, while the latter show a broader dy- er itself and the x-ray tube are programm a-
namic rangein respectto rad iation exposure. ble withi n a wide range. This has made pos-
Clinically, both are accepted and proven to sible a variety of cross-sect ional imagi ng
deliverequal or even better images than con- methods, w hich include cross -sect io nal
ventional radiograp hy?- 11 Projections and views of the jaws, the sinus, and the tem-
views in digital systems are identical to those poroma ndibular joints."
of conventional radiog raphy. Digital image
processing and enhancement, however, al-
low operators to adjust brightness and con-
trast scales over a broad range. From that
point of view, digital systems may be superi-
orto conventional systems in describing ear-

35
4: Use of Rad iography in Diagnosing Odontogenic Tumors and Allied Lesions

4. Computed tomography olution has gradually been improved, and


spiral CT, multislice CT, and combinations of
4 .1 Axial and coronal views both have been lntroduceo.t' These atlowtor
fast imaging and considerably improved im-
Differentiation of a ben ign lesion from a ma- age qua lity with a reduced number of arti-
lignant one may be difficult with only plain facts .' 6 ,' 8
film radiographs. Therefore, it is easy to un- Imperative, however, is the secondary re-
derstand that CT was a cruc ial advance in construction-also called multiplanar reco n-
imaging the highly differentiated anatomy of struction-of freely selectable or predefined
the skull. l" layers of the primarily reconstructed axial
The main advantage of classic CT was that views . Denta l examination protoco ls are
it cou ld eliminate superimposition of skull available for most CT units and especially the
structures . This provided a tremendous gain Denta -CT software 16 .18 ,19 and offer reco n-
in information abou t t he size and spat ial ori- structed pano ramic as well as reconstructed
entation of any findings in (at that time) pri- cross-sectional Images, Iacilitatinq and im-
mary reconstructed axial tomograms. Years proving the interpretation offindings seen on
before general d igital radiography, CT was plane film radiographs. In addition , artefacts
able to identify tissues in respect to their at- resulting from dental restorations have often
tenuat ion in the radiograph . With the attenu- interfered with evaluation of lesional struc-
ation factor, expressed in Hounsfield units tures, especially in primarily reconstructed
(HUj, a physically calibrated charactenstic coronal CT views, wh ich were produced by
was found that may, along with the structure reclin ing the patient's head . With recon -
observed, contribute to differential diagno- struction of the coronal view from the axial
sis. Thus, differences in density of less than high-resolution images, the number and size
1% can be detected, but this does not nec- of these artifacts have decreased consider-
essarily apply to the imaging of soft tissues . ably.!"
Metal dental restorations may cause mas- For the diagnosis of diseases of the jaws,
sive superimpositions both in primarily axial includ ing odontogenic tumors, CT interpre-
or coronal reconstructed views. By and large, tation covers both topography and fine struc-
it is possible to partially eliminate these prob- ture of the lesion. 2o The involvement of sur-
lems by using appropriate algorithms. Nev- rounding tissue,the cort ical margins, and the
ertheless, conventional CT is recommended extent and relationship to adjacen t teeth or
in dentate patients for the demonstration of roots are easily seen on dental CT images.
lesions outside the alveolar process. The Slow-growing benign lesions often expand
evaluation of tumor ex1ent into the paranasal the cortex, while rapidly grow ing malignant
sinuses , the nasopharynx, the base of the tumors destroy adjacent structures. Thus,
skull , or the cervical spine are typical appli- additional valuable information about the tu-
cations. mortype may be achieved when the findings
from conventional radiography are exhaust-
ed .16 ,2 1- 23
4 .2 Secondary reconstructed views With the combination of adequate bone or
soft tissue window algorithms and thin sec-
At present, state-of-the-art CT is character- tions, the resolution of recent CT images al-
ized by a couple of Improvements that have lows one to demonstrate the fine structures
enhanced both image quality and simplicity of mixed lesions . Subtle calcificat ions, bone
of application and evaluation: The spatial res- and marrow changes, and even desquamat-

36
Rad ionuclide imaging

ed keratin may be seen with app ropriate set- demonst ration af fine intraiesional fibrou s tis-
tings either d irectly or as increased atten ua- sue and its mineralizatio n. In addition, the
tion areas. 23.24 The presence and kind of in- spatial orientation of mineraiization as cen-
tralesional calcif ications, bony septa, and tral, mural, or fleck ed appearance may be of
other solid masses may be crucia l in the dif- impo rtance in the different ial diagnosis.25
ferential diagn osis of odo ntogenic tu- With this detailed info rmation available, MRI
m ors .20,2 1,23,25 may considerably increase know ledge in the
field about the pathology of odo ntogenic tu-
mors.
Finally, MRI has been described as supe-
5. Magnet ic resonance ima ging rior to CT when evaluating the mandible, due
to t he registration of both cort ical and
med ullar involvement.2 126 In summary, the
Magnetic resonance imag ing has for some main advantages of MRI in evaluating odon-
time been considered inap propriate to re- togen ic tumors, compa red to CT, are the ab-
solve the alveolar regions, due to the weak sence of artifacts, the improved soft tissue
signals from hard tissues. However, it has co ntrast, and the capacity to image exact tu-
been shown that even fo rthis anatomi c area mor borders and small intralesional mass-
adequate imaging will be possible. By ren- es.30
dering MRI data sets to commercial dental
CT software reconstructed panoramic and
cross-sectio nal images from MRI may be
available soon.26 6. Radionu clid e imagin g
The general use of MRI for the differential
diagnosis of jaw lesions that exceed the alve-
olar process and co ntain soft t issues has Scintig raphy requires the ingestion or injec-
been demonstrated for years.2 7 - 2 9 Thi s tion of specific radionuclides with short half-
method produces superior imaging of the lives. Appro priate choice of these age nts
soft tissues, d ifferentiates exactly betw een means that radionu cli des conce ntrate se-
cysts and solid tumors, and can reveal the tu- lectively in the region or tissues of interest. In
mar-tissue margins in a singu lar manner. classic scintigraphy, the y-rays from isotopes
MRI is also able to detect essential macro- are detected by a gamm a came ra that
pathologic details like mural nod ules, fibrous reco rds the scintigram. Thus, radionuclide
or incomplete calcified septa, or solid con- imag ing meth od s delineate regions of in-
tents of a cYSt. 2 125 For example, it has been cre ased or decr eased metabolism . As al-
postulated that MRI might be the only way to ready described , the true extent of bone re-
demonstrate a mural ame loblastoma in a sorption , such as around an od ont ogenic
preexisting fol licular cyst. 2 1 Martin-Duver- tumor, is in most instances larger than that
neuil et al25 recently reported on the use of depicted in conventional radiographs. Since
CTand MRI in the diagnosis of calcifying ep- radionuclide imag ing is based on the bio-
ithelial odo ntogenic tum ors and calcify ing logic activity of a given lesion, it is able to
odontogenic cysts with odo ntoma. It must be demo nst rate changes not only mo re pre-
emphasized that the value of CT and MRI in cisely but also earlier than other techniques.
diagnosing odo ntog enic tum ors is not sale- In a case of intramural ameloblastoma, for
Iythe imaging of the tum or margins or the re- examp le, the intramedu llary exte nsion of
action of surrounding tissues, but rather the the tumor beyond the cystic wall could be

37
4: Use of Radiography in Diagnosing Odontogenic Tumors and A llied Lesions

demo nstrated as an increased activity in 8. Youssefzade h S, Gahleitner A, Bernhart D, Bern-


sclntlqraphv" The imaging field of radio nu- hart T. Konventione lle Dentalradiologie und Zu-
kunftsperspektiven. [Conventional dental radiog-
elide methods can coverthe who le body, pro- raphy and futu re prospectives]. Radiolo ge 1999;
viding an excellent overview of co ndit ions 39 :101 8- 1026.
like bony metastases or unknown primaries. 9. Schu lze R, Krumme nauer F, Sch alld ach F,
Radionuc lide imaging, however, does not d' Hoedt B. Precision and accuracy of measure-
reveal the cause of bone resorption or bone ments in d igita l panoramic radiography. Den-
formatio n, such as tum ors, inflamm ation, de- to rnaxillotac RadioI 2000;29 :52- 56
generative changes, or traurna.F However, 10. Stamatakis HC, Welander U, McDavid WD. Phys-
scintigraphy has been postulated to be part ical propert ies of a photostimu lable phosphor sys-
of the standar d d iagnostic prog ram for the te rn for intra-oral radiography. Dento maxiltofac
Rad lol 2000;29:28 -34 .
evaluation of malignant tumo rs of the oral
cavity, includ ing odontogen ic ca rcinomas 11. Borg E, Attaelmanan A, Grond ahl HG. Subjective
image quality of solid-state and photostimulable
and sa rcomas.' ?
phosphor systems for digital intra-oral radiogra-
phy. Dentomaxillofac RadioI 2000;29;70-75 .
12. Oikarinen VJ, Calonius PE, Meretoja J. Calcifying
epithelial odo ntogenic tumor s (Pindb org tu mor)
References
case report. Int J Oral Surg 1976;5:187 - 191.

1. Pasler F, Visser H. Zahnmeoizinische Radioloqie: 13. Floyd P, Palmer P, Palmer R. Rad iographic tech-
Bildgebende Verfahren. 2 ed . Stuttgart and New niques. Br Dent J 1999 ;187:359- 365.
York: Thieme, 2000 , 14. Farman AG, Farman Tf". Extraoral and panoram-
2. Dare A, Yamaguchi A, Yoshiki S, Okano T. Limi- ic systems. Dent Clin North Am 200 0;44:25 7-
tation of panoramic radiography in diagnos ing 272.
adenomatoid odo ntogenic tumors. OralSurg Oral 15. Molander B. Panoramic radiography in dental di-
Med Oral Pathc l 1994;77 :662- 668. . agnostics. Swed DentJ SuppI 1996;119:1-26.
3. OliverRG , Hodges CG. Delayed eruption of a max- 16. Abr ahams JJ. Dental CT imaging: A look at the
illary central incisor associated with an odo ntom e: jaw. Radiology 2001 ;2 19:334- 345.
Rep ort of case. ASDC J Dent Chi ld 1988;55:
368 - 371.
17. Vannier MW, Hildebo lt CF,Conover G, Knapp RH,
Yokoyam a-Crothers N, Wang G. Three-dimen-
4. Horner K, Shearer AC, Walker A, Wilson NH. Ra- sional dental imaging by spiral CT. A progress re-
d iovisiog raphy: An initial evaluatio n. Br Dent J port. Oral Surg Oral Med Oral Pathol Oral Radiol
1990: 168:244-248. Ended 1997 ;84:561 - 570.
5. Mouyen F, Benz C. Sonnabend E, Lodter JP. Pre- 18. Lenglinger FX, Mu hr T, Krennmair G. Dental CT:
sentation and physica l evaluat io n of Rad ioVi- Exam inat io n method , rad iatio n dosage and
sioGraphy. Oral Surg Oral Med Oral Pat hol anatomy. Radiologe 1999;39:10 27-1034.
1989 ;68:238- 242.
19. SpitzerWJ, BingerT. Roentgen diagnosis in oro-
6. Kashima I, Sakurai T, Matsuki T, et at. Intraoral maxillofacial surgery. Mund Kiefer Gesichtschir
computed radiograp hy using the Fuji computed 200 0;4 (suppl 1):270 -277.
radiography imaging plate. Correlation between
image quality and reading cond ition. Oral Surg 20. Bodner L, Bar-Ziv J, Kaffe l. CT of cystic jaw le-
sions. J Comput Assist Tomogr 1994;18:22-26.
Oral Med Oral PathoI 1994 ;78:239- 24 6.
21. ErasmusJH, Thompso n 10, van Rensbu rg LJ, van
7. Yoshiura K, Kawazu T, Chikui T, et al, Assessment
of image quality in dental radiography, part 2: Op- der Westhuijzen AJ. Central calcifying odonto-
genic cyst. A review of the literature and the role
timum exposure conditions for detection of small
mass changes in 6 intraoral radiograp hy systems. of advanced imaging techniques. Dentom axillo-
fac Radiol 1998;27:30- 35.
Oral Surg Oral Med Oral Pathol Oral Rad ial En-
dod 1999;87 :123- 129.

38
Referenc es

22. Scholl RJ, Kellett HM, Neumann DP, Lurie AG. 28. Lee YY, Van Tassel P, Nauert C, Raymond AK,
Cysts and cystic lesions of the mandible: Clinical Edeiken J.Craniofacial osteosarcomas: Plain film,
and radio log ichist opathologic review . Radi- CT, and MR findi ngs in 46 cases. AJR Am J
ographies 1999;19:110 7- 1124. RoentgenoI1988:150 :1397 - 1402.
23. Han MH, Chang KH, Lee CH, Na DG, Yean KM, 29. Becker J, Schuster M, Reichart P,SemmlerW, Fe-
Han MC. Cystic expansile masses of the maxilla: lix R. Principles of the clinical application of mag-
Differential diagnosis with CT and MR. AJNR Am netic resonance to mography (MAT) in oral rneoi-
J NeuroradioI 1995;16 :333-338. cine.Il: Clinical app lication of MAT. Dtsch Z Mund
Kiefer Gesichtsch ir 1986;10:46- 59.
24. Yoshiura K, Tabata 0, Miwa K, et at Comp uted
tomographic features of calcifying odo ntog enic 30. Wood NK, Goaz PW. Differential Diagn osis of Oral
cysts. Dentomaxillofac Radial 1998;27:12- 16. and Maxillofacial Lesions. 5th ed. St. Louis: Mos-
by. 1997.
25. Marttn-Duvemeuil N, Horsm-Chausson MH, Behin
A, Favre-Dauvergne E, Ohiras J. Co mbined be- 3 1. Shibuya H, Hanafusa K, Shagdarsuren M, Okada
nign odontoge nic tu mors: CT and MR finding s N, Suzuki S. The use of CT and scintigraphy in di-
and histomorpho logic evaluation. AJNR Am J agnosing a cystic ameloblastoma of the jaw. Clin
Neuroradiol 2001 :22;86 7-872 . Nucl Med 1994;19: 15- 18.
26. Gahleitner A, Solar P, Nasel C, et at Magnetic res- 32. Hardt N. Knoch enerkrankungen und turno rahn-
onance tomography in denta l radiology (dental liche Knochenerkrankungen. In: Sitzmann F, ed.
MRI). Radiologe 1999 ;39: 1044 -1 050. Zahn-, Mund- und Kiefererkrankungen. Atlas der
bildgebenden Diagnostik. Munich and Jena: Ur-
27. Heffez L, Mafee MF, Vaiana J. The role of mag-
netic resonance imaging in the diagn osis and ban & Fischer. 2000 :245- 390.
management of ameloblastoma. Oral Surg Oral
Med Oral Pathol 1988 ;65:2-1 2.

39
Section Two

Benign Neoplasms and Tumor-like Lesions


Arising from the Odontogenic Apparatus
Showing Odontogenic Epithelium With Mature
Fibrous Stroma, Without Ectomesenchyme

Introduction to Amelo blastom as list of the first th ree co mmonly accepted vari-
ants because recent studies2 - 6 lend support
to the co ntention th at it may well qua lify as a
A recently published biologic prof ile based subtype of ameloblastoma. The atypical mor-
on 3,677 ameloblastoma cases ,1 has clearly pho logy of the ep it helial co m po ne nt, th e
demonstrated that it is no longer appropriate marked stromal desmo plasia,th e unusual ra-
in any scientific study to use the diagnosis of d iologic appea rance, and the difference in
ameloblastoma withou t specifying the type . anato mic location compared to other fo rms
Based on clinical and rad iograph ic c harac- of ameloblastomas sugg ests that this tumor
teristics, histopathology, and behavioral and variant may be consid ered a c linico patho-
prognostic aspects ,three orfour subtyp es or logic entity and not just a histologic variant of
variants of ameloblastomas can presently be the SMA.
distinguished: Chapters 5 to 8 deal with each of th e fo ur
- The c lassic solid/ mult icystic ame lob las- variants separately. Each subtype has its own
toma (SMA) c linica l, radiographic, and histologi c charac-
- The unicystic ame loblasto ma (UA) teristics and th us is wort hy of ind ividual con-
- The peripheral amelob lastoma (PA) sideration. As previously mentioned, it is only
- The desmo plastic amelobiasto ma (DA), within the last 10 years or so that it has be-
including so-called hybrid lesions co me evident that a spl itting up of the old
amelobl astoma concept into several variants
The first two variants (SMA and UA) may be is appropriate. It is of paramou nt impo rtance
broken dow n further accord ing to their his- to patholog ists and maxillofacial surgeo ns to
tomorpholog ic cha racteristics (see c hapte rs understand the tru e nature and biologic be-
5and 8). The last variant (DA) is added to the havior of the ind ividual variants oft he amelo-

41
Introd uction to Ameloblastomas

blastoma tumor complex. If ignored , it may The tumors to be described in chapters g, 10


lead to unnecessary extensive and often mu- and 11, respectively, have for years been
tilating surgical lnterventio ns. cons idered ent ities, a viewpo int that has not
The term solid/multicystic ameloblastoma been changed in rece nt years.
deserves some discussion. This "classic" in-
traosseous ameloblastoma commences as
a solid epithelial tumor. In some cases , the References
epithelial islands rema in relatively small, and
1. Reic hart PA, Philipsen HP, Sonner S. Am elob las-
co nsequen tly there is litt le tendency towa rd
toma: Biological profi le of 3677 cases. Eur J Can-
cystic degenerat ion of the ep ithelial compo- cer B Oral Oncol 1995;3 1B:86- 89.
nent. The tumors remain so lid. In other cas-
2. Phi lipsen HP, Orm isto n IW, Reichart PA. T he
es, the neop lastic epithelial islands g row and desmo- and ost eop lastic ame loblastoma. Histo-
become cystic; this degenerat ive pro cess logic variant or cl inicopathologic ent ity? Case re-
starts in the center of the islands where the ports. Int J Oral Maxillofac Surg 199 2;2 1:352 -35 7.
cells cannot receive suffic ient supplies of nu- 3. As hma n SG, Cor io RL, Eisele OW, Murphy MT.
trients . This pheno menon may sp read to sev- Desmop lastic ameloblastoma . A case report and
eral islands, where it is first recognized mi- literature review. Oral Surg Oral Med Oral Pathol
1993;75 :479- 482.
croscopically and later grossly. This has led
to the use of the term cystic ameloblastoma, 4. Kaffe I, Buchne r A, Taicher S. Rad iologic features
of desmop lastic variant of ame loblasto ma. Oral
pr imar ily by cl inicians . Unfo rtunately, this
Surq Oral Med Oral PathoI 1993;76:525- 529.
term causes confusion with the unicystic
5. Thomp son IOC, van Rensb urg JL, Phillips VMJ.
ameloblastoma, which has a basically differ-
Desmop lastic ame lob lastom a: Co rrelat ive histo-
ent behavior-and a much better prognosis- pathology, rad iology and CT-MR imaging. J Oral
than the typical so lidjmulticystic amelob las- Pathol Med 1996;25:405 -410.
toma .Thus, it is imperative to unders tand the 6. Sak ashi ta H, Miyata M, Okab e K, Kuramaya H.
difference between a un icystic ameloblas- Desmo plastic amelob lastoma in the maxilla: A case
toma and one that is merely cystic. report. J Oral Maxillo!ac Surg 1998 ;56:783 -786.

42
Chapter 5

SolidjMulticystic Ameloblastoma

1. Terminology 2. Clin ical and radiographic


profile
The tumor that meets today's diagnostic en- The SMA is traditionally cons idered a benign
terra for solid/mu't icyst ic ameloblastoma epithe lial neop lasm with virtually no tenden-
(SMA) has been known for about 180 years. cy to metastasize. It Is slow-growing but lo-
In 1827 Cusack ' publ ished a report de- cally Invasive, with a high rate of recurrence
scribing what obviously was an amelob las- if not removed adequately. It is of utmost im-
toma. Broca- gave the first deta iled descrip- portance to unders tand that t he local bio-
tion of an SMA in 1868. During 1884 and logic behavior of an SMA Is that of a low-
1885 Malassez-v' studied odontogen ic tu- grademalignanltumor.lt is located centrally
mors and proposed the name "epithe lioma or intraosseously in bot h jaws, and there are
adamantin" for the SMA; he also showed it few or no clinical signs in the early stages.
could arise from odontogenic epithelial rem- Later there is gradually increasing facial de-
nants ("debris ep lthe liaux") . The term formity, teeth in the area may becom e loose,
adamantinoma was changed In 1930 ,5 es- and sponta neous fracture may occu r in cas-
peciallyin the English-speaking countries, to es whe re only a rim of normal bon e forms the
the more appropriate term ameloblastoma, base of the mandible. The affected part of
which is still In curre nt use.The term adaman- the jaw is bony hard and bulky. Pain occurs
tinoma may be cons idered a misnomer in as with varying, often quite low, freque ncy. It is
much as adamantin (enamel) is not a prod - not know n whether the cause of the pain is
uct of th is tumor. The characteristic periph - pressure from the tumor o n peripheral
eral cylindrical cells of the tumor islands are nerves or secondary infection. Tumors that
not true amelob lasts in that these cells are continue to enlarge may cause t he sur-
not capable of producinq enamel stroma , In rounding bone to beco me so thin that crepi-
particularbecause the tumor islands are em- tation or eggshe ll crackling may be elicited.
bedded In a mature , fibrous connective ns- Perforation of t he bon e, however, is a late fea-
sue. An accou nt on the term inology (with his- tu re. An unusually large amelob lastoma was
torical aspects) of the ameloblastoma was reported by Partrlella et al.7
published by Baden in 196 5.6 Radiog raphically,the SMA may show con-
siderable variation. The typical pictur e is of a
multi loc ular destruction of bone (Fig 5-1),but
unilocu lar appearances also occu r. In the
multilocular type the bone is replaced by a

43
5: Solid/MulticysticAmeloblastoma

Fig 5-1 Radiograph of an operation specimen Fig 5-2 An SMA with typical multilocular, soap-
showinga large, multilocular, follicularSMAolthe bubble appearance and extensive bone destruc-
molar/ascending ramus reg ion of the mandible tion in the molar/ascending ramus area. Histo l-
co ntaining a displaced, une rupted th ird molar. ogy showed a mixed follicular/plexiform SMA

Fig 5-3 Small multilocular SMA Fig 5-4 UnilocuiarSMA of the firstand second premolar mandibu-
in the canine/ first premolar area lar region. Not ice the embedded supernumerary premolar at the
of the mandible. periphery of the radiolucency and resorption of the mes ial root of
the mandibular first mola r.

number of small, well-defined radiolucent ar- area of radiolucencythatforms a single com-


eas, giving the whole lesion a honeycomb or partment. If this type is associated with an
soap-bubble appearance and ranging in size unerupted tooth (Fig 5-4), the appearance
from extensive destruction of half the man- closely resembles that of a dentigerous cyst
d ible (Fig 5-2) to a sma ll lesion confined to or an odontogenic keratocyst. Ueno et al8
the alveo lar process (Fig 5-3). In the unilocu- found that among 97 cases of SMAs, 47%
lar type (not to be misinterpreted as "un icys- were un ilocular and 37% were multilocular;
tic" ame loblastoma) there is a well-defined 16% had a soap -bubble or a combination of

44
Epidemiological data

soap-bubb le and multiloc ular appearance.


Figures 5-5 and 5-B show the result of ap-
plying co mp uted tomography (CT) software
for three-di men sion al rec on st ruct ion of a
SMA located to the ang le and ascending ra-
mus of the mandi ble.

3. Epidem iological data

3.1 Prevalence, incidence, and


relat ive freq ue nc y
Fig 5-5 CT showing buccal, multilocular expan-
Prevalence and incid ence figures could not sion of an amelob lastoma located in the rno-
be derived form the study by Reichart et at.? lar/ ascen dinq ramu s area.
Accurate figu res of thi s typ e can only be ob-
tained If every new case of SM/,< in a def ined
population is recorded in a tum or registry and
the microscopic material is reviewed by a
pathologist wh o is expe rienced with odo n-
togenic tum ors. A reasonabl e estimate of the
Incidence of ameloblastomas in a white pop-
ulation (in Swedes) was reported by Larsson
and Alrneren.' ? They fo und the annual inc i-
dence rate to be 0.6 new cases per one mil-
lion peop le. A second study was that of Shear
and Singh ,11 who investigated the incide nce
of amelob lastom as among the w hite and
Fig 56 Three-dimensional reco nstruction of the
black populations in a we ll-defined region
expand ing ame loblastoma shown in Fig 5-5.
around Johan nesb urg, South Africa. Gard-
ner' 2 recalculated the figures in Shear and
Singh's report and found the inc idence for
both sexes to be 2.29 new cases each year ings from recent years with tho se of the his-
per one millio n peopl e for blacks and 0.31 torical review by Small and wa ldron." who
for whites. Relative frequency data, on the evaluated 1,046 cases of ame loblastomas.
other hand, can be retrieved from several The retrospective study by Reichart et al9
sources and show gr eat variat ion, from suffers , ho wever, from several di sadvan-
11.0% to 95.4%. tages , includ ing the inconsistencies of the
The article by Reichart et al9 reviewed the data prov ided in the 262 papers reviewed
biologic profile of 3,677 cases of ameloblas- and the classifications used. The gene rally
tomas retrieved from the literature from 1960 well-accep ted co ncept develop ed during re-
to 1993, making lithe most extens ive review cent years of d ividing arnelob lastornas into
of ameloblasto mas ever published . One of three entities-csolld/rn ultlcystlc or co nven-
the aims of th e article was to compare find- tional; unicystic; peripheral-was applied to

45
5: SolidjMulticystic Ameloblastoma

th e data co llected. However, in ce rtain in- wit h the sub seq uent calcul ations made by
stan ces, pa rticu larly regard ing the elucid a- Gardnerl -' and find his estim ate of 39 years
tion of the mean age at diagn osis of the clas- for th e mean age at diagnosis of the classic
sic ameloblastoma (SMA), th e out come was SMA, 22 years for the unicystic, and 5 1 years
less clear du e to the circumstances involved for the peripheral ameloblastoma to be rea-
in produ cing the review w hich have already son able at this time.
been mentioned (see the fo llow ing section). The mean age of patients with tumors of
the maxilla was 47.0 years (n ~ 17 1) co m-
pared to tumors of the mandib le with a mean
3.2 Age age of 35 .2 years (n = 393; P < 0.00 1). Ueno
et alB rep orted a sig nificant d ifference in
The mea n age of patients at the time of di- mean age between SMAs with a unilocular
agnosis for all three types of SMA (n ~ 2,280, radiographic ap pearance and SMAs with a
includ ing reviews and case reports)wa s 3 5.9 multi loc ular/soap-bubb le appearance (26.4
years with a range of 4 to 92 years. On the years vers us 37.5 years). It s ho uld be
basis of case reports alon e (n ~ 650), the stressed that th e authors d id not st ate
mean age at ti me of diagnosis was 3 7.4 years whether cases of unicystlc ameloblastom as
(with a rang e of 4 to 92 years) (Fig 5-7). The were inc luded in their mate rial.
mean age of 39 .2 years for men was signifi-
ca ntly different (P < 0.05) from th at of 35.2
years fo r women. The present authors ag ree

No. of cases

160
'156 (Women + Men)
140 n =650
120
100
98 '99
80 86 '78
60
40 '50 '39
S7
20 7
o r=TI
0-9 10 - 19 20 -29 30 - 39 40 - 49 50- 59 60 -69 70 -79 80 +
Age in decades

Fig 5-7 Age dist ributio n? of 65 0 cases of arnelob lasto rnas, including unicystic and peripheral vari ants.
The peak in the 2nd decade most likely mirrors the inclusion of 102 cases of unicystic arneloblas-
tomas (mean age: 22.1 years). Similarly, the rather large number of cases in the 5th and 6th decades
may be ascribed to the inclusion of 63 cases of peripheral ameloblastomas (mean age: 51.0 years).

46
Pathogenesis

3.3 Gender 3.5 SMA associated with unerupted


teeth
The distribution amo ng men and wo men (n
= 3,677)9was 46.7% wom en and 53 .5% men Figu res fo r th e occu rrence of une ru pte d
(1:1.1 ). teet h associat ed with SMAs can be retrieved
from the review by Reichart et al.9 Ueno et
al8 investigated gO cases of SMAs with re-
3.4 Location gard to the presenc e of im pacted or un-
erupte d teet h. They fo und th at 34 cases
When case reports we re evaluated the ratio (38%) were associated with impacted teeth,
between maxillary (n = 185 ) and mandibu lar of which 82 % involved the mand ibular third
(n = 404)ameloblastomas was 1:2.2.9 If, how- molar, 15% the seco nd molar , and 6% a pre-
ever, case repo rts and reviews were co nsid- molar. In an additi onal case the tumor con -
ered together (n = 1,932), the ratio betw een tained a fourth molar. Non e of the examined
maxillary and mandibu lar tu mors was 1:5.8. maxillary SMAs (n = 5) includ ed impacted
This difference is du e to th e fact that maxil- teeth.
lary tumors are reporte d mo re often in case
reports. Based on the data reported by Re-
ichart et al? the topogr aphic locati on of
amelobiastomas in the maxilla was 284 and 4. Pathogenesis
in the mandible was 1,648 (Fig 5-8). Whe n
location and gender we re c ross-ta bulated , a
statistical sig nificance (P < 0.05 ) was re- It is ge nerally agreed that most SMAs occur
vealed. The inc isor region and ramus of the as growths arising from rem nants of od on-
mandi ble we re affect ed more ofte n in toqenlc epithelium, more specifically rests of
women than in men. In men th e premola r re- the de ntal lamina (see chapter 3). It should
gion and th e maxillary sinus were affecte d be noted that resid ues from the dental lami-
more frequently than in women, whe reas the na, if situated outs ide the bon e in the soft
molar regio n was affected equ ally in both tissues of t he gi ngival and edentu lous al-
sexes. veolar mu cosa (together with the basal cell

--- O . 5 --~

Fig 5-8 Topographical distribution of 1,932 cas-


es (case reports and reviews) of am eloblastorn as
(all variants) based on data from Reichart et al."
Figures represent pe rcentages of the tota l num-
ber. Cases involving an entire quadra nt are indi-
cated betwee n arro ws. Cases located in the max-
illary sinus (2.1 %) and nasal cavity (0 .7%) are not
shown. Numbers at the top and bottom of the
broken lines ind icate cases involving both ad-
joining reg ions: anterior/ premo lar and premo-
lar/molar.

47
5: Solid/Multicystic Ameloblastoma

layer of the oral epithelium), may give rise to whic h case t here may be a cl ose resem-
peripheral ameloblasto ma (see chapter 6). It blance to a unicystic ameloblastoma or an
is also agreed that SMAs may arise as a re- od ontogenic cyst. However, if one or more
sult of neoplastic changes in th e lining or small nodul es of growth protrude from an
wall of a non-neoplastic odontogenic cyst, in otherwise smooth lining, a preliminary diag-
particular in dentigerous and odo ntogenic nos is of a unicystic ame loblastoma (see
keratocysts. Op inions d iffe r regarding the chapter 8) must be considered. One or more
incid ence of these so-called mural amelo- teeth may be involved by the tumor.
blastomas. Baden 14 ind icated an incidence
varying from 17.8% to 30% and co rrelates
with the preferred locati on for SMA-the 5.2 M icroscopy
mandibular third molar. As early as 1885,
5.2. 1 Histologic definitions
Malassez" suggested th at Intraosseous
amelobl astomas may originate from "tes de- Acco rding to the 1992 World Health Orga-
bris epitMliaux" (epithelial restsof Malassez). nization (WHO) definition, an SMA is "a poly-
Early (microscopic) ameloblastomas located morph ic neoplasm consist ing of proliferating
between teeth, near the crest of the alveolar odo ntoge nic ep ithelium, which usually has a
ridge, document suc h a histogenesis and follicular or plexiform pattern, lying in a fi-
have been reported, espec ially in literature brous strorna.v"
from the mid-1 950sand earlier.Similarly,sev- The definition used by the present authors
eral authors of reports appearing in the first is as follows:
half of the 20th cen tury tho ug ht that the A polymorphic neoplasm consisting of pro-
enamel organ was a likely orig in of the SMAs. liferating odo ntogenic epithelium, usually oc-
curring in two main patterns. In the follicular
type of growt h the tumor co nsists of enamel
organ- like islands or follicles of epithelial
5. Pathology cells, while in the plexiform type the epitheli-
um forms continuous anastomosing strands.
In both types the ep ithelial tum or co mpo-
5.1 M acroscopy nents are embedded in a mature, connective
tissue stroma. Generally, a tumor shows one
The operation specimen will, depending on ort he other pattern throughout. However, not
the treatment modality, co nsist of the tumor infrequently both patterns are present in the
with a surrounding margin of normal bone. same tumo r.
The tumor appears as a grayish wh ite or gray-
ish yellow mass replacing the bone. The tu-
5.2.2 Histopathologic findi ngs
mor tissue cuts readily and cont ains no cal-
cified material. Some lesions are comp letely In the previously mentioned follicular pattern
solid, but in most cases cystic spaces are (Fig 5-9),the islands con sist of a central mass
present. These are generally quite small and of polyhedral cells, or loosely connected an-
scattered randomly. Less freq uently the cysts gu lar cells resembling stellate reticulum, sur-
are larger and the who le lesion has the ap- rounded by a layer of cubo idal or colum nar
pearance of a mu lticystic lesion. The cyst cells resemb ling internal dental epithelium or
content varies from straw-colored fluid to preameloblasts. Cystic degeneration co m-
semiso lid, gelatinous material. Somet imes monlyoccurs within the epithelial islands (Fig
the lesion cons ists of only a single cyst, in 5-10). In the plexifo rm pattern (Fig 5-11) the

48
Pathology

Fig 5-9 Solld/ rnulticystic ameloblastoma show- Fig 5-10 Sobd/multicystic ameloblastoma with
ing a follic ular pattern with central cystic degen- extensive cystic degeneration of follicular tumor
eration and some squamous cell metaplasia islands (multicystic ameloblastoma) (H&E, x25).
(hematoxylin-eosin [H&E] xso;

Fig 5-11 Solid ameloblastoma of plexiform type


(H&E, xsu).

tumor epith elium is arrang ed as a netwo rk are not a good indicator of cell proliferation
which is bou nd by a layer of c uboidal to but represent variations in metabolic or tran-
columnar cells and inc ludes ce lls resembling sc riptional activity.
stellate retic ulum. Cyst form ation occu rs but Histologic variants of the two main pat-
is usually d ue to stroma l degeneration rather terns of SMAs are described in the fOllowing
than to a cystic c hange with in the ep ithelium. sections. It sho uld be emphasized that these
Reichart et al9 found that in 397 case reports variants are not tumo r entities. It seems of no
the follicular patte rn was present in 3 2.5% of significance to prog nosis or c linical man -
tumors and the plexifor m pattern in 28.2%. age ment w hether a tum or can be diagnosed
Coleman et al ' 6 and do Carm o and Silva 17 as a follicular SMA, a plexiform SMA , or one
both used silver-staining nuc leolar organizer of the numerou s variatio ns outlined here.
region (AgNOR) counts in the investigation How ever, in the past it was suggested that
of possible differences in behavior between the granu lar cell SMA (see section 5.2.2.2)
arneloblasto rnas and other odontogenic tu- had a more aggressive behavior. This sug-
mors. They concluded that AgNOR cou nts gestion has not bee n substantiated and is to-

49
5: Solid/Multicystic Ameloblastoma

Fig 5-12 Follicularameloblastomashowing acan- Fig 5-13 FollicularameloblastomaWith extensive


thomatous changes(squamousmetaplasia)of al- granular transformation of the stellate reticu-
most all tumor islands (H&E. x SO). lum- like cells (H&E, x 140).

day co nsidered invalid. The clear cell SMA reticulum- like cells. In some lesions all cells
(see section 5,2.2.5), on the other hand. re- of the tumo r islands or nests are co mposed
quires some attention because in at least of granular cells. In a survey of 20 cases of
some instances it is capable of locally de- granular ce ll SMAs, Hartman' ? fou nd t hat
structive growth and both nodal and distant this variant acc ounted for 5% of all amelo-
metastases, These tu mors are today co nsid- blastomas, The granu lar c ells may be
ered clear cell odo nto genic carcinomas (see cuboidal, columnar, or round ed, and the cy-
chapter 27), to plasm is filled with acidophili c granules.
The cytop lasmic granules have been identi-
5.2.2. 1 Acanthomatou s SMA (Fig 5-12). fied ultrastr ucturally as lysosom al agg re-
This term is app lied when there is extensive gates.20 - 22 Kumamoto and Ooya22 also per-
squamous metaplasia. sometimes with ker- formed immunohistochemical studies on six
atin formation. within the islands of tumor cases of granula r ce ll SMAs and demon-
cells, The horny pearls may become calci- strated th at the granularity might be caused
fied, Usually the general pattern of this tumor by increased apoptotic cell death and asso-
variant is of the follicular type. Acco rding to ciated phagocytosis by neig hboring neo-
Reichart et al?the acanthomatous variant ac- plastic cells.
co unted for 12,1% of th e reviewed 397 case Altin i et al23 reported on two cases of what
reports and is the third most common histo- th ey termed "plexiform granular ce ll odo nto-
logic type,This variant must be disting uished ge nic tumor " (PGCOT). Both lesions con-
from the squamous odo ntogenic tumor (see sisted of interlacing strands of odon to genic
chapter 9). in which t he peripheral ce lls of epithelium, with each strand being two cell
the tumor islands are flat rather than co lum- layers thick . The ce lls were large and poly-
nar. hedral in shape. with granular acidop hilic cy-
to plasm. No amelob lastoma-like tissue was
5.2.2.2 Granular cell SMA (Fig 5- 73). found in either case. The authors suggested
This term is applied when the tum or, most of- that these lesions might represent previous-
ten of the folllcular type, shows an extensive ly und escribed histologic variants of SMA.
granular transform ation of the central stellate However, t hey co uld not exclude the possi-

50
Pathology

bility that the lesions represented a new en- the highest labeling indices for both PCNA
tity. Siar and coworkers 24 .25 descr ibed com - and Ki-67, indicating that the basal cell type
bined granular cell ame loblasto ma and PG- is the most actively proliferating type and
COT, butthe true nature of these lesions have therefore th e most immature cells in an SMA.
yet to be clarified. Granular cells may occ ur
invarious odo ntogen ic and nonodo ntogenic 5.2.2.5 Clear cell SMA.
tumors. SMAs may co nta in clear, periodi c-acid-
Mirchandani and Sciubba 26 prod uced a Schiff (PAS) positive cells most often local-
comprehensive study of 44 oral granular cell ized to the stellate reticulum-like areas olthe
lesions, including four granular cell arnelo- fo llicular SMA. It is important to realize that in
blastomas, pr esent ing clinicopatho log ic , recent years at least some clear cell SMAs
immunohistoch emical, and ultrastructural have proved to be malignant tumors. Details
findings. A similar but less intensive study about this rare entity are descr ibed in chap-
was perfor med by Ruh l and Ak uamoa - ter 27.
80ateng.27
5.2.2.6 Keratoamelobiastoma (KA) and
5.2.2.3 Desmoplastic SMA. pap illiferous KA.
This term is used, especially in the fo llicu lar In 1970, Plnd borq -? prod uced a radioqraph
type of tumor, when there is a marked hyalin- and three photomicrographs of an unusual
ization (desmoplasia) of the connective tis- type of ameloblasto ma consisting partly of
sue stroma (for details, see chapter 7). keratin izing cysts (Fig 5-15) and partly of tu-
mor island s with papillifero us appe arance
5.2.2.4 Basal cell SMA (Fig 5-14). (Figs 5-16 and 5-17); he suggested the term
in rare cases, an SMA may show a predom- papilliferous keratoameloblastoma (PKA) for
inantly basaloid pattern. This variant occ urs this lesion. Later, Altini et al30 described a
in only 2.02% of the reviewed case repo rts." similar tumor that differed from the one de-
in a recent immun ohistochem ical study by scribed by Pind borg in that IT d id not show
Sandra et al28 using monoclonal antip rolifer- the pap illiferous epithelium nor the extensive
ating cell nuc lear antige n (anti-PCNA) anti- necrosis and debris in the middle of the fol-
body and monoclonal anti- KI-67 antibody, licles. Altini et al raised the question as to
theauthorsfound thatthe basal cell SMA had whethe r bot h lesions represented the same
tumor. In 1993, Siar and Ng 3 1 reported four
cases resembling KAs to some extent, with
the except ion that papilliferous epithelial tu-
mor islands were notfound .Thetumors were
cha racte rized by th e simultaneo us occur-
rence of areas of ameloblastoma with pro-
nounced keratinization and cystic areas re-
sembling odo nto genic kerato cysts. In 1997
Said-AI-Naief et al32 added a fifth case to
those reporte d by Siar and Ng.
KAs, PKAs, or possible hybrid lesion of th e
two are extremely rare neop lasms and an ac-
curate evaluation of the clinical spectrum, ra-
Fig 5-14 Solid ameloblastoma withtumor islands diology, and behavioral potentiai must await
showing a basaloid pattern (H& E, x140). further case acc rual.

51
5: Solid/Multicystic Ameloblastoma

Fig 5-15 Papilliferous keratoameloblastoma. In Fig 5-16 Papilliferous keratoameloblastoma


this area of the tumorthere are several keratiniz- (same tumor as shown in Fig 5-15). In this part of
ing, irreg ular cysts with massive parake ratiniza- the tumor the islands show a papilliferous, ep-
lion (H&E, x60). ithelial lining of small cysts containing a homog-
enous eosinophilic content (H&E, x60).

Fig 5-17 Higher magnification of the tumor


shown in Fig 5-16. The papilliferous appearance
is evident. The tumor stroma is rest ricted to deli-
cate bands of fibrous connective tissue (H&E,
x 140).

5.2.2.7 Muco us cell differentiation in SMA. the unlcystic (see chap ter 8), desmoplastic
In a recent pa per, Wilson et al33 rep orted (see c hapter 7), and hemang iom atou s ame-
what was th oug ht to be only the fourth case lob lastoma (hemangioameloblasto ma). The
of an Intraosseous, follic ular ameloblastoma HA is a SMA in whic h part of the tumor con-
showing foca l mucous cell differentiation. On tain s spaces filled with blood or large en-
th e other hand , the presence of vacu olated dothelial-lined ca pillaries, first described by
and muco us cells in radicular and residu al KOh n in 1932.35
cysts has been well docu rnented.>' Van Rensburg et al36 recently reported a
case of this rare tum or variant in a 26-year-
5.2.2.8 Hemangiomatous ameloblastoma old wom an who had a gradually enlar9ing
(HA). symptomatic swel ling in the posterior region
Variations in the histomorphologic patterns of the left mandi ble. Panoramic radiog raphs
of ameloblastomas do not app ear to have a and CT revealed a mix ed rad iolucent-ra-
significant bearing on th eir biologic behavior diop aque lesion with bu ccolin gu al expan-
or progn osis, with the possible exceptions of sion and mild root resorpti on s of the second

52
Pathology

molar. On MRI the tu mor contents disp layed 5.2.2.9 Extragnathic (tibial) adamantinoma
an intensity suggestive of bun dles of vascu- (ETA).
lar struct ures or blo od vessels in various The adamantinoma (an obsolete synonym
stages of thrombosis or slow flow. A vaso- for ame loblastoma) was first described by
formative neopl asm or a tumor with a vas- Fischer in 1913.3 8 It is a rare, primary intra-
cularstroma was considered the most likely osseous epit helial neoplasm of low-grade
diagnosis. Enucleation of the vascu lar tissue malignancy with a marked predilection for
caused profuse bleeding. Histology revealed the tib ia, where 90% of cases arise in the mid-
a plexiform ameloblastoma with a pro minent d le third of the bone . Czerniak et al3 9 distin-
vascular compon ent cons isting of numerous gu ished two types of ETA: the classic form
endothelial-lined channe ls and large bloo d- and the d ifferentiated form. The classic form
filled spaces with multiple thrombi located in usually presents in older patients , grows be-
thetumor stroma . The lesion was diagnosed yond the co rtex, and some times metasta-
as HA. The patient refused a planned sub- sizes. Histologically, the classic ETA is char-
sequent rad ical operat ion. acterized by an abundance of epithelia l cells
The origin of the vascu lar com ponent of which stain strongly for cytokeratin . The dif-
the HA is not clear and several theo ries have ferentiated form, on th e other hand , occurs
been advanced ; among them are excess ive at a young age (during th e first two decades)
stimulation of angioge nesis during tumorde- and has an intracortical location. Histology
velopment and trauma such as to oth extrac- shows that it has a uniform predom inance of
tion (in the preced ing example, th e secon d an osteof ibrous dysplasia-like pattern, with
molar had been extracted 11 years earlier). on ly a scattered, inconspicuous epithel ial
Ithasfurther been sugg ested that the HA rep- cell component. The interesting relationsh ip
resents a co llision tumor. Whether the vas- of osteofibrous dysp lasia to t he ep ithelial
cularcomponent of the HA is part of the neo- component of ETAs has recently been ad-
plastic process , represents a separate dressed in several reports 4 0 - 43 The ETA was
neoplasm, or is a hamart omatous malforma- once thought to be related to the SMA of the
tion remains to be seen. t.ucas-'? believed jaw bones because of some histo logic re-
that the unusual vascularity is not due to a semblance to the latte r; however, a relation-
neoplastic process.According to this author, ship between the two has never been estab-
there is an entire absence of vasoforma tive lished . At one time the ETA was also tho ught
activity. In the process of format ion of stro- to be endo thelial, synovial, or mesenchymal
mal cysts in the ordinary type of plexiform in origin.
ameloblasto ma, the blood vessels often per-
sist and dilate instead of disappearing; thus,
5.2.3 Histo chemical/immunohistochemi-
it is likely to represent a purely secondary
cal findings
change.Van Rensburg etal 36 con cluded that
findings on CT scans in association with an Th ere have been few stud ies desc ribing his-
angiomato us/vascular stro ma on MRI are toch em ical find ings in ame lobl astomas ,
suggestive of HA. whereas imm unoh istochem ical demo nstra-
tion of a great var iety of im portant su b-
stances, ant igens , and markers has been
abundant , especia lly with in t he last two
decades. A few of these reports have already
been referred to in the preceding para-
gra phs . Almost all the publications have

53
5: Solid/ Multicyslic Ameloblastoma

compared the findings in ameloblasto mas to squamous ep ithel ium. It shou ld be men-
those of other odo ntogenic tumors, odonto- tioned that according to th e clinical data giv-
genic cysts, and human fetal too th germs. In en for the plexiform variant, at least 10 tumors
summary, the follow ing areas of ame loblas- may qua lify for th e tumor curre ntly know n as
toma imm un ohi stoch emistry have been the plexiform, unicystic ameloblastoma (see
covered in th e literature: cell surface carbo- chapte r 8).
hyd rate co mp osition (lectin histo chem- Lee et al67 descr ibed the ultrastructu re of
istry)44.45; blood group ca rbohydrates A, B, a "simple" ameloblastoma (SMA), th e occ ur-
and H type 246,47; involucrin express'vity": rence of cells possessing single cilia which
expression of amelogen ins, enamelin49-51; arose from a basal body and occasional cells
intermediate filaments (cytokeratins and vi- co ntaining Langerhans granules. In additi on,
mentin )52.53; laminin-554;osteo lytic cytokines th e tumo r stroma conta ined oxytalan fibers.
and adhesion mo lcules55; PCNA56-58; bone Muci n-produ cing cells were reported by Min-
slalop rote in' P: bo ne morphogenetic pro - cer and Mc Ginnis68 to occur in a multicystic
tein60; and bcl-2 protein.61,62 ameloblastoma. The discovery of these cells
had earlier led Hodson69 to propos e a sub-
class of mucoe pidermoid ameloblastoma.
5.2.4 Ultrastructural findings
Occ urrence of int racytoplasmic d esm o-
The first reports on the fine structure of SMAs som es in a maxillary ameloblastoma was re-
appeared around 1960 63.64 Moe et al64 were ported by Cut ler."? The presence of intracel-
the first to ack nowledge that the peripheral lular desmos omes could, accordi ng to the
cells of the so lid, follicu lar ameloblasto ma author, suggest a high degree of membrane
were ult rastructu rally similar to the inn er polymorphi sm between tumor cells and thus
enamel epithelium. This viewpoint was sub- ind icate a more aggre ssive lesion. Occ ur-
sequently supported by several studies. Kim rence of so-called hyaline bodies, ultrastruc-
et al65 found that, in add ition to the strong re- tu rally similar to those found in odo ntogenic
semblance of the co lumnar cells of the tumo r cyst epithelium and cyst walls, have been
to the cells of the inner enamel epithelium at demo nstrated in a case of plexiform amelo-
an early stage of differentiation, the stellate blastoma by Takeda et at.71
cells of the tumor epithelium were similar in Ultrastructural studies have concentrated
many respects to the stellate reticu lum of the on the epithelial components of SMAs as op-
normal enamel organ . In areas of metaplas- posed to the tumor stroma. The stroma has
tic squamo us cell changes, th e aut hors been described as co nta ining fibroblasts
found that these cells had ultrastructural fea- and collagen fibers, butTothouse et al72 also
tures similar to those observed in basal cells demonstrated the occurrence of rnyofibrob-
and lower prickle cells of th e oral mucosa, lasts th at showed for mation of plaqu elike
especially in the epith elium of the palatal mu- stru ctu res o n exten ded c ell p rocesses,
cosa. In a transmission electro n microscopy w hich the auth ors identified as intracellular
(TEM) study of 12 plexiform and 9 follicu lar septate junctions. Smith and Bartov73 con-
amelob lastomas, Nasu and Ishik awa 66 firmed the findi ng of abundant rnyofibrob-
found that the follicular variant consisted of lasts in a case of recurr ent SMA.
two cell types, one resembling the stellate
reticu lum and the other resemb ling the inner
enamel epithelium of the normal enamel or-
gan. The plexiform variant, on the oth er hand ,
did not show two cell types but resembled

54
Notes on treatment and recurrence rate

5.2.5 Ameloblastomas in tissue culture 6. Notes on treatment and


Thefirst attempt at studying primary cultures
recurrence rate
from explants of a follicular, sol id ame lo-
blastoma in roller tu bes was do ne by Niiz- No slngle standard type of therapy should be
irna. ?" who had pr eviou sly don e tissue advoc ated for patients with SMAs. Rather,
culture studies of enam el eplthelturn." Epi- eac h case shou ld be judged on its own mer-
thelial elements of squamo us typ e, whi ch its. As stated previously, modern classifica-
formed widespread sheets, acco unted forth e tions divide the ameloblastomas into three or
major part of the outgrowth. The epithelial four entities. This classification is of utmost
cells were similar in structure and behavior importance becau se the cli nical behavior
to those obtained fro m culture of th e enam- and treatment of these ameloblastomas dif-
el organ, aitho ugh in so me respects- such fer. The solid/rnulticystic ameloblastoma re-
as the vigorous movem ents of und ulating q uires radical surgical intervention. Unicystic
membranes, pinocytosis, and the formation ameloblastomas (see chapter 8) requ ire only
of perinucle ar vacu oles- th e tumo r cel ls co nservative surgical enucleation, unless in-
showed much more activity t han did those of filtration from th e epithelial cyst lining into the
the normal tissue. During the last decade or cyst wall has been demonstrated, in which
so, investigators have tried to produce long- case the treatment should follow that out-
term cu ltures of human ame loblastomas. lined for SMAs. Peripheral ameloblastomas
The ultrastructural three-di mensional growth should be treated co nservatively.Two recent
of follicular amelob lastoma ce lls in co llagen repo rts 78.79 can be reco mmended as an
matrix in vitro was reported by Yasuda et al.76 overview of the current status of the surgical
The result demonstrat ed that th e cells de- management of ameloblasto mas. Gardner' "
veloped in this short-term cult ure system had points out that the characteristic slow growth
characteristics of amelo blastoma cells. of the SMA is significant in th at it may take
in 1998, Harada et al 77 succeeded in pro- years before a recurrence becom es evident.
ducing-by transfection with HPV-16DNA- As a result, clinici ans and patients tend to be
an immortalized human amelob lastoma cell lulled into a false sense of security, and con-
line which th ey designated AM-1. This ce ll seq uently follow-up exam ination s may be
line maintains epithelial cel l morpholog y and neglected after the first few years. Recur-
expresses cytokeratins 8, 14, 18, and 19 but rences may occ ur 5 to 10 years after surgery,
not 10 or 16. The express ion of vimentin was and it is the refore imperative that the surgi-
weakly positive. Furthermore, bcl-2 protein, cal sites be exam ined thoroug hly (includi ng
which prevents apo ptos is, was co nsistently radiographs) for at least 10 years and prefer-
expressed. The behavior of these ce lls on a ably long er. Recurrences fo llowing different
collagen matrix was investigated and treatment modalities have been reported by
showed that the ce lls grew in a monolayer Reichart et al9 and Gardner ,78
over foci of co llagen deg radation and could
invade the collagen gel at such sites, thus
mimicking the behavior of in situ ameloblas-
toma cells. The authors co nc luded that AM-
1 appears to be an app ropriate model sys-
tem which might be used in determ inin g
various mechan isms that influence the biol-
ogy of amelob lastomas.

55
5: So lid / M ult icystic Amelo blasto ma

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200 1;91;576- 578. Scand [AJ 1985;93:25- 34.
34. Slabbert H, Shear M, Altini M. Vacuolated cells 47. Gard ner DG, O' Neill PA. Inabi lity to distingu ish
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1995;24 :309- 3 12. Su rg Oral Med Oral Pathoi 1988 ;66:480 - 482
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nom mit Harnanqiorn als zent rale Kieferge- mu nostai nin g of invo luc rin in odonto genic ep-
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36. Van Rensburg LJ, Thompson 10C, Kruge r HEC,
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200 1;9 1:374-380. A Pathol Anat Histopathol 199 1;418 :319-325.
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51 . Snead ML, Luo W, Hsu DD-J, et al. Human amelo-
39. Czerniak B, Rojas-Coro na RR, Dorfm an HD. Mo r-
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phologic d iversity of long bone adama ntinoma.
Oral Surg Oral Med Oral Pathol 1992;74: 64-72 .
The conc ept of d iffe rent iated (regressing)
adaman tinoma and its relat ionship to osteo -fi- 52. He ikinheimo K, Hormia M, Stenman G, et al. Pat-
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40. Ueda Y, Blasius S, Edel G, W uisman P, Bocke rW,
Oral Pathol Med 1989;18:264-27 3.
Roessne r A. Osteo fi bro us dysplasia of long
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Taminiau AH , Hogendoo m PC. Distribution of ex- 54. Salo T, Kainu lainen T, Parikka M, Heikinheirno K.
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to ada manti noma. A clinicopathologic study of 30
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57
5: Solid/Mull icysli c Ameloblastoma

55 . Pripatnanont P, Song Y, Harris M, Meg hjiS. ln situ 67 . Lee KW, EI-Lab ban NG, Kramer IRH. Ultrastr uc-
hybrid izatio n and im mu nocyt oc hem ical loca liza- ture of a sim p le a m elo blastom a. J Pat hoi
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68. Mince r HH , McG in nis J P. Ultrastructure of three
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histo logic variants of the amelo b lasto ma. Cancer
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1994;306: 126 - 13 1. ta in m uco-ep id erm oid variat io ns. Br J Plast Surg
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70 . C utler LS. Intracyt op lasm ic de smosomes in hu-
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22 1-2 26.
328 -332.
71. Takeda Y, Kikuc hi H, Suzuki A. Hyaline bodies in
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am e lob lasto ma: Histolog ical and Ultrastructu ral
p ressio n of p ro liferating c ell nuclear antige n in
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ame lo b lasto mas an d od o ntoge nic cysts. O ral O n-
00119 98:34:4 08 - 4 12. 72. Totho use LS, Majac k RA, Fay JT. An am e lobl as-
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61. Mits uyas u T, Ha rad a H, H ig uc h i Y, et a t Im- 75 . Niizima M . Enam el epith elium in tissue c ultu re.
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26:34 5- 348. of human amelo b lasto ma cel l in co llagen matrix
62 . Kumam oto H. Detectio n of a po ptosts-related fac- in vitro: An ultrast ructu ral study. J Oral Patho l Med
to rs and apo ptotic cells in arneloblastom as: Analy- 19 91 ;2 0:43 8-44 2.
sis by immu nohistoc hemistry a nd an in situ DN A 7 7. Harada H, M itsuyasu T, Naka mu ra N, et al. Es-
nic k end -labelling metho d. J Or a l Patho l Med ta b lishment of ame lob lastoma ce ll line, AM-1 . J
199 7;26:4 19 - 425 . Oral Pat ho l Med 199 8 ;2 7:20 7- 2 12.
63. Kitamu ra K. The stud y on the ame lo blasto ma by 78 . Gard ner DG. Con trov ersies in th e no menclatu re,
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19 58 ;3:17-34. Wormin gton P, Evans J R, ed s. Co ntroversies in
64. Moe H, Clausen F, Philips en HP. Th e ultrastru c- Oral and Max illof acia l Surgery . Philade lph ia: WB
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19 79 ;8 :3 19-3 32. 383-388.
66. Nasu M, Ishik awa G. Amelob lastoma. Lig ht and
elect ro n mic roscopic stud y. Virchows Arc h Patho l
Anal 1983 ;39 9:163- 17 5 .

58
Chapter. 6

Peripheral Ameloblastoma

1. Termino logy should not be considered peripheral ame lo-


blastomas. The cases reported by Gullifer 17
The pe riph eral ame loblasto ma (PA)- also and Ch'in 18 likewise leave much to be de-
known as th e extraosseous amelob lastom a, sired in fulfilling the requ irements of true PAs.
soft tissue amel obl astoma, amelo blastoma The first co mplete ly documente d case of a
of mucosa l origin, or ameloblasto ma of the PA must be attr ibuted to Stanley and
gingiva-has several of the same histo logic Kroqh.l ?
characteristics as a solid/ rnulticystic amelo- T he tumor profile presented in this c hap-
blastoma (SMA), but it occurs in the soft tis- ter is based on data from 160 cases of PAs
sues overlying the tooth-bearing areas of the published by Philipsen et al.20
maxilla and mandible. PAs do not invade the
underlying bo ne. (This definition exclud es
five qu estionable cases reported as PAs in
extraqinqival locations.l t'') Six cases of basal 2. Clinical and radiologic profile
cell carcinomas (BCCs) arising in th e ging i-
va have also been repo rted and are inc lud-
ed in this c hapte r. Currently, there is general The PA is a painless, sessile, firm, and exo-
agreement that the PA and the BCC are es- phytic growth, the surfac e of which is usual-
sentially the same lesion and thus should be ly relatively smooth but in several cases has
regarded as a single entit y 6 - 9 Sc iubba 10 been described as "granular" or "pebb ly." In
claimed that in spite of many histologic sim- other cases th e surface exhibits a "papillary"
ilarities betw een PA and BCC, the PA de- or "warty" appearance. The color of the le-
serves to be a separate entity in a bio logic sion varies betwee n normal or pink and red
context. or dark red. During mastication the PA may
Several autho rs 1 1-1 3 referto Kuru 14 as hav- be tr aumatized, an d the lesio n may thus
ing repo rted on the periph eral amelo blas- sho w an ulcerated surface or appear kera-
toma for the first time. However, what Kuru tot ic (frictional keratosis). The durat ion of the
described was not a peripheral but rather an lesion is reported to be anywhere between 2
intraosseous SMA that penetrated throug h days and 20 years, and the size ranges fro m
the alveolar bon e, fused with th e oral epi- 0.3 to 4 .5 cm in diameter with a mean of 1.3
thelium, and eventually presented itself clin- cm.
ically as a "peripheral lesion ." Kuru's case In the vast majo rity of cases there is no ra-
and similar cases reported by Tongdee and diologic evide nce of bone involvement. Ra-
Ganqqavakinl'' and Stevenson and Austinl '' diog raphically or at surg ery a superficial ero-

59
6: Peripheral Ameloblastoma

-
Fig 6-1 Orthopantomograph showinga peripheralameloblastoma Fig 6-2 Intraoral radiograph of
in the area of the left mandibu lar second premolar. Not ice th e shal- the same case as shown in Fig
low saucerization of th e bone (arrow) . 6-1.

sion of the bone or a superficial bony de- showthatthe PA comprises from 2% to 10%
pression-cupping , orsaucerlzatlon-rnay be of all ame lob lastomas. The PA is genera lly
noticed (Figs 6-1 and 6-2), a find ing that is described as an exceed ingly rare lesion. The
thought to be caused by pressure resorption following prof ile tends to indicate that the PA
rather than resorption caused by neoplastic is actually more prevalent than hitherto an-
invasion. tic ipated.
PA is rarely made as the initial preopera-
tive diagnosis. The most common diag-
noses, depending on morphology, texture, 3.2 A g e
and color of the lesion ,are epulis (42 .6%) and
benign tumor (26.0%), followed in decreas- The age range of patients with PAs (n ~ 135)
ing order by papilloma and pyog enic granu- varies between g and 92 years at t he time of
loma. When the PA arises on the edentulous d iagnosis, w ith an overall mean of 52 .1 years
alveolar mucosa in denture-wearing patients, (Fig 6-3). The mean age of men is slightly
it may be diagnosed as denture irritation hy- higher (52.9 years) than that of women (50 .6
perplas ia. The correct diagnosis requires his- years), w ith 63 .7% of all cases occurring in
tolog ic evaluation . th e 5th , 6th , and 7th decades (men , 45 .2%;
women, 18.5%). Men reach a peak In the 5th
and 6th decades, wh ereas women show two
peaks, one in the 4th decad e and one in the
3. Epidemio logical data 7th. T he mean age for SMA s 2 1 was reported
to be 37.4 years. T hus, it is important to note
tha t the PA occurs at a significantly high er
3. 1 Incidence, prevale nce, and age than its central "counterpart" (if this term
rel ative f requency is applicab le). This may seem puzzling be-
cause most other per iphera l odontogenic tu-
Information on the relative frequency of PAs mors , such as the adenomatoid odontogenic
is very scarce. Data from various sources-? t umor or t he ca lci fyi ng epithelia l oconto-

60
Epidemiological data

No. of cases

30
OJ Wom en
21 21
19
OJ Men
20 n= 135

10 11 10 11
10 9

0 -9 10 -1 9 20 -29 30-39 40-49 50 -59 60 -69 70 - 79 80 -89 90 +


Age in decades

Fig 6-3 Distribution ot 135 cases of PAs by age (in decades) and gender.

genic tumor, occ ur at a not iceab ly low er


mean age than their correspon ding (true) in- 11
traosseous counterparts.
0 ,, 4
:
3.3 Gender
,,I CD
n = 13 5
When considering the distribution of PAs ac-
cording to gende r (n = 160 ), 104 (65.0%) oc-
curred in men and 56 (35.0%) in wo men, the
male:fe male ratio be ing 1.9 :1. The co rre-
spond ing figures for SMAs are 54.5% in men
and 45.5% in women,givinga ratioof 1.2:1.2 1

Fig 6-4 Anatomic distribution of 135 cases of PAs


3.4 Locat ion accord ing to Japanese cases (n = 73, num bers
circled) and non-Japanese cases (n = 62. num-
bers not circled).
The soft tissues overiaying the tooth-bearing
areas of the mandible are clearly the most
common site for PAs (n = 135; as no statisti-
cally significant d ifferences co uld be fo und
between the Japanese and th e non-Japan- the soft tissues of the mandibular premolar
ese location data, th e data w ere poo led) as region with 3 2.6% of all lesions found here.
shown by the occ urrence of 9 7 (7 1.9%) le- Second was the anterior mandibular region,
sions in the mandible and 38 (28.1%) lesions accounting fo r 20.7%. In the maxilla, howev-
in the maxilla. A detailed location analysis is er, the most commo n location was the soft
shown in Fig 6-4. By far the most co mmon palatal tissue of the tuberosit y wh ic h ac-
site for PA develo pment with in the jaws was counted for 11.1% of all cases. The maxi1-

61
6: Periphe ra l Ameloblastoma

la:mandi ble ratio was 1:2.5 , a figu re that ameloblastoid variant of the squamous cell
should be compared to 1:5.4 for solid/mu lti- carcinoma. It is characte ristic that the re-
cystic ameloblastomas. It is of furt her inter- ported five extragingival cases all developed
est that the majority of the mandibu lar PA around the orifices of either the Stensen duct
cases were located on the lingual aspect of or the Wharton duct and could thus repre-
the gingiva. sent tum ors of salivary gland orig in.

3.5 Extraging ivallesions reported as 3.6 Inclusion of the odontogenic


PAs gingival epithelial hamartoma (OGEH)
under a peripheral ameloblastoma
As mentioned earlier, five extraging ival le- diagnosis
sions have been report ed under the term pe-
ripheral ameloblastoma . Four of the lesions The OGEH, also referred to as a hamartoma
involved the buccal mu cosa and one , the of the dental lamina rests, is a rare, as yet in-
floor of the mouth. The authors argued that co mpletely defined , periph erally localized
because of the histologic similarity to amelo- hamartomatous lesion initially described by
blastomas, and with co nsideration given to Baden et al. 22 Details of the six cases re-
the pluripotentiality of the oral epithelium, ported so far are summarized in Table 2 in
these lesions could be consi dered to be ex- Philipsen et al.2oThe OGEHs occurred in one
amples of PA. Zhu et al' 3 believed the term male and five female patients with a mean
peripheral ameloblastoma should be used age of 57 years at the time of diagnosis. The
not only to desc ribe a neoplasm arising in the maxilla:mandi ble ratio was 1:5 and the ie-
soft tissues overlying a tooth-bearing region, sions were located in the anterior gingival (5
but also to include those found in more re- cases) and premolar (1 case) regions of the
mote locations such as the buccal mucosa, jaws. The lesions p resented as asympto-
lips, palate, and other parts of the oral mu- matic, small rounded masses, often on the
cosa. The authors based their view on an an- lingual aspect of the alveolar ridge.
imal experiment, where co mbined oral ep- Radiographically or at surgery a slight cup-
ithelium and dental pap illa we re cut from ping of the adjac ent bone was a common
17.5-day-old C3H mouse embryos and trans- finding. Histologically the lesions showed is-
planted to the renal subcapsu lar space of 3- lands, clusters, and thin bands of odonto-
month-old syngeneic mice. After 3 weeks the genic epithelial cells scatte red in a mature fi-
formation of teeth and odontogenic kerato- brous stroma w hich became loose and
cysts were apparent. These findings were lat- slightly myxomatous in the depth of the le-
er interpreted by Zhu and coworkers 13 as the sion.The epithelial cells sometimes occ urred
oral epithelium having the potential to differ- in a lobu lar pattern and te nded to be
entiate into arneloblasts and to form teeth arranged in an outer layer that was cuboidal
and odo ntogenic lesions, an interpretation orco lumnar shaped with closely packed cen-
that may be d ifficult to accept regarding the tral cells, oval to polyhedral in shape. Half of
development of PAs. t he cases reported revealed continuity be-
Extragi ng ival lesions have not been in- tween the tesional tissue and the overlying
cluded under the diagnosis of PA in th is rete ridges of the oral ep ithe lium, while in the
book. They most likely represent basal cell ot her half no such con nectio n co uld be
ade nomas w ith a histopatho logic resem - found. In considering the histogenesis of the
blance to an am elobl astoma or the rare OGEH, two major sources of origin must be

62
Pathology

considered: the basal ce ll layer ofth e surface um , and are separated from the surface ep-
epithelium and remnants of the de ntal lami- ithelium by a band of collagenous tissue like-
na. Following excision, no recu rrences were ly arise from remnants of the dental lamina
reported in the five cases where follow-up located in the soft tissues overlying the tooth-
data were available. bearing areas of the jawbones. These cell
A comparison between the clinical and be- rem nants, or Serres pearls, are ofte n en-
havioral features of the OGEH with those of co untered in the normal tissues adjacent to
the PA leads to the assum ption th at they PAs.
could likely be considered th e same lesion. Alternatively, lesions may arise from the
Data on age, clin ical find ings such as loca- surface epithelium, in so me cases at one or
tion, radiog raph ic appearance , behavioral a few sites and in oth ers m ultit ocally.?" The
pattern, and histol ogy app ear to be identical. hypothesis that the continuity between the
Whereas know ledge and und erstand ing of tum or and the surface epithelium is fortuitous
the biologic profile of PA is well document- and simp ly represents fusion of the underly-
ed, the same cannot be said of the OGEH, ing tumor with the surface epithelium seems
the characteristics of which are based on unl ikely because of its frequent ap pear-
only six repo rted cases. In 1989 , Moskow ancs ."
and Baden23 pub lished a report of four cas-
es of what they termed odontogenic epithe-
lial hamartoma (OEH). Unfortunately, no data
were given as to gender, age, or c1i nico radi- 5. Pathology
ologic features. The authors described two
variants of OEH, a peripheral or gingival type 5.1 M ac roscopy
(formerly known as OGEH) and a second , in-
traosseous or ce ntral type not hit herto re- The gross spec imen cons ists of a firm to
ported. The authors believed it is likely that slightly spong y mass of pink to pinkish gray
OEH can occ ur wherever epith elial resid ues color. The cut surfac e may contain minute
fromthe developing too th and the dental lam- cystic spaces filled with clear, pale yellow flu-
ina exist. Th us, both gi ngival and int ra- id. As occasional areas of dystrophic calcifi-
osseous lesions may occur . A final co ncl u- cation are very small, they are not disclosed
sion as to terminology , relationship to PA, by cutti ng th rough the spec imen or detect-
and peripheral odontogenic fibroma awaits ed on a radiograph of th e operation speci-
assessment of additional pub lished cases of men.
OEH.

5.2 M icroscopy
4. Pathogenes is 5.2. 1 Histologic definitions
The 1992 edition of the WHO c1asification 25
When discussing the ce llular origin of PAs does not co ntain a histologic definition of the
that continue to provide an academic chal- PA (and/ or BeC) in spite of the fact that al-
lenge, two major sources shou ld be co nsid- most 50 pub lished cases were available for
ered. Those lesions that are located entirely analysis at the time of pub lication. It receives
within the con nective tissue of the gingiva only a brief (three-line) mention under amelo-
show no co ntinuity with the surface epitheli- blastoma ("othe r variations"), simply indicat-

63
6: Peripheral Ameloblastoma

Fig 6-6
Follicular
Fig 6-5 Photomicrograph showing epithelial tu- tumor islands
mor cell nests that are continuous with the oral showing
epithelium (hematoxytin-eosin [H&E], x20). acanthoma-
taus features
(H&E, x160).

ing that "some ameloblastomas (peripheral thomatous areas (Fig 6-6) is difficult to dis-
ameloblastoma) appearto arise directly from ting uish from the basal cell carcinoma. Some
the surface epithelium orfrom residues ofthe of the squamous cells in the acanthomatous
dental lamina lying outside the bone ." nests may show "ghosting" (ghost cell for-
The histologic definition used by the pres- mation and foreign body reaction to th is ma-
ent authors is as follows: terial within the connective tissue), features
The peripheral ameloblastoma is a benign ge nerally associated wit h th e ca lcifying
neoplasm (or hamartomatous lesion) con- ghost cell odo ntogenic cyst (see chapter
fined to the soft tissue overlying the tooth- 17).6.26
bearing areas of the jaws or alveolar mucosa A number of cases of PAs exhibiting areas
in edentulous areas. The tumo r consists of composed of clear cells have been report-
proliferating odontogenic epithelium that ex- ed.24 .27,28 In some parts of the tumors, vac-
hibits the same histomorphologic cell types uolated or clear cells occurred as discrete
and patterns as seen in the solidjmulticystic clusters or in d irect transit ion from arnelo-
ameloblastoma. The stroma isthat of mature, blastic (often acanthomatous) tumor cells.
fibrous con nective tissue. Occurren ce of cal- These clear cells are cytorno rpholoq ically
cifications, dentinoid, bone like, or cemen- and histo ch emically ide ntical to th ose re-
tum-like masses are not characteristic histo- ported to occur in the dental lamina and in
log ic featu res of the PA. several other lesions of odo ntogenic origin-
notably the lateral periodontal cyst, the gin-
gival cyst of adu lts, the calcifying ghost cell
5.2.2 Histop athologic findings
odo ntog enic tumor (see chapter 17), the cal-
Most of the epithelial islands exhibit palisad- cifying epithelial odontogenic tumo r (see
ing of columnar basal cells,butastellate retic- chapter 10), and the clear cell odo ntogenic
ulum is seldom co nspicuous (Fig 6-5). A carcinoma (see chapter 27).
basatoid lesion witho ut the classical follicu- It is of the utm ost impo rtance for oral
lar co mponent but oft en exhib it ing acan - path olog ists and oral surgeons to under-

64
Notes on treatm ent and recurrence rate

stand that, irrespective of the nomenclatu re, trum of th e periph eral ameloblastoma awaits
the peripheral ameloblastoma exhibits a d if- further clarification.
ferent biologic behavior t han the solidjm ulti- Of the three lesions, POF constitu tes the
cystic amelob lastoma . This knowledge can most important differential diagnostic prob-
help avoid the unnecessary , extensive, and lem. It must be stressed, however, that al-
sometimes mutilating surgery that has been though the differential diagnosis relating to
performed in som e cases.i''' PA is cha lleng ing, it remains an academic ex-
ercise because all th e lesions concerned are
ben ign neop lasms andjor hamartom atous
5.2.3 Malignant variants of PA
lesions requirin g only conservativetreatme nt
The noso logy of odontogen ic carcino mas modalities.
has varied over the years since the first ed i-
tion of the WHO classification in 1971 . A re-
cent nosologic approach was propos ed by
Eversoie.29 A total of six cases of malignant 6. Notes on treatm ent and
PAs (ameloblastic ca rcinomas) have been
published ' 2.30-34(see Tab le 3 in Philipsen et recurrence rate
aI20) .
As noted by Cardncr," the term p eripheral
ameloblastoma is pote ntially dangerous in
5.2.4 Differential diagnostic
that th is d iagnosis may lead to unnecessari-
consideratio ns
ly aggressive treatmen t. Whereas the solidj
Three lesions may be considered by the mu lt icystic ame loblastoma is a locally ag-
patho logist in the differential diagnosis of PA. gressive neoplasm capab le of invasive be-
The first is the p eripheral odontogenic fibro- havior and destruct ion of bon e-and thus re-
ma (POF) (WHO or complex type, Gard - qu ires extensive surg ical treatment, the PA
ner35). The pro liferation of stran ds and is- does not manifest such behavior. The cur-
lands of odontogenic epithelium in th istumor rent treatmen t of cho ice, conservative supra-
may be so extensive as to make the distin c- periosteai surg ical excision w ith adequat e
tion from PA very difficult.36 Siar and Ng 37 in- disease-free margins, is often confo unded by
vestigated the immunohistochemical char- the om inous connotat ion the term amelo -
acteristics of POF and PA in an attempt to blastoma has in the mind of the surgeon. A
elucidate their histogenesis but co uld not cha nge in nomenc latur e to the term p eriph-
confirm or exclude an origin in th e surfac e eral ame/oblastoid hamartoma, which has
epithelium for the epithelial elements . The been suggested by Richardson and Greer,"9
second lesion is the rare peripheral variant of may, however, create co nfusion and th e
the squ amous odontog enic tumor (SOT). present autho rs do not subscribe to its use.
The SOT was recently reviewed 3s based on Recurrent PAs develop from the general
36 cases from the literature, of which five site of the original lesion and are th ought to
were of the periph eral type. The oral pathol- be a sign of incomplete removal rather than
ogist should, however, not encounte r severe aggressiveness. A lthough the rec urrence
problems when differentiat ing PA from SOT. rate is much lower (16% 28 to 19%4o)thanthat
The third lesion is the odontogenic gingival of SMAs, long-term follow-up is mandatory ,
epithelial hamartoma discussed previously. espec ially in light of the report of a benign-
The quest ion of wh eth er this lesion shou ld app earing PA recurring as an ame loblastic
be included und er the histopathologic spec- carc lnorna.' ?Th ere is at least one major fac-

65
6 : Peripheral Ameloblastoma

tor respo nsible for the good prog nosis of References


PAs. The co rtical bone of the jaws, which
1. Braunstein E. Case report of an extraosseous
represents a strong barrier to the infiltrative
adamanti nob lastoma. Oral Surg Oral Med Oral
power of SMAs, is also an efficient barrier to Pathal 1949:2:726- 728.
invasion by PAs. Some authors have quest-
2. Klinar K, McManis JC. Soft-tissue ame loblasto ma.
ioned , based on the benign behavior of PAs, Re port of a case. Oral Surg Oral Med Oral Path ol
whether th ey are truly analogous to SMAs.2a 1969 :28:266 -272 .
The biologic behavior ofthe PA seems in line 3. Ramnarayan K, Nayak RG, Kavalam AG . Periph-
with that of a hamartoma or persistent hy- eral ameloblastoma. Int J Oral Surg 1985 ;14:
perplasia rather th an that of a neoplasia. 300 -301 .
Since th e first review in 1987,40 the num- 4. Woo 8-S, Smith-Williams JE, Sc iubba JJ, Lip per
ber of published cases of PAs has increased S. Perip heral ame loblastoma of the buccal mu-
from 26 to 160 (at the end of 2000), making cosa: Case rep o rt and review of the Engl ish liter-
at ure. Ora l Su rg Oral Med Ora l PathoI 198 7;6:78-
the fairly detailed prof ile in this chapter pos-
84 .
sible. This tumor must be viewed as a rela-
tively innocuous lesion totally lacking the per- 5. Shibata T, Keneko N, Hokazono K, et a t. An
amelo bla sto ma-like neo plasm of the b uccal mu-
siste nt invasiveness of t he intraosseous cosa. Repo rt o f a ca se. lnt J Max ill ofac Surg
amelob lastoma. There remain, however, un- 1990:19:203-204 .
solved PA-related problems, like tumor ori- 6. Gardn er DG. Periphe ra l amelo blastoma. A study
gin, the origin of "extragingival PA lesions," of 2 1 cas es, incl ud ing 5 report ed as basal ce ll car-
the relation ship betwee n OGEHs and PAs cinoma of the ging ival. Canc er 19 77;39 :1625 -
(one or two entities), and th e malign ant po- 1633.
tentiality of PAs to mention a few. 7. Wa ld ron CA. Co mmen t on the basal ce ll carcino-
It is highly recommended that clinicians ma of the oral cavity. J Oral Surg 1972;30 :66.
report cases that involve data and/ or infor- 8. Simpson HE. Basal-cell carci noma and pe rip her-
mation relevant to the areas where know l- al ame loblastoma. O ral Su rg Oral Med Ora l Patho l
edge is lacking. It may be worth stressing that 1974:38:233- 240.
any published report should include all rele- 9. Moskow BS, Baden E. T he periph er al am e lo-
vant data-age, gend er, exact tumor locat ion blastoma of the gingiva. Case repo rt a nd literatu re
review . J Periodo nto I 1982;53: 736 -742.
(preferably with clinical photographs), radi-
ographi c docu mentation, and histopat holo- 10. Sci ub ba JJ. Discussio n of EI-Moft y S, Ge rard NO,
Farish SE, Rod u B. Periphera l ame lo blasto ma: A
gy (microgra phic docu mentation th at in-
c linical an d histolog ic study of 11 cases . J Oral
clud es low as well as high magnif ications),to Maxillafac Surg 1991 ;49:970-97 5.
mention but a few. It is the (sad) experience
11. Kan eko Y, Ueno S. Perip heral ame loblastoma re-
of the present authors that, in the past, a co n- semb ling a pa pillo ma : Rep ort of cas e. J Oral Max-
siderable number of publi catio ns t hat illafac Surg 1986;44 :737- 739.
seemed to represent valuable contrib utions 12. Baden E, Doyle JL, Petriella V. Ma lig nan t trans-
had to be exclud ed from a given review du e format ion of pe rip heral amel ob lastoma. Oral Bu rg
to inadeq uate and insufficient case presen- Oral Med Oral PathoI1 993:75:214- 21 9.
tation. 13. Zhu EX, O kad a N, Tak ag i M. Peripheral amelo -
blasto ma: Case repo rt and review of literature. J
Oral Max illafac Sur9 1995;53:590 -5 94.
14. Ku ru H. Ueber das Ada manti nom. Zen tratb l Allg
PathoI 1911:22:29 1- 295.

66
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15. Tongdee C, Gangg avakin S. Perip heral amelo- 29. Eversole LR. Malig nant epithelial odontoge nic
blastoma (repo rt of a case and review of litera- tumors. Sem in Diag n PathoI 1999; 16:3 17- 324.
ture). J Dent Assoc Tha i 1978;28 :3 1- 38 .
30. Edmo ndson HD, Browne RM, Potts AJC. Intrao-
16. Stevenson ARL, Austin BW. A ca se of am elo- ral basal cell carcinoma. Br J Oral Surg 1982;20:
blastoma presenting as an exophytic gingiva l Ie- 239-247 .
sion. J PeriodontoI1 990;60:3 78- 38 1.
3 1. Lin S-C, Lieu C-M, Hahn L-J, Kwan H-W. Periph-
17. Gullifer W. Adamantinom a. Dental Cosmo s 1936: eral amelob lastoma with metastas is. Int J Max-
78:1256 - 1259. iIIol ac Surg 1987;16:202- 20 4.
18. Ch'in K. Adamantinom a in Ch inese. Chin Med J 32. McClatchey KD, Sullivan MJ, Paugh DR. Periph-
1938;(Suppl ll): 9 1- 130. eral arneloblastic carcin oma: A case report of a
rare neoplasm. J Oto laryngol 1989 ;18:109 ~ 111.
19. Stanley HR, Kro gh HW. Peripheral arnelo blas-
toma. Report of a case. Oral Surg Oral Med Oral 33. Bucci E, Lo Muzio L, Mignogna MD, de Rosa G.
Patl101 1959 ;12:760- 765. Peri pher al am eloblasto ma: Case rep ort . Ac ta
Sto matol Belg 199 2;89 :267-269.
20. Philipsen HP, Reichart PA, Nikai H, Takata T,
Kud o Y. Periph eral ameloblasto ma: Biolog ica l 34 . Califano L, Maremonti P, Soscai no A, et al. Pe-
profile based on 160 cases from th e literature. ripheral ame loblastoma: Repo rt of a case with ma-
Oral On col 200 1;37: 17-27. lignant aspe ct. Br J Oral Maxillofac Surg 199 6;
34:2 40 -242.
21. Reichart PA. Philipsen HP, Sonne r S. Ameloblas-
toma: Biologi ca l profile of 36 77 cases. Oral On- 35. Ga rdner DG. Centra l odontoge nic fib roma cur-
col 1995;31 8 :86- 99. rent co nce pts. J Oral Pathol Med 1996 ;25:5 56-
56 1.
22. Baden E, Moskow BS, Moskow R. Odontogenic
gingival epithelial hamartoma. J Oral Su rg 1968; 36. Gardne r DG. The perip heral odontogenic fibro-
26:702- 7 14. ma: An attemp t at clarification . Oral Surg Oral Med
Oral Pathol 1982;5 4:40- 48.
23. Moskow BS, Bade n E. Odo ntogenic ep ithelial
hamartomas in periodontal struct ures. J C lin Pe- 37 . Siar CH , Ng KH. An imm unohistochemical stud y
riodo nto I1989;16 :92- 97. of tw o cases of either peripheral odo ntog enic fi-
bro ma (WHO type) or peripheral ameloblastoma.
24. Anneroth G, Johansson B. Peripheral amelob las-
J Nihon Univ Sch Dent 1996;38:52- 56.
toma. lnt J Oral Surg 1985;14:295 -299.
38. Philipsen HP, Reichart PA. Squamous odo nto-
25. Kramer IRH, Pind borg JJ, Shea r M. Histo log ical
genic tumor (SOT): A benign neoplasm of the pe-
Typing of Odon togenic Tum ou rs. 2d ed. Berlin:
riod ontium. A review of 36 reported cases. J Clin
Springer-Verlag, 1992.
Periodont oI1 996 ;23:922- 926.
26. Pansino FA, Meara JW. Case report : Peripheral
39. Richardson JF, Greer RO. Ameloblastoma of mu-
ame lob lasto ma . J Mic h Dent Assoc 19 75 ;57:
co sal or ig in. A rch Otol aryngoI 1974 ;100: 174-
129-1 30.
175.
27. Ng KH, Siar C H. Perip heral ameloblastoma with
40. Buch ner A, Sc iubba JJ . Periph eral epithelial
clear cell different iation. Oral Surg Oral Med Oral
odontog eni c tum ors: A review. Oral Surg Oral
PathoI1990;70:210-21 3.
Med Oral PathoI1987 ;63:688- 697.
28. Redman RS, Keegan BP, Spector CJ, Patterson
RH. Peripheral amelo blastom a with unusua l mi-
totic activity and con flicting eviden ce regard ing
histog enesis. J Oral Maxillofac Surg 1994;5 2:
192-1 97.

67
Chapte r. 7.

Desmoplastic Ame loblastoma

1. Terminology the chief initial co mplaint in most cases. A


characteristic feature is an almost equal dis-
Two reports from Japan, the first in 198 1' tribution in location between the maxilla and
and the second in 1983,2 first called atten- mandibl e. The size of the tumor varies be-
tion to an unusual variant of the solid/ multi- tween 1.0 and 8.5 em at its greatest diame-
cystic ameloblastoma (SMA). However. Ever- ter. A true peripheral variant of DA witho ut
sole and coworkers" are usually credited for bone involvement, and thus similar to the pe-
the first English-language publication on the ripheral amelob lastoma (PA), has not been
desmoplastic ameloblastoma (DA). This tu- reported so far.
mor is cha racterized by an unusual histo- The radiographic features of DA differ in
morphology,including extensive stro mal col- most cases from those of SMA. The rad i-
lagenization or desmop lasia, leading to the ographic features of SMA are classically de-
proposed term ame lobl astoma with p ro- scribed as uni- or multilocular radiolucencies
nounced desm op lasia, or des mo plastic with relatively well-defined borders. Howev-
amelob lastoma. A possib le "transitional" er, borders were well defined in only 7% of
torm of DA, showing microscopic features of the DA cases where data were available. The
the desmop lastic variant together with areas conte nt of the lesion was mixed rad iolu-
typical of "c lassic" follicular or plexifo rm cent/ radiopaq ue in 53% of the cases (Figs
ameloblastoma, has been called a "hybrid" 7-1 to 7-3 ). Thus , in many cases the pre-
lesion of ameloblastoma and is described operative rad iographic diagnosis was that
later in this chapter. The following data are of a fi bro-osseous lesion. Resorption of
based on a review of 100 cases (Philipsen et tooth roots is a common finding (Fig 7-4). The
al4 )supplemented with data from a recent re- fact that new bo ne formation has been re-
port (Kishino et aI5 ), bringing the total num- ported in several cases of DAs may explain
ber of DA cases reviewed to 109. the mixed radiolucenljradiopaq ue appear-
anc e."- 14 Tak ata et al 15 believed that the
mixed radiolo gic appearance expresses the
infilt rative pattern of the tumor. When the DA
2. Clinical and radi ologic profile infiltrates the bone marrow spaces, as ob-
served in their seven reported cases, rem-
nants of the original nonmetaplastic or non-
DA is a benign, locally infiltrative epithelial neoplastic bone remain in the tumor tissue.
neoplasm believed to be a variant or subtype The infiltrative behavior of the DA may also
of the SMA. A painless swelling represents explain one of the characteristic features of

69
7: Desm op lastic Ame loblasto ma

Fig 7-1 Orthopant omo graph re-


vealing a fib ro-osseous-l ike DA
occupying the entire left max il-
lary region in a 53-year-old man.

Fig 7-2 Radiograph of the pat ient in Fig 7-1, show-


ing involvement of the entire left maxilla.

Fig 7-3 Computed tomography ICT) scan of the Fig 7-4 Intraoral rad iograph showing ma rked root
same patient. There is obliteration of the left max- resorpti on of both lateral and central upper inci-
illary sinus by a rad iolucent/radiopaque t umor sors. Note scattered rad iopacities.
mass.

70
Epidemiological data

No . of ca ses

15
15
12 OJ Women
11
10
OJ Men
n =72
6
5 4
Fig7-5 Distributionof 72
DA cases acco rd ing t o
gende r and age g roups 0-9 10-19 20 - 29 30-39 40 - 49 50 - 59 60 -69 70 -79
(where a specific age Age in dec ades
was identified).

this tumo r, the ill-defined bord er. Takata et 3.2 Age


ai's interpretation of the mixed radiologic ap-
pearance does not, howe ver, explain why The age range of patients with DA varies be-
thisfeature is neverfo und in the co nventional tween 17 and 72 years (n = 72) at the time
SMA. An association between DA and an of diagno sis (Fig 7-5), the overall mean age
unerupted or impacted tooth has been found being 42.8 years (men, 42.9 years; women,
in only three cases (3.4%) so far ' 6 ,17 com- 40.3 years) co mpared to 35 .9 years (men,
pared to 8.7% amo ng SMA. ' 8 39 .2; wo men, 35. 2) for SMAs. The age dis-
tribution in Fig 7-5 shows female peaks in the
4th and 5th decades; a single male peak ap-
pears in the 6th decade. Of all the tu mors
studied , 70.8% were within the age range of
3. Epidemiological data 30 to 59 years.

3.1 Incidence, prevalence, and 3.3 Gender


relat ive frequency
The male:female ratio was 1:0.9 (n = 109).
DAs acco unt for 4% to 13% of all SMAs.14- 26
Data retrieved from different geographi c re-
gions27 seem to suggest that the relative fre- 3.4 Location
quencyof DA is slightly less in th e Japanese
population compared to American and Eu- Figure 7-6 shows the site distribution within
ropean popu latio ns. How ever, to evaluate the jawbones of 85 cases of DA (in which the
some true geographic differences in relative site was id entified ). Not e that 7 cases in-
DA frequencies, more studies are needed. volved the entire maxillary quadrant. Given
Ng and Siar23 indicated a 3% rate fo r DA th at 43 (50 .6%) of th e tumors were located
based on all odo ntogenic tumors. in th e maxilla and 42 (49.4%) in the mandi-
ble, the maxilla:mandible ratio was close to

71
7: Desmoplastic Ameloblastoma

_ __ _ __ 7 5. Pathology

0, ~,
5.1 Macroscopy

:I '
5 : 22 The gross specimen most often consists of
, ' resected po rtions of the jaws. The t umor
: :
0 =85 mass is often solid. whitish. and has a gritty
or "frozen ice-cream"-like consistency.

5
5.2 Microscopy
5.2. 1 Histologi c definitio n
The relatively small num ber (approximately
Fig 7-6 Anatomic distribution of DAs(n = 85)with
20) of pub lished cases of DAs availab ie when
known location. Circled numbers above and be-
the 1992 ed ition of the World Health Orga-
low the vertical broken lines indicate numbers of
nizatio n (WHO) cla sslficatlon-? was pu b-
cases involving two adjacent areas of the jaw.Sol-
id horizontal line at top indicates involvement of lished d id not allow the autho rs to produce
an entire maxillary quadrant. a detailed histologic definition for DA. The
definition used by the present authors is as
follows:
1:1. This is in sharp con trast to the corre- A benign but locally invasive variant of the
sponding figures for SMAs which showed a solid/ rnulticystlc ameloblasto ma consisting
ratio of 1:5.4.' 8 Only 5 out of 85 cases (5.9%) of p roliferating. irregular. ofte n bizarrely
of DA were found in the mandi bular molar re- shaped islands (Figs 7-7 and 7-8) and cords
gion as opposed to 39% of SMA cases." of odontogenic epithelium of varying sizes
emb ed ded in a desmop lastic, con necti ve
tissue stroma.
4. Pathogenesis
5.2.2 Histop athologic findings
Although the biologic behavior of the DA is The occ asional large tumor islands in DAs
still unresolved. it is generally agreed that the are often very irregular in shape with a point-
tumor is a variant of SMA. It seems unlikely ed. stellate appearance. The morphology of
that the DA is derived from sources diffe rent these islands is often bizarre wit h an almost
from those of the SMA. Oxytalan fibers have patho gno mon ic. "animal-like" configuration
been identified in the stromal tissue of one or outline. The epithelial cells at the periph-
case reported by Kawai et al.28 This finding ery of the islands are cuboidal. occas ionally
was Interpreted by the authors as indicating with hyperchromatic nuclei. Columnar cells
a tumor derivation from the epithelial rests of demonstrating reversed nuclear polarity are
Malassez in the periodon tal mem brane of a rarely conspicuous. although an occasional
related tooth. isolated island may exhibit focal ameloblast-
like peripheral cells (Fig 7-9). The center of
the epithelial islands appears hypercellular
with spind le-shaped or squarnatoid, ceca-
sionally keratinized, epithelial cells. Micro-

72
Pathology

Fig 7-7 Photomicrograph showing a large ep- Fig 7-8 Higher magnification of the epithelialtu-
ithelial tumor island with an irregular outli ne. The mor island. Note the marked desmoplasia of the
central part of the island IS hypercellular (hema- stroma (H&E, xeo).
toxylin-eosin [H&E] x50).

Fig 7-9 Peripheral part of a tumor island. The


cuboidal or low cylindrical (ameloblast-like) cells
are present only focally. Toward the center there
is hypercellularity of spindle-shaped or polygonal
cells arranged in a whorled or fasciculated pat-
tern. A stratum reticulare- Iike appearance is lack-
ing (H&E, x 150).

cysts th at co ntain eosino philic amorphous seem to compress or "squeeze" the odo nto-
deposits o r appea r em pty are com mon ly genic epithelial islands from the periphery.
found within the tum or islands. Kawai et al28 T he mec hanism of desmoplasia is not un-
reported an unusual DA case whe re a large derstood . Myxoid changes of the stroma may
cavity lined by degenerated epithelial cells be ob served surround ing the odontogenic
constituted a cystic part of the tum or. Foci of epithelium. Formation of metaplastic bone
keratinization occ ur spo radically. True gla n- t rabecu lae (osteop lasia) rimme d by active
dular d iff ere nt iation with mucus cells has osteoblasts has been descr ibed in several
also been described in tumo r nests." Thus, cases 6 - 9 , " , 16 , 17 A periph eral fib rous con-
the general histologic pattern of DA resem- de nsat ion suggesti ve of a ca psule is not
bles, to some extent, that of a fo llicular SMA characteristic.
with acanthomatous features.
Extensive stromal desm oplasia is a co n-
5.2.3 Imm unohistoch emical findings
stant and striking finding c haracterized by a
moderately cellular fibrous co nnective tissue Using various imm unohi stochem ical tec h-
with ab und ant th ic k co llagen fibe rs t hat niqu es, Siar and Ng 17 de monstrated that DA

73
7: Desmoplastic Ameloblasto ma

tumor cells showed variable expression of S- tic amelob lastoma have lower recur rence
100 protein and desm in, similar to other rates than other ameloblastornas.Y ? Howev-
types of SMAs. However, keratin immunore- er, even today, when as many as 109 cases
activity was inconstant and co nfined to tumor of DAs are available for assessment, it is pre-
cells showing squa mous differentiation. Vi- mature to estimate recurrence rates. The ra-
mentin was not expressed by either squam- d iolog ic and histologic findings of poor en-
atoid or spind le-shaped cells. The authors capsulation or total lack of a capsule requ ire
concl uded that the differences in th e ex- long-term follow-up, and the findings likely in-
pression of th ese antige ns among various dicate that the DA has a potential for recur-
ameloblastoma types may be attributed to di- rence similar to SMAs, excluding so me sub-
verse factors such as ded ifferentiation or the types of the unicystic ameloblasto ma. The
rate of proliferation of the neop lastic cells, in- answer can be foun d only when more infor-
herent cellular potentials, or extracellular me- mation beco mes available in the literature.
diators.
In a co mparat ive immunohistochemical
study, Becker et al30 showed that the co n-
nective tissue stroma in a DA- contrary to that 7. "Hybrid" lesion of
of an SMA--ex hibited a strong positive reac-
tion for co llagen type VI. This was interpret- ame loblastoma (HLA)
ed as indicating an active de novo synthesis
of extracellular matrix protein. In other wo rds, The HLA was first described by Waldron and
the desmoplastic stroma of DAs is not sim- EI-Mofty21and is yet another tumor variant in
ple scar tissue but newly produced co nnec- w hich , histolog ica lly, areas of follicular or
tive tissue. In contrast to SMAs, marked im- plexiform SMA coexist with areas character-
mun oexp ression of transform ing growth istic of DAs. It is much too early to specu late
factor (TGF-P) was observed in 6 out of 7 DA wh ether desmop lastic changes occ ur sec-
cases.15 The authors sugg ested that TGF-p ondarily in th e stroma of a preexisting SMA,
produ ced by DA tumo r cells plays a part in or whetherareas of primary DAtransform into
the prominent des mo plastic matrix forma- an SMA. It has been suqqested that the hy-
tion. brid lesion should be considered a collision
tum or. Melrose31 wrote that th e designation
hybrid tumor serves no real purpose and, if
taken literally, might overstate th e sig nifi-
6. Notes on treatm ent and ca nce of find ing a DA in co mbination with is-
land s of a SMA. Many mo re cases than the
recurrence rate nine publi shed so far7.16.21.32_with detailed
clinical and radiologic data and correspon-
Current knowledge must lead to th e recom- ding histopathologic analysis-are needed to
mend ation that the same radical treatment clarify the biologic behavio r of this variant.
modalities used for SMAs be used for DAs. Until then it is advisable to treat cases of HLA
The biologic behavior of th e DA, includ ing like those of SMAs.
recurrence rate, still cannot be fully appr eci-
ated due to the relatively few reported cases
with sufficiently long follow-up periods. Ac-
co rding to the 1992 WHO classification, "uni-
cystic, peripheral, and possib ly desmo plas-

74
References

References 13 . Lud vikoya M, M ichal M , Zam ecn ik M, et a l.


Desm o p lastic am elo blastoma. Ces k Pate l 1998 ;
34:94 - 98.
1. Takigawa T, Matsumoto M, Se kine Y, et al. A ca se
report of ame lob lastoma p roliferated like epul is of 14. Ashman SG, Co rio RL, Eisele OW, Murp hy MT.
maxi lla [in Japanese]. Niho n Univ Dent J 19 81 ; Desmoplastic a me lo blastoma. A case report and
55:920 - 924. literatu re review . O ral Surg Oral Me d O ral Path ol
1993;75 :4 79-482.
2. Uji Y, Kod ama K, Sakamoto A, Teen A. A n amelo-
b lasto ma w ith inte resting histo log ic al fi nd ing s [in 15 . Ta kata T, Miyauchl M, Ito H, et al. Clinical and
Jap anese]. Jpn J Oral Maxillofac Surg 19 83 ;29 : hi st o pat hol o g ica l a nalyses of d esm oplast ic
151 2- 151 9. ameloblastoma . Pat ho l Res Prac t 19 99;195 :
669-675.
3. Eversole LR, Leider AS, Hans en LS. Am elob las-
l o mas w ith p ro no unced desmop lasia. J Oral Max- 16 . Higuc hi Y, Nakam ura N, Onish i M, Tashiro H. Un-
illofac Surq 1984;42:735- 740. us ual a melob lastoma w ith extensive stro ma l
desmoplasia. J C ranio maxillotac Surg 199 1;19 ;
4. Phi lipsen HP, Reichart PA, Takata T. Desm o-
32 3-327 .
p lastic am eloblasto ma (incl ud ing "hyb rid " lesio n
of amelobl ast om a). B iolog ical pro file ba sed on 17. Siar CH, Ng K H. Patterns of expressio n of inter-
100 cases from the literatu re and own files. Oral med iate fi lame nts and 8 -100 protein in desmo-
Oncol 2001 ;37:455-460. plastic am elo blastom a. J Nihon Uni v Sch Dent
1993;35:104- 108.
5. Kishino M, Murakam i S, Fuk ud a Y, Ishida T.
Pathology of the desmoplastic a me lo blastoma. J 18 . Reic hart PA, Philipsen HP, So nne r S. Ame loblas-
Oral Pathal Med 2001 ;30:35 -40. to ma: Biolog ical p rofile of 3677 cases. Oral On-
co l 1995;31 B:86 - 99.
6 . Okada Y, Sug imu ra M, Ish id a T. Amelob lastoma
accompanied by prom inent bo ne fo rmatio n. J 19. Keszle r A, Papa rella ML , Doming uez FV. Desmo-
Oral Maxilla!ac Surg 1986;44 :555- 557. p lastic and non -desmoplastic ame lob last oma: A
comparative c linicopatholog ica l a nalysis. Oral Dis
7. Philipse n HP , Orm isto n IW , Re icha rt PA. Th e
1996;2:228- 231 .
c esrno- and osteoplastic amelo blast oma. Histo-
logi c variant o r cl inicopatholog ic enti ty? Case re- 20 . Kaffe I, Buch ner A, Teich er S. Rad iologi c features
po rts. Int J Oral Maxillo!ac SUr9 1992 ;2 1: of d esm oplast ic var iant of amelo blasto ma. Oral
352 - 357. Surg Oral Med Oral Patho I1993;76:525 -529.
8. Yos himura Y, Sa ito H. Desmo p lastic varia nt of 2 1. Waldron CA, EI-Mofty SK. A histopatho log ic study
amelob lastoma: Report of a case and revie w of of 116 ame lob lastomas w ith s pecial references to
the literatu re. J O ral Maxillofac Surg 1990;48: the desm op lastic var iant. Ora l Surg Ora l Med Oral
1231-12 35. Pathcl 1987;63 :441 - 45 1.
9. Th o mpso n 10C, van Rens b urg LJ, Phill ips VMJ . 22 . Lo Muzio L, Orabo na P, Cos taJunga C, Della Valle
Desm op lastic am elob lastoma; Correlative histo- A. Ame lobla st om a de sm oplastico. Presentaz io ne
path ology, rad iology and CT-M R imag ing . J Ora l d i u n caso c1 inic o. Mi nerva Sto mata l 1996 ;45 :
Pathoi Med 1996;25:405- 4 10. 28 5-288 .
10. Ta nimoto K, Takata T. Sue i Y, W ad a T. A cas e of 23 . Ng KH , Star CH . Des moplastic variant of am elo-
des mo p lastic variant of a mand ibu lar a meloblas- blast o ma in Malaysians. Br J Oral Maxillofac Surg
to ma. J Ora l Max illofac Su rg 1991 ;49:94-9 7. 1993;3 1:299-303.
11. Takemoto T, Yamas hita T, Ito A, et al. A case of 24. Lam KY, Ch an ACL, Wu PC. et al. Desmoplastic
ameloblasto ma of maxilla w ith bone tissue in the variant of am e lo blasto ma in Ch inese patients. B r
tumor [in Japanese]. Jpn J Oral Maxil lofac Su rg J Oral Maxil'ofac Surg 1998 ;36:129- 134.
199 1;37:234- 239.
25 . Fukushima 0 , Kobayash i H,Takeda I, et al, A case
12. Ishigami T, Sugiha ra K, Uchiyama T, et al. Am elo- of d esmoplastic ame lob lasto ma of the ma xilla.
blast om a of the max illa w ith bone tissue in the tu- Bull Tok yo Dent Coli 1997;38:223- 227.
mor: Repo rt of a case [in Ja panese] . Jpn J Ora l
26 . Morita S, A rika T, Nak ajima M, et al. A cl inical, ra-
Maxillo!ac Surg 199 1;37:2 103 - 2 104.
d io logi c and pathologic study of d esmo plastic
am elo blastoma [in Japanese). Jp n J Ora l Max-
HlofacSurg 1994; 40:988- 996.

75
7: Desm op lasti c A m el obl astom a

27. Lu Y, Xuan M, Takata T, et at Odontog enic tu- 30. Becker J, Reichart PA, Philipsen HP. Compara-
mors: A demographic study of 759 cases in a Chi- tive immunohistoch emical study of the follicu lar
nese po pulation. Oral Burg Oral Med Oral Pathol and the desmop lastic ameloblastoma. Pathol lnt
1998;86:707- 714. (in press).
28. Kawai T, Kishino M, Hiranuma H, et al. A uniq ue 31. Melro se RJ . Des moplastic amelob lastoma.
case of desmoplastic ameloblastoma of the man- Pathol Rev 1999;4:21- 27.
dible: Report of a case and brief review af the Eng-
32. Takata T, Mlyauc hi M, Ogawa I, et al. So-called
lish language literatu re. Oral Surg Oral Med Oral
"hybrid" lesion of desmo plastic and co nventio nal
Pathol Oral Radial Endod 1999;87:258- 263.
ameloblasto ma: Repo rt of a case and review of
29 . Kramer IRH, Pindborg JJ, Shear M. Histolog ical the literature. Pathol lnt 1999:49:1014- 10 18.
Typing of Odo ntogenic Tum ors. 2d ec . Berlin:
Springer-Verlag, 1992.

76
Chapter 8

Unicystic Ameloblastoma

1. Terminology On removal of the cyst, whether in toto or


as a cyst wall curettage, it is important forthe
Much confusion still exists when it com es to surgeon and the pathologis t to examine both
the terminology used for unicyst ic arnelo- the interior and exterior of the cyst sac. Care-
blastomas (UAs). Some of the terms used for ful macroscopi c inspection of the specimen
this lesion priorto 1977, when Robinson and may reveal import ant diagnostic clues. The
Martinez' introduced the concept of UA, inner surface of the cyst (facing the lumen)
were cystic (intracystic) ameloblasto ma, may show one or several polypoid or papil-
ameloblastoma associated with dentigero us lomatous, pedunculated , exophytic masses,
cyst, cystogenic amelob lastoma, extensive which in rare cases almost fill the entire cyst
dentigerous cyst with intracystic ameloblast- lumen. This subtype of UA has been called
ic papilloma, mural amelob lastoma, denti- intracystic, luminal, or int raluminal amelo-
gerous cyst with amelob lastomatous prolif- blastoma and co rresponds to the plexiform
eration, and ameloblastoma developing in a UA, th e histological equiv alent coined by
radicular (or "globulomaxillary") cyst. Gardner." The present authors strongly sup-
The present authors propose the follow- port the use of the term intraluminal UA when
ing nom enclature, whic h w ill be used describing this type of tumor, because it in-
throug hout this chapter. The term untcvstic d icates precisely the location of the tissue
is derived from the macro- and microscopic proliferation.
appearance, the lesion being essentially a In ad d ition to the intralu minal exc res-
well-defined, often large monocystic cavity cences, the cyst capsule may show one or
with a lining, focally but rarely entirely com- several rounded and slightly protruding nod-
posed of odo ntoge nic (amelo blastomatous) ules that may also be seen macroscop ically
epithelium. The term unilocular, on the other when viewing the cyst wall from the outside.
hand, is drawn from the radiograp hic inter- These formations have been named mural
pretation of a radiolucency having only one or intramural nodu les in the literature, thus
loculu s or comp artment. Much co nfusion creating conf usion with the intraluminal ex-
stems from the fact that a unicystic amelo- crescences already desc ribed. This is unfor-
blastoma may appear not on ly as a unilocu- tunate because the latter represent thicken-
lar but also as a multilocular bone defect. 2 .3 ings of the cyst wa ll proper due to the
The term unicystic ameioblastoma is, how- occurrence of infiltrati ng and invadi ng is-
ever, so well established , that a change in lands of SMA tissue. With regard to these
nomenclature could create even more con- nod ules,the authors suggest using the terms
fusion. intramural nodules and intramura l UA for this

77
8: Unicystic Ameloblastoma

Fig 8-1 Orthopantomograph


showing a well-defined unilocu-
lar UA (dentigerous variant) as-
soc iated with an uner upted
mandibular right second molar
in a 10-year-old girl. The anlage
of the right third molar is dis-
placed by the expanding tumor.

Fig 8-2 A 24-year-old man with


a UA (dentigerous variant)
appearing as a multilocular
radiolucency occupying the
mandibular right third molar and
ramusarea.The second molaris
unerupted and the tooth germ
for the third mo lar is markedly
displaced.

Fig 8-3 Orthopantomograph


showing a unilocular UA (non-
dentigerous variant) m imicking
a radicula r cyst near the mand-
ibular rig ht first molar in a 45-
year-old man.

subtype , as it is characterized by the occu r- mate rial into two cat egories: histo logically
rence of tumor tissue within the wall proper verified UAs assoc iated with an unerupted
(murus is Latin for "wall"). tooth (the dentigerous variant, n = 90 ) and
The fo llowing profile and data are based UAs lac king an association w ith an unerup t-
on a critical review of 193 cases of UA from ed tooth (the non denti gerou s variant, n =
around the worlds (See Philipse n and Re- 10 1).Tw o cases could not be diagnosed du e
ichart'' fo r spec ific details and a co mp lete list to insuffic ient information.
of references.) In reviewi ng th e literatu re it be-
came evide nt that one feat ure divided the

78
Epidem iological data

No . of case s

13
[]J Women
OJ Men

0 - 10 11- 20 21-30 31- 40 41-50 51 - 60 61- 70 71-80 Age in


decades
1 1
3

Fig8-4 Ageand gen-


der distribution of 23
dentige rous and 17
nondentigero us vari- No. of cases
ants of UA.

2_Clinical and radiologi c profile involved tooth crown waS displaced by the
cystic tumor rather than being projected into
Local swelling, occasional pain, and sig ns of the cyst lumen. The interpretation of this find-
lip nu m bness, as w ell as d isch arge or ing is disc ussed further in section 4 of this
drainage in cases of seco ndary infection, chapter.
were com mon findings in both variants.
When the radiograph ic appearance of all
UAs is divided into the two main patterns, 3. Epide miological data
unilocu lar (Fig 8-1) and multilocu lar (Fig 8-2),
there is a c lear predomin ance of the un iloc-
ularconfigu ration in all studies whe re this fea- 3.1 Prev alence, in cidenc e , and
ture was evaluated . Th is predominance was relative frequency
exception ally marked for the dent ig ero us
variant wh ere the unilocular:multiloc ular ra- No data are available concerning prevalence
tio was 4.3:1.2 For the nondentigerou s type and incid ence of UAs. The relative frequen-
this ratio was 1.1:1 (Fig 8-3). Eversole et al2 cy has been rep orted as between 5% and
were able to identify six radiog raphic patterns 22% of all types of ameloblastomas.7 Li et al3
for UA, ranging from well-defined uniloc ular found 33 UAs among 175 cases of amslo-
to multilocular appearance. Root resorptions blastomas (18.9%).
have been desc ribed in 40 % to 70% of cas-
es.36 Li et al3 recently mad e an interesting
observation whe n th ey careful ly examined 3 .2 Age
seven UAs olthe dentigerou s variant. In none
olthese Cases could they find a true dentiger- The mean age at time of diag nosis differs
ous cyst-impacted tooth relation ship. The con siderably accord ing to the UA variants

M~~CO i' {!)


'! 79

.
~=:::f:i'""{<
8: Unicystic Ameloblastoma

n =24

Fig 8-5 Location within the jaws of 24 dentiger- Fig 8-6 Location within the jaws of 17 non-
ous UA variants. dentigero us UA variants. Circled num bers at the
bottom olthe broken lines indicatet hatthe UAin-
volved bo th adjoin ing reg ions.

(Fig 8-4). From the total num ber of cases re- 3.4 Location
viewed, it was possible to obtain individual
data from only a relative few. Those d iag- The location of the UA within the jawbones
nosed as dentigerous (n ~ 23) occ urred in shows a marked predom inance tor the man-
much younger patients (mean 16.5 years dible irrespective of th e variant, the maxilla:
wit h 78.3% occurring in the 1st and 2 nd mandible ratio being 1:7 versus 1:4.7 for th e
decades ) th an those d iagn osed as no n- nonden tigerous type (Figs 8-5 and 8-6). The
dentigerous (n ~ 17; mean 35.2 years with posterior mandible, including the ascending
29.4% occurring in the first two decades). Al- ramus, is the region most often affected in
most 20 years in mean age separated thetwo both variants. An unerupted mandibularth ird
variants, mainly due to cases occurring in the molar was associated with UA in 58.3% of 24
5th to 8th decad es in the nond entigerous dentigerous variants evaluated. If both sec-
grou p. ond and third (mand ibular) molars are in-
cluded, th ey cover a total of 83.3% of the
dentigerous UAs.
3.3 Gender

In regard to gen d er d istrib ution, the UA


dentigerous variant shows a slight male pre- 4. Pathogenesis
dominance with a male:female ratio of 1.6:1.
However, when the tumor is not associated
with an unerupted tooth, the gender ratio is So me invest igato rs believe th e UA arises
reversed to a male:female ratio of 1:1.8. from preexisting odontogenic cysts, in par-
ticular a dentigerous cyst, while others main-
tain that it arises de novo. Robinson and Mar-
tine z' argued that as t he ep ithelium of
odontog enic cysts and ame lo blastomas

80
Pathology

have a co mmon ances try, a transition from a en cases of the denti gerous variant. This find-
non-neoplastic cyst to a neoplastic one could ing was interpreted as an argument against
be possi ble , even th ou gh it occ urs infre- the hypothesis th at UA may originate from a
quently. Leider et al8 proposed three patho - preexisting dentigerous cyst. Similar obser-
genic mechanisms fort he evolution of UA:(1) vations were made by Philipsen et al ' 2 when
the reduced enamel epithelium assoc iated th ey exam ined the dentigerous app earance
with a developing tooth und ergoes amelo- c haract eristic of another odo ntog enic tum or,
blastic transformation with subseq uent cys- t he fol lic ular variant of th e adenoma to id
tic develop ment ; (2) ameloblasto mas arise in odon togenic tumor (AOT; see Fig 11-1). The
dentigerous or other typ es of odo ntog enic lack of a t rue d enti gerou s cyst- impacted
cysts in whi c h the neoplastic ameloblastic too th relationship did not support the AOT
epithelium is preceded temporarily by a no n- originating from a preexisting dentigerous
neoplastic stratified squamous epithelial lin- cyst but rather favored the "envelopmental"
ing; and (3 ) a solid amelobl astoma und er- co ncept- that is, an unerupted tooth being
goes cystic deg enerati on of ame lo blasti c embedded in an expand ing t umor mass,
islands with sub sequ ent fusion of multiple whether cystic or solid. The most important
microcysts and develop s into a unicystic le- point in this co ntext is whether lesions that
sion. Ac kermann et al9 stated that based on clinically and radiographically appea r to be
57 cases of UAs there was absolutely no ev- odontog enic cysts of any type may prove his-
idence that any other odontoge nic cyst ex- tologically to be one of several amelob las-
isted prior to th e development of the lesions. toma variants (or other odo ntoge nic tumors).
Although these authors were not able to un-
equivoca lly exclude origin from preexisting
odontogenic cysts in a few cases, they felt
that all available evide nce was against this 5. Pathology
possibility and strongly favored the idea that
these lesions are cystic neop lasms de novo.
Gold ' o disagr eed , suggestin g th at the UA 5.1 Macroscopy
has a cystic origin and is derived from odon-
togenic keratocysts, lateral periodo ntal cysts, If removed in toto, the operation specimen is
and dentigerous cysts. Li et a!' made a co m- that of a partially or totally co llapsed cystic
parison of proliferating cell nuclear antigen sac. By careful examination of the inner and
(PCNA) express ion in the cystic tumo r lining outer aspects of the cyst wall, it may be pos-
of UAs with pub lished data on odo nto genic sible to spot characteristic UA features: one
cyst linings. They found that all areas of UA or several intraluminal papilloma-like tissue
lining co ntain ed significa ntly more PCNA- prolife rations and/ or intramural focal thick-
positive cells than dentigerous cyst linings, enings or nodules. Lac k of these findings
even in areas wh ere epithelial morph ology does not, however, co ntradict a diagnosis of
was similar to that of th e dentigerous cyst lin- UA. The diagnosis of UA can only be made
ing. This find ing was interp reted as favorable histologically and cannot be predicted pre-
to the con cept that UAs are de novo cystic operative ly on c linical or rad iographic
neoplasms. gr ou nds. Exami nation of th e ent ire lesion
It is difficu lt to produ ce convi ncing evi- through sectionin g at many levels is manda-
dence for any of the theories presented . As tory fo r sec uring the final diagnosis.
alluded to earlier, Li et al3 did not find a true
dentigerous arrangement in any of their sev-

81
8: Unicystic Ameloblastoma

5.2 M icrosco py Table 8-1 Histologic UA subgrouping (mod-


ified after Ackermann et a19 )
5.2. 1 Histologic definit ions
In the 1992 edition of the World Health Or- Subgroup Interpretation
ganization (WHO) classiflcatlon." a sectio n
on UA was adde d in view of its clinical im- 1 Lumi nal UA
port ance. The classification dist ingu ishes 1.2 Luminal and intraluminal UA
betw een th ree histolog ic subtypes of UA 1.2,3 Luminal, intraluminal , and intra-
which correspond to subgroups 1, 1.2, and mural UA
1.3 in Table 8-1 . 1.3 Luminal and intramural UA
The histologic features of UA have been
established by several autho rs," all of who m
recognize various subtypes determin ed by The luminal type of tum or is called UA
the pattern and extent of am eloblastom a- subgroup 1 (Figs 8-7 and 8-8) and is defined
tous proliferation in relation to the cyst wall. as having an epithelial lining of which parts
The sepa ration into fo ur histologic sub- may show t ransfo rmation to cubo ida l or
group s (see Table 8-1) was chosen by the co lumna r basal cells wit h hyperchr omatic
present authors as a basis for evaluating UA nuclei, nuclear palisad ing with polarization,
cases in a recent review'' and is a modifica- cytopla smic vacuolization with intercellu lar
tion of the classification suggested by Ac k- spacing, and subepithelial hyalinization. This
ermann et al.9 The minimum criterion for di- definition was originally suggested by Vick-
agnosing a lesion as UA is the demonst ratio n ers and Gorlin 14 (informally know n as the V
of a single (often macro-) cystic sac, wit h an and G criteria) as representat ive of early
odo ntogenic (amelob lastomatous) epithe li- ameloblasto ma changes, UAs often show a
um, which is usually present only in focal ar- co mbination of histologic features, so UA
eas. It is often accompanied by an innocu- subgroup 1,2 (Figs 8-7 to 8-10) shows sim-
ous ep ithelium of varying histo log ic ple and intraluminal features. UA subgroup
appearance that may mimic the lining of a 1.2.3 (Figs 8-7 and 8-11) covers cases where
dentigerous or radicular cyst. there is an occurrence of intramural amelo-

Fig 8-7 Histologic classification of UAs.


1 = a fibrous cyst wall lined by
ame loblastomatous epithelium; 2 = an
intraluminal "papillomatous" mass of
plexiform, epithelial hyperplasia; 3 = in-
. tramural nodules with pro liferatin g
arnelobastorna tissue. Different combi-
nations of these features result in the
four UA subgroups (1 , 1.2, 1.2.3, and
1,3).

82
Patho log y

Fig 8-8 Am elobl ast omatous lini ng of a UA sub- Fig 8-9 UA sub group 1.2. Th e pl exiform, intralu-
group 1 (hem atoxy lin-eosin [H&E], x 80 ). minal p rolife ratio n occupies a large portion of th e
cyst cavity (H&E, x5 ).

Fig 8-1 0 Higher mag n ific at ion of t he intralum inal Fig 8-1 1 UAsub grou p 1.3 int ramu ral nodule co n-
pro liferation in Fig 8-9. Th e V and G c rite ria for an ta ining am elo blastoma t issue of t he follic ular type.
early am eloblastom a are not fu lfilled in t his case. Each tumor island is surroun ded by a thic k fibrous
Notice the loosely stru ctured and ric hly vasc ular layer of con ne ctive tissue, giving th is subgroup a
conne ctive t issue st ro ma (H& E, x80 ). nodular ap pearance. Th ere is pro nou nced cyst ic
d egeneration of the tu m or islands (H&E, x 80).

83
8: Unicystic Amelob lastoma

blastom a tissue as well as subg roup 1.2 fea- Table 8-2 Distribution (in perce ntag e) of his-
tures. The last subgroup (1.3) exhibits a cyst to logic UA subgroups accord ing to clin ical
with a luminal lining in combination w ith in- variants".
tramural nod ules of SMA tissue. The intra-
mural ameloblasto ma tissue may be seen as Subgroups
an infiltration from the cyst lining or as free is-
lands of follic ular SMA, ofte n wit h centra l cys- 1.2 1.2.3 1.3
tic degeneration (see Fig 8-11). It is important
to stress that these fo ur su bgroups all occur Dentig erous 8 25 17 50
in both the denti gerou s and t he non- Nondentigerous 17 12 12 59
dentigerous variants. It sho uld be added that
UA subgroup 1.2 is so met imes referred to as
the plexiform un icysti c amelobtastorna.s"
Althou gh th is epithelial proliferation (or hy-
perp iasia) do es not exhibit the V and G c ri- c hemical studi es are needed , with specia l at-
teria 14 as do most epithelial linings of UAs, te ntion to a comparison of the different sub-
Gardne r' " maintains that it represents SMA groups. Studies aim ed at resolving the ques-
tissue. tio n of w hether th e intraluminal exophy1ic
masses (subgroup 1.2, or plexiform UA) are
truly tum orous or merely represent a non-
5.2.2 Histopathologic find ings
neop lastic , plexiform epithelial hyperplasia
As shown in Table 8-2, where the histologic are also needed.
subgroups are distribute d accord ing to c lin-
ical variants, abo uttwo third s of bot h variants
showed intramural invasive SMA tissue
(subg roups 1.2.3 an d 1.3) w ith a sligh tl y 6. Notes on treatment and
stronger tende ncy for occ urrence in the non-
dentigerous variant. It is also not ewo rthy that recurrence rate
cases of UAs show ing intralum inal prolifera-
tions (plexiform UA) occur more than tw ice Treatme nt planning depends on the final
as frequently in UAs of the dent igerous type. histopathoiogic diag nosis. The present au-
thors are entirely in ag reement wit h the view-
points expressed by Ackermann et al9 and
5.2.3 Immunohistochemical findings
Gardner' " that UAs diagnosed as subgroups
Several attempts have been made to d istin- 1 and 1.2 may be treated conservatively
guish the lining of UAs from that of odo nto- (caref ul en ucleation ), whereas UAs belon g-
ge nic cysts. Altho ugh immunocytochemical ing to sub grou ps 1.2.3 and 1.3 sho uld be
express ion of blood cell carbo hydrates and treated aggressively in the same manner as
epide rmal growt h factor receptor showed no the classic SMA. Stoe linga and Bronk horst 19
cons istent d iffe rence between odontogenic used Cam oy's solutio n after en ucleatio n in
cysts and UAs, imm unocy1ochemi cal mark- the treatment of UA and rep orted no recur-
ers fo r lectins (Ulex europae us agg lutinin I rences in five patients treated by this meth od.
and Bandeirea simpl icifol ia aggluti nin I) and Thei r follow-up period in three of their cases
proliferating cells (proliferating cell nuc lear was 2 to 2.5 years and co nse quently too
antigen and Ki-67) may assist in their differ- sho rt to be meani ngf ul. Therefore, th eir re-
ential diag nos is.11 17 . 18 More im munocy1o- sults sho uld not be interpret ed as pro of that

84
References

the addit iona l use of Carnoy's so lution is rate reported to date) than other subg roups
more effective than enucleat ion alone. More (6,7% for both 1 and 1,2), The authors fur-
studieswith adequate follow-up periods (7to ther found that the average interval between
10 years or more) are needed. initial treatment and obvious recurrenc e was
A preope rative incisional biopsy is repre- approxi mately 7 years, and all their recur-
sentative of the entire lesion in very few in- rences we re record ed 4 years or more after
stances and will probably result in an incor- initial surgery, Thus , inclusion of patients with
rect class ification of the lesion w it h a less than 4 years of follow-up may result in
subsequent faulty diagnos is. As repeatedly an underestimation of the recurrence rate, so
mentioned, the true nature of these lesions it may be somewh at optimistic when some
becomes evident only when the entire spec- auth ors 8 ,9,2 1 categ or ically cla im that UAs
imen is available for microscopy. Thus, the have a recurrence rate of approximate ly 10%
authors strong ly recommen d abs ta ining to 15% after enucleation, Due to inadequate
from incis ional biops ies. Ope ration spec i- follow-up, the largest of UA cases pub lished
mens, whether a complete, cleanly enucl e- to date (57 by Ackermann et a1 9 ) unfortu -
ated UA or a curettage, shou ld be subjected nately lacks info rmat ion about recurre nce
to multiplesamp ling or (preferably)serial sec- rates,There are ind ications thatthere may be
tioning to spec ifically search for cell and tis- a lower recurrence rate for cases diagnosed
sue configurations of an ameloblasto matous as UA subgroup 1,2 compared to UA sub-
nature in intramura l nodu les. If invading tu- groups 1,2,3 and 1,3, However , sufficient
mor islands or strands are found intramural- data to substantiate this assumption are not
Iy,their presence indicates an aggressive sur- yet available, On the other hand, whatever
gical approach, possibly involving a second true recurrenc e rate future studies may dis-
operation where bone adjacent to the initial close, it is generally held that the UA has a
operation site is removed . The patient must lower recurrence rate than that of the classic
be followed close ly for at least 10 years be- SMA following the same conservative treat-
cause recu rrences often become appa rent ment. Commonly cited SMA recurrence
many years after surgery . rates of 50% to 90% should , however, be
Recurrence rates for UAs after conserva- viewed cautiously."
tive surgical treatment (curettage or enuc le-
ation) are generally reported to be less than
25%, and a figure as low as 10.7% has been Ref erences
calculated for the UA subgroup 1,2,'5 Many
reports in the literature indicate a less ag- 1. Robinson L, Martinez MG. Unicystic ame loblas-
gressive nature for UAs, butfew are prosp ec- toma. A prog nost ically d istinct entity. Ca ncer
tive stud ies that have examined ind ivid ual 1977 ;40:227 8- 2285 ,
histologic variants with respect to behavior 2. Eversole LR, Leide r AS, Strub D. Radiographic
and treat ment." In Li et ai's study of 33 characteristics of cysto ge nic ame loblastoma.
Chinese patients with UA,3 the authors Oral Surg Oral Med Oral Pathol 1984 ;57:572-
577,
addressed the previously mentioned clinico-
3. u T-J, W u Y-T , Yu S-F, Yu G-Y. Unicvstic ame lo-
patho logic correlation , In five of six re-
blastoma. A clinicopathological study of 33 Chi-
currences , the init ial enuc leated UA co n- nese patients. Am J Surg Pat ho t 2000;24 :1385-
tained int ramural ame lob lastoma islands 1392.
(UA subgroups 1,2,3 and 1,3), Overall, tu- 4 . Gardner DG. Plexiform unicystic a meloblastoma.
mors exhib iting intramu ral invasion had a A diagnostic problem in dentigerous cysts. Can-
higher recurrence rate (35,7%, the highest cer 1981 ;47 :1358 -1363.

85
8: Unieystie Am elo blastoma

5. Philip sen HP, Reic hart PA. Un icystic ame loblas- 15. Ga rd ner DG, Co rio RL. Plexifo rm unicystic amelo-
to ma. A review of 19 3 case s from the literature. blasto ma. A variant of amelo blastoma with a low-
OraI OncoI 1998:34:3 17- 325. recu rrence rate after enuc leation. Cancer 1984;
53: 1730- 1735.
6. RODS RE, Raubenheim er EJ, van Heerd en W FP.
Clinico-pathologi cal stud y of 30 unicys tic amelo- 16. Gard ner DG. So me current co nce pts on t he
blastomas. J Dent Assoc S Afr 1994;49 :559- 562. pat ho log y of ame loblastomas. Oral Surg Oral
Med Oral Pathoi Oral Rad ial Endo d 1996:82:
7. Reic hart PA, Philipsen HP, Sonne r S. Arne lobla s-
660 -669.
toma: Biological profile of 36 77 cases. Eur J Can-
cer B Oral Oneol 1995:31 B:86 - 99. 17. Li T-J, Brown e RM, Matthews JB. Epithelial cell
proliferation in odon togenic keratocysts: A com -
8. Leider AS, Eversole LA, Barkin ME. Cyst ic amelo-
parative immunocytochemical study of Ki6 7 in
blasto m a. Oral Burg Oral Me d Oral Patho l
simple, recurrent and basal cell naevus syndrom e
198 5:60 :624-630 .
(BeNS) associated lesions. J Oral Pathol Med
9. Ack ermann GL , Altini M, Shear M. The unicystic 1995:24:221- 226.
ameloblastoma: A clinicopathologic study of 57
18. Saku T, Shibata Y, Koyama Z, C heng J, Okab e H,
cases. J Oral Pathoi 1988 :17:54 1- 546.
Yeh Y. Lect in histochemistry of cystic jaw lesions:
10. Gold L. Biologic behaviour of ameloblastoma. An aid fo r diff erential diagnosis between cystic
Clin Oral Maxillofac Surg Nort h A m 1991 ;1:21 - ame loblasto ma and odo ntogenic cysts. J Oral
71. Pathol Med 199 1:20 :108 -1 13.
11. Li T J. Browne RM, Matthews JB. Expressio n of 19. Stoelinga PJW, Bronkhorst FB. The incide nce,
proliferating cell nuclear antigen (PCNA) and Ki- multiple presentation and recurrence of aggres-
67 in unicystic ameloblastoma. Histopathology sive cysts of the jaw s. J Cranic maxillofac Surg
1995:26:2 19- 228. 1988:16:184- 189.
12. Philipsen HP, Samman N, Ormiston IW , Wu PC, 20, Li T..J , Kitano M, Arimura K, Sugihara K. Recu r-
Reich art PA. Variants of the adenomato id od on- rence of unicystic amelob lastom a: A case report
togenic tum or with a note on tumor or igin. J Oral and review of the literatu re. A rch Pathol Lab Med
Pathol Med 1992:2 1:34 8-3 52. 1998:122:37 1-3 74.
13. Kramer IRH, Pindborg JJ, s near M. The histolog- 2 1. Gardner QG. Co ntroversies in the nom enclature,
ical typing of odo ntoge nic tum ours. 2d oo. Berlin: diagnosis, and treatment of amelob lastoma. In:
Sp ringer-Verlag, 1992. Worth ington P, Evans JR. Con troversies in Oral
14. Vick ers RA, Gor lin RJ. Am elo blasto ma: Delin - and M axillofa cial Surgery. Philad elphia:W B
eation of early histopatholog ic featu res of neo- Saund ers 199 4:301 -3 14.
plasia. Cancer 1970:26:699- 7 10.

86
Chapter. 9~------------------.

Squamous Odontogenic Tumor

1. Terminology reactive, inflamm atory hyperp lasias of the


cyst epitheliu m. Therefore, the ter m sug-
Pullon et al' first described a particular odon- gested by Batsakis and Cleary6- m ura l vari-
togen ictumor located in the periodon tium as ant of SOT- should be discou raged .
squamous odontogenic tumo r (SOT) in
1975. The authors described a series of six
tumors which "caused radiolucent areas of
bone dest ructio n adjacent to the roots of 2. Clinical and radiologic profile
teeth."
According to the World Health Organ iza-
tion (WHO) classification of 1992,2 the SOT The squamous odontogenic tumor is a
belongs to t he family of ep ithelial odo nto- benig n but locally infiltrative odontogenic
genic tumors. The term SOT has been wide- neopl asm . It is slow growing with few clinical
ly accepted , although others such as squa- signs and symptoms . Mob ility of the teeth,
mous odo ntogen ic hamartoid lesion have swelling of the alveolar process, and moder-
been suggested . The following characte ri- ate pain are possible ind icato rs of the un-
zation of the SOT is based on a recent review derlying tumor. Mostcasesdevelop in the pe-
of 36 cases pub lished in 1996.3 Two addi- riodontal ligament of perman ent teeth;
tional cases were pub lished by Favia et al in .theretore, the most common variant is the in-
19974 and Ide et al in 1999 .5 The latter was trabo ny or cent ral type of SOT. A rare pe-
of special significance since the SOT was as- ripheral variant has also been desc rlbed."
sociated with a squa mous cell carcino ma. Some SOTs are localized in edentulous ar-
The authors suspected a maligna nt variant eas, and multicentric occ urrence has been
of the SOT. reported .? This fact stresses the need for
A number of cases pub lished in the litera- tho roug h clinical and espec ially radiologic
ture discussed purpo rted SOTs, which are examinat ion of a patient with a neop lasm di-
considered to be other tumo rs by the pres- agnose d as SOT. Of particular significance
ent authors.Squa mous odo ntogenictu mors, is the observation that SOTs occurring in the
among others, were confused with periph- maxilla seem to be mo re aggress ive t han
eral ameloblastoma, desmoplastic ame lo- those in the mandib le, a behavior common
blastoma, and particularl y squam ous odon - to several odontogenic tumors.A familial pat-
togenic tumorlike islands arising in th e walls tern of SOT was observed by Leider et al,?
of odontogenic cysts ." SOT-like islands in who reported multiple lesions in three sib-
cyst walls are non-neop lastic and represent lings. SOT seems to be associated with im-

87
9: Squamous Odontogenic Tumor

lar radiolucency between the roots of adja-


cent teeth (Fig 9-1). Radiopacities seen in
other odontoge nic tumors are not found in
SOTs. Embedded teeth have been found in
a few SOT cases. Extensive SOT lesions may
have a mult ilocular pat1ern involving the
mandible or the maxillary sinuses. The pe-
rip heral variant of SOT may reveal some
"saucerization" of the underlying bone which
is explained as a pressu re phen ome non
rather than a result of neop lastic infiltration.

3. Epidemiological data
Fig 9-1 Radiograph of a resectio n specimen of
SOT. A triangular, multilocular rad iolucency is
3.1 Prevalence, incidence, and
seen betwee n the roots of a mand ibular cani ne relative frequency
and first premolar. Differential diagnosis should
include ameloblasto ma and odontogenic myxo- Since the number of repo rted cases of SOT
ma. is still rather small, no data are available.

pacted teeth only rarely in contrast to many 3.2 Age


ofher odo ntoge nic tu mors. Its assoc iation
with squamous cell carcinoma (primary, in- The age of 39 patients with SOT3-5 ranged
traosseous) is not clear." from 8 to 74 years with a mean age of 38.7
Radiology of the central variant of SOT years. Patients in the 3rd decade of life seem
shows a well-defined unilocular and triangu- to be affected most frequently (Fig 9-2).

No. of cases

8
7 7 ['j] Women
(jI Men
6
5 n =39
4
4
3
3
Fig 9-2 Distribution of 2
SOT cases according to
age and gender. There o I I!J ! I) I !l U ! !J U I IJ U I 11 !J I IJ U I !J
is a peak for both men 0 - 10 11 -20 2 1-30 31-40 41-50 51- 60 61 - 70 71-80
and women in the third Age in decades
decade.

88
Pathology

3.3 Gender

The gender ratio among the 39 SOT patients


was 1:1.4 (worne n.menj.? 5 7

n = 28
3.4 Location

Figure 9-3 shows the location of SOTs (n =


28). 3- 5 Th e ce nt ral or intraosseous SOT,
which is byfarthe most commo n variant, usu-
ally begins to develop in one periodontal lo-
cation adjacent to the roots of erupted , per-
Fig 9-3 Location of tumors. In addition to the 28
manent teeth. However, the coexistence of singletumor sites shown,5 SOTs had multiplelo-
bilate ral, posterior maxillary SOTs and a cations in both the maxi lla and the mandible, 4
mandibular, primary carcinoma in associa- were located in both the anterior and posterior
tion with an impa cted third molar has also maxilla, and 1 tumor had a bilateral, maxillary lo-
been reported. Recently another case of an cation (total n ~ 38).
intraosseous SOT associated with a squa-
mous cell carc inoma and an impacted third
molar has been oescnbeo ."
5. Pathology

4. Patho genesis 5.1 Macroscopy

No descriptions of the mac roscopic app ear-


The origin of the SOT is unclear; however, ance of SOTs are available.
there are indications that it may arise from ep-
ithelial rests of Malassez located in the peri-
odontal ligament. Peripheral SOTs may orig- 5.2 M icroscopy
inate in the gingival surface epith elium as a
5.2. 1 Histologic definition
"dropping off" ph enome non or from rem-
nants of th e dental lamina. In cases where The present authors use the following defi-
the origin of the SOTs was supposed to be nition for SOTs: A benign but locally infiltra-
the surfac e epithelium, the tumors appe ared tive neop lasm consisting of islands of well-
histologically as pseud oepitheliomato us hy- d iffere ntiated sq uamous epit heiium in a
perplasias or periph eral ameloblastomas. In- fibrous stroma . The epithelial islands occa-
flamm ato ry stimu li d o not seem to be in- sionally show fo ci of central cystic degener-
volved in th e initiation of pr oliferation of ation.
epithelial remnants, in co ntrast to SOT-like
proliferations observed in odontogenic cysts.
5.2.2 Histopa thologic finding s
Some authors have considered that the SOT
may have a hamartomatous nature.',4 Histologically, th e SOT is composed of is-
lands of well-d ifferentiate d squamous ep-
ithelium of varying size and shape (Fig 9-4).

89
9 : Squa mous Odontogenic Tumor

Fig 9-4 Low-powe r microgra ph of the spec ime n Fig 9-5 A higher magnification of the same spec-
shown in Fig 9-1. Between the roots of the canine imen showing several ep ithelial nests a nd islands
and first premolar, mu ltiple isla nds of odo nto- bordering a root surface (right) . Some of the is-
genic epithelium a re see n. Som e of these have lands exhibit ce ntral cystic deg eneration. Tumor
undergone cystic degeneration (Mallory stain, isla nds are e mbe dded in a spa rse con nective tis-
x1.2) sue stroma (hematoxyl in-eosin [H&EJ, x50).

Often the islands are rounde d or oval, but


they may also reveal irregular and cordlike
structures (Fig 9-5),as is characteristic tor the
desmoplastic ameloblastoma. Individua l tu-
mor island s reveal a peripheral layer of low
cuboidal or even flat epithe lial cells. This is
different from the hig h cylind rical epithelial
celis obs erved in SMAs . Individual epithel ial
islands may undergo cent ral micro cystic de-
generation of the spino us ceils fo llowin g sin-
gle-celi kerat inization (Fig 9-6), Some islands
Fig 9-6 The interfacebetween tumor islands and may bec ome large and co ntain laminar cal-
connective tissue strom a. Epithe lia l cells are flat c ified mate rial. Mit otic activity of the ep ith e-
and lose intere pithelial contact toward the ce nter lial tumor cells is not inc reased. Tumo r is-
of the islands (microcystic degeneration) (H&E, lands are surrounded by mature co nnective
x 100). tissue w ith litt le or no inflammatory reaction.
Ghost ce lls orclear ceils have not been found
in SOTs.
The SOT may be mistak en for an acan-
th om atou s or a desmoplasti c ame loblas-

90
Notes on treatment and recurrence rate

toma, a well-differentiated squamous ce ll ies) are also contained in the cytop lasm. In
carcinoma , or a pse udo epit heliomatous some areas the myelin bodie s and glycog en
hype rplas ia co mparab le to a keratoacan- granules take up a major portion of the cy-
thoma. A histopathologic misinterpretation toplasm and seem almost to replace the nu-
may thus lead to overtreatment or under- cleus. Dense tonof iiament bands are also ob-
treatment. served in the cytop lasm. Nuclei are large and
contain evenly distributed chromatin and an
occasional nucleolus. Keratin formation and
5.2.3 Histochemical/immun ohistoch emi-
calcification are not observed.
cal findings
Tatemoto et al8 and Yamada et al9 repo rted
on immunohistochemical findings in cases
of SOTs. Immunohistoc hemical staining of 6. Notes on treatment and
keratin proteins was performed using po ly-
clonal antikeratin antiserum (TK, detecting recurrence rate
41- to 65-kd keratins) and monoclonal anti-
bodies (KL 1, 55 to 57 kd ; PKK 1, 40, 45 and The SOT is generally considered a benign
52.5 kd). Staining for PKK1-detectable ker- odo ntogenic neoplasm, and therefore most
atin was negative in tumor islands; staining authors reco mmend conse rvative surgical
with KL1 and TK immunoreagents was con- procedures such as enucleation, curettage,
fined to squamo us epithelial cells." The pro- or local excision. However,tu mors located in
liferative activity of the odo ntoge nic epitheli- the maxilla have to undergo a more radical
um of SOTs was also conf irmed by heavy treatme nt because of the aggressive poten-
staining fo r keratin 13 and 16. The centers t ial of SOTs in t his location. Recurrences
of the epithe lial islands of the squamous d if- have been described, but they seem to be
ferentiating cells revealed strong positive re- rare and are probably due to incomplete re-
actions for lnvolucrtn." In the latter study, moval of the tumor. When considering treat-
however, acanthoma tous and follicul ar ment, one also must be aware that SOTs may
SMAs with foci ot squamo us differentiation occ ur in a multicentric pattern.
were also positive for involucrin. Since the number of reported cases of
SOTs is still rather small, the biologic profile
of this entity is still not clear, especially its as-
5.2.4 Ultrastructu ral findings
soc iation wit h squ amous cell carcinoma (pri-
Pullon et a!' were the first to describe ultra- mary, odontogenic). From the histopatho-
structural features of the SOT. Neoplastic ep- log ic point of view, waysto differentiate SOTs
ithelial cells are arranged in nests or islands from aca nthomatous and desm op lastic
in a stroma of sparse collagen bund les. Ind i- ameloblastomas have to be found. In addi-
vidual islands are surrounded by a well-de- tion, cases originating from the surface ep-
fined basal lamina.Squamous epithelial cells ithelium should be studied in great detail to
are surrounded by intercellular ede ma as confirm that they are true SOTs.
seen in cells of the stratum spinosum of the
oral mucosa. Desmoso mes are numerous,
and the cytoplasm contains abundant glyco-
gen granules, a few mitochondria, and flat-
tened cisternae of g ranular endop lasmic
reticulum. Laminar structures (myelin bod-

91
9: Sq ua mous Od o ntog enic Tum o r

References 6. Batsakis JG, Cleary KR. Patho logy cons ultation.


Sq uamous odon to genic t umor. Ann Otol Rhinol
Laryn9011993 ;102:823-824.
1. Pullon PA, Shafer W, Elzay RP, Kerr OA, Corio RL.
Squamous odo ntogenic tumor. Oral Surg Oral Med 7. Leider AS, Jonker AL, Cook HE. Multicentric famil-
Oral PathoI 1975;40:61 6- 630. iar sq uamous odontogenic tumor. Oral Surg Oral
Med Oral PathoI1 989;68:175- 18 1.
2. Kramer IRH, Pind borg JJ, Shear M. Histolog ical
Typing of Odontogenic Tumo urs. 2d ed. Berlin: 8. Tatemoto Y, Okada Y, Mori M. Squamo us odonto-
Springer-Verlag, 1992. genic tumor: Immu nohistochemical ide ntification
of kerat ins. Oral Burg Oral Med Oral Path ol
3. Philipsen HP, Reichart PA. Squamo us odo ntog enic
1989;67:63- 67.
tumor (SOT): A benign neoplasm of the periodon-
tium. J Clin PeriodontoI1996;23 :922 - 926. 9. Yam ada K. Tatemoto Y, Okada Y, Mori M . Im-
munostaining of involucrin in odontogenic epithe-
4. Favia 8 F, Oi Alberti L, Scarano A, Piattelli A. Sq ua-
lial tumors and cysts. Oral Surg Oral Med Oral
mous odo ntoge nic tumou r: Report of two cases.
Pathol 1989;6 7:564 - 568.
OraI OneoI 1997;33:451- 453 .
5. Ide F, Shim ovama T, Hone H , Shimi zu S. Intra-
osseous squamous cell carcinoma arising in asso-
ciation with a squamous od ontogenictumour of the
mandib le. Oral Oncol 1999 ;35:43 1- 434.

92
Chapter 10

Calcifying Epithelial Odontogenic Tumor

1. Terminology 2. Clinical and radiologic profile


In 1955, Pindborg 1 repo rted three cases of The CEOT is a benign neoplasm located ei-
a benign but locally aggressive tumor which ther intraosseously or extraosseously. When
he called th e calcifying ep ithelial odonto- occu rring intraosseo usly (by far t he most
genic tum or (CEOT), today known as the common), it may occas ionally show local in-
intraosseous variant of CEOT. Pindb org fol- vasiveness. The intraosseous CEOT ofte n
lowed his abstract with two more publica- prese nts as a painless mass with slow
lions,' 3 the latter reporting on the 24 cases g rowth. When located in the maxilla, patients
known at the time. The tumo r had been re- may sometimes complain of nasal conges-
ported prior to 1955 under different names tion , epistaxis, and headache.
such as ameloblasto ma of unusual type with The char acte ristic radiographic appear-
calcification, calcifying amelo blastoma, ma- ance is of an irregular unilocular or multiloc-
lignant odo nto ma, adenoid adamantoblas- ular rad iolucent area containing radiopaque
toma, cystic comp lex odo ntoma, and a vari- masses of varying size and opacity (Figs 10-
ant of the solid/rn ulticystic ameloblastoma 1 to 10-3). In many cases, especially in tu-
(SMA). The term calcifying epithelial odonto- mors of relatively short duration, the calcified
genic tumor has been gene rally accepted co ncrements are minute and may be unde-
and adopted by the World Health Organiza- tectable on radiographs.
tion (WHO) since the pu blication of Histo- When an unerupted tooth is associated
logical Typin g of Odontog enic Tumours, Jaw with the tum or, the radiopacit ies tend to be
Cysts, and Allied Lesions in 1971 4 For al- located close to the tooth crown (Fig 10-4).
most 40 years the CEOT has been known At the periphery, the radiolucent margin may
eponymously as the Pindborg tumor. The fol- or may not be clearly demarcated from the
lowing profile of the CEOT is based on a lit- norm al bone. Clinically,the peripheral soft tis-
erature review of 181 cases." sue, or exlraosseous, CEOT appears most
com monly as a painless, firm gingival mass
with a preope rative clinical d iagnosis that in-
cludes fibrous hyperplasia, peripheral giant
cell granuloma,and epulis.The overlying mu-
cosa may show ulceration due to local trau-
ma. On surg ical removal, an underlying bony
depr ession or sauce rization has been re-
ported in a few cases.

93
10: Calcifying Epithelial Odontoge nic Tumor

Fig 10 -1 Orthopantomograp h
show ing a CEOT in the left max-
illa aroun d the roots of the third
molar with invo lvement of the left
sinus.

Fig 10-2 Com puted tomography (CT) scan ofthe Fig 10- 3 Transversal tom ographs showing a
left maxillary sinus containing multiple, partly co- mixed radi olucent/rad iopaque CEOT lesion
alescent, radiopaque bod ies. (same lesion as in Figs 1(}-1 and 1(}-2).

Fig 10-4 Radiog raph of the left mandibular mo-


lar region showing an unerupted first molar with
a pericoronally iocated CEOT.

94
Epidemiological data

3. Epidemiolog ica l data according to the two topographic variants,


the age ranges and means are as follows:
The intraosseous type has a range of 8 to 92
3.1 Incidence, prevalence, and years (mean 38.9 years), and th e ex-
relative frequency traosseous type has a range of 12 to 64 years
(mean 34.4 years). Alth ough th e total num-
Information on incidence and prevalence of ber of reported cases of the ex1raosseous
CEOTs is not available. Data from d iagno s- variant is still small (see Table 2 in Philipsen
tic biopsy services from various sources do, & Reichart S and Fig 10-5), the mean age
however, provide information about the rela- seems to ind icate that the peripheral variant
tive tumor frequency (as a percentage of all Is diagnosed a few years earlier than the in-
odontogenic tum ors), and it varies between trabony type. This is not surprising since the
0.4% and 3%.S- 7 The CEOT has one of the peripheral type presents as a gingival mass
lowest frequency rankings on a "hit list" of (ep ulis), whic h lends itself to an earlier diag-
odontogenic tumors. The peripheral or ex- nosis than does an intraosseous lesion. Al-
traosseous variant co nstitutes about 6% of most two thirds (64%) of the intraosseous
the total numb er of CEOTs. variants are fou nd in the 3rd, 4th, and 5th
decades of life (see Fig 10-5).
When age and gend er data from cases of
3.2 Age white patients with intraosseous CEOTs are
compared w ith a comp arab le number of
The age range of all patients with CEOTs Asian (Japanese and Chinese) patients with
varies betw een 8 and 92 years at th e tim e of intrabony CEOT variants it is revealed that
diagnosis with a mean of 36.9 years (n ~ 172, Asian CEOT cases seem to be diagnosed a
Fig 10-5). However, if the tumors are d ivided few years earlier than the ir white co unter-

No. of cases

25
~ Tota l wom en
(] Total men
20
[ ] Extraosseous wom en
15 OJ Extraosseo us men
n=1 72
10

o A'l
0 -9
([]
10 -1 9
9-=;,
20 -29
1J"
30 -39
b;, b;,
40- 49 50 - 59
~ A'l"
60 - 69 70-79
A'l
80 +
Age in d ecades

Fig 10-5 Bar graph showing the distribution of 17 2 extra- and intraosseous CEOTs according to age
and gender.

95
10: Calcifying Epithelial Odontogenic Tumor

parts-the difference being especially obv i- 3. 4 Location


ous for rnen.? An explanation for this differ-
ence cannot be offered at present. As mentioned earlier, th e CEOT appears in
tw o clinicoto pog raph ic variants: the intra-
osseo us (intrabo ny or central) and fhe ex-
3.3 Gender traosseou s (peripheral). The forme r is by far
the most common, accounting for 93.6% of
The male:female ratio for 16 1 cases ofthe in- all tumors. It may be further subd ivided into
t raosseou s variant w ith kn ow n gender is cases with and wit hout association with an
80:8 1, or a nearly even d istribution. If gender unerupted tooth (or odontoma) . Figure 10-6
is distributed accord ing to age groups (see shows the distribution of 181 cases of both
Fig 10-5), th e pea k incid ence for men is var iants with in the jawbones. The intra-
reached a decade earlier (3 Cd decade) than osseo us tu mors are fo und primarily in the
that for women (4' h decade). Although the re- mand ible (maxilla:mand ible ratio, 1:2), and In
ported cases of extraosseous CEOTs are stili 82% of th e cases where the exact site of the
few in number, the trend in gender distribu- tumor has been registered they are located
tion seems to follow that of the intraosseous in the premolar and mola r regions. It is too
variant (male:female = 6:5). early to assess the pred ilection site for the ex-
traosseous variant.
Amo ng 181 cases of CEOT, two patients
presented with the rare phenomenon of two
isolated tumors . Cho mette et al8 descrlbed a
40-year-old woman with two intraoral swell-
ings, the first located in the left maxilla in the
second and third molar region and th e sec-
- maxill ary N D - 6
- maxillary unilat-1 2
ond in the left mandi ble in th e th ird molar re-
gion. Radio graphs showed two well-defined
radiolucenc ies, both co ntaining numerous
,, small radiopacities, as well as an unerupted
,,
29(2) :9(2)
mandibular third molar.
n= 181 After revising a case initially reported as
th e simultaneous occurrence of two amela-
:, blastic fibromas in th e same pat ient.? Busch
81 (2) 115 and Hoppe 10 came to the co nclusion that the
:(5) 48-year-old man d iscussed actually had two
CEOTs (and not two ameloblastic fibromas)
- mandibular unilat- 5 located in the right maxilla and the left man-
- mandibular bilat - 3 dible.
- mandi bular ND--l 0

Fig 10-6 Topographic distribution of extra- and


intraosseous CEOTs within the jawbones. Num-
3.5 CEOT in associati on with
bers in pare ntheses indicate the numb e r of ex- uneru pted permanent teeth
traosseousvariants. NO = no details available; uni-
lat = thetumorinvolves onequadrant (right or left); The d istribution of unerupted permanent
bilat = the tumor crosses the midline, involving teeth in association with th e int raosseous
two quadrants. variant of CEOT shows that 53% of these

96
Pathogenesis

No. of cases

n=50

Fig 10-7 Distribution of


50 cases of CEOT asso-
ciated with an unerupted
permanent toothaccord-
flblb,----...L..-'CTI"'-dJbrnooJ
o 876543 2 1 1 2 3 4 5 6 7 8 Unerupted tooth
ingtotheidentified tooth.
1
1 = central incisor;
2 =: lateral incisor;
~2
3 = canine;
:g 3

4 = first premolar;
:g 4
~ 5
5 = second premolar; 6
6 - first molar; 7
7 = second molar;
8 = third molar.

CEOTs have a definite association with an ripheral variant- it became evident that other
unerupted tooth (or odontoma). Based on 50 sourc es than reduced enamel ep ithelium
of the most recently reported cases of intra- should be considered when discussing the
osseous CEOTs associated with unerupted histoge nesis of CEOTs. The peripheral loca-
teeth, 52% of the teeth we re identified as tion strongly suggests the possibility that the
mand ibular molars (Fig 10-7). tumo r arises from rests of the dental lamina
or from the basal cells of the oral epithelium.
To co nceptualize a unified source of origin
forthe d iverse locations of CEOTs, one must
4. Pathogenesis look for a widespread occurrence of odon -
togenic epithelium, Of the possible candi-
dates only one matches the requirements of
Because the first few repo rted cases of widespread d istribution: epithelial remnants
CEOTs were all assoc iated with an unerupt- of the dental lamina complex. Disintegration
ed tooth, Pindbo rq'' was initially of the opin- of the co mplex syste m of dental laminae
ion that the CEOTwas of odo ntoge nic origin gives rise to a countless number of epithelial
and developed from the reduced enamel or- remnants persisting in the jawbones and gin-
gan of the unerupted toot h. Later. Chaud hry giva after co mp letion of normal odontogen-
and associates 11 emphasized that the tu mor esis. This argum ent also seems relevant for
cells exhibit mo rpho logic characteristics of the histogenesis of severa l other odon to-
squamous epithelium; they stated catego ri- gen ic tumors and hamartomatous lesions,
cally that. in their case, the cells had been de-
rived from the reduced enamel epithelium of
the closely related unerupt ed tooth. With the
appearance of report s of cases of int ra-
osseous CEOTs without an associated un-
erupted tooth- and particular cases of the pe-

97
10: Calcifying Epitheiial Odontogenic Tumor

Fig 10-8 Photomicrograph showing anastomos- Fig 10-9 Higher magnification of epithelial sheet
ingsheetsof epithelial, eosinophiliccellswith cel- shown in Fig 10-8. Note the nuclear polymor-
lular and nuclear polymorphism (hematoxylin- phism and intercellular bridges (H&E, x 150).
eosin [H&EJ, xSO).

Fig 10-10 Calcified amyloid-like bodies revea ling


Liesegang rings. ~ root dentine (H&E, xSO).

5 . Pathology hard de ntal structures of an odontoma) can


be fo und embedded in the tumor mass.

5.1 Macroscopy
5.2 Microscopy
The int raosseously located CEOT is often
5.2. 1 Histologic definitions
easily enucleated , and the tumor size varies
from 1 to 4 em in diameter. Th e mass varies According to the 1992 WHO classif ication, 12
in co lor from grayish w hite or yellow to tan- a CEOT is "a locally invasive ep ithelial neo-
pin k. Bisecting the spec imen usua lly reveals plasm cha racterize d by the development of
calcified particles th at make a c ru nch ing intraepithelial structures, p robably of an amy-
sound during cutting. The tu mor may be so l- loid-like nature, w hich may become calc ified
id or contain minute cystic spaces. If associ- and which may be liberated asthe cel ls break
ated with an unerupted tooth, th e cro wn (or do wn ."

98
Pathology

The definition used by the present authors like, pseudo amyloid) tumor cell prod uct oc-
is as follows: curring in CEOT is still creating controversy.
A locally invasive ep ithelial neoplasm co n- The biologic and biochem ical significance,
sisting of sheets and strand s of polyhedral, as well as th e origin ofthis material, is far from
pleom orphous ce lls with we ll-defined ce ll being und erstood. An origin from light chai n
borders often showing interce llular bridg es fragmen ts of immunog lobu lin molecules has
(Figs 10-8 and 10-9). A chara cte ristic featur e been prop osed for some forms of systemic
is an amy loid-like mat erial that may beco me arnyloid.!" Anot her type is possib ly associat-
calcified (Fig 10-10 ), is formed intraepithe- ed w ith en docr ine tu mors suc h as th e
lially,and may be libera ted as the cells break medull ary carcinoma of the thyroid der ived
dow n. from the endocrine polypep tide cells of the
am ine precu rso r uptake decarboxylation
(APUD) syste m. Obv iously, these sou rces do
5.2.2 Histopathologic findings
not ap ply to th e CEOT amyloid. Mor i and
The basic histologic pattern of CEOTs, usu- Makino 15 found that most ofthe calcified and
ally described as ch aracteristic and unique, homogeneou s ace llular materia ls were pos-
is an unusua l and variab le co mbination of itive fo r prot ein reactions, wh ich resembled
odo ntogenic epithelium and calcified stru c- those ob served in enamel matr ix. In a thor-
tures. There is no fundamental diffe rence in ough hist oc hem ic al and im munolog ic
histomorphology between the intraosseou s study.'? the auth ors we re unable to dete r-
and extraosseous variants of CEOT exc ept mine the precise natu re of this materia l, but
for the mi nimal amount or total lack of calci- suggested that the CEOT protein ap peared
fied material in the latter. A i-Ru et al? sug- to be a distinct protein moiety derived fro m
gested in their report of 9 cases of CEOTs immune amyloid or amy loid of unkn own ori-
that the histolog ic features be subtyped into gin.
four main patterns. Th is c lassificatio n has, The homogeneous substance seen histo-
however, not been wid ely used . log ically appears in the electron mic roscope
The use of fine-needle aspiratio n biops y in as eith er a fibrillar or gra nulof ibrillar material.
the diagnosis of CEOT was recently repo rt- Yamagu c hi et al' ? supported th e amyloid
ed. 13 Cytologic smears were characterized co nc ept, but ag reed w ith Page and cowo rk-
by clusters, sheets, and rare iso lated pleo - ers'Bthatthe material w ith a beta protein co n-
morphic cells of the sq uamoi d typ e; blocks figuration is likely similar to enamel mat rix. It
of amorphous material encircled by fibrob- is interesting that althou gh there are few case
lasts; and occas ional calcifications. A cyto- reports of intraosseous CEOTs w ith minimal
logic diag nosis of CEOT was made, wh ich or no calcification, '9-2 ' it is the gene ral view
was confirmed by histopathologic exam ina- that lack of calcification is mo re common in
tion. Evaluation of DNA ploidy by semlauto- the periphe ral or extrao sseou s variant.
mated image cyto metry produced an ane u-
ploid histog ram. 5.2.2.2 Cementum-like components of
CEOTstroma
5.2.2.1 Occurrence of amyloid-like material In th e scanty fibro us connective tissue stro-
in CEOT ma of CEOTs, studies have demo nstrated
Though investigated intensively during the th e pr esen ce of c ementum-lik e co mpo-
past 40 years or mo re using histochem ical, nent s.22-24 The m echanism of formation of
immu nologic, and ultrastructura l met hods, the cementu m-like material is still unc lear. It
the true nature of the eos inop hilic (amyloid- shoul d, however, be rememb ered that th e

99
10: Calcifying Epithelial Odontogenic Tumor

majority of calcif ied homogenous masses of erably higher (46 .3 years) than for the ex~
CEOT stroma is thoughtto be dystroph ic cal- traosseous variant (34.3 years). The male:fe-
cification . In the study by El-Labban--' it was male ratio for the intraosseously located clear
found that the outer layer of the calcified cell type is 1:2 compared to 1: 1 for the ex~
lamellar bodies consisted of typical banded traosseous variant.
calcified collagen w ith an arrangement like It should be remembered that not oniy
that seen in cemental Sharpey fibers . Sloot- clear ce ll CEOT but also several other odon-
weg 24 suggested that the amyloid-like mate - togenictumors such as SMAs25,26 (see chap-
rial is an inductive stimulus for the stroma ter 5 ), calc ifying ghost cell odontogenic tu-
cells to differentiate toward production of a rnors" (see chapter 17). and occasionally
collagenous matr ix that is destined to miner- adenomatoid odontogen ic tumors (AOTs)28
alize and resemb les cementum . (see chapter 11) may show clear ce ll differ-
entiat ion . It is not yet known whether c lear
5.2.2.3 Occurrence of cfear cells cell variants of odontogenic tumors behave
Variations in the typical histo- and cytornor- bio logically d ifferent from the claSSIC CEOT,
pholog ic CEO T appearance occasionally although the two cases of clinically aqq res-
occur. Sheets of classic polyhedral ep itheli- sive clear ce ll ameloblastoma reported by
urn wit h abundant eos inoph ilic cytoplasm Waldron et al 29 may ind icate that such a
may alternate with zones of epith elium char- possibility does exist. Primary jaw tumors of
acte rized by large cells with clear , foamy cv- p utative odontogenic origin , composed prin-
top lasm and d istinct cell borders. Yarn- cipally of clear cells, have recently been de-
aguchi et ai ' 7 believed that the clear tumor scribed under the d iagnos is of c lea r ce ll
cells represent a feature of cytod ifferentiation odontogen ic tumor (CCOT) .30,31
rathe r than a simp le degenerative phenorn- The CCOT is a rare tu mor but is estab -
enon. Fifteen cases of documented exam - lished in the 199 2 WHO ciassification 12
pies of clear ce ll CEOT (CCCEOT) (Figs under the definition of a benign but loca lly
1O ~ 11 and 1O ~ 12) have been published so far invas ive neoplasm orig inating from odont-
(see Table 5 in Ph ilipsen and Heichart''), ogenic epithelium and characterized by
Overall ages ranged from 14 to 68 years w ith sheets and islands of uniform . vacuolated ,
a mean of 4 1.5 years. The mean age for the and clear cells. CCO T can be distinguished
intraosseous CCCEOT is, however, consld- from the clear ce ll variant of CEOT because
it lacks the chara cte ristic calc ifications and
the amyloid-like deposition .
:-"li<~s.."rri ~,"-i';;"{-, ~ '~~ \'~~:t~"
,, jr::: 1;'I !.~.-f';o
-:;f)>r. - ;" ~1 It should be ment ion ed that certa in odon-
,,;-:i .....(;~, .;~~R
l>. / . ~ "
1"...;"

.f'~4:;
'"
I ' l.t;,....' '/ ~
'~ .." . 'Io... ~t) ..".......
...,1.t ~..c4
-#~ ~ ; : \,.J ~~. .. I . ~ ,- /
. .::.;~~ ,~ . . : ~r~'
-,t
... '11 -
' :<
; ' '!../~ :-0 ," \(fJf~~f .,j\, ~ ' :0 ,j I. ~ i f; ' ;. ~~....
;4.'.' '-."- .,'
~ " !W
,1 . .. ,( "

togenic lesions of developmental origin- like


the lateral periodontal cyst and the gingival
...
.-- ' ''' ' ' , v .. , " '
~K.}~"'~~ : ~ l ..,;:t. _ , t.~ ~ < ' :"' , ,-# '-~ ~~ .
~ ,, .",,~
cyst of adu lts-contain conspicuous foc i of
~ _.. _~;.;. _..'tJlF- , ~~ ~ .... ~ ."1;. l : ~~;;"-'.,, . . P';' i;"-t.-;:; o,;. . .
~r---l' . ?, /I:" ,k ' } t ",~,;' .~.;?' ''! -~ 1 " ,;.:.Ii i ,:
'~x- : ,. . ;;; ~c , " '4'.;: :%",~ \ , -~,'. ~ l ~--.... .....lJ!"!l-~ clear cells in their epithelial lining identical to
~" ~-""" ~ ~~. ~.\\ ,." .,. .~ .,.....,. ,:.. , ' >'~ '-' -~~
p'"
. ...-!
....
A. ~ .~ -r t. o ., " ..~(. \ .~. .. , i .-=.""
; :t ,. t,' :- 'I '~ :'~,",~.
:>lie~''''' . "-:;~ ,~ -:::~ \/ ",
J ,.. "'.:. ,
.....
, ,> ,, ~
~, ~ i'r:.
those described here. Th e fact that ceiiular
remnants of the dental lamina com p lex con-
'.' ~ . ., .1''':'' ''' "..'''': ~t'' :~ ~'' \ ) - \ , i "~ ,r ~
"", . .,.., . ! ~. ,
.. ~ . ~' ''"' ':', {1o';"l-- i. ' ,~
.~. ,
,'--
.'c}.- -;:....
-~.
" '? ' ;.....
t Jt
' / :'; - ' ~ ta in clear ce lls as a typ ica l feature strongly
:i\~
':'i :.. ~.t..
, ~; ;" ::'f' ~~ ~ ' !i , . .r/ .f,,"
"' ;i~lj, ~-:'
't .-..f",'
.. , (,"Ojl 'fl- t .\: . . . ", suggeststhatthe previously mentioned cysts
~
:K.c;,. ~ ,:~~ . '--"'''.l.,.::;r~. , "Jt~:r~~ ') :." .,," ...~ ; , ~?...~
~~ " .. . '~, -," - ' ''''''''' ' " ~ O ~." arise from clear cell rests of the den tal larni-
~ ""f"':;yJ,'t :. , J(..'/O~.l?r-':~ ':l~~~~""'\f\. rt-.i 1
,. , ' 1":"-"' , - ' , ,-
J
.!II- .~ .~ ...... , ...... \~~ ."' ..~ ~'-"~ na. Thus. it seems log ical to the present au ~
Fig 10-11 CEOTWith clearcelldifferentiation and thors to suggest that th e CEOT originates
scattered calcified bodies (H&E, x60). from the dental lamina or its remnants.

100
Pathology

The distinction of an extraoss eous CEOT 8 -100-pos itiv e ce lls w ere id entified as
clear ce ll variant from so me clea r ce ll salivary Langerhans cells based on the finding of rod-
gland tumo rs, m etastatic renal cell carcino- and tennis racket- shaped Birbeck granules.
ma, and od ontogen ic lesio ns (such as the With on ly two p ubl ished cases p resent ly
clear ce ll odo nto ge nic carcm orna and pe- availa b le, it is ob viously too early to specu -
ripheral am elob lastoma with clea r ce li differ- late on the im portance of th e presence of
entiation) represents a diagnostic cha llenge. Langerhans ce lls on tu m or beha vior and
The same can be said about the ide ntifica - p rognosis. Lange rhans ce lls belong to the
tion of an intraosseous c lear cell CEOT when mononuclear phagocyte system, are of bone
only a small incisional b iopsy specimen is marrow origin, and are ofte n found in the skin
available. Although the gingiva is not a typ i- and oral mucosa. It has been clearly ascer-
cal location for a salivary glan d neoplasm , tained that Lang erhans cells function as anti-
mucoepide rmoid carc inoma, ac inic cell car- gen -present ing cells and as alloge nic stimu-
cinoma, c lear ce ll ca rcinoma of the salivary lat ory cells t o primed T lymp hocytes in the
gland, and clea r cell variant of oncocyto ma ep ithe lium.35,36 As there are several reports
must be conside red in th e mi croscop ic dif- suggesting some co rrelation between tumor
ferential d iag nosis. Rece ntly, Mi lch grub et regression and th e num ber of Langerhans
al32 reported a uniq ue salivary gland neo- ce lls, Takata and coworkers>' theorized that
plasm und er the term hyalinizing clear cell the Lange rhan s ce lls in CEOTs may play a
carc ino ma of the salivary gl and (HCCC ), role eith er in ant igen presentation or in re-
which also may be co nfuse d with th e clear gre ssion of the tum or.
cell variant of CEOT. The differential diagno-
sis sho uld inc lud e a glycogen-rich ade no - 5.2.2.5 Com bined epi thelial odon togenic
carcino ma, either metastatic or de rived from tumor
a mucoepiderm oid or an ac inic ce ll ad eno- In 1983 Damm et al37 first des cribed the pres-
carcino ma. T hese conside rations are valid enc e of CEOT-like areas within two cases of
for the intraosseous as we ll as for th e ex- ade nom atoid odonto genic tu mo rs an d
traosseo us CEOT. A recent article by Maio- nam ed th em co m b ined epithelial odonto-
rano et al 33 summarizes the p roblem of clea r g enic tum ors (C EOTjAOTs). A total of 24
cell occurrence in the heteroge neous gro up cases of the histologic CEOT j AOT variant
of lesio ns, which may be eithe r odo ntoge nic , have now bee n reported." There is nothing
salivary gland , or metastatic in or igin. to indicate that a CEOTjAOT lesion reflects
a true co m binatio n of two distinct and sepa-
5.2.2.4 Occurrence of Langerhans cells in rate odontoge nic tumor entities, and there
CEOr are no rep orted cases of AOT in wh ich CEOT-
Asano et al21 and Ta kata et al34 d escribed like areas pred om inate. Lastly, all published
yet anothe r histolog ic var iant of the intra- cases of the CEOT j AOT variant show a bio-
osseo us CEOT in two Japanese patients. In logi c be havio r id entical to that of an AOT,that
bot h cases the tumor chiefly co ns isted of is, a truly benig n (hamartomatous) odonto-
scatte red small islands of ep ithelia l cells. In ge nic lesion (see also cha pte r 11).
some nests there we re a few, occasionally
several, c lear ce lls pos itive for 8-100 prote in, 5.2.2.6 Occurrence of myoepithelial cells in
Iysozome, MT1 , LN-3 , and OKT6 antibodies, CEOr
but no t for keratin anti body. Al most no Ultrastruct ural findings in a case of CEOT dis-
calcific ation of homog eno us eosi no p hilic clos ed th atthe tumor sheets and islands con-
materials was observed . Ultrastructurally,the sisted of two ce ll populatlon s.s? One popu-

10 1
10: Calcifying Epithelial Odontogenic Tumor

lation constituted the classic polyhedral ep- mation is requ ired for the CEOT in order to
ithelial cells, and the other comp rised cells choose the best treatment modality and as-
arranged peripherally with elongated profiles sess the incidence of recurrence. Some au-
and juxtaposed to the tumor epit helial cells. thors have seen recurrences even after sev-
The latter cells exhibited a large number of eral decades and recommend a radical line
cytoplasmic fine filaments with occasional of treatment. Others consider conservative
electron-de nse areas similar to those seen in surgery as the treatme nt of choice. In its abil-
the smooth muscle- typ e cell. These cells ity to recur if treatment is not adequate, the
were found to extend basally around the tu- CEOT is similar to the solid/ rnult icystic
mor epithelium in most of the epithelial is- ameloblastoma, and although its growth pat-
lands examined. They showed a lamina den- tern may be slowe r,some believe thatthe two
sa continuous with that of the neighboring should be treated with an identical app roach.
epithelial cells and de monstrated a large Methods of treatment have ranged from sim-
num ber of hemid esmosomes. However, ple enucleation or curettage (shelling ) to
desmosomes between these cells and the tu- hemimandi bulectomy or hemimaxillectomy.
mor epithelial cells were not present. The ul- Eleven cases of clear cell CEOT wit h limited
trastructural characte ristics of these cel ls follow-up information do not allow conclu-
were interpreted to be those of myoepithelial sions to be drawn rega rd ing the bio logic
cells.This cell type,although found in tumors behavior, treatm ent, and prognosis of this
of glandu lar origin, has not been desc ribed variant. However, as reported ,29.30 the oc-
previously in any of the odo ntogenic tumo rs currence of clear cells may prove to be a sign
and its occ urrence in CEOT has so far not of inc reased tumor aggressiveness, indicat-
been co nfirmed in other electron micr o- ing the need for a more radical surgical ap-
scop ic studies of this tumor. proach .
Cor relation betwee n the prognosis of
CEOT and occ urrence of Langerhans cells
also needs further investigation. In view ofthe
6. Notes on treatme nt and biolog ic behavior of the CEOT, destructive
proced ures such as a wid e resection or
recurrence rate hemiresection of the mandible seem unwar-
ranted. Enucleation with a margin of macro-
When first described,' the CEOT was con- scopic normal tissue is therefore the recom-
sidered to be a locally invasive tumor, and mended treatment for lesions involving the
some subsequent publications supported mandi ble. CEOT of the maxilla, how ever,
this concept. This view was based on evi- should betreated mo re agg ressively,as max-
dence suggestive of bone marrow involve- illary tumors generally tend to g row more rap-
ment from radiographs and histological sec- idly than their mand ibular counterparts and
tions' However, Vap et al40 maintained that do not usually remain well con fined. This be-
the tumor is not of a very agg ressive dispo- havior is dramatically docum ented in a re-
sition; rather, it is an expansile lesion that cent report by Bou ckaert et ai41 where a
does not extend into th e intertrabecular large, maxiliaryCEOTwas diagnosed in a 54-
spaces as does the solid amel oblastoma. year-old black man. The tum or appeared to
Franklin and Pind bo rq" repo rted a recur- have developed from the left anterior maxil-
rence rate of 14%, which was mostly attr ib- la and wal l of the left maxillary sinus, ex-
utable to inadequate treatment. pand ing to the ethm oid sinus, eroding the
It is evident that long-term follow-up intor- cribriform plate into the anterior cranial tos-

102
Refe rences

sa, and invading the left orbit with displace- 6. Franklin CD, Pindborg JJ. The calcifying epithe-
ment of the eye. The situation was further lial odon togen ic tumor. A review and analysis of
113 cases. Oral Surg Oral Med Oral Patho11976;
complicated by the presence of an abscess 42:753-765.
located in the anterior cranial fossa with sur-
7. Ai~Ru L, Zhen L, Jian S. Calcifying epithelial odon-
rounding brain edema. The patient was treat- toge nic tu mors : A clinico-patholog ic study of nine
ed with methylprednisolone to alleviate the cases. J Oral Patho11982;11:399- 406.
edema. He showed d ramatic recov ery,
8. Cho mette G, Auriol M, Guilbert F. Histoenzymo-
asked to be discharged, and was then lost to log ical and ultrastructural study of a bifocal calci-
follow-up. fying epith elial odo ntogenic tum or. Characteris-
Treatme nt sho uld be individu alized for tics of epithelial cells and histogenesis of amyloid-
each lesion because the radiographic and like material. vlrcncws Arch A Pathol Anat Histo-
pathol 1984;403:67-76.
histologic features may differfrom one lesion
to another. Although it has not been estab- 9. Domarus H, Hopp e W. Ein multilokulares amelo-
blastische Fibrom. Dtsch Zahnarztl Z 1976;31 :
lished in the literature, 5 years should be the
260- 263.
absolute minimum follow-up necessaryto as-
10. Busch HP, Hop pe W. Multilokularer kalzifizieren-
sessthe cure for CEOT.Although many more
der epitheli ale r odo nto gener Tum or (CEOT).
cases are needed to evaluate the prognosis Dtsch Z Mund Kiefer Gesichtschir 1988;12:193-
for the extraosseous or peripheral variant of 194 .
the CEOT, none of the 11 cases published 11. Chau dh ry AP, Holte NO, Vickers RA. Calcifying
so far has shown signs of recurrence after epithelial odonto genic tumor. Report of a case.
conservative enucleation . Oral Surg Oral Med Oral Pathoi 1962;15:843-
Although an unsubstantiated case of ma- 848.
lignant CEOT in a 92-year-old patient was cit- 12. Kramer IRH, Pindborg JJ, Shear M. Histological
ed by Franklin and Pind borg,6 the first well- Typing of Odontogeni c Tumou rs. 2d ed . Berlin:
documented case was reported by Basu et Springer-Verlag, 1992 .

al.42 13. Fulcinit i F, Vetrani A, Zep pa P, etal. Calcifying ep-


ithelial odo ntogenic tumor (Pindborg's tum or) on
fine-needle aspiration biopsy smears: A case re-
port. Diagn Cytopathol 1995;12:71- 75.
14. Glenner GC, Page DL. Amyloid, amyloidosis and
Refere nces amyloidgenesis. lnt Rev Exp PathoI 1976;15:1- 32.
15. Mori M, Makino M. Calcifying epithelial odo nto-
1. Pindborg JJ. Calcifying epithelial odo ntogenic tu-
genic tumor: Histochemical properties of hom o-
mors. Acta Pathol Microbial Scand 1955;suppl
geneous acellular substances in the tumor. J Oral
111:71.
Surg 1977;35 :63 1- 638.
2. Pindborg JJ. A calcifying epithelial odontogenic
16. Franklin CD, Martin MV, Clark A, et al. An investi-
tumor. Cancer 1958;11:838-843.
gation into the origin and nature of "amyloid" in a
3. Pind borg JJ. The ca lcifying epit helial od onto- calcifying epithelial odon togenic tumour. J Oral
genic tumors. Review of literature and report of PathoI 198 1;10:4 17-4 29.
an extra-oss eou s case. Acta Odontol Scand
17. Yamaguchi A, Kokubu JM , Takagi M, Ishikawa G.
1966 ;24: 419- 430.
Calcifying epith elial odo ntoge nic tu mo r: Histo-
4. Pindb org JJ, Kramer IRH. Histolog ical Typing of chemical and electron microscopic observations
Odontogenic Tumo urs, Jaw Cysts, and Allied Le- on a case. Bull Tokyo Med Dent Univ 1980:27:
sions. Berlin: Springer-Verlag, 1971 . 129 - 135.
5. Philipsen HP, Reicha rt PA Calci fying epithelial 18. Page DL, Weiss SW, Eggleston JC. Ultrastructur-
odontogenic tu mou r: Biologi cal profile based on al stud y of amyloid material in the calcifying ep-
18 1 cases from the literature. Oral Oncol 2000 ; ithelial odo nto genic tumor. Cancer 197 5;36:
36:17-26. 1426 - 1435.

103
10 : Calc ifyi ng Ep it he lia l Odo ntogen ic T u m o r

19 . Mopsik ER, Gab riel SA. Ca lcifyi ng ep ithel ial odo n- 32 . Milc hgrub S, Gnepp DR, Vuitc h F, Delgado R, AI-
togenic tu mor (Pind borg tumor ). Report of tw o bo res-Saavedra J. Hyalinizing c lear cell ca rcino-
cases. Oral Surg Oral Med Oral Patho I 197 1;32: ma of sa liva ry gland . Am J Surg Pathol 1994 ;
15- 21. 18 :74- 82.
20. Wallace BJ, MacDo nald GD. Calcifying ep ithelial 33. Maio rano E, A ltini M, Favia G . Clear cell tumors of
od ontog enic tumo ur ("Pindborg tumor"): A case the salivary gland s, jaws, and oral mucosa. Sem in
report. Br J Plast Surg 197 4:27:28- 30. Oiag n Patho J19 97;14 :203 - 2 12.
2 1. Asano M, Takah ashi T, Kusa ma K. A var iant of cal- 3 4. Takata T, Ogawa I, Miyauc hi M, Ijuh in N, Nikai H,
c ifying epithelial odonto genic tumo r with Lang er- Fujita M. Noncalc ifying Pind borg tu mo r w ith
f-ens cells. J Oral Patho JMed 19 90 ;19:430-434. Lan gerhans ce lls. J Oral Pat ho l Med 19 93 ;
22: 378 - 3 83.
22. Marand a G, Gourg i M. Calcifying epithelial e de n-
to genic tum or (Pind bo rg tumo r). Review of the lit- 35 . Lasser A. The mon onucl ear p hag ocyte syst em. A
e rature and ca se repo rt. J Can Den t As soc 19 86 ; review. Hum PathoI 1983;14:108- 126.
52 :1009- 10 12.
36 . Shelley W , Ju hlin L. Langerhans ce lls from a retic-
23. EI-Labb an NG. Cem entu m-like material in a case uloend othelial trap for external co ntact allergens.
of Pindborg tumou r. J Oral Patho l Med 199 0;19: Nature 19 76;26 1:46 - 47.
166 - 169 .
37 . Damm DO, White OK, Drummond JF, et al. Co m-
24. Siootweg PJ. Bone and cementu m as st roma l fea- bine d ep ithe lial od ontogen ic tu mor: Adenoma-
ture s in Pindborg tumo r. J Oral Pathoi Med 1991 ; tol d odo nto genic t umor and ca lcifying ep ithelial
20:9 3- 95. odonto gen ic t umor. Oral Surg Ora l Med Oral
Patho l 1983 ;55:487- 496.
25. M uller H, Slootweg P. Clear cell d ifferent iation in
an amelobl astom a. J Maxillo fac Surg 19 86;14: 38. Philipsen HP, Reic hart PA. Ad enom atoid odon -
15 8- 160. tog enic tu m our: Fact s and fig ures . Oral Onc ol
1999 ;3 5:125- 131.
26 . De Agu iar MCG, Gom ez RS, Silva EG, de Ara ujo
VC. Clear-cell ame lob lastom a (c lear-celJ od onto- 39 . EI-Labban NG, Lee KW , Kramer IRH. The duality
genic carc inoma). Report of a case. Oral Surg O ral of t he c ell popu lati on in a calc ifying epithe lial
Med Oral PathoI 199 6:8 1:79 - 83. o d ontogenic tum ou r (C EOT ). Histo pathology
198 4;8:67 9 - 691.
27. Ng KH, Siar CH . Clear cell cha ng e in a ca lcifying
odontogenic cyst. Oral Surg Ora l Med O ral Pathol 40. Yap DR, Dahlin DC, Tu rlington EG. Pind borg tu-
198 5:6 0:4 17- 4 19. m or: The so-ca lled ca lcifying ep ithelial odo nto-
genic tu mor, Cancer 1970;25 :629 - 63 6.
28. Pbilipsen HP, Reichart PA, Nikai H. The adeno-
matoid odo ntogenic tum our (AOT): A n up date. 4 1. Bou c kae rt MM R, Raub en heimer EJ, Jac ob s FJ.
Oral Med PathoI 1998;2:55 - 60. Calcifying ep ithelial o dontogen ic tu mor w ith in-
trac ranial extensio n: Report of a case and review
29 . Waldron CA, Small lA, Silverma n H. Clear ce ll
of the literature. Oral Surg Oral Med O ral Pathol
am elo blastoma: An odonto genic carc inoma. J
Oral Rad ial Ende d 2000;90 :656 - 66 2.
Oral Maxillofac Surg 198 5;4 3:70 1- 717.
42 . Basu MK, Matt hews JB, Sear AJ, Brow neR M. Cal-
30. Hansen LS, Eversole LR, Green TL, Powe ll NB.
ci fying ep ithel ial od onto g enic tu mou r: A case
Clear ce ll odo ntogenic tumor: A new histologic
sho w ing features of malignancy. J Oral Pathol
variant with <J.gg ressive pot ent ial. Head Nec k Surg
19 84 ;13:31 0-3 19.
19 85;8:115- 123.
3 1. Koppang HS, Bang G, Hans en SL, Gilhu us Moe
0 , Aksdal E. Hellzellige r odon to ge ner Tumor. Ka-
su istischer Beit ra g. Dtsc h Z Mu nd Kief er
Gesichtsc hir 1988 ;12:356 - 3 60.

10 4
Chapter 11

Adenomatoid Odontogenic Tumor

1. Term inology 2. Clinical and radio logic profile

The tumor that meets today's diagn ostic c ri- The AOT is a benign , non-neoplastic (hamar-
teria for an adenomatoid odontog enic tu- tom atous) lesion wit h a slow but progressive
mour (AOT) has been known for more than growt h. It occurs in both intraosseous and
90 years. The pr ese nt authors agree with pe ripheral fo rms (Fig 11-1).
Unal and cowo rkers' that Steensland 's re-
port from 1905 of an "epitheliom a adaman-
tinum" represents the earliest identification
of an AOT fo r which suffic ient doc ume nta-
tion is available. A variety of terms has been
used to desc ribe th is lesion, of which ade-
noameloblastoma was in co mmon use for
many years because the tum or was co nsid-
ered a histologic variant of the solid/multi-
cystic amelo blastoma. Unal et at' produ ced
a list of related terms that was used fro m
1905 to 1969.
In 1969, Philipsen and Birn 2 prese nted a
review bas ed on 76 cases of AOTs that
proved the tum or to be an entity c learly dis-
tingu ishable from the SMA. They introduced
the term adenomatoid odontogenic tumor,
which was ado pted by the World Health Or-
ganization (WHO) in 1971.31t is now the gen- Fig 11-1 Schematic of AOTvariants. In the intra-
erally accepted nomenclature.' A co mpre- osseous follicular type variant (F) the tumor is lo-
hensive study app eared in 199 15 reviewing cated around the crown and often- as shown
500 cases of AOTs. This report was followed here-covers part of t he root ofan uneruptedtooth
by stud ies on AOT variants" and ultrastruc- (envelopmental). Among extrafollicular types, E,
= no relation to tooth structures either erupted or
tural aspects ." Since t he ear ly 199 0s ap-
unerupted; E2 = interradicular, adjacent roots di-
proximate ly 250 to 30 0 publishe d cases verge apically due to tumor expansion; E3 = su-
have been added to the previous 50 0. The perimposed on the root apex (radicular/periapi-
fo llow ing profile of the AOT is based on a re- cal); E, = superimposed at the midroot level. The
view by Philipse n and Heichart.f extraosseous peripheral epulistypevariant (P)ex-
hibits slight erosion of the bo ne crest.

105
11: Adenomatoid Odontogenic Tumor

Fig 11-2 A typicalfollicular AOT fhat has


developed around an unerupted left
maxillary ca nine.

Fig 11-3 Computed tomography (CT) scan ot a follicular


AOT occupying the entire left maxillary sinus. Notethe dis-
placed unerupted third molar closeto the nasal cavity.

Fig 11-4 Operation specimen from the tumor shown in


Fig 11-3. It exhibits a cloud of minute radiopacities sur-
rou nd ing the uner upted third mol ar. Note the unusu al find-
ing of root resorp tion of t he first and second premolars and
molars.

Radi og raphically, th e intrab ony vari ants with an un erupted tooth, and th e well-de-
co mp rise a fo llicular and an extrafol licular fined, unilocular radio lucen cy is found be-
type.Thefollicular type shows a we ll-defined, tween (Fig 11-5), above, or superimposed on
unilocular (round or ovoid) radiol ucen cy as- the roots of erupted permanent teeth (Fig
sociate d with the crown and often part of th e 11-6). These locations often lead to a tenta-
root of an un erup ted too th, m imic king a tive pre ope rat ive diagnosis of a residual,
dentigerous or fo llicu lar cyst (Figs 11 -2 to radicular, "globulo maxillary," or lateral peri-
11-4). In fact, 77% of fo llicular type AOTs are odontal cyst, depend ing on the actual intra-
initially d iagnosed as dentigerous cysts." osseous site of the lesion. In approximately
The extrafollicular type is not assoc iated two thirds of the intrabony variants, th e radi-

106
Clinical and radiologic profile

Fig 11-5 Extrafollicular variant of AOT Fig 11-6 Orthopantomograph demonstrating an extrafol-
(type E2 in Fig 11 -1) betweenthe roots of licular variant of AOT (type E3 in Fig 11-1) superimposed
the maxillary right canine and first pre- on the apical half of the maxillary left canine root. Tumor
molar. growth has caused the roots of the adjacent lateral incisor
and first pre molar to deviate.

Fig 11-8
Intraoral radi-
ograph of the
tumor shown
in Fig 11-7.
A bony pock-
et (sauceriza-
tion) along
the palatalas-
Fig 11-7 Clinical app earance of a periph eral vari- pect of the
ant of AOT. Epulis-like growth is seen on the maxillary
palatal gingiva of the maxillary right central inci- right central
sor. incisor root is
evide nt.

oluce ncy shows d isc rete radi opaqu e foc i expansion is m uch more common than root
with a floccu lent pattern . If the AOT co ntains reso rption .
minimal quantities of ca lcified deposits, in- T he periph eral variant (Figs 11-7 and
traoral periapica l rad iog raph s are superior to 11-8) appears as a ging ival fibroma or ep ulis-
orthopantom ograph s in d etecting t he ch ar- like growth attac hed to the labial or (mo re
acter istic (although not path ogn om on ic) ra- rarely) the palatal gin giva. This type of AOT
diopacities.?Growt h ofthe intrabony variants may show slight erosion ("sauce rization") of
com mo nly results in cortica l exp ansion . Dis- the alveolar bo ne crest, bu t rad iog raphic
placement of neighboring teeth du e to tumor c hanges are often difficult to d etect.

107
11: Adeno matoid Odo ntogenic Tu mor

3. Epidemiologi cal data occur w ithi n the tee ns (13 to 19 years). Th is


age distr ibuti on , with a very tall peak in the
2nd d ecade, makes the AOT un ique among
3 . 1 Inci d en c e , p revalence, and odontogenic tumors.
re lative frequency

Information on incidence and prevalence of 3.3 Gender


the AOT is still not available. Surveys of oral
pathology bi opsy services from various The female:male ratio for all age gro ups and
sources d o, however, pr ovide inform ation AOT variants to gether is 1.9:1 (see Fig 11-9).
about relative tumorfrequ encies. The relative If geograp hic/ eth nic aspects are accou nted
freq uency of the AOT extracted fro m 12 oral for in the gend er distr ibutio n, differences ap-
biopsy surveys" shows that AOTs accoun t pear betwee n Asian and non-Asian cases.
for 2.2% to 7.1% of all odo ntog enic tumors, Asian AOT cases (reported from Jap an, In-
whi ch gives it a ranki ng of fourt h o r fift h dia, China [includ ing Hong Kong j, Thailand,
am ong th e odonto g enic tu mor s. It is sur- Taiwa n, Sri Lanka, and Malaysia) show a te-
passed on ly by odontomas, myxoma s, and male:male ratio of 2.3 :1. If cases rep orted
so lkf / rnulticystlc amelob lasto mas. Based on from Sri Lanka and Japan are conside red
these figur es, it is hard ly reaso nable to main- separat ely t hey s how ratios of 3.2:1 and
tain that th e AOT is a part icularly rare odon- 3.0:1, resp ect ively.,o,11 Th is marked female
tog enic tum or. pre dominance may reflect real ethno geo-
graphic variations, but the q uestion needs
furth er investigation .
3.2 A g e

The age rang e of patie nts with AOTs varies 3 .4 Location


betw een 3 and 82 years at the time of diag-
nosis," No less than 68 .6% of the tumors are The AOT appears, as mentioned earlier, in
diagnosed in the 2nd decade of life (Fig 11- three clin lcotopoqraphic variants: follicu lar,
9), and more than half of the case s (53.1%) extrafolli cul ar, and pe rip heral (see Fig 11-1 ).

No. of cases

250 ~3
UJ Women
200
(JI Men
150 c!J2 n =532

100
~
50
15~
0
~ 8 ~ r=T1 II
Fi9 11-9 Distribution of all
0-9 10 -1 9 20- 29 30 + types of AOT variants (n =
Age in decades 53 2) according to gender
and age.

108
Epidemiological data

192 202
t'" .=

CD femal es [D maxilla
OJ males (]J mand ible
n:::: 41 1
n = 412

~ ~

~ ~n
I F e( P I AOT va riants I F IF' p
I AOT variant s

J
35
1

'37
2

L-
~
91
100

Fig 11-10 Distribution of AOT vari ants by gender Fig 11-11 Distribution of AOTvariants according
(n ~ 412). F = follicular; exF = extrafollicular; P = to location In = 411 ).
peripheral. Based on data from Philipsen and
Reichart,' Table 2.

The follicular and extrafo llic ular variants are teeth found in association with the follicular
both intrabony or centraltumors and account AOT (Fig 11-12) show s that all fo ur canines
for 95.6% of all AOTs (of wh ich 71.3% are of account for 59% and th e maxillary canines
the follicu lar type ). Th e fo llicul ar variant is alone fo r 40% . Unerupted first and second
close to three times as frequ ent as the ex- molars are the teeth most rarely involved in
trafollic ular variant in bot h men and women. AOTs, only four cases having been reported.
Distrib ution of AOT variants by gender is Asso c iation betw een ce ntral AOT s and
shown in Fig 11-10. The two central variants un erupted decidu ous teet h is exceedingly
together are more co mmo nly found in the rare, on ly two cases having bee n pu b-
maxilla than in the mand ible, with a tota l ra- lished."
tio of 2.1:1. The rare peripheral type oc curs Th e pe rip he ral varia nt is still the most
almost exc lusively in th e anterior maxilla, with rarely reporte d typ e, constituting only 4.4%
this location acco unting fo r 88 .9% of such tu- of all AOT cases. Of the 18 cases reported
mors. Distribution of AOT variants accord ing so far (see Table 4 in Philipsen and Re-
to locatio n is show n in Fig 11-11. lchart"), the mean age at the tim e of opera-
The distribution of unerupt ed permanent tion was 13.0 years; this is 3 and 10 years

109
11: Adenomatoid Odontogenic Tumor

No. of cases
,
140 135:
120 UJ Maxilla
100 OJ Mandible
80 n = 34 1

60
40 ;
40

20o ~ 4 2 6

8 :3 2 ;2
Fig 11-12 Distribution
20
of une rupted perrna-
40
nent teeth associated
60 : 66 with follicular AOT ac-
2 3 4 5 6 7 8 cording to maxillary
Tooth groups and mandibular tooth
groups (n = 341).

earlierthan the corresponding mean ages for srtion to answer questions such as why the
AOT of follicular and extrafollicular types, re- follicular variant- and in particular the one as-
spectively. The distributi on by ge nder (fe- soc iated with unerupted perm anent ca-
male:male = 14:1) makes this type of AOT nines- is so much more frequent than the
unique. The anterior maxillary gingiva is by other variants.
far the most common location of the periph-
eral AOT variant. Two cases found in infants
were recently reported.l-F
5. Pathology

4. Pathogenesis 5.1 Macroscopy

The intrabo ny AOT variants are roughly


The fact that all AOT variants show identical spherical in shape with a well-defined fibrous
histoloqy'' strongly points toward a common capsule. The cut surface may reveal a solid
origin, and most autho rs agree on an odon- tum or mass or show one large or several
toge nic source. Based o n present know l- small cystic spaces containing a yellow ish,
edge of the biology of the AOT, Philipsen et semisolid material. In the follic ular type, a
al6 have strongly argued in favor of AOT be- c row n and often part of the root of an
ing derived from the dental lamina or its rem- unerupted tooth is found embedded in the
nants. Until more is known about the fate of tumor mass or projecting into a cystic cavity.
the numerous epithelial remnants persisting Estimation of the total protein level in aspi-
in the jawbones and gingiva after completion rated fluid from cystic spaces in two intra-
of odo ntoge nesis, clinicians are not in a po- bony AOTs6 revealed a total protein content

110
Pathology

of 5.2 g/ 100 ml and 7.0 g/ 100 ml. Acco rd- with minimal strom al co nnective tissue. Be-
ing to Toller,' :' if the protein level in cystic flu- twe en the epithelial cells of nodules and in
id is 5.0 g/ 100 ml or more, then the cyst ep- the ce nter of the rosettelike co nfigurations,
ithelium is likely to be nonkeratinized.Acystic eosinoph ilic amorphou s material (often de-
cavity, if present within an AOT, is always scribed as "tumor dro plets") as well as calci-
lined by non keratinized stratified squamous fied bod ies are present (Figs 11-13 and
epithe lium .Thus,the biochemical data of the 11-14). Spindle-shaped or polygonal, close-
two AOT cases mentioned here are in agree- ly opposed epithelial cells with dark eosin-
ment with Toller's findings. op hilic cytoplasm and round hyperch romat-
ic nucl ei fill in t he spaces between the
epithelial nodules. Conspicuous within the
5.2 Microscopy
5.2. 1 Histologic de finitions
The 1992 WHO classiticatlon" defines the
AOT as "a tumor of odontogenic epith elium
with ductlike struct ures and with varying de-
grees of inductive change in the con nective
tissue. The tumor may be partly cystic, and
in some cases th e solid lesion may be pres-
ent only as masses in the wall of a large cyst.
It is generally believed that the lesion is not a
neoplasm."
The definition used by the present authors ':~ ."
is as follows:
.\ . -
A hamartomatous lesion of odontogenic ep- Fig 11-13 Tumor nodule composed of spindle-
ithelium producing solid nodu les of cuboidal shaped or cuboidal epithelial cells forming
or columnar ce lls, here and there forming rosettelike structures. There are several calcified
convoluted bands arranged in complicated bod ies with Liesegang pattern. Note the cribri-
form pattern of tumo r cell strands at the nodu le
patterns. Throug hout the lesion the c ells
periphery (hematoxylin-eosin [H&E], x50).
form structures of tu bular or d uctl ike ap-
pearance. The lesion may be part ly cystic
with the solid tumorous tissue constituting
part of a large cyst wall. The fibrous co nnec-
tive tissue stroma is rather sparse and may
contain dysplastic dentinoid as well as calci-
fied material that may be quite extensive.

5.2.2 Histopath ologic findings


Irrespective of tumor variants, th e histology
of AOTs is identical and exhibits a remark-
able con sistency. At low magn ification the
most striking pattern is that of mu ltisized solid Fig 11-14 Cell-rich portion of an AOT with a
nodules of cub oidal or co lumnar epithelial whorled cell arrangement. Note the several
cells forming nests or rosettelike structu res eosinophilic tumor droplets (arrow) (H&E, xl 00).

111
11: Adenomatoid Odontogenic Tumor

(CEOT)/ AOT lesion, However, the presence


of CEOT-like foci within an AOT does not in-
fluence its biologic behavior or growth po-
tential. A total of 24 cases of the histologic
CEOT/ AOT variant have been repo rted so
far a There is noth ing to indicate t hat a
CEOT/ AOT lesion reflects a true comb ina-
tion of two distinct or separate entities, and
there are no reported cases of AOT in which
CEOT-like areas predominate. CEOT-like ar-
eas occurring in AOTs should be considered
Fig 11-15 Characteristic tubular orductlikestruc- a normal feature w ithin the continuous his-
tures lined by a single row of cuboidal or low tomorphologi c spectr um of AOT. Areas in
columnar epithelial cells (H&E, x150), AOTs mimicking calcifying ghost cell odon-
togenic cysts.!" develop ing odo ntornas.J' v' "
or other odontogenic tumors or hamartomas
cel lular areas are structu res of tu bular or also should be regarded as histologic vari-
ductlike appearance (Fig 11-15), The duc t- ants of AOTs.
like spaces are lined by a single row of low Yet another epithelial pattern is found be-
columnar epithelial cells, the nuclei of wh ich tween and connecting the cell-rich nodules
are polarized away from the lumenal surface. and particularly at the tumo r periphery. This
The lumen may be empty or contain a vari- pattern is composed of strands of epitheli-
able amount of eosinophili c material or cel- um, one to two cells in thickness, forming a
lular deb ris. The ducts vary conside rably in trabecular or cribriform configuration. Occa-
diameter and may not always be present. sional foci of mitotic activity among AOT tu-
However, due to the overall distinctive histo- mor cells may be traced, although they are
morphology of the AOT, the diagnosis can not a prominent feature, Epithelial atypia has
usually be secured without the presence of not been reported. In rare instances melanin
ductlike struct ures. In addition to formin g pigmentation of both tumor and stroma cells
ducts, the cuboidal to columnar cells form and the presence of rnelanocytes may be
convoluted cords or bodies in com plicated found in AOTs,17,18 as in several other odon-
patterns that often exhibit invaginations. toge nic tum ors or hamartomas.
Another characteristic cellular pattern is The occurre nce of a hyaline, dysplastic
nodules composed of polyhedral, eosinop h- dentinoid material or calcified osteodentin in
ilic epithelial cells of squ amous appearance AOTs has been descri bed by several au-
exhibiting well-defined cell boundaries and thors4 .8 Dentin or dentinoid containing denti-
prominent intercellular bridges. Their nuclei nal tu bules is exceedingly rare." As the stro-
may occasionally show very mild (degenera- ma is that of a fibrous, mature con nective
tive) pleomorphism. These islands may con- t issue without ectom esenchymal features,
tain pools of amorphous amyloid-like mate- the production of dysplastic dentinoid is like-
rial and globular masses of calcifie d ly the result of a metaplastic process and is
substances (Fig 11-13). Occurrence of one not to be interpreted as an ep it helioec-
or several nod ules in this cellular arrange- to mesenchym al ind uction pheno menon .
ment in AOTs has led a number of authors Calcified material in varying amounts occ urs
to suggest th e existe nce of a combined in most lesions. Irregular calcified bodie s are
calcifying epithelial odonto ge nic tumor common; they often exhibit a concentric or

112
Pathology

Liesegang pattern that most likely represents


dystrophic calcification of tissue elements in
areas of loose co nnect ive t issue stroma
(CEOTj AOT-iike areas; Fig 11-1 3). Scattered
throug hout the tu mortissue are small or large
masses of calcified bodies or glob ules often
found adjacent to rows of tall co lum nar cells
resembling ameloblasts.
The co nnective tissue stroma of the AOT
is generally loosely structured and contains
thin-walled con gested vessels characteristi-
cally showing marked degenerative (fi bri-
noid) changes of the endothelial lining, ves-
sel wall, and perivascular co nnective tissue.

5.2.3 Histochemical findings


Fig 11-16 Electron micrograph showing the ex-
Histochemical studi es of th e AOT have main- tracellular location of tumor droplets of varying
ly focused on the nature of the hyaline or electron density (transmission electron mi-
eosinophilic deposits (tumo r drop lets) and croscopy ITEM], x8,OOO).
the calcified structures." However, previous
conventional and inadequ ate histochemical
techniques failed to disclose whether these
5.2.5 Ultrastructural findings
structures are of epithel ial or mesenchymal
origin. The controversy over the oc currence Alt hough almost all ultrastructu ral studies
(or nonoccu rrence) of amyloid , amyloid-like, have been focused on the follicular type of
or pseudoa myloid sub stances in AOTs is not AOTs, it is unlikely that ultrastructural d iffer-
surprising since the interp retation of amyloid- ences shou ld exist between the three vari-
like substances is far from being uniform . ants given their identical histology. The ep-
ithelial nature of the AOT has been confirmed
through findings of well-developed gap junc-
5.2.4 Immunohistoc hemical findings
tions, des mosomes, and desmosome-like
In recent years a number of stud ies have junctions. Tight jun ctions have not been de-
added to th e knowledge about the immuno- scribed . Tonofilaments are present in vary-
histoc hem istry of AOTs. Tatemoto et al ' 9 ing amounts. Three ultrastructurally different
demon strated coexpression of keratin and vi- types of epithelial tumor cells have been rec-
mentin in the tum or cells at the periphery of ognized as correspondi ng to the th ree cell
the ductal, tubular, or whorled st ructures. pop ulations seen with light microscopy.i The
Whereas tum or cells were positive for keratin material found in th e ductlike spaces has a
stains, mineralized and hyaline material were granul ofibrillar appearance. This material is
negative. Mori et al20 and Saku et al2 1 both separated from the adjacent tumor cells by
studied enamel proteins in AOTs and found a basal lam ina- like zone, a finding that lends
amelogenin and enamelin in small mineral- support to earlier theories sugge sting that
ized foc i in both t umor ce lls and hyaline the ducts are formed as a result of degener-
droplets. atio n of the stromal tissue. Hem idesmo-
somes are found between the cells and this

113
11: Adenomatoid Odontogenic Tumor

proven the treatment mo daiity of choice. In


only 3 (all Japanese) of 750 AOT cases has
the tum or recu rred ." and in only one instance
was extensio n olthe rec urring tumor into the
intracranial space rocordod."

References

1. Unal T, Cetingu l E, Gun ba y T. Peripheral adeno-


matoid od o nto gen ic tumou r: Birth of a te rm. J Clin
PedialrDenI 1995;19:139-1 42.
Fig 11-17 Finer details oft hegranulotubularcom-
2. Phllipsen HP , Btm H. The ad enomatoi d odonto-
ponentsof tumor droplets (TEM xi 00 ,000).
g eni c tum o ur. Amelob lastic ad en ornatoid tumour
or adeno-ameloblastoma. Acta Pathol Microbial
Scand 1969;75:375-398.
3. Kra me r IRH, Pind bo rg JJ . H istolog ica l Typ ing of
matrix. Tum or cells demo nstrating sq ua- Od o ntog eni c Tumo urs, Jaw Cysts, and Alli ed Le-
mous cell metaplasia (represe nting CEOT- sions. Ber lin: Springer-Verlag. 197 1.
like areas) are polyg ona l, co ntain an abu n- 4. Kram er IRH, Pindbor g JJ, She a r M. H isto log ical
dance of to nofi lament bundles, and possess Typing of Odontogenic Tum o urs. 2d ed . Ber lin:
well-formed des mosomes. El-Labbarrf re- Sp ring er-Verlag , 19 92.
ported t hat th e eos inophilic amo rpho us 5. Philipsen HP, Reichart PA, Zhang KH, et at Ade-
masses are heterogeneous and consist of ne m atoid odonto ge nic tumor: Bio logic profile
th ree types offibrils: thin co llagen fibrils, elec- based on 499 cases. J Oral Pathol Med 1991 ;
tron-dense fibrils, and amylo id filaments. A 20:149- 158.
recent study? disclosed that the most co n- 6. Philipsen HP, Sam man N, Ormi ston IW, Wu PC,
spicuo us feature of the amorphous (noncal- Reichart PA Variants of the adenomatoid odon -
togen ic tumor with a note on tumor origin. J Oral
cified) eosinophilic material (tumo r droplets) Pathol Med 1992;21:348- 352.
is co nce ntrically arranged tubular structures,
7. Phi lipsen HP, Reicha rt PA T he ad enomatoid
the surface of which may be coated with a odo nt ogenic tumour: Ultrastructure of tumou r
fine granular material (Figs 11-16 and 11-1 7). cells and no n-calcified amor ph ous masses. J Oral
The authors suggested t hat the t umo r Pathol Med 1996;25:491 - 496.
dro plets pro bably represent some form of 8. Philips en HP, Reich art PA Ade noma toid odon -
enamel matrix. Amyloid filaments or col lagen tog enic tumour: Facts and figu res. Oral Oncol
fibrils were not enco untered in this study. 1998; 35:125- 131.
9. Dare A, Yamaguchi A, Yoshiki S, Oka no T. Limi-
tation of panoram ic radiog raph y in diag nosing
adenomatoid odo ntogenic tumo rs.Oral Surg Oral
Med Oral PathoI1994;77:662-668.
6. Notes on treatment and 10. M endis BRR N, MacDonald DG. Adenom atoid
recurrence rate odontogenic tumour. A survey of 21 cases from
Sri Lanka . Int J Oral Maxiilotac Surg 1990;19:
141- 143.
As all variants of AOT reveal an entirely be-
11. Felda M, Hyodo I, Oku da T, Tatematsu N. Ade-
nign biologic behavior and in almost all re- nomatoid odo ntog enic tum or : Repo rt of two cas-
po rted cases are well enca psulated, co nser- es and survey of 126 cases in Japan. J Oral Max-
vative surgical enucleati on or cu rettage has illotac Surg 1990;48:404- 408.

114
Ref erences

12. Kearns GJ, Smith R. Adenomatoid odo ntoge nic 19. Tatemoto Y, Tanaka T, Okada Y, et al. Adenoma-
tumour: An unusual cause of ging ival swe lling in told odo ntoge nic tumour: Co-expression of ker-
a 3-year-old patient. Sr Dent J 199 6;18 1:380- atin and vimentin. Virchows Arch A Pathol Anat
382. HistopathoI 1988;413 :341 - 347.
13. TolierPA. Protein substances in odontogenic cyst 20. Mori M, Yamada K, Kasai T, et al. lrnrnunohisto-
fluids. Br Dent J 1970;128:317 - 322. chemical expression of amelogenins in odonto-
genic epithelial tumours and cysts. VirchowsArch
14. Zeitoun 1M, Dhanrajani PJ, Mosado mi HA. Ade-
A Pathol Anat Histopathol 1991;418:3 19-325.
nem atoid odontogenic tu mor arising in a calcify-
ing odontogenic cyst. J Oral Maxillofac Surg 21. Saku T , Okabe H, Shimo kawa H. Immunohisto-
1996;54:634- 63 7. chem ical demon st ration of enamel proteins in
odo ntogenic tum ors. J Oral Pathol Med 1992;
15. Miles AEW. A cystic co mp lex co mposite odo n-
21:113- 119.
tom e. Proe R Soc Med 1951 ;44 :51-55.
22. EI-Labban NG. The nature of the eosinophilic and
16. Dunlap Cl, Fritzlen TJ. Cystic odontoma with con-
laminated masses in the adenomatoid odon to-
com itant ad enoameloblasto rna (ad enoamelo-
blast ic odontoma). Oral Burg Oral Med Oral genic tumor : A histochemical and ultrastructural
stud y. J Oral Pathol Med 1992;21:75- 81.
Pathol t 97 2;34:450 - 456 .
23. Takigami M, Uede T, Imaizumi T, et al. A case of
17. Warter A, George-Diolomb i G, Chazal M, Ang o A.
adenomatoid od ontogenic tumour with intracra-
Melanin in a dentig erou s cyst and associa ted
nial extension . No Shinkei Geka 1988;16:775-
adenc matold odo ntog en ic tu mo r. Cancer
779.
1990;66 : 786 -788.
18. Aldred MJ, Gray AR. A pigmented aden omatoid
odo ntog eni c tumor. Oral Surg Oral Med Oral
PathoI1 990;70:86- 90.

115
Section Three

Benign Neoplasms and Tumor-like Lesions


Showing Odontogenic Epithelium With
Odontogenic Ectomesenchyme, With or
Without Dental Hard Tissue Formation

Introduction to conv inc ing ly sho w that the lesions are differ-
ent in Important respects (relative freq uency,
Mixed Odontogenic Tumors
locat ion )and that separation seems to be jus-
tified irrespective of the fact that both odon-
tomas can receive the same (conservative)
treat ment. Therefore, Philipsen et a!' advo-
There has been considerable debate about cated that the two type s be registered as sep-
whether and how the so-called mixed odon- arate ent ities in future studies and case re-
togenic tumors are interrelated. In rece nt ports.
years Philipsen et al.' Takeda,' and Tomich" When di scussing the relationsh ip be-
have reviewed the different aspects of inter- tween members of the be nign mixed odon-
relationship between ben ign mixed od onto - togenic tumors,the following entities have to
genic tumors. be ad dressed: ame loblast ic fibromas (AFs),
Philipsen et a!' clear ly pointed out that, amelo biastic fibrodentinoma (AFDs), amelo-
based on their findings, complex and com - blastic fibro-o dontomas (AFOs), and the two
pound odontomas should be regarde d as types of odontomas (com plex and com-
two separate entit ies. This is in contrast to pound).
some authorities in the field' who suggested Cahn and Slums proposed the "continu-
that complex and compound odontomas um concept" based on the assumption that
should-for therapeutic reasons-be consi d- an AF will, over t ime, mature and finally result
ered the same. Clinical and radiol ogic data in the formation of an odontoma. This con-

117
Mixed Odontogenic Tumors

cept, however, was not widely accepted, be- sta ge w here dentin like or d ent inoid sub-
cause residual or recu rrent cases of AF have stances are produced in the ectomesenchy-
never shown fu rther steps of diffe rentiation mal tumor compon ent.
or maturat ion into a de ntal hard tissue- fo rm- Line II w ould comprise the hamartoma-
ing odontogenic tumor of more advanced tous or developing complex odonto ma line,
histodifferentiation . Anothe r reason was that incl uding a variety of stage s of the com p lex
AFs are kno wn to occur at ages beyon d com- odontoma. T he ameloblast ic fib ro-od on-
plet ion of odontogenesis,th at is,afterthe age toma was not considered to be a member of
of 20 years. Philipsen et a!' agre ed w ith th e the neoplastic line but to rep resent a stage
authors of the 1992 World Health Organ iza- precedi ng t he co mp lex odontoma of th e
tion (WHO) class ification" that AFs- and in DCO line. The likelihood that AFOs which are
part icu lar those 22.3% of cases occu rring at- c haracterized by irregularly arranged odon-
ter the age of 20-are true benign neop lasms . to genic tissues-including odontogenic ep-
All the cases of AF developi ng d uring the en- ithelium, ectom esenchyme, abortive dentin,
tire per iod of odontogenesis (childhood and and enamel- wil l d eve lop into com po und
adolescence), how ever, may rep resent non- odonto mas seems very small. Available data
neoplastic, ham artomatous les io ns wh ic h po int atthe complex odontoma bein g the ter-
over time may develo p into AFOs and finally min al stage of th e line of hamartomatous le-
into mineralized complex odontomas. Both sio ns. Comparison s of age distr ib utio n at the
AFOs and odo nto mas go through stages of time of diagnosis of ame loblast ic fibra-odon-
mineralization and calcification; no ne of t omas and complex od ontoma sho w that a
them arise as calcified lesions de novo. On higher age is common in the cases of com -
these grou nds Phil ipsen et al ' proposed plex od ontom as.
some hypothet ica l cons ide rati ons o n the There is general agr eem ent that the com-
pathoge nesis an d relatio nsh ip between po und odontoma is a malformation. Age and
mixed odontogenic tu mors and odontom as: dist ribution of location support the hypothe-
A neoplastic line of d evelopment (I) and a sis that the pathogenes is of the com pound
hamartomatous line (II) should be consid- od ontoma differs from that of the complex
ered along w hich mixed odo ntogenic tu mo rs od ontoma. Philipsen et a!' did not agree with
may develop . In th is con text the autho rs ful- the 1992 W HO classitication't which claimed
ly suppo rt the view of Hansen and Ficarra? that the distinction between compound and
that some am elo blas tic fi b ro mas may complex odontomas is arbit rary based on a
represent the early stage of a d evelop ing preponderance of toot hlike structures in the
complex odonto ma (DCO) line. Based on fo rme r in cont rastto a prepond erance of hap-
these assumptions there may be tw o lesion s hazard ly arranged soft and hard odonto-
with the histologic criteria of AFs: the neo- genic tissues in the latter, rather than on any
plastic AF an d th e early, p rimitive, or fi rst absolute difference. Philip sen and cowork-
stage of a DCO. Final p roof for th is hypothe- ers suggested that t he f or mat ion of com-
sis is missing because at p resent the re is no pound odontomas may be th e result of "mu l-
way to differentiate betwe en the histology of tip le schizodontia " of unknown cause but
the neoplastic and the hamartomatous le- probably due to a loca lly hyperact ive dental
sion with the histolo gic features of the AF. lam ina. The finding that 56% of maxilla ry
Philips en et a!' suggested that line I wo uld su pe rn ume rary tee th are located in the
on ly inc lud e the AF and poss ibly the clos ely anterio r ma xilla may lend su p port to this
related AFD. Prese ntly there is no proof that hypot hesis. Altho ugh transitional cases of
th is tumor line woul d develop furt her than the odontomas showing microscopic features of

118
References

both types of odont omas do exsist, the clin- comprising calcifying cystic odo ntoge nic tu-
ical data and histologic evaluation will, in mor (corresponds to 2Aaa in Table 17-1 of
most cases, lead to a diagnosis of either a the present book) , dentin ogenic ghost cell tu-
complex or a compound odo ntoma. mor (co rresponds to 2AbP in Table 17-1 of
The concept expressed by Philipsen et a!' the present book) , and ghost cell odon to-
and summarized here does not form the ba- genic carc inoma (described in chapter 28 of
sisfor the presentation of mixed odo ntoge nic the present boo k).
tumors in chapters 12-16, as all data stem
from retrospective studies. Thus, the authors
intend to fo llow the currently accepted
classification expressed both in the WHO
classification of 1992 6 and in the forth com-
ing WHO volume Tumours ofthe Head and
References
Neck.
1. Philipsen HP, Reichart PA, Praetorius F. Mixed
od ontogenic tumou rs and odontomas. Consid -
erations on interrelationship. Review of the litera-
ture and presentation of 134 new cases of od on-
Comments tomas. Oral OncoI1 99 7;33:86-99.
2. Takeda Y. Amelob lastic fib roma and related le-
Thetwo lesions descr ibed in chapters 17 and sions: Current pathologic concept. Oral Onco l
1999 ;35;535-540.
18 do not belong to the mixed odo ntoge nic
tumor family (chapters 12 to 16). Mo reover, 3. Tomich CEoBenign mixed odontogen ic tu mors.
Semin Diaqn Pathol 1999;16:308-316.
chapter 17 ("Calcifying Ghost Cell Odo nto-
genic Cysts/ Tumo rs" [Odontogenic Ghost 4. Regezi JA, Kerr DA, Court ney RM. Odontoge nic
tumo rs. Analysis of 706 cases . J Oral Surg
Cell Lesions]) requires some introd ucto ry 1978;36: 771-778.
notes.
5. Cah n LR, Blum T. Am eloblastic odo ntoma, case
Gorlin et al 8,9 first identified the calcifying
report critic al ly analyzed (letter). J Oral Surg
odontoge nic cyst (COC) as a spec ific odon- 1952;10: 169-170.
togenic lesion. Controversy and confusion
6. Kramer IRH, Pindborg JJ, Shear M. Histologi cal
later ensued after the lesion was shown to Typing of Odontogenic Tumours. 2d ed. Berlin:
be of extrem e divers ity in its clinica l and Springe r-Verlag, 1992.
histopat hologic features, as well as in its bi- 7. Hansen LS,Ficarra G.Mixed odo ntogenic tumo rs,
olog ic beha vior. Toda y, several non-neo- analysis of 23 new cases. Head Neck Surg 198 8;
plastic (simple cystic), benig n neoplastic, 10:330-430 .
and malignant variants have been described 8. Gorlin RJ, Pindbo rg JJ, Clausen FP, Vickers RA
(for references, see chapter 17). In chapter The calcifying odo ntogenic cyst- A possible ana-
17 t he authors have combined t he four logue of the cutaneous epitheliom a of Malherbe.
published classificatio n attem pts '0-13 into Oral Surq Oral Med Oral Pathol 1962;15:1235-
1243.
one comp rehensive classification (see Table
17-1 ). Because current research activities in 9. Gorlin RJ, Pindborg JJ, Redman RS,et al. The cal-
cifying odontogenic cyst. A new entity and possi-
this field are considerable, further attempts ble analog ue of t he cutaneous epithelioma of Mal-
to classify th ese com plex lesio ns are in- herbe. Cance r 1964 ;17:723- 729 .
evitab le. In the forthcom ing WHO volume 10. Toida M. So-called calcifying odo ntoge nic cyst:
Tumours of the Head and Neck, three odon- Review and discussion on the terminology and
togenic g host ce ll tu mo rs are described classif ication. J Oral Pathol Med 199 8 ;27 :4 9- 5 2.

119
Mixed Odontogenic Tumors

11. Praetc rius F, Hlertinq-Hansen E, Gorlin RJ, Vick- 13. Hong SP, Ellis GL, Hartman KS. Calcifying odon-
ers RA. Calcifying odontoge nic cyst. Range, vari- togenic cyst. A review of ninety-two cases with
ations and neop last ic potentia l. Acta Odonto l reevaluation of t heir nature as cysts or neoplasms,
Scand 1981;39 :227- 240. the nature of ghost celts, and subclass ification.
12. Buch ner A. The central (intraosseous) calc ifying Oral Surg Oral Med Oral Pathol1991 ;72:56- 64.
odontogenic cyst: An analysis of 215 cases. J Oral
Maxillo!ac Surg 199 1;49 :330-339.

120
Chapter 12

Ameloblastic Fibroma

1. Terminology t io n. Th ese lesion s are th e ameloblastlc fi-


brod ent ino ma, t he am eloblastic fib ro-odo n-
In 189 1 Kruse ' first desc rib ed cystic t umors torn a. and the odonto mas. The interrelatio n-
of the mandib le, whic h are known today as ship between t hese lesion s has been
ameloblastic fibromas (AFs). In 198 1, 8 100t- d iscussed recently by several autho rs.s-'1
weg 2 pu blished a com prehensive review of
this ent ity in w hic h he d escribed 55 cases of
AFs, 54 of wh ic h were retrieved fro m the lit-
erature covering the period between 1946
and 1978. In 199 7 Philipsen et al3 reviewed 2. Clinical and radiologic profile
"mixed odontog enic tumo rs," includ ing AFs.
Based o n a worldwide literat ure review, a to-
tal of 122 cases of AFs were evaluated . The AF is a painless, slow-grow ing expansile
Since 199 7 a number of new cases have lesio n of t he jaws. Since th e clin ical symp-
been des cribed inthe literatu re. Dallera et at" to ms are mild , about 20% of AFs are di scov-
reported on six cases of AFs w ith fo llow-up. ered acc ide ntally on radicq raphs." Impact-
Plesold and Meerbach '' report ed a case of a ed , unerupted teeth are assoc iated with AFs
maxillary AF. Other sing le case reports wer e in th ree q uarters of the cases. Also , AFs may
published by Brethaux-Bard ino n et al,6 Bock- d evelop in areas of co ngenitally missing
lage et at." and Mos by et al.8 Mosq ueda-Tay- teet h." In op e rcu la of unerupted first and
lor et al'' reported a series of 349 cases of second permanent mo lars, AFs co uld be de-
odontogenic tumo rs fro m Mexic o; am ong tect ed microsco pically in 7 out of 74 speci-
these, f ive cases of AFs were regis tered mens.P 'The size of the tumor varies between
(1.4%). In an earlier study fro m Canada 10 sev_ 1 and 10 ern in d iameter; in Philipsen et al,3
en cases of AFs were inclu ded, althoug h wit h 9 of 16 lesions were co nsid ered large, wit h
no details on age , gen der , and locati on. the g reatest d iameter more t han 4 em.
The AF is g enerally con sid ered to be a t rue Radi olog ically, the tumor is c haracterized
mixed odontogenic tumo r in w hic h bot h t he as a we ll-defined, un i- o r multilocular rad i-
ep it he lial and ectom esenc hym al co mpo- olucency, often with a rad io paqu e bo rde r as
nents are neoplastic. While t here is no hard observed in cysts . Wh ile smaller lesions re-
t issue format io n in AFs, oth e r lesio ns b e- veal uniloc ular pattern s, large lesio ns tend to
longing to the family of mixed odontogenic have a multilocul ar appearance. The latter
tumors are cha racte rized by hard tissue fo r- co nfig urat io n is o bserved in 75 % of th e
mation suc h as calcificat ion and mineraliza- cases. Since t he majo rity of cases of AF are

121"
12: Arneloblastic Fibroma

Fig 12-1 AF of the right mandi-


b le in associat ion with an im-
pacted first molar. The anlage of
the second premolar is missing
on both sid es. The lesion ap-
pears as a follicular cyst.

Fig 12-2 AF of the left mandible.


The second deciduous molar is
impacted and the anlage of the
second premolar is missing. The
cystic lesion is located mesial to
the first mandibular molar which
also has not erupt ed.

associated w ith imp act ed t eeth , d en t igero us 3 .2 Age


cysts have t o b e considered in d ifferent ial
d iag no sis (Fig s 12-1 an d 12-2 ). AFs are m o st fre qu ently obs erved d uring the
first t w o decad es of life (Fig 12-3), and 77.7%
of all case s of A Fs are d iagno sed befo re the
ag e of 20. Mean age of 121 cases of AF s was
14 .8 years w ith a rang e of 0 .5 t o 6 2 yea rs." If
3. Epidemiological data all c ases d iagnose d after age 30 are exclud-
ed , the aver ag e is 12.4 years.

3. 1 Prevalence, incidence, and


relative frequency 3 .3 Gender

Fig u res ind icat ing the rel ati ve frequen c y of Ac c ord ing to a review by Philipsen et al3 the
A Fs rang e be tween 1.5% and 4 .5%.3 m ale .temate ratio w as 1.4: 1.

122
Pathogen esis

No. otcases

30 27

25
22 " 21
20

10

Fig 12-3 Distribution of 0- 9 10-19 20-29 30-39 40-49 50-59 60 69 70-79


AFs according to age k]e in oeceoes
and gender.

3.4 Location anterior + posterior ma xilla - 1

Most AFs are located in the poste rior man- .:


dible (Fig.1 2-4). If cases involving mo re th an
one quadrant are exclud ed, 69% of AFs oc-
25
,
: 5

cur in the posterior mandible. Also, the pos- n - 122


terior mandible is affected mo re ofte n than
the maxilla bya factor of 3.1.lt should be not-
.,
ed that AFs seem to occur as central variants 78 ,: 5
and only recently has the first case of a ~
ripheral AF has been oescnceo."
posterior maxilla. posterior mand ible = 1
anterior + posterior mandibJe = 6 (unilat j
anterior + poste rior ma nd ible 1 (b il at )

4. Pathogenesis Fig 12-4 Locat ion of 122 cases of arneiobtastrc


fibromas.

According to th e World Healt h Organization


{WHO, 1992),1 5the AF is clearly a neopl asm
of odontogenic origin wit h an epithelial and itive to induce the c ells of t he ectornes-
an ectomesenchymal component. Morpho- enchyme. Little is currently know n about the
logically, the AF is similar to the normal toot h interactions between epithelium and the ec-
anlage before hard tissue fo rmation has start- tom ensenchymal tumor stroma. and it is un-
ed. Due to the similarity of t he AF to denta l known why, in contrast to physiologic tooth
follicular tissue, the latter may be misinter- formation. the step of induction of odonto-
preted as an odo ntogenic tumor.I'' blastic differentiation is lacking in the AF.1l
Pathoqeneticatlv. the epithel ial co mpo- However, as has been discussed in the in-
nents-the amelo blast-like cell-are too prim- trod uct ion to these chapters, the present au-

123
12: Ameloblastic Fibroma

t hors entertain the theory th at tw o variants of liferat ing o do ntogenic ep it he lium embed-
t he AF exist: a neo p lastic type w ith no in- d ed in a ce llu lar ectomesenchymal tissue
duction phenomena and a hamartomatous t hat resembles the d ental pap illa, and with
type showing inductive capa bilities. varying deg rees of induct ive c han ge and
den tal hard tissue formation."
The definitio n used by t he present authors
is as fo llows:
AF com prises two subtypes : a neoplasm and
5. Pathology a hamartomato us lesion.The two vertantsa re
histop ath ologi cally undistinguishable, both
be ing com pos ed of p roliferating ep ithelial
5. 1 Macroscopy od ontogenic ep it helium embedde d in a cel-
lular, odon to genic ectomesenc hymal t issue
The c ut surface of AFs is usually round or that resembles t he dental pap illa. Induction
oval, well ci rcumscrib ed, and of a grayish does not take place in t he neoplastic sub-
white co lor. The soft mass app ears to be sur- type.
round ed by a t hin, t ransparent, capsule-like
border.
5.2.2 Histopathologic findings

Th e epithe lial t umor co mponent is arranged


5.2 M icroscopy in stran ds, cords, and islands of proliferat ing
odo ntoge nic ep ithelium. The strands often
5.2.1 Histologic definition s
reveal a do ub le or trip le layer of cu bo idal
The 1992 W HO class ification 15 d oes not in- cells, t hus resemb ling the dental lamina of
clude a definition of the AF as an entity. The early tooth develop ment. In co ntrast, t he is-
authors pooled t he AF with "related lesions" lands ofte n show a pe ripheral row of high
whic h also cove rs t he ame lob last ic fib ro- cu bo ida l or co lum nar amelob last-like cells
de nt inoma, and the ame lob lastic fibro-odon- (Figs 12-5 and 12--6). The ce nte rs of individ-
toma. The suggested def inition forthis group ual tumor islands may enclos e a numb er of
of lesions was "Neop lasm co mposed of pro- c ells resem b ling stellate ret icu lum. The

~---..,

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.-:, . ~\ ,.,J

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'
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- \'

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..c.' , .. " "i ,t. .,. ."" .,.' .... '. .' ... ~ ~"'\
't' ,' .
::~~ ':;;,;..-;;-:o:-..Jot- "' << : '"~". , ' . ' f- " ' .
- . '
" . "~" "

Fig 12-5 Strands and islands of odontogenic ep- Fig 12-6 Several smaller and larger islands of ep-
ithelium in a cell-rich ectomesenchyme (hema- ithelium in ectomesenchymal tissue (H&E, x80).
toxvnn-eosm [H&E], x60).

124
Pathology

amount and density of the epithe lial compo- purposes." Papanicole ou-statneo slid es re-
nent of the A F may vary w ith in t he sa me vealed branch ing epithe lial structu res and a
tumor. Cyst fo rmation w ith in t he epithe lium hypercellularstroma. Stromal port ions of the
is uncommon, and cysts usua lly remain as pirat e w ere composed of p laq ues and
small. stream ing uniform ce lls w ith distinct cellular
The ectomesenc hyma l cells are round ed bo rders and hyperc hroma tic, slightly sp in-
or angular, and the re is little co llagen wh ich dled or round nuclei. Cytologic atypia, mitot-
is represented by a few de licate collagen fib- ic activity, and necros is we re not observed.
rils.The deg ree of cellu larity varies wit hin t he Ano the r variant of AF, the granular cell
same tumor and amon g tumors. ame lob lastic fibroma, w as de sc ribed in
Occasionally , some pa rts of t he ectomes- 1962 ,13 and until 1991 only 16 cases had
enchymal component may reveal a loose bee n rep orted . Characterist ica lly, t he ec-
myxomatous st ructu re (Fig 12-7) w ith weak- tomesenchymal com pon ent is dominated by
ly positive metach romatic subst ance. Th ere granu lar cells. Pro lifera tive act ivity of t he
may be a ce ll-free zon e bo rd ering the ep- odontog enic ep ith elium and different iation
ithelial islands and strands, and in rare in- toward enamel organlike st ruct ures are not
stances j uxtaepithelial hyalinizat ion of t he present. Foci of dyst rop hic ca lcification have
type see n in so lidj m ult icyst ic ameloblas- been fou nd among the granular ce lls. Ultra-
tomas may occu r. Occ asionally hyalin ization structural st udies of this variant of AF have
maybe more diffuse. The AF does not reveal revealed the granular ce lls to be sim ilar to
a definite capsu le histo log ically. In some those in t he granu lar cell myoblastoma and
cases of AFs, melanin granu les have been the congen ital granular cell t umor. Furt her
found in the epithelial tu mor component.'' u ltrast ruc tural and immunohistoc hemical
While t he histopat holo gic diagnosis of studies have shown that the granular cells
odonto genic tumors is usua lly made from have a st rong assoc iation with t he prec urso rs
representat ive biopsy tissue, fine-needle as- of Lanqe rhans ce lls. The h isto logic, im-
piration has also been applied for diagnostic munoh istoc hemical, and ult rastruct ural find-
ings, comb ined w ith a c haracteristic mean
age at the time of diagno sis of 47 years as
op posed to the 1st and 2nd decade s for AF,
have led most autho rs to consider th e gran-

ular ce ll AF a variant of the odon togenic fi-
b roma (see c hapter 19) rather than a variant
of the amel ob lastic fib roma."
In the papilliferous ameloblastic fibroma, a
rare variant of AF, a marked pro liferation of
the epit helium with a plexiform arrangement
"
~
, and cyst formation have been desc ribed.
In rare cases the AF may t ransfo rm into an
,., " amelob lastic fibrosarcoma (see c hapter 29).

Fig 12-7 Higher magnification of an epithelial is-


land. High columnar ameloblast-like cells are
seen at the periphery of the island. The ectornes-
enchymal cells are slender or angular (H&E,
x 100).

125
12: Ameloblastic Fibroma

: ..:l,s'l;o.....)"'_tr.i i ._~.-. 'o. :.~....: ~ I;


r" ..' '\ -( t:~ .,.. . .. r-:-;;........::.".....
.... ,A.. ~ - . ....... ~;J ') '" ~
~;,~.~!", ~J;~~~?;~":.~~;~;;\[~.;~ ,,:.. 7"':;.! .~
~~ A... ~~.;. :.~;.~.t:. I;;-. . ~4~ .::~ :;:.. .'i'/-';'.,~ .'=..~.i ~
~~~ ;.,. . . . .~ :!.v..~ . ~~~ '(-:'4 -r; :~ :....-: i'4.'...: .. .:'1 : ."'lo:/
i'it~... . l~o.: SJ;:~~ ~e; ~'7.:;.~ .....; ~ ~ Ir- : ~ !:..,,:: : ' ~
t; .~;..jf'-':.}>~ .~v~~.re ;...'".....~~~ ..~
..
. ....t~, ~ ....'" _ ~"" " :.' - .... ' .~ c:s .r..~ . ~ .l::. . ~ -:
~.. - . :~~'.f!-1~~~.~~(f-~[~~~ c . , .J1.~~~,
~.:; :-";;~~.. , ,~..,;~-7 -~:.~:: . /~'~ ..~JfJ J.:
ij. i-{.~_~"""' : _:~~< ~
.......,-.. ~ " ,~" "", . ~ ""''''.;...~
' ,h . "'f. ' ~' -~
n . J'. .,- \. 't-l;:;IJ6 ,.I.
-e.. ' ": . ~' _,' ~ -;;.~ . s. rr- ' , " ".1.
~ . ,\~ t '-"':;.,:r-' i ~ ',' ", ,~ "':: ~ l ~,"\" f \~" 'J/
~.~~,;~~
. ~. ~ oo~:.tl
, "-' . , .,.~ ,,;~~f""',
~ .-. . .-
.,., .. ~ , <, ,.i~"~'
i' .. +1.: ~ ,':-!'. ) --' .'
... - , ,--',:;.-- ,. .,. , ... , .., n,
......
"' , .r:'.~
~ >
. ":'i:': :"" ..lr"'~ ,( '!\r.. .'i"..,d ~ "}. "
~
'"It::.
Fig 12-8 Collagen type I conc entrated in tumor Fig 12-9 The ectomesencnymal component of
regions with high cellularity. Staining is weak and the AF.An amorphous staining pattern is seen for
diffuse in the matrix surrounding the epithelial is- procollagen type III, in contrast to the adjacent
lands (APAAP, x 125). subepithelial connective tissue where fiber bun-
dles positive for procollagen type III are found
(APAAP. x200 ).

Fig 12-10 Marked staining for collagen type VI


in the ectomesenchymal component. The zone
of hyalinization is only faintly positive with epithe-
lial islands being surrounded by a distinct rim of
collagen type VI (APAAP, x 125).

5.2.3 HistochemicaVimm unohistochemi- w ere hig h for recur rent AFs an d amelo blast-
cal fin din gs ic fib rosarcom as compared to AFs. These
findi ngs suggested th at evaluatio n of g rowth
Sano et at" assessed the growth potential of pote ntial in the AF could help to und erstand
arnelobtastic fib romas an d related lesions by tumor aggressiveness.
MI B-1 immunohistochemistry. M IB-1 is a In another stu dy Bec ker et ar" stu died the
monoclonal an tibody aga inst p ro life ratio n- d ifference between t he ectomesenchymal
associated nuclear antigen; it recoqnlzes the and adj acent conn ective tiss ue p ro per of
epitope of Ki-67 antigen. In th eir study. t he AFs. While t he ecto m esenchym al compo-
authors showed that MI B-1 label ing indices nent of ame lo bl astic fibromas revealed
in th e epit he lial compone nt ran ged fro m marked sta inin g fo r collage n types I and VI,
2.9% to 7.5%, whereas those in the ec- the surrounding mature connective tissue re-
tomesenc hymal component ranged from mained almost un stained. Procollagen type
1.5% to 13.5%. In particu lar. label ing ind ices III. on the ot her hand , was less prom inent in

126
References

the ectomesenchyme, in cont rast to the nonaqq ressrve biolog ic behavior of AFs does
strong staining pattern observed for collagen not justify radical initial t reatment, atthough
type I in the adjacent con nective tissue. The large tumors, and those of th e maxilla may
authors demonstrated that the characteris- haveto be treated more radically. As with otb-
ticsof the extracellular matrix composition al- er odontogen ic tumors , "reappearance" may
lows for a clear distinction between the e c - not represent true recurrence but rather
tomesenchyme of the AF and the adjacent residua! tumor tissue, as t he result of inade-
connect ive t issue of mesodermal origin . quate init ial surgery. Therefore, the tenden-
Findings also indicated th at epithelial cells of cy to "recur" does not always indicate ag-
AFs invade the adjacent no rma l mes- gressive behavior of t he AF.
enchyme, possibly inducing de novo forma-
tion of eclomesenchymal stroma (Figs 12-8
to 12-10). Other immunohistoc hemical stud-
iesconcent rated on proliferating cell nuclear References
antigen (PCNA).1 5.19
1. Kruse A. Obe r die Entwick lung cvstrscner Ge-
schwOlste im urnenoeter.Arch Pathol Anal 1891 ;
5.2.4 Ultrastruc tural finding s 124: 137- 189.
2. Slootweg PJ. All analysis of the interrelationship
Ultrastructural stud ies of AFs have focused 0 1 the mixed odontogenic tumors-ameloblastic
on the epithetium-ectcmesenc hvrnat inter- fi bro ma. ameloblastic lib ro-od o ntom a. and th e
face.22.23 Changes in the basal lamina region odontomas. Oral Surg Oral Pathol Oral Med 198t;
were consistent wit h an attempted indu ctive 5 1 :266-276.
stimulation with some sim ilarities to normal 3. Philipsen HP, Reichart PA, Preetonu s F. M ixed
odontogenesis. Amelobtastic fibrom as re- odontogenic tumou rs and odontomas. Co nsid-
eration s on interrelatio nship. Review of th e litera-
vealed differing degrees of thickening of the
tu re ere presentation of 134 new cases of 0000-
lamina densa by a granulofilamentous ma- tom es. Oral Oncol 1997;33:86-99.
terial.However,the granulofilamentous zone
4 . Dallera P, Bert oni F, March ett i C, et ar. AmeIo-
wasnot wide enoug h to account for the hya- bla stic fibrom&-a fOllOw up of stccaees.jnt J Oral
line,cell-free bands seen histolog ically. Maxillofac Surg 1996;25 :199- 202.
5. Piesold J. Meerbach W.AmeIobIastlSChes Fibrom
im o reooete- M und Kiefer Geslchtsc hir 199 7;1:
174- 178.
6_ Brethaux-Barcinon M.P , Ferkadji N, Dettez J-P_A
6. Notes on treatment and p ropos des noromes ameloblastiq ues. Rev Stom-
ata l Chir Maxillofa c 1994 ;95 :75- 77 .
recurrence rate 7, Boc klag e JT, Ardernan T, Sc haffn er D. Amelo-
blastic fib roma: A fine-needl e asp iration case re-
Recurrences of AFs have been described. po rt. Diagn CytopathoI 1997 ;17:28o-286.
Trodahl 2o recorded a recu rrence rate of 8. Mos by EL, Russell D. Noren S, SCott Barke r BF.
43.5% in a series of 24 cases of AFs. Zallen Ameloblastic fibroma in a 7-week-old infant : A
case repo rt and review of th e literature. J Oral Max-
at al21 esti mated a cu mu lat ive recurren ce
illofac Su rg 1998;56:368---372.
rate of 18%; these authors suggested a mod-
9_ Mosqueda-Taylor A. teoesme-vcotes C , Ca-
ified block resection rathertnan asimple enu-
banero-Sarooeat S, et at Odontogenic tumors in
cleation. Gund lach 24 also stated that enu- Mexico. A coll aborative retrospectrve studyct 349
cleation of the AF would not be sufficie nt in cases. Oral Surg Oral Moo Ora! Pathol Oral Radi-
most cases. Most author s agree that th e 01 End od 199 7;84 :6 72--675.

127
12 : A m e lo b last ic Fib ro m a

10. Daley T, Wys ocki GP, Pring le GA Relative inc i- 18. Sano K, Yos hid a S, Nino miya H, et al. Assessment
dence of odo ntoge nic t umo rs and o ral and jaw of g rowth pote nt ial by M IB-1 im m cn onstocnern-
cysts in a Canad ian pop ulation. Oral Surg Oral istry in em eio biasnc fibro ma and related lesions
Med Ora l PathoI 1994 ;77:276- 280. of the jaws com pared with arneloblastic fibrosa-
co ma. J Oral Pathol Med 1998;2 7:59-63.
11. Takeda Y. Arnelo bla stic fibroma and related le-
sions : Current patholog ic c once pt. Oral Onco l 19. Yamamoto K, voneoe K, Yamamoto T, et al. An
1999;35:535- 540 . im m u nohi stoc hem ical study of odo ntoge nic
m ixed t um ors. Oral Oncot 1995:3 1:122- 128.
12. Sc hm idt-Westhausen AM , Philipsen HP, Reichart
PA Das ame lob lastisc he Fibro m----ein odo nto- 20. Trodahl J N.A melohlastic ftbrom a. A survey of cas-
generTumor im Wachstumsalter. Dtsc h Za hnarztl es from t he A rmed Forc es Institute of Pathology,
Z 19 9 1;4 6:66- 68. Oral Surg Oral Med Oral Patner 19 72 ;33:547-
558.
13 Philipsen HP, Tb osapor n W , Reicha rt PA, Grundt
G. Od ontogen ic lesio ns in ope rcula of permane nt 2 1. Zallen RD, Presk ar M H, McCl ary SA. Am eloblast-
mo lars delayed in er uption. J Oral Pat hol Med ic fibro ma , J Oral Maxillofac Surg 1982;40:513-
1992 ;21 :38-4 1. 5 17 .
14. usarna K. M iyake M, Moro L Perip heral amero- 22 . Csiba A, Lapis K. Ultrastr ucture de I' ameloblas-
blastic fib roma of the mandible, report of a case. tom e fibro mateux. Bull Group Int Rec h Sci Stom-
J Oral Maxillofac Surg 1998 ;56 :399-40 1. atoI 1972; 15:233- 250.
15. Kram er IRH, Pind bo rg JJ , Shear M. Histolog ica l 23. Farm an AG, G ou ld AR, Me rrell E. Epithelium-
Typing of Odo nto genic Tumours. 2d eo.
Ber lin: co nnective tissue junctio n in follic ular ameloblas-
Sp ringe r Verlag, 1992. toma and ame lo blastic fibroma : A n ultrastructur-
al analys is, Int J Oral Maxillofac Surg 1986;15:
16. Kim J , Ellis GL. Dental fo llic ular tissue: M isinter-
176-186.
pretation as odontogenic tumors, J Oral Maxillo-
lac Surg 1993;51 :762- 76 7. 24. Gund lac h KK . Odontoqe ne T umoren. Munc
Kiefe r G esic ht sc hir 200 0 ;4{Su ppl 1): 8 187-
17. Bec ker J, Reic hart PA, Sc hup pan 0, Philipsen HP.
S195.
Ecto m ese nc hyme of am elo blastic fib ro ma re-
veals a characteristic distributio n of ext race llular
matrix p roteins. J Oral Patb ol Med 1992 :2 1:156-
159.

128
Chapter 13

Ameloblasti c Fibrod entinoma

1. Terminology been conside red different from the AFD


based on histologic features. The interrela-
The ametoblastic fib rodent inoma (AFD) has t ion ship between arnetobt ast!c fib romas.
up until now been called d ent inoma and was amel oblasti c fib re-odonto mas. and t he
first described by Stra ith in 1936. 1 Hedefined odontomas is discu ssed in the introduction
the AFD as "a very rare neoplasm composed to this section.
of odo ntoge nic epit helium an d immatu re
connective tissue, an d characterized by the
formation of dysplastic dentine.~
In a 199 7 review of m ixed odontogenic tu- 2. Clinical and radiolog ic profile
mors.t 25 cases of AFDs were retri eved fro m
the literature. Ulmansky at al3 p ublished two The AFD has been desc ribed as a slow-grow-
cases in 1994, and two more cases were re- ing, often asymptomatic tumor wh ich may
ported by Akal et al4 in 1997. beco me qu ite large. It may be associated
The concept of a dentinoma being an in- w ith une rupted teeth in some c ases. Al-
dividual entity has bee n q uest io ned by some though few cases of AFDs have been re-
authors, and doubt has been expressed as
to the exact nature of such lesion s. In pa rtic-
ular, the so-ca lled immatu re dentinoma? has

Fig 13-1 Radiograp h of an early AFD. A small, welklelin- Fig 13- 2 Periapical rad iograph of the
eated translucency with minor early calcifi cations is seen cystic lesion shown in Fig 13-1. It ap-
above the right permanent maxillary lateral incisor. peared to have developed from t he per-
manent maxillary right lateral incisor. An
irregular radi opa city is seen overlying
the apex ofthe tooth. Histopat ho logy re-
vealed the presence of an ameloblastic
fibrod ent inom a.

129
13: Ameloblastic Fibrodentinoma

No. of ca ses

tn
to []] Wcme ,
9
[]] M~
8
t n =28
r
6
5
4
3 3
3

,
2 ,,
o l l lJ IlnJl lJ
lJI l~lJlJ llrn
lJ l lJ nrn
IJ IJ Fig 13-3 Distribution of
0-9 10- 19 20 -29 30 -39 40-49 50 - 59 60 -69 70 - 79 ameloblastic fibrodentin-
Age in decades omas by age and gen-
der.

po rted to date, the t um ors seem to behave 3.2 Age


bio logically as do ameloblastic f ibromas or
ameloblastic f ibro-odontomas. The age at the time of diagn osis falls within
Radiologically, th e AFD appe ars as a fair- the t st an d 2nd d eca d es; 75% of AFDs
ly wcu.ocuncatc o radiolucency with varying (n=28) are diagnosed befo re t he age of 20.
d egrees of rad iopac ity, depending on the Figure 13-3 shows t he age dist ribution of
amo unt of de ntin p rodu ced-eit he r osteo- AFDs acco rding to age groups and ge nder.
dent in or th e rare tu bu lar type of dent in (Figs The mean age of 24 cases was 13.6 years
13-1 and 13-2). In cases of AFDs associated (range, 4 to 63 years).2
wit h embe dded teet h, t he tu mor and t he
tooth c rown are usually in c lose con tact .
3 .3 Gender

Th e A FD shows a male predilect ion, t he


male:female rat io being 3: 1 (n=28).2- 4
3. Epidemiological data
3 .4 Location
3.1 Prevalence, incidence, and
relative frequency The majo rity {71.4%} of AFDs are loc ated in
the posterior mand ible (n = 29 ).2 - 4 The dis-
Due to the rather small num ber of reported t ribution of AFDs accordin g to location is
cases of AFDs in the literature, data are not shown in Fig 13-4. A case of a peripheral AFD
availab le. o cc urr ing in t he ging iva has been de-
scroeo," but it seems that th e majority of cas--
es occur as a ce ntral. intraosseous tumor.

130
Pathology

5. Patholog y

5.1 Macroscopy
3 4

0 =2 9 Mac roscopy of amelob last ic fibrode nt ino-


mas has not been desc ribed in t he literature.
,,
ao ,, ,
5.2 Microscopy
5.2. 1 Histo log ic definitions
The WHO d efinition? of AFD is "a neoplasm
Fig 13-4 Location of AFDs. One case (indicated
byanasterisk) involved boththe anteriorand pos- s imilar to amelob last ic fib rom a. bu t also
terior mandible. showing inductive c hanges t hat lead to for-
mation of de nt ine."
The definit ion used by the present authors
is as follows:
A hama rtomat ous lesion similar to the arnelo-
4. Pathogenesis blastic fibroma, but also showing inductive
ch ang es th at lead to formation of de ntinoid .

The AFD is a member of th e mixed odo nto-


5.2.2 Histopatholog ic findings
genic tumor fam ily and, as such , is clearly of
odo nto genic origin. It has been con sidered Histo patholog ically, the AFD has t he same
by some to be an intermediate stage be- ep it he lial and ectomesenc hymal compo-
tween the amelob last ic fibro ma and t he nents as the ameloblastlc fibroma. It is com-
arnelobtastlc f ibro-odontoma in term s of his- posed of stra nds and islands of odontogen ic
tologic diffe rent iation (t he hamartom ato us
line descr ibed earlier by t he present aut hors).
In t he 199 2 World Health Organ izat ion
(WHO) classlflc atlon ? it was stated t hat "un-
til more exp erience has been gain ed it may
be worthw hile to separately identify the dif-
fering patte rns or types of ame lobl astic fi-
brom a and relat ed lesions, even t houg h
some of these may later p rove to be nothing
more than stages in the evolution of a single
type tumou r."

Fig 13-5 Two islands of odontogenic epithelium


embedded in cell-rich ectomesenchyme.An area
of abortive dentinoid with a number of entrapped
ectomesenchymal cells is also observed (hema-
toxylin-eosin [H&E], / 50).

131
13 : Ameloblastic Fibrodentinoma

...... ~!f 6. Notes on tre atment and


e rec ur rence rate
'::>iU~
." . >&~ .
:"'~. ""':" :;. The recommend ed treatmen t of AFD is sur-
~" ~;';1 '~. " gica l excision. Recu rrences have not been
"": ~("'".1~ ~~
~':"
"'1' 1~$"'
:' ~~~~~y
7:"
desc ribed.
"! ~~ 3 "l
:'f.t:;#
~.r:
tt .,.:.~~~~g;

~,:;-."W'
.',1~""
": "
t, -
~l i::~... . ; ~ ' .~ Referenc es
Fig 13-6 Islands of odontogenic epithelium. Two
1. Straith FE. Odo ntoma : A rare type . Dent Dig 1936;
islands show formation of dentinoid at their pe-
42:196- 199,
riphery (H&E, x70).
2. Philipsen HP, Reichart PA, Praetonus F. Mixed
odon toge nic tumours and odontomas. Considera-
tions on interrelationship, Review of the literature
and presentation of 134 new cases of odonto mas.
ep ithelium in a cell-rich prim itive cctomcs- OraI OncoI 1997;33 :86-99.
enchyme resem bling the de ntal pap illa. 3. Ulmansky M. Bodner L Praetonus F. Lustmann J.
Dentinoid or osteodentin is de posited, often Ameloblastic fibrodentinoma: report 0fI two new
preceded by a zon e of hyalinization . Abortive cases J Oral Maxillofac Surg 1994;52:980-984.
or poorly mineralized dentin may co ntain en- 4. Akal UK. Gunhan 0 , Guier M. Ameloblastic nbo-
trapped o dontog enic ep ithelial and ec- dent inoma. Report of two cases. Int J Oral Maxillo-
tomesen ch ymal cells. Acti ve ooontoblasts tao Surg 1997;26:455-457.
are rare; as a co nsequence tubular de ntin is 5. Takeda Y. So-called -immatcre oeonnona'.Acase
rarely seen in AFDs . Enamel matrix is not in- presentation and histo logical com panson wi:h
du ced by the p resen ce of osteod entin or amelob lastic fibrodentinoma. J Oral catno Med
1994:23:92-96.
dentinoid structures (Figs 13-5 and 13-6 ).
The arnelo btast!c fibrodenti no sarcoma 6. Grodjesk JE. DobIinsky HB. SChneider Lc. Amelo-
blastic rercoeonnome in the gIngiva: Report 01
(see c hapte r 30), a very rare malign ant 0000"-
case. J Oral Mad 1980;35:59-61.
toge nic neoplasm. is thought to result from
7. Kramer IRH, Pinclborg JJ . Shear M . Histological
malignant transfo rmation of t he ect o m es-
Typing of oocotcceoc Tumours. 2d eo. Berlin:
enchymal compo nent of the AFD.8 Springer-Verlag, 1992.
8. A~l:ini
M, Smith I. AmeIoblastlc ceotmcsarcorre-e
5.2.3 Uttrestructuret findings case report. Int J Oral Surg 1976;5:142-147.
9. van Wyk CW, van der Vyver PC. Ame!oblastj c fi-
Van Wyk and van de r Vyver9 descri bed ul- broma WIth dentinoid formationjimmature deren
trastructural featu res of the AFD, inc lud ing oma. J Oral PathoI 1983;12:37-46.
early formation of de ntinoid. The authors ob-
served a spectrum of abortive features at the
epithelium-ectomesenchymal intertace.

13 2
Chapter ~ 4==-================::J

Ameloblasti c Fibro-odontoma

1. Terminology 2. Clinical and radiologic profil e


The ame'oblastic flb ro-c dontoma (A FO) has T he A FO is a well-circum sc rib ed, pa inless,
been de sc rib ed using a variety of ter ms such slow-grow ing , and ex pan d ing tumo r with no
as immature ame /ob/asOe odo ntoma 1 ; how- propensity for bony invasion . It tends to pro-
ever, Ho o ker- desc ribed it as an entity un der d uce sw elling and has a cen tral locat ion in
the name amelob/astic odo ntoma. It is a rare t he jaws. In th e majority of cases (83%) th e
odo ntog enic tu mo r composed of mo rpho- A FO is asso ciated w ith an uneru pted tooth .
logic feat ures c haracteristic of am elobtastlc Frequently the noneru ption of the associat-
fib rom as on th e one hand and complex ed tooth has led to the tumor's d iag nos is.T he
odontom as on the ot he r. Ameloblastic fib ro- size of the t um or var ies from lesio ns that ca n
odontomas show relatively uniform c linical o nly be detected m icroscopically to large cal-
and biolog ic behavior. A literature review c ified masses of seve ral ce ntim eters ' d iam e-
of 50 cases of AFOs was published by ter .
Slootweq'' in 1981 ; Philipsen at ar' pub lished Rad iol ogi ca lly the A FO prese nts as a uni-
an updated review wi th a to tal number of 86 o r mu ltilocul ar rad io lucency w ith a w ell-de-
cases ; and in the 1990s an ad d itional 8 cas - lineated rad io paq ue border . The central part
es w ere reporteo."! ' T he am elobtestlcflb ro- of th e tumo r reveals rad io pacity , t he d ensity
od ontoma is a member of t he fam ily of mixed of which rese m bles t hat of dental hard t issue
odon togen ic tumors. Th e interrelat io nship as o bserv ed in od ontomas. Th e rad iopacities
between A FOs and asso c iated lesions is cov- may be irreg ula r in sh ap e an d d en sity . In
ered in th e introd uct io n to th is sect ion. so me A FOs t he rad io pac it ies appear as ho-
mogeno us, ro unded , ca lc ified masses. In
cases of assoc iation with an unerupt ed tooth,
t he A FO is usually located co rona lly to the
c rown of the tooth. Reso rption of t he roots of
neighbo ring teet h has bee n reported . Oc-
c lusal rad iog raph s may reveal t he thinn ing
and pe rfo ration of t he cortical bone and t he
de gree of displacem ent of asso ciate d teeth
(Figs 14-1 to 14-3).

13 3
14: Ameloblastic Fibre-odontoma

Fig 14-1 Panoramic radiograph of a 15-year-old boy with an Fig 14-2 Periapical radiograph of
AFO in the left maxilla. The seco nd premolar and the first mo- the area of the maxillary left second
lar are retained, the latter being located high up in the maxil- premo lar shown in Fig 14-1. Within
lary sinus. A radiolucent area with a central radiopacity is seen a small radioluce nt area overlying
coronal to the second retained premolar. the crown of the second premolar,
an irregular ca lcified mass is evi-
dent. The AFO inhibited the perma-
nent tooth from erupting.

Fig 14-3 Panoramic rad iograph


showing a large, irregular, calcified
mass ove rlying the impacted
mandibular lett first molar. Histolog-
ically, this lesion was diagnosed as
an AFO.

3. Epidemiological data 3.2 Age

3.1 Prevalence, incidence, and T he f irst two decades are c haracte ristic for
relative frequency the occurrence o f AF Os (Fig 14-4 ), w ith
98 .9% of cases (n=94) occurring be fore the
Figures ind ic atin g t he re lat ive f requency of age of 20. The mean age of 86 cases wa s
A FO s vary between 0 .3% an d 3. 7%.12 Th is 9.0 years (rang e, 1 to 22 yea rs)." As such th e
rate rises to 7% if patients un der t he age of A FO is a t um o r of ch ild hood and ado les-
16 are co ns idered separately. cence.

3.3 Gender

A review of 9 4 cases (see Fig 14-4) has re-


vea led a m ale:fem ale rati o of 1 .4:1.

134
Pathology

No. of cases

ac
31
30

20
20

Fig 144 Distribution of


94 cases of AFO by age
and gender. Note that 0-9 10- 19 20- 29 30- 39 40-49 50 -59 60 -69 70 79
only one patient was old- Age in decades
er than 20.

3.4 Lo c at io n
anteri o r + pcstenor m axilla = 2

,.
Abo ut half (53.2%) of AFOs are found in the
poste rior mandible (Fig 14-5). The posterior
mandible is affected 2.4 tim es m ore often
than the entire maxi lla.T he AFO seems to oc-
cur exclusively as a central intraosseo us tu-
mor.
The occurrenc e of m ult iple AFOs in a fa-
SO
,
:10
ther, his two so ns, and a daug hter was re-
po rted by Schmidtsed er and Hausamen.P
In ad dition to m ultipl e AFOs, esop ha geal
sten osis, he pato pat hy, dyspepsia . and in-
creased susceptibili ty to infection we re ob- Fig 14-5 Location of 94 cases of AFO. The ma-
jority of tumors appeared in the posterior mandi-
served . A do m ina nt autosomal inher ite d d is-
order was sus pected .
ore.'

4. Path ogenesis
5. Pathol ogy
The AFO is anoth er member of the m ixed
odontogenic tumor fam ily, making it of odon- 5. 1 Macroscopy
tog enic origin. Compa red to th e ameloblast-
ic fibro ma and the arneioblastc ftbrodentrn- Macroscopically, the AFO appears as a ci r-
oma. the ind uct ive changes in the AFO are cu mscri bed sol id mass of varyin g size wit h a
more advanced and enamel is present in ad- smooth surface. The cut surface of the so ft
dition to dentin. pa rt of the tumor may appear pi nki sh w hite

135
14: Ameloblastic Fibro-odontoma

. .".. ..':.-}:..,~~-<,':".: ~', .- , "" ....


'~ :"
"'::,
;::O."j.
Fig 14-6 Photom icrographic overview of a com - Fig 14-7 Peripheral zone of the lesion shown in
plex odontoma. Note th e surro und ing co nnective Fig 14-6, This isolated area resembles an arr ete-
tissue capsu le (hematoxyli n-eosin [H&E], x 30 ). blastic fibro ma (H&E, x9 0).

Fig 14-8 Intermed iate zone characterized by the Fig 14-9 Area close to the tumor center exhibit-
production of dentin (..) and a few narrow areas ing orooucnon of dent in. The enamel matrix ( ..) is
of enamel matrix (H&E, xeD). produced by pre-ameloblast-like cells (H&E,
x 22 0 ).

136
Pathology

and gelatinous . The calcified masses are a epithelium; there were also agg regations of
yellowish white color. large, round ed melanophaqes w ith large
amounts of melanin similar to nevus cells in
areas of the ectomesenchymal co mponent.
5 .2 M icrosc opy
5.2.1 Histologic definitions 5.2.3 HistochemicaVimmunoh istochem;'
cal findings
The World Health Organization (WHO)14 de-
fined the AFO as "a lesion similar to amelo- Miyauchi et al6 studied AFOs by imm uno-
blastic fibrom a, but also showing inductive histochemistry using ant ibod ies against a
changes that lead to the formation of dent ine numb er of cytokeratins. Findings revealed
and enamel." t hat epithelial co mponen ts showed expres-
The definition used by the present authors sion of cytokeratins 8, 13, 16, 14, 18,and '9 .
is as follows: In addit ion, a coexoression of these cytoker-
A hama rto matou s lesion similar to t he atlns and vimentin were found. Sekine et al?
amelo btastic fibroma and fibrodenti noma, studied t he cell ki netics of AFOs by bro-
but show ing further inductive changes that modeoxyuridine (BrdU ) and proliferating cell
lead to the formati on of enamel matrix in ad- nuclear antigen (peNA). The results of the if')-
dition to dentin (dentinoid). vestiq atto n suggested t hat th e ectomes-
enchymal com ponent was more pro liferative
than the epithelial component.
5.2.2 Histopa thologic findings
The tissue masses of an AFO show the char-
5.2.4 Ultra stru ctural findings
acteristic structu re of an immature complex
odontoma cons isting of irregularty arranged Using elect ron mcroscoov." the epit helial
enamel, dentinoid. cementum , and pulplike cells reveal large indented nuclei with chro-
ectomesenctwmalt issue (Fig 14-6). At the tu- matin condensation in the periphery. Bun-
mor periphery . next to the fibrous capsu le, dies of tonofilaments are occasionally seen
there is a zone of strands and islands of ooo n- in the cyto plasm . Rough endop lasmic retic-
toqenic epithelium embedded in typica l cell- ulum is sparse and Golgi co mplexes are
rich ectomesenchyme (Fig 1 4~7 ). Dentin pro- poorly developed. The intercellular spaces
duction takes place toward the center of the are large, showing microvilli-like projections
lesion (Fig 14-8). The de ntin may vary struc- extend ing into the lumina (Figs 14-10 and
turally from dent inoid to tub ular dentin. as 14-11). A basal lamina of the epithelial cells
shown in Fig 14-9. App roach ing t he tumor is seen at the epithetium-ectomesenchvrnet
center, enamel matrix is laid down by the interlace. Adjacent to the basal lamina a rim
odontogenic epit helium and may appea r of fine, ape riod ic filaments indicating initial
columnar or pre-ameloblast-like (Fig 14-9). predentin form ation may be evident. In some
The amount of ecto mesehchvme gradually areas these filaments may show continuity
decreases as the hard tissue mass domi- between intracellula r and extracellular fila-
nates the central part of the lesion. The find- ments, sugg esting a probable epithelial ori-
ing of extensive pigmentation in a case of gin. Collagen fibers are rarely observed inthis
AFO in a 9-year-old Japanese girl was de- zone. Generally, the arnelobtastic compo-
scribed by Kitano et al.'" The authors ob- nent is similar to that of the developing odon-
served an abund ant deposition of melanin tog enic tissue except that th e ectornes-
widely distributed in nests of odontogenic enchymal ce lls have not developed into

13 7
14 : Ameloblastic FibrO<>don toma

Fig 14-1 0 Ep ithelia l tu m or cells of an AFO re- Fig 14-1 1 The eprt h elium-ectomesenchymal in-
vealing ind en ted n uclei and peripheral conden- terface showing a band of aperiodic filaments ad-
sation o f chromatin. In the intercellular spaces mi- ja cent to the basal lamina represe nting early denti-
crovilli-like extensions are seen p rOjecting into t he noid. Bundles of torouraments a re noted in the
lumen. A few perin uclear tonofi laments are ob- c ytoplasm o f the e p it he lia l tumo r c ells (TEM,
se rved in t he cytoplasm (tr ansmissi o n electro n xlO.000).
m icr oscopy [TEM J, x 3,500).

columnar ooo ntoblasts. This findi ng may ex- References


plain why osteodentin/ dentinoid material is
produced instead of tubu lar dentin . 1. Siootweg PJ, Rademakers LHPM.lmmaturecom-
plex odo ntoma: A light and electron microscopic
study with reference to eosinophilic material and
epithe lia-mesenchymal interaction. J Oral Pathoi
1983;12: 103-11 6.
6. Notes on treatm ent and 2. Hooker SP. Ame loblastic odontoma: an analysis
o f twe nty-six cases. Or al Sur g Oral Med Oral
recurrence rate Pathol 196 7;24:375--3 76.
3. Slootweg PJ. An analysis of the interrelationshi p
Conservative surg ical enu cleatio n is the of the mixed odontoge nic tcrrors-emeic tsesncn.
treat me nt of choice for A FOs. and recur- oro ma . am eloblastic nbro-ocontoma. and the
rences have not been reported. In large la- odontomas.Oral Surg Oral Mad Oral Pathol1981;
51:266-276.
stone. the removal of an assoc iated unerupt-
ed tooth cannot always be avoided . In small 4. Philipsen HP, Reichart PA, Preetodus F. Mixed
odontogenic tumours and odontomas. Consid-
lesions with minimal prod uction of dental erations 00 interrelations hip. Review of the litem-
hard tissue, however. the associated too th ture and presentation of 134 new cases 01odon-
may be left in situ. The prog nosis for eruo- toma s. Oral OncoI1997;33 :86-99.
tlon of these teeth has proved good.

138
Refe re nc es

5. Baker WR,Swift JO. Amelob lastic f brocdonto ma 11. Kitano M, Tsuda-Yamada S, Semb a I, et at. Pig-
of the ante rior maxilla- report of a case. Oral Surg mented amelo blastio fibro-odontorna with melan-
Oral Med Oral Patho l 1993 ;76 :294-297 , ophages. Oral Surg Oral Med Oral Patho11994 ;
77:271-275.
6, Miyauchi M, Takata T, Ogawa I, et at. Immuno-
histochemical o bservations o n a possible amelo- 12. Lu Y, Xuan M, Takata T, et at. Odontogenic tu-
blastic fibre-odo ntoma. J Oral Pathol Med 1996; mo rs. A demographic study of 759 cases in a Chi-
25:93-96. nese po pulation. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 1998;86:70 7-714.
7. Sekine J, Kitamura A, Ueno K, et at. Cell kinetics
in mand ibu lar arnerobtastlc fibre-odo nto ma eval- 13. Sc hmidtse der R, Hausamen JE. Multiple odo nto-
uated by b rom odeoxyurid ine and p rolifer ating genic tumo rs and other ano malies. Oral Surg Oral
cell nuclear antigen immunohistochemistry: Case Med Oral PathoI 1975;39:249-258.
repo rt. Br J Oral Maxiilofac Surg 1996;34:450-
14. Kramer IRH, Pind borg JJ, Shear M. Histo log ic
453 ,
Typing of Odontogen ic Tumo urs. 2d eo. Berlin:
8. Favia GF, Di Alberti L, Scarano A, Piatelli A. Am ero- Springer-Verlag, 1992,
blastic fibro-odontoma: Report of two cases. Oral 15. Reic h R, Reichart PA, Ostertag H. Ameloblastic fi-
OncoI1997;33:444---44 6. b ro-cd c ntom e. Rep ort of a case, w ith ultrastruc-
9. Siegert J, Friedric h RE, Do nath K, Schmelzle R. tu ral study. J Maxillofac Surg 1984;12 :230-234.
Das arneloblastische Fibrood onto m. DIsch Zahn-
arzn Z 1999; Sup pl I S. 24.
1D. Ozer E. Pab uccuoqtu U, Gu nbay U, et at. Ame lo-
blastic toro-coo ntorna of the maxilla:Case rep ort,
J Clin Pediatr Dent 1997;2 1:329-33 1.

139
Chapter. ~5

Complex Odontoma

1. Terminology the ind ivid ual d ata are referred to in this chap-
ter and chapter 16 as the odontoma survey.
In recent years several reports on larger
The term odontoma has been used as a de- series of od ontom as have been publi shed.
scripto r fo r any tum or of odonto genic or igin. Mac p o nald-Jankowski" repo rted on 40 cas-
However, odontomas have become known es of odonto mas in a Chinese pop ulation. In
as mixed odonto ge nic tu mors because they 199 7 Owens et al3 pub lished a retro spective
are co mposed of both ep it he lial and ec- study of 104 cases of "dental odo nto mas,"
tomesenchymal co mpo nents. Bot h the ep- and in 2000 Garci a-Con sue g ra et al 4 de-
ithelial and t he ecto m esenc hymal t issues scr ibed data fro m 4 6 cases of od ontomas in
and the ir respective ce lls may app ear no rmal Spa nish patient s. A number of sing le case re-
morp hologically, b ut t hey see m to have a po rts also have been publis hed.v' A large
defic it in structu ral arrange me nt. This defect eru pt ing com p lex odontoma," pe ripheral
has led to the op inion that odontom as are ooo ntornas.v' a co mpoun d odontoma as-
hamarto matou s lesions or malform ations sociated with a prima ry rnola r.!? and a cystic
rath er t han true neo p lasms . com pound odo ntom a 11 have all been d e-
Two typ es of odontom as have been iden- scribed. Hirshberg et al12 reported a case of
tified: the com plex and the compound odo n- an odo ntoma assoc iate d wit h a ca lcifying
to ma. The distinction between t hese two odo ntogenic cyst, d rawing attention to this
typ es is some what arb itrary , because it is int erest ing assoc iat io n of whi ch th ey re-
based on either the appearance of well-or- view ed 52 cases and sugge sted the term
ga niz ed tooth lik e structu res (c om pou nd odontoca lcifying odontogenic cyst (for fu r-
odontom as) o r on a mass of d isorganized tt er o etaus, see chapter 17). Th e association
odo nto gen ic tissues (complex odontom as). of odonto mas w ith Ga rdner's synd rome also
Philip sen et a ll review ed both types of is of d iag nostic lmportance.t''
odontomas and eight reviews, including a to-
tal of 1,040 cases, betw een 197 6 and 1989.
Due to inacc uracies in tre atment data , lac k
of info rmation, and presentatio n of poo led 2. Clinical and radiologi c profile
data, a num ber of pub lished reviews were
excluded ; 225 cases of odontomas co uld be
evaluated from the remaining review s. Ind i- Complex odonto mas are slow-grow ing, ex-
vidual d ata for anot her 282 cases were also pand ing , an d (in most cases) pai nless le-
availab le. The pooled data of the reviews and sio ns. Pain and inflammation associated with

14 1
15: ComplexOdontoma

Fig 15-1 Dental radiograph showing a complex Fig 15-2 Periapical radiograph of a large malt-
odontoma between the left mandibular seco nd dibular complex odontoma. Displacement of a
premolar and first molar. There is a radiol uc ent mandibular molar roc occurred. Somo co mplex
areawithin a radiopacityof different densities. odontomas may have a peripheral location, and
are often known as erupting odontoma.

odontomas was reported in only 4% of Span- one permanent tooth totaled 74%. and in
ish patients." 42 % of these pati ents. canines were in-
Complex odontomas are often detected votved."
on rout ine radiographs or d iagnose d
through failed eruption of a permanent tooth.
The size of co mplex odontomas may vary
from 3 to 4 cm to th ose that are only d e-
tectable mic roscopically. In a series of 46 3. Epidemiological data
ca ses of odontomas (com ple x and corn-
pound) from Spain," the averag e size was
15.4 mm (range , 7 to 30 mm). 3.1 P revalence, inciden c e, an d
The rad iolog ic appearance of complex rela t ive frequency
odontomas de pends on t heir devel op mental
stage. Three stag es exist based on th e d e- Relative frequency of complex odontomas
gree of mi neral ization. The firs t stage is varies between 5% and 30%.1 This makes
cha racterized by radiolucency du e to lack of the com ple x odontoma one of th e most
calcification (weiches Odontom '" so ft odon- common odontoge nic lesions. superceded
toma). Partial calcification is observed in the in frequency on ly by t he compound odon-
intermediate stage , while in the third and fi- toma.
nal stag e t he lesion usually appears ra-
diopaque with amorphous masses of d ental
hard tissue surrounded by a thin radiolucent 3.2 Ag e
zone (Figs 15-1 and 15-2 ). Resorption of
neighboring teeth is rare. Unerupted teeth Based on 137 cases from the odontoma sur-
are associated with 10% to 44.4% of com- vey ' the mean age at the time of diagnosis
plex odontomas.' Patients with odontomas was 19.9 years (range. 2 to 74 years). Figure
who experie nced de layed eruption of at teast 1 ~ shows the age and g end er distribution

142
Epidemiological data

No. of cases

40
[j] Women
[]JMe n
30
n = 137
22
20
13 13
10
10
6
1 1
Fig 15-3 Distribution of
0- 9 10- 19 2 0- 29 30 -39 40-49 50 -59 60 - 69 70- 79
complex odontomas ac-
Age in decades
cording to age and gen-
der.

at the t ime of dia gnosis fo r co mplex odon-


tomas in th e survey;83.9 % of cases occurred 20.1 25.2
10.0 15.0
before the age of 30 with a peak in the 2nd
decade of life. tr.t --j:~--::- ~,
20.0 25.0

3.3 Gender

The ma le:fema le ratio varies f ro m 1.5 :1 to


1.6:1 to 0 .8 :1, accord ing to d ifferent studies.'
1
n: 2

4
3
13
20'
ve
20

The Spa nish st ud y" of 46 od ontomas re-


ported a male:fem ale ratio of 1 :1 .6 ,4 wh ic h
differs from most other reports.

3.4 location

Althoug h some d ifferences exist in t he liter-


ature, m ost auth o rs ag ree that the majo rity of Fig 15-4 Location of complex odontomas ac-
comp lex odontomas are located in t he pos- cording to the odontoma survey by Philipsen et
terior mandib le; t he second most com mo n at,' which evaluated four main reviews (numbers
in boxes) on complex odontomas, compare with
site is the anter ior maxilla." Figu re 1 5-4 shows
Fig 16-4.
the distribution of sites of d ifferent series of
com p lex odonto mas.'

143
15: Complex Odontoma

4. Pathogenesis 5 .2 M icroscop y
5.2. 1 Histolog ic defin itions
The odontogenic origin of the com plex The World Health Organization 15(WHO j de-
odontoma has never been question ed. It is fined a complex odo ntoma as "a martorma-
considered a sett-Hrrutinq developmen tal ten in whic h all the de ntal tissues are repre-
anomaly or hamarto matous malformation sented, individu al tissues being mainly well
characterized by nondescript masses of de n- formed but occ urring in a more or less dis-
tal t issues. Recently, it has bee n suggested orderly patte rn."
that odon tomas tend to increas e in size with The definition used by the p resent authors
the age of the patient, suggesting continu- is as follows:
ous growth .2 This view, however, is not held A hamartomatou s lesion in wh ich all the den-
by the majority of authors in this field. tal tissues are represented, individual hard
The etiolog y of complex odonto mas is un- tissues being mainly well developed but oc-
known. Several theories have been p ro- c urring in a mo re or less disorderly pattern.
posed. including local trauma, infection, fam-
ily history, and genetic mutation. It has also
5.2.2 Histopa tholog ic findings
been sug gested that odontomas are inherit-
ed from a mutant gene or interference, pes- Histopatholog ically, the co mplex od ontoma
sibly postnat ally with the genetic con trol of consists primarily of a disordered mixtu re of
tooth development. 3 dental tissues , oft en of sp herical shape. Oc-
Several factors may cause anomalous tis- casi ona lly, the ca lcif ied masses may include
sue development in od ontomas. Th ese in- tooth-like structure s as in compound od on-
clude unsuccessful or an altered ectomes- tomas, indicating that the degree of rnor-
enchymal interaction in the earliest p hase of pnoo.tterentiation varies greatly. Cementum
dental germ development and/or alterations or cementum-like struct ures ofte n admixed
in the subsequent p hases of t he develop- with the dentinoid substance, small spaces
ment of t hese tissues. It has also bee n as- with pulp tissue, enamel matrix, and ep ithe-
sumed that alterations in the mine ralization lial remnants may be observed within the cal-
mechanisms with mod ifications of the min- cif ied/ mineralized masses of den tin of dif-
erai com pone nt in t he enamel may lead to in- ferent qual it ies. Empty sp ace s an d clefts
com plete maturation.!" cause d by t he process of d ecalc ification,dur-
ing which mature enam el is lost, are evident.
At the periphery of the lesion, island s of pulp
tissue and nests and strands of odontogenic
epithelium may be foun d (Figs 15-5 and
5. Patholo gy 15-6 ). The enam el present in d ifferent types
of odontomas is never completely matu re but
shows numerous minera lization and struc-
5. 1 Macroscopy tural anomalies.
A thin , fibrous capsule and occasional ly a
Cut sections of large lesions wi ll reveal the cyst wall are seen surrounding the lesion. In
calcified masses as a white to yellowish hard 16% of complex odontomas, areas of ghost
surface surrounded by a capsule of collage- cells have been identified. I Some of these
nous tissue. may present wit h melanin pigmentation.

144
Pathology

Fig 15-5 A complex odontoma showing irregu- Fig 15-6 Higher magnification of the complex
larly formed dental hard structures with pulp tis- odontoma shown in Fig 15-5. Enamel matrix and
sue (hematoxylin-eosin [H&E], / 25). odontogenic epithelium are evident (H&E, x60).

Histo logic feat ures of th e com plex odon- layer and de ntinoi d structures. The auth ors
toma largely d epend on t he develop mental co ncluded that expression of tenasci n in t he
stage of t he lesion, as do its radiologic char- stromal t issue of odo ntogen ic tumors differs
acterist ics. The refo re, it maybe difficult to dis- accord ing to t he potential of the tumor cells
tinguish od onto mas in the very early stages form ing calcified structures, irrespective of
of development fro m amelobtastlc f ib romas the tu mor cell morphol ogy.
and arneloblastic fib ro-odontomas. Even af- Papaqerakis et al'? studied late p heno-
ter growth and mineralizat ion have been typ ic ma rke rs of ametobtasts and odo n-
completed, residues of the odontog en ic ep- tob lasts, in part icu lar prote ins invo lved in
ithelium may still be identified. b iom ineralizat ion (arn eloq eotn s, keratins,
The interrelationship betw een the differ- co llagen types III and IV, vimentin, f i-
ent types of odontomas and other mixed b ron ectin, ost eon ectin, and osteocalcin).
odontog enic tumors is discu ssed in the in- The patt ern of p rote in exp ression showed
troduction to t his section. som e simi larities betw een the amelob lasts
and od ontoblasts in normally de velo p ing
teet h and cells p resent in tissues of complex
5.2.3 Histochemical/immunohistochemi-
odon tom as.The study confirmed t hat the dif-
cal findings
ferent iati on of norm al an d tumo r odonto-
Small nu mbers of odo ntomas, incl udi ng genic cells is accompanied by t he expres-
some complex odo nto mas, have been st ud- sion of some c omm on molecu les. A
ied immun ohistochemically. Mo ri et al16 plausible exp lanat ion for t he results (w hic h
studied t he exp ression of tenasc!n in a vari- also relates to ot her od ontoge nic t umors)
ety of odontoge nic tumors. In five cases of could be t hat t he o don to gen ic t umor ep-
odontomas t here was a w idespread strom al ithelial cells are recapitulating ge netic pro-
immunoreactivity w hich was, however, neg- grams exp ressed during normal cocntoqen-
ative in t he c alc ifi ed masses. Th e most esis , but t he tumo r cells d emonst rate
marked immunoreactivity was seen in t he abn ormal exp ress ion patterns for t hese
pulplik e t issue adjacent to the od ontoblast genes.

145
15 : ComplexOdontoma

5.2.4 Ultrastructural findings References

March ett i et aP4 st udied co mplex odon- 1. Philipsen H P, Reich art PA, Praeto rius F, Mixed
odo nto genic tu mours and odo nto mas Co nsid-
to mas by sca nning elec t ron mic rosco py
erations on interrelationship , Review of the litera-
(SEM) and tr ansm ission elect ron mi cros- t ure and prese ntatio n of 134 new cases of odon-
copy (TEM). The stud y was pe rformed be- tom as, Oral On coI 199 7;33 :86- 99.
cause odonto mas p rovide an alte rnative 2. MacDonald-Jankow ski DS. Odo ntomas in a Chi-
model fo r observing the formation of dental nese po pulatio n. Dentom axillo fa c Radiol 1996;
ti ssue at diffe rent stages of mat u ration si- 25:18 6-192 .
multaneously. Given th e TEM findings, th e 3. Owe ns 8 M ,S c humann NJ, MincerHH , eta l. Den-
theory that an ectomesenchym al induct ion tal od ontom as: A retrospective study of 104 cas-
failure occurs in od onto mas was not co n- es, J Clin Ped iat r Dent 1997 ;21 :26 1- 264,
firmed. The defect seen at the beginning of 4. Garc ia--Consuegra l, Junqu era lM , Albertos J M,
the differentiated and anomalous tissue mat- Rodr ig uez O. Odo ntom as. A cl inica l-histolog ical
a nd retros pect ive ep id em io lo gica l study of 46
uration may be related to later develop men-
cases. Med O ral 2000 ;5:36 7- 3 72.
tal events in th e enamel organ.
5 , Ow ens BM, Schuma n NJ , Pliske TA, Culley W L.
C om pou nd co m po site odontom a associated
w it h an im pacted c usp id , J Clm Pediatr Dent
1995 ;19 :293- 295.
6. Piatelli A, Perfett i G, Ca rrero A. Com plex odon-
6. Notes on treatment and toma as a peri apical and interradi cular radiopac-
ity in a primary m olar,J Endod 1996 ;22 :561- 563.
recurrence rate
7. Ragalli CC, Ferreria Jl , Blasco F, large erupting
com plex odo nto ma . Int J O ral Max illofac Surg
Conservat ive enuc leat ion is recommended 2000 ;29 :37 3- 37 4.
as the treatment of choice for com plex odon- 8. Led esm a-Mo ntes C, Perez-Bac he A, Garc es-Ortiz
tomas. Spec ial surgical co nsiderations we re M. G ing ival co m po und od ontoma. J O ral Max-
describe d for cases of large ma ndi bul ar morae Surg 1996;25 :296-29 7.
odontomas by Blinder et al.18 The autho rs 9. C astro GW, Ho uston G, Weyra uc h C Peripheral
suggested excision by an int raoral, lingual od ontoma: Reportof case and review of literature.
J Dent Child 1994 ;61 :209---213.
approach. As odonto mas are often associ-
ated with unerupted , im pact ed tee th, the 10. Piatelli M , Paoentorno M. Co mpound od ontoma
assoc iated w ith a primary mo lar. Acta Stornatol
poss ibility of eruption after surgical removal
BeI91 995; 3: 129- 130.
of the odontoma should be considered. In
11 Platelf A, Tr isi P, Ro masco N. Cystic com pound
cases wit hout involvement of an impacted
odo ntoma in an unusual peric oronal poste rior lo-
tooth, im mediate surgical intervention is not cat io n. Acta Sto mato l Belg 1993 ;90 :25 9-2 60.
always necessary co nsideri ng t he limit ed
12 . H irshberg A , Buc hner A. Calcif ying odo ntog enic
growth potential of suc h lesions. cysts associated w ith odo ntoma: A pos sible sep-
Recurrences have not been reported. Al- arate entity (Od ontocalc ifying odo ntoge nic cyst),
though the com plex odontoma seems to be J O ral Maxillofac Surg 1994 ;42 :555-558.
self-limit ing, th e lesion may recur if it is in- 13 . Takeuchi T, Takenoshita Y, Kubo K, lida M. Nat-
co mp lete ly removed at its early, predo mi- ural co urse of jaw lesions in patients with familial
nantly soft t issue staqe." ad enoma to sis co li (Gardner ' s synd rome). Int J
Ora l Maxnlotac Surg 1993 ;22 :226- 230.

146
R eferen c es

14. March etti C, Piace ntini C, Men gh ini P, Reg uzzon i 17. Papaqerakis P, Peuc hmaur M, Hotto n D, et al.
M. Observations on the enamel of odo ntom as. Abe rrant g ene expression in epithe lial ce lls of
Scanning M icrosc 1993 ;7:9 99- 100 7, mixe d od ontog enic t umo rs, J Dent Res 1999;
78 :20-30.
15. Kramer IRH, Pind borg JJ, Shear M. The Histo-
log ical Typin g of Odo ntog en ic Tumo urs. 2d eo . 18 . Blinder D, Peleq M, Teic her S, Surg ical co nsider-
Berlin: Springer-Verlag , 1992 . atio ns in cases of large mand ibular angle. Int J
Oral Maxillofac Surg 1993 ;22:163- 165.
16. Mori M, Yamada T, Doi T , Ohmura H, Tak ai Y,
Shrestha P. Exp ressio n of Ten asc in in od onto-
geni c tu mours . Eur J Ca nc er 8 Oral Onea l
1995;31 8 :2 75- 279 .

14 7
Chapter j 6 _

Compound Odontoma

1. Terminology non . Occ asion ally, compound odo ntomas


may be seen in Garc ner's syndrome." A case
The aspects of term inology for odontomas of six compound odontomas occurring in
were exte ns ively prese nted in Chapter 15. In- th ree male members of a family of seven was
formation abo ut the co mpound odo ntoma is reported." Periph eral co m pound od on-
based o n the odontoma survey prepared by tomas are rare, arising extraosseously and
Philipsen et al.' having a tend ency to exfoliate.
Radiolog ic ally, compound od ontomas
are ch aracterized by a radiopaque mass of
varying size wh ich is composed of a numbe r
of toot hlike st ructures in a disorderly pattern.
Th e de nt icles are mi n iat u rized and ma l-
2. Clinical and radiologic profi le formed. Persistence of one or several de cid-
uo us teeth is ob served t og et her w ith im-
pact ion of one or several perman ent teeth.
Comp oun d odonto mas are painless, ben ign Nonerupt ion of t he normal den tit ion or
lesions w ith a mo re limited growth potential supernume rary teeth is associated with com-
than com plex odontomas. In fac t, the growth pound odonto mas in 40%6 to 56%7 of re-
potential ends with t he tooth-fo rming period. po rted cases. The lesion is usually su r-
Since t here are few clinical sympto ms asso- rou nd ed by a narrow , rad iolucent rim
ciated w ith com pound od ontomas, a fr e- corres ponding t o a f ib rous capsule (Figs
quent cause of discovery is the failure of a 16-1 and 16-2). The radiographic app ear-
permanent tooth to erupt and/ or t he persist- ance is so characte ristic that t he diagnosis is
ence of a deci du ous toot h. The lesio n is also often made solely from radi og raphs and
often d iscovered incidentally on panor amic macroscopic findings.
radiographs. Com mo n ly, t he com pound
odo ntom a is located between the apex of a
root of a prima ry toot h and the crown of a
permanent tooth, preventing the latter from
erupt ing. The size otthe .lesion varies as do es
the num ber of oentcres. Cases of mult iple
compound od ontomas have be en de-
scnoeo.s-' p romp ting Mani 3 to propose t he
term odontoma syndrome for t his phenome-

149
16: Compound Odontoma

Fig 16-1 Panoramic radiograph showing a com- Fig 16-2 Periapical radiograph of the region
pound odontoma in the right anterior mandible.The of the compound odontoma shown in Fig 16-
mandibularright lateral incisor is missingand the de- 1. The permanent right central incisor is ens-
cidous incisor persists. The mandibular right canine placed. The compound odontoma is com-
appears to be retained when compared with the ca- posed of a number of denticlesarranged in a
nine on the lett side. disorderfy pattern.

3. Epidem iological data of cases were diagnosed before the age of


20 years, wit h a marke d pea k in the 2nd
decade of life. The compound odontoma is
3 .1 Pr evalen ce, in cidence, and clearly a lesion of c hildhood and adoles-
relative freq ue ncy cence.

The compound odontoma is the most com-


mon lesion/malformation of odontog enic ori- 3.3 Gender
gin. Its relative frequency varies betwe en
4.2%and 73.8% .8 Sato et al9 record ed odon- The matefernale ratio varies between 1.2:1
tomas in 47% of their Japanese patients with and 1: 1, according to the odontoma su rvey
benign od onto genic tumors (n=90 ). of Pbilip sen at at t

3.2 Ag e 3.4 l ocation

Based on the data of the odontoma survey Figu re 16-4 shows the distrib ution of com-
by Philipsen et at' the mean age at the time pound odontomas accordi ng to location.
of diagnosis was 17.2 years. Figure 16-3 Accord ing to all except one of the reviews
shows the distribution of compo und odon- evaluated, the impo rtant finding was that the
tomas accord ing to age and gender; 74.3% anterior maxilla is the most frequent location

150
Pathogenesis

No. of c ases

39
OJ Womoo
30 28
OJ Men
n~ 140

20
16

10

2 2
Fig 16-3 Distribution of
compound odontomas 0-9 10- 19 20 -29 30 -39 40-49 50 -59 60-69 70 -79
according to age and Age in decades
gender.

fo r com po und odontomas. When co mpa r-


ing c o mpound wit h co mp lex odo ntomas
(see c hapter 15), co mpound odonto mas are
10 .5 -
11.4~
:I:,:===:: M .'
45.4
25. n ~
more f requ ent in the anterior max illa, whe re-
,
47. 2
17... . --t~ r--- 27.6
as co mp lex odo ntomas see m to have a
,
predilect ion fo r t he poste rior ma nd ible.' I,
,,

4. Pathogenesis
9 .8 --f ~ ~ 2U

As w ith the complex odo ntoma, t he com- 5 .n i31---. t B.2

pound odontoma is of odontogenic o rigin. 8.3 2 19 .4


41.4 1 1 ~.8
The theo ry that the co mpou nd odontoma d e-
velops fro m an ameloblastic fibroma if th e lat-
ter is left untreated is qu estio nab le but still a
matter of debate. Th e interrelation ship be- Fig 16-4 Distributionof the location of compound
tween t he d ifferent memb ers of the mixed odontomas according to the survey prepared by
odontogenic tumors family are d iscusse d in Philipsen et at.' The numbers 1 to 4 (in square
the int roduction to t his section. boxes) refer to four literature reviews that were
used in the survey.

151
16: Compound Odontoma

~
~,
. .. ,
fl
Fig 16-5 Macroscopic aspect of denticles that
have been surgically removed.
Fig 16-0 Partof a compound odontomareveal-
ing cross sections of some of the oeoncies em-
bedded in a fibrousstroma (Mallory stain, x2.5).

5. Pathology 5.2.2 Histopathologic findings

5.1 Macroscopy Due to a higher degree of morphoditterenti-


ation than that of the com plex odontoma,
Macrosco pically. the co mpound odontoma co mpo und odontomas are easily recogniza-
is easily distinguished due to the often large ble even macroscopically. Com pound odon-
numbers of tooth like structures which are re- tomas are usually small, but large lesions
moved during surgery (Fig. 16-5). The lesion containing up to 100 denttcles have been re-
is usually encapsulated. ported. Denticles are composed of enamel,
dentin, cementum , and pulp tissue w ith a
more or less regular arrangement. Mer-
5.2 Microscopy phodiffe rentiation and histodifferentiation of
the dental hard tissues in compound odon-
5.2.1 Histologic definition
tomas have been studied in detail by Piatelli
Both the World Health Organization (WHO)10 and Trisi. 11 Three percent of odon to mas may
and the present author s d efine the com- contain ghost cens.t"
pound odontoma as follows:
A malformation in whic h all the dental tissues
5.2.3 Histoc hemical/immunohistochemi-
are represented in a mo re orderly pattern
cal findings
than in the co mplex odontoma. so that the
lesion consists of many toothlike structures. Along with oth er odontog enic tumors , Gao
Most of these structures do not morpholog- et aP3 studied co mpoun d odontomas using
ically resemble the teeth of the normal den-- immunohistochem istry. The aim of their
titian, but in each one enamel, dentin. ce- study was to describe the expression and dis--
mentum , and pulp are arrang ed as in the tribu tion of bo ne morphogenetic proteins
normal tooth. (BMPs) in odo ntogenic tum ors. BMPs. rnem-

152
Refere nces

ocrs of the transforming growth factor-beta References


(TG F-~) superfamily, playa role not only in
bon e formation, but also in eplthenomes- 1. Philipsen HP , Reichart PA, Prartonus F. M ixed
odootogenic tumours and odontomas. Consid-
enchymal interactio ns. The auth ors found
erations on interrelationship. Review of the litera-
that tumors and lesions of epithelial and/ or ture ancl presentation of 134 new cases of coco-
ectornesenc twrnal origin. inclu ding the co m- l omas . Oral Oneal 199 7:33 :86-99 .
pound odon tom a, demonstrated positive re- 2. Kaugars GE. M iller />S. Peezick B. Odontomas.
actions while epithelial odontogen ic tumors Oral Surg Oral Med Oral Patbor 1989:67:172-
were negative. The authors co ncluded that 176.
BMPs may playa role in the formation of cal- 3. M ani NJ . Odontoma syndrome. Re port of an un-
cified tissues and the developmen t of odon- usual case w ith mul tiple mu ltiform odontomas of
togenic tumors containing such tissues. both jaws, J Dent 19 74 :2:149-152.
4, Ant on iade s K, Elftheriades I, Karak asis D. The
Gar d ner sy nd ro m e. In! J Oral Maxillof ac Surg
5.2.4 Ultrastru ctural findings 1987;16 :480- 4 83 .
Not surprising ly, relatively few studies on the 5. Etnie r SH, Fast TS. Complex composite odo n-
ultrastruct ure of com pound odontomas have to ma, J tndtanao Dist De nt Soc 1969;23 2 2-23.
been performed. Abati et al 14 described 6. Bodin I, Julin P, Tho msson M. Odontomas and
scanning electron microscopic findin gs in th eir pat ho logica l sequels. Dentomaxillof ac Rad i-
0 11983;12:109- 114 .
the case of a co mpound odontoma.
7. Morning P. Impacted teet h in relation to odon-
tomas. tnt J Oral Surg 1980:9:81 - 91.
8. l u Y, Xuan M . Takata T. et at. Odontog enic tu-
mors. A demographiCstudy or 759 cases in a Chi-
nese population . Oral Surg Oral Moo Oral Pathol
6. Notes on treatment and Ora! Rad ial Endod 1998;86 :707-714.

recurrence rate 9 . Sato M , Tanaka N. sere T. Ama gasa T. Oral and


max illofacia l tum ours In ch ildren: a review. Br J
Oral Maxillofac 1997 ;35 :92-95.
The treatment of compound odont omas is 10. Kramer IRH, Pindborg JJ. Shea r M. Histol og ical
conservative enucleation of the lesion. Care Typ ing of Odontogenic Tumours. 2d ed. Geneva:
must be taken that all dentic1es are removed Sprinq er-Vertaq , 1992.
because some may easily be overlooked. A 11. Piafe lli A, Trisi P. Morphodiffercntiation and his-
postoperat ive rad iog raph is indicated . tod ifferentiation of the dental hard tissues in com-
Unerupted neighboring teet h may be saved pou nd od ontom a: astudvot undcmineralized ma-
in those cases where th e prognosis for loa th terial. J Oral Patne r Med 1992 :21 :34 0-342

eruption is good . 12. Sedano H, Pindborg JJ, Ghost ce ll epithelium in


od ontomas. J Oral Patho I 19 75 :4 :27-30 .
13. Gao YH, Yang U, Yamag uchi A. Imm unohisto-
c hemica l demonstration of bon e mo rphogenetic
protein in coontcqe ncmmors. J Oral Patho l Med
1997:26:2 73-2 77.
14. Aba ti S. Grattini G. carrass t A. SEM rnor-
ph ostructural findings in a ca se of compound
odontoma. Dent caoros 1988:56 :50-55.

153
Chapter 17

Calcifying Ghost Cell Odontogenic Cysts/Tumors


(Odontogenic Ghost Cell Les ions)

1. Terminolog y Althoug h the COC was recognized as a


distinct pathologic ent ity at first,l,2the lesion
has later show n to be of extreme diversity in
Ever since Gorlin et a11,2 first identified the its c linical and histopat holog ic features, as
calcifying odon toge nic cyst (COC) as a spe- well as in its biologic behavior. Because of
cific o donto gen ic les ion, co nt rove rsy and this diversity, there has been disag reement
confusion have existed regarding the rela- concerning th e te rmino logy used over the
tionship between non-neop lastic, cystic le- past 40 years as t he following list of terms
sions and solid tumor masses that share the c learly reveals: ca lc ifying odontog enic cyst.
cellular and histomorp hologic features de- Gorlin cyst, keratinizing and calcifying odo n-
scribed by t he authors. No spec ial recogn i- togenic cyst , atyp ical ameloblasto ma, calci-
tion w as g iven to solid lesions bu t the autho rs fying ghost ce ll odo ntog enic tu mor, cyst ic
did state that the one lesion amo ng the 15 calcifying odonto ge nic tu mor , de ntinogeni c
repo rted cases that recurred w as "a so lid tu - ghost cell tu mor, calci fying odon togenic le-
mor-lik e mass." They also wrot e, ''T hese sion, ep ithelial odo ntogenic ghost celltumor,
masses may be extensive, largely f illing the odonto ge nic ghost ce ll t umor, and ghost cell
cyst ic cavity." cyst.
The 1971 World Health Orga nizat ion Not on ly has confusion plagued the ter-
(WHO) classiflcattcn'' described the coe as minology used forthis co mp lex lesion, but a
a "no n-neoplast ic cystic lesion ." In the 1992 significa nt sou rce of disagreement stems
edmon- t he authors rep laced th is p hrase w ith from t he fact that t here ap pear to be two dif-
"most lesions ap pea r to be non-neoplastic." ferent co nce pts or sch ools of thought w hen
The present authors believe th at the lesion looking at the nature of COC: the mo nistic
has been wrong ly classified as a group 1.1.2 an d th e dualistic co ncept. Toid a" mad e a
lesion, beca use the stroma is not cha racter- c omp rehe nsive review of th e atte mpts at
ized by ectomesenchym e but rathe r by ma- class ificat ions presented during th e last 25
ture, collagenous con nect ive tissue. The na- years and added a new dualistic classifica-
ture of the de ntinoid material p rod uced in tion sche me.
COCs has not bee n fully cla rified , but the Although th e 1992 WHO classificatio n"
prod uction of th is material is prob ab ly not the cited t he term s dentinog enic ghost cefl tumor
result of true induct ion (t hrough a seque nce (DGCT, suggested by Praetortus et a16) and
of reciprocal epitheuo-ecto mesenc hyrnal in- odontoge nic ghost cell tum or (OGCT, sug-
teractions) but rat her as a resu lt of a meta- gested by Colmenero et aI7 ), especially for
plastic process. t he so lid lesion whose neoplastic natu re is

15 5
17: Calcifying Ghost cell Odontogenic Cysts[Tumors

apparent, the authors " continue to use the The suggested classification is mainly based
term calcifying odontogenic cyst, although on the pro liferative activity and growth pat-
this nomenclature may not be appropriate to tern of the lining cyst epithelium, as sug-
represent a neoplastic lesion. However, if all gested by Hong et al.10 In this context it is rel-
COGs are neoplastic in nature, the term orig- evant that Takata et er" demonstrated that
inally proposed as a substitute for COC by the proliferative features of the cyst lining are
Fejerskov and Krogh 8--cafcifying ghost eel! the main factors influencing the proliferative
odontog enic tumor (CGCO T)-would be activity of COCs. Except for subtype 2AbP
preferable. The cystic (non-neop lastic) and and according to present knowl edge, all le-
t he solid (neop lastic) variants may then be sions may occur peripherally or cen trally,
called cystic CGCOT and solid CGCOT, re- with the rat io between the two locations be-
spectively. Recent investiqationsv-" and cur- ing 1:5.9 The rest of this section provides an
rent thinking strongly support the dualistic interpretation of this classification.
concept, and should this prove tr ue, the
WHO classification will have to undergo thor-
ough revision when this lesion is reevaluated Type 1a
in a revised classification .
The three classifications of COC previ- The non-neoplastic (simple cystic) and non-
ously proposed6 .9.10 are all commonly based pro liferative variant is lined by a nonkera-
on the dualistic concept. However , Toid a'' tin ized odontogenic epithelium of 4 to 10
raised the point that in these classifications cells in th ickness, containing isolated orclus-
the authors seem to have used the term cys- tered ghost cells, some of which may be cal-
tic as a synonym for non-neoplastic. Cystic is cified. Juxtaepithelial dentinoid and foreign
basically a morphologic term that does not body reaction are not commonly present, but
necessarily cover the term non-neoplastic, occur frequently with cholesterol granulo-
whic h is a biologic one. In other words, there mas and hemorrhage.
may well be neoplastic lesions wit h a cystic
histoarchitectu re.To eliminate the co nfusion
arising from the previous classifications and Type 1b
terminolog ies, Toid a" proposed a new, sim-
ple, and basic classification based on the du- It was not unt il 1994 (Hirshberg et a113 ) t hat
alistic concept. He divided the group of COC COCs associated with an odontoma (co-
lesions into th ree main groups: (1) the calci- CaO) were first reviewed in an attempt to clar-
fying ghost cell odontogen ic cyst, w hich ify the pathogenesis of this particular variant.
should be classified with developmental The authors accepted 52 cases of CaCaO
odontogenic cysts; (2) the neoplasms, which published in the English language literature-
comprise a benign and a malignant variant; 1B men and 34 women with a mean age of
and (3) lesions described under the first two 16 years, most patients being in their 2nd
groups and associated with odontomas, decade. COGs have been reported to be as-
amelobtastornas. and other odon togenic le- sociated w ith an odontoma in 22 %14 to
sions. 47%1 5 of cases. The detailed location of the
Combining these four classification at- cocaOs is shown in Fig 17-1 . Oral exami-
tempts,5.6.9.10 each of wh ich contain accept- nation revealed a hard swelling in 52% of the
able single components, into one compre- cases. The lesion was accidentally discov-
hensive and manageable classification ered during routine radiog raphic examina-
results in the outcome shown in Table 17-1. tion in one fifth of cases. The radiograph ic

156
Term in o logy

3'
,,
,,
5 : 24
,

,,
F ig 17- 1 T opographic distribution of coes as- 4 ,
: 11
sociated with oooraorres." Numbers with aster- 5'
isks ind icate that these lesions occupy both the
anterior and the posteri o r reg io n s.

Tabl e 17-1 Suggested classification of COCS

1. Non-neop lastic (simple cystic) variants (CGCOC")


a. with nonpro liferative epithelial lining
b. with nonproliferative (or proliferative) ep ithelial lining associa ted wit h c oon-
tornas''
c. with proliferative epithelial lining
d . with unicystic, plexiform arneloblasto rnatous proliferation of epithelial lining C

2. Neoplastic variants
A Benign type (CGCOT")
a. cystic subtype (cystic CGCOT)
ex) SMA ex epithelial cyst lining"
b. solid subtype (solid CGCOT)
ex) peripheral ameloblastom a-like'
~ ) SMA-Iikeg

B. Malignant type (malignant CGCOT or OGCCh)


a. cystic subtype
b. solid subtype

See Comments, page 11 g


calcifying ghost ce ll odontogenic cyst .
b Also classified as co mpou nd (or complex) cystiC ghost ce ll odontomas.
< Does not complelely fulfill the histopathologic criteria of ear1y ameloblastoma as suggest ed by VICkers and GOI1in."
d Calcifying ghOO cell odontogenic tumor
c WJ!tlhiStOpathologIC featu res of earty ameloblastoma as suggested byVickers and Gor1in. 12
I Resembl ing a penpn erar amelo blastoma (see chap!:er 6). hence termed pe ripheral ecereuer OOOntogenic ghost cell
ru= .
g Often called central epithelia l odontogeniC gtlOst ceetumor.
Odontogenic ghost cell carcinoma (for details. see chapt er 26 ).

157
17: Calcifying Ghost Cell Odontogenic Cysts!Tumors

appearance (n = 36) showed a wen-defined, tested in odontogenic tumors belonging to


mixed radio lucent-radiopaque lesion in 29 group 1.1.2 in the WHO classificat ion'
cases. The radiopaq ue foci varied in amount (rodontoqenic epithelium with odontogenic
from flecks to well-defi ned toothlike stru c- ectomesenchyme, with or without dental
tures. In fo ur cases, the lesion appeared ra- hard tissue tormatio n"). It is, however, im-
di olucent, thu s demonstrating the ear ly portant to stress that t here seems to be no
stages of development of the odontoma. In substantial evidence that the epithel ial com-
20 cases (38.5%), the CaCaO was associat- ponent of t he non-od ontoma-produ cing
ed wit h impacted teeth, the canine being the COC (CGCOC) is supp orted by ecto mes-
toot h most frequent ly involved. enchyme rather tha n by mature mesenc hy-
Hist omo rphologic information was re- mal, fibrous conn ective t issue. It is the refore
trieved from 16 cases, includ ing six cases very unlik ely that a CGCOC at some stage
from the authors' files. In most cases, the le- develops into a CaCaO simply because the
sions consisted of a single large cyst, the ep- reciprocal epithelio-ectomesenchymal inter-
ithelialli ning of wh ich showed a basal cell lay- actions respons ible for a possible develop-
er wi th hyperchromatic. polarized nucl ei. ment of an odontom a are not operational un-
Masses of "qhost" epithelial cells were pres- der these conditions .
ent in the lining or in the fibrous tissue cap- The majority of odontomas associated
sule. Elements of toothlike structures were with a COC (CGCOC) seem to be of t he
found adjacent to the COC components ei- compound type. When the mean age (see
ther in the connective tissue capsu le or in d i- section 3.2 of th is chapter) at the time of di-
rect continuation with the ep ithelial cyst lin- agnos is of cocao is compared to the cor-
ing, occasionally protrud ing into the lumen. respo nd ing number retrieved from a recent
The components of the cae and those of literature survey" and a similar comparison
the Odonto ma were intermingled and con- is made concerning location (Fig 17-2), the
tinuou s giving the imp ression of a single le- following sugg estion as to the pathogenesis
sion. of Oocaos may be made. There is a re-
Hirshberg et al13 suggested several pos- markable similarity betwee n the two sets of
sibilit ies regarding th e pathogen esis of data, and the present authors interpret these
Oocao s. One was that t he COC and t he findings as follows: The CaCaO may be re-
odontoma may rep resent co-incidental jux- garded as a com pound odon toma (in vari-
taposit ion of a COC and an odontoma. be- ous stages of development ) in wh ich the ep-
cause other odontogenic tumors, such as ithelial component- in add ition to initiating
SMA, have been reported associ ated with the developm ent of a compound (or more
COCS.15 However, the rarity of coexistence rarely a complex) odontoma-at a certain
of two separate odon togenic tumors and the stage forms an epithelial cyst lining. eventu-
relatively frequent occurrence of COCaOs ally enveloping the odontoma. This interpre-
make it an unlikely explanation for the patho- tation co ncurs with that of Nagao et al 14 and
genesis of COCaOs . The present authors Hong et al. ' O Because the cyst component
agree with th is viewpoi nt. and the odontoma are continuous with each
A second suggest ion as to the pathogen- other. it has in th e past been thought that the
esis of cocaOs is that the odontoma oevel- epithelial lining of t he cyst participates in the
ops second arityfrom the lining epithe lium of formation of the ooontcma.s- " a co ncept
the COC (or CGCOC, accord ing to Toida 5 ), that Hirshberg et al 13 accept. The latter au--
because the odo ntogenic epithelium has the thors suggest ed that the caCao should be
potential for induction phenomena as manl- regarded as a separate entity and classified

158
Terminology

Iy show some prolife rative activity. Thus, it

11.4
:\
: 54.6
shou ld be classified as an odo ntoma variant
that may be called com pound complex cys-
(10.5) !(54.5) tic gho st cell odo ntoma. It should be men-
, tioned th at compound (as well as complex)
n ~ 44
(n = 14 3) odontomas may co ntain ghost cell s in as
,,, many as 11% to 18% of examined cases."
9 .1
, Th e feat ure that distingu ishes the COC as-
: 25 soc iated wit h an odontoma f rom an odo n-
(9.8)
(25 .2)
toma co ntaining ghost cells is the definite for-
mat ion of a cyst lined by odo ntogen ic
Fig 17-2 Topographic distribution (in percent- epithelium in the former.
ages of all lesions) of COCaOs and compound
odontomas (in oarentbeses)." The eight cases
(see Fig 17-1)wherethe lesion occupied both the Typ e t c
anteriorandthe posterior regions areleft out. Note
the remarkable similarity between the two sets of In t his subgroup the cyst lining shows prolif-
data. erat ive activity with the format ion of multiple
da ug hter cysts in the fibrous co nnective t is-
sue wall (Figs 17-3 to 17-5). Extensive ghost
cell formation with a marked tendency for cal-
cification is fo und in the centers of t he cyst.
as a benign mixed od ontogen ic tum or ca lled J uxtaepit helial de nt ino id is rarely seen,
odo ntoca lcifying odontogen ic cyst. Th is ter- w hereas fo reign body react ion to herniated
mino logy see ms inapprop riate in that , ac- ghost cells is prominent.
cording to the p resent authors' concept, this
lesion is not a cyst but a compound odo n-
toma in wh ich an epit helial cyst has formed
secondarily. Th e cyst lining may occasional-

Fig 17-3 COC,type tc.located inthe gingivawith


formation of mult iple daughter cysts (hema-
toxylin-eosin [H&E], x30).

159
17: calcifying Ghost cell Odontogenic CystsfTumors

Type 2Abn

Lesions of this subgroup are located in the


gin gival soft tissue o r alveolar mu cosa and
bear a stri king resemblance to the peripher-
al am elo blastoma (see ch apter 6) except that
c lusters of ghost ce lls are present in t he
central portions of th e tu mo r cell nests and
-,~. dentino id can be found adjacent to the most
periph eral ce lls. Multifoc al do w nwa rd prolit-
eratton of the o ral surface ep ithel ium is a
characteristic find ing , but some lesions are
Fig 17-5 Higher magnification of the framed (bro-
ken line) area in Fig 17-3 showing a large island entirely wit hin the lamina prop ria. The basal
of ghost cells (H&E, x80). epithelial ce lls lac k palisading of the cell nu-
cle i. Seven Of 13 cases reported by Hong et
et'? occurred in ed entulo us pat ients and 5
were seen in de nture wearers. The clinical
Type 1d appearance of th is soft t issue tumor has var-
lously been descri bed as exophytic and pe-
This non-neo plastic, cystic subgroup is char- dunculated. nodular and plaquellke with a
acteriz ed by un i-or muttifocal proliferative ac- hard , soft. or friable consistency.
tivityof the epithelial lining, resembling a plex-
ifonn unicystic amelob lasto ma exce pt for the
presen ce of ghost cells and dystrophic cal-
c ific ation s within the p ro liferating cyst ep-
ithelium. In contrast to SMA ex COG (g ro up
2Aaa in Table 17-1), the g host cells and cal-
cifications are confined to the cyst lumen. It
is further d ifferentiated from lesions in gro up
2Ab by its obvious cyst ic histo archi tecture
and lack of juxtaepit heltal de nti noid.

Type 2Aaa

This neoplastic variant is rare. The cyst lining


shows uni- and mu ltifocal , intramural and in-
tralum inal proliferatio n of classic SMA tissue.
Fig 17-6 Neoplasticvariant of COC (type 2At$ )
ofte n in a plexiform pattern with histo patho-
wrtha largeislandof proliferative odontogeniceo-
logic featu res of early ameloblastoma ac- ftteuum resembling SMA. Note the small, ceo-
cording to Vickers and eo-no." The cyst lin-- trally located ghost cell clusters, some of which
ing contains a considerable number of g host show caicmcenon. A small ghost cell cluster has
cells. wh ereas the transform ed ameloblas- broken through the basement membraneof the
tomatous port io n shows little o r no gh ost island (a rro w) , provoking a giantcell reaction (pe-
cells. Juxtaepltnelial dentinoid is not present. riodic acid-SChiff, x100).

160
Clinical and radiologic profile

Type2A b ~ plastic variants. d eriving clinical data specif-


ic for each of the variants is d ifficult if not im-
This intraosseously located subtype is com- possible at this stage. Intraosseous lesions
posed of nests or clusters of proliferative may p rod uce a hard bony swe lling of the jaw,
odontog enic epit heli u m resembli ng SMA and periph eral lesions may ap pear as local
(Fig 17-6) o r occ asionally ad enomato id g ingiva l growt hs (resembling f ibromas or
odontogenic tum or. Ghost cells are usually fib rous hype rplasia). Whethe r centrally or pe-
encountered centrally in the epit he lial is- ripherally located. a remarkably large num-
lands. and juxtaepithe1ial dentinoid is also ber of cases have been completely symp-
present. Only three cases of th is lesio n we re tomless . irrespective of the varian t.
included in the report by Ho ng at al lo b ut they Radiographically, all intraoss eous lesio ns
all lacked the arneroblastic histopathologic appear as either uni- or occasionally multi-
criteria su ggested by Vickers and Gorlin. 12 locular rad io lucencies (Fig 17-7). Irregu lar
The above subclassification is, as alluded calcified bod ies of varying size seen thr ou gh -
to earlier, the resu lt of an amalgamation of o ut th e rad io luce ncy are typ ical feat ures.
four different attempts at cieeemcencov-" 0 La rger rad iopaq ue masses ma y be found in
of compl icated cyst/tu mor variants. The clas- cases associated with odontomas (Figs 17-8
sification is mainly based on patholog ical an d 17-9). Reso rption of too th roots and root
principles a nd it must be admitted th at it divergence has been repo rted ? a nd one
tends to be more of an aca dem ic exercise third of intraoss eo us lesions we re associat-
than an attem pt at finding a manageable so- ed with one or more unerupted teeth (Fig
lution to a d ifficult problem. 17-10). Extraoss eous lesions may show ei-
It should be mentioned th at o pinio ns d if- ther no rad iograph ic alterations or a superfl-
fer among autho rs as to the need for cla ssi-
ficatio n of the COC (see chapter 28) . Thus,
Johnson et al 18 c lai m th at "th e solid variant
of COC se e ms to represent the u ltimate
phase of evolution of the COC and not nec-
essarily a separat e entity. Because rec ur-
rence is uncommon (no recur rences w ere
found among the 57 ca ses reported by these
authors) , there seems to be no clinical justi-
fication for subclassifying th ese lesio ns."

2. Clinical and rad iolog ic profile

Because of the relativ ely small num ber of


cases in the various variants and subg roups Fig 17-7 Intraoral radiograph showing a well-de-
(see Tabl e 17-1 ) and because the m ajority of fined unilocular radiolucency in the maxillary right
PUblished stud ies have not sufficiently dif- central-lateral incisor region. Histology proved
ferentiated between no n-neoplastic and nee- this lesion to be a COC, type 1A.

16 1
17: Calcifying Ghost Cell Odontogenic Cysts/Tumo rs

Fig 17-8 Orthopantomogram


of a COC associated with an
odontoma (type 1b) in the
maxillary right can ine- first
premolar region.

Fig 17-9 Intraoral radiograph of Fig 17-10 Intraoral radiograph


thetumorshown in Fig 17-8.The demonstrating a COC associat
dislocationof the canineand first ed with a comp lex odontoma.
premolar caused by th e pres Note the persistence of the lat
ence of the odontoma is evident eral incisor and impaction of the
canine.

cia! erosion (sau ce rization) of the un derlying uation of mand ibu lar lesio ns because it can
cortical bo ne. Erasmus et al9 described how depict bot h cortical and medullary invo lve
magn etic reso nance im ag ery (MR I) ac cu ment. The COC, however, lacks pathogno
rately d ifferentiates between cysti c and solid mon ic clin ica l, rad iolog ic, CT, and MRI fea
var iant s. T his method is regarded as superi t ures. The defin itive di agnosis rem ains
or to com puted tomog raphy (CT ) in the eval- dependent o n histo log ic evaluation .

162
Epid emiological data

3. Epidemiological data num ber g iven by Hirshberg et at" (16 yea rs),
Shamas kin et al 15 (15 .7 years) , and Praeto
rius et al" (16.9 years ), w hereas the mean ag e
3.1 Prevalence, incidence, and repo rted by Ng & Siar- " is sligh tly lower{ 13 .5
relative frequency yea rs). T he latt er auth ors foun d a mean ag e
of 39.5 years in t he rem ain ing non-neo plas
Data on p revalenc e and incid ence are not t ic (cystic ) variants (g ro ups t a, t c, and 1d ).
available, irresp ectiv e of the variants of the In g roup 1c the re is a fairly even age distri
COc. T he re are several sou rces regard ing buti on in the 15 cases reported . to In group
relative fr eq uency, showing a ran ge of 1.0% 1d, wit h only 10 report ed cas es,1 there see m
to 6.8%. All these data, howe ver, suffer from to be tw o m ino r pea ks in the 2nd and 6t h
being pooled-that is, th ere is no d iffe rentia decades. in t he neoplast ic variants there are
tion betw een non-neop last ic, ben ign neo very few cases represented in Ho ng et aI's
plastic . and malignant variants of CDC-and matenal." ? However, fo r subtypes 2A bo: an d
are thus of hard ly any relevance. Only o ne re 2Abj3 a mean age of 62 years and 45 years ,
port20 has p rodu ced figures for malignant res pec tively, was indi cated . Accord ing to
COC (od ontog enic ghost ce ll carcino ma): Lombard i et al,22 the neopl astic, periph eral
0.4% of all odontoge nic tumo rs (of a total of var iant sho wed a mean age of 59. Thus, t he
759 lesio ns) an d 6.5% of all ma lig na nt odon mean ages are, no t surpr ising ly, hig her in t he
to genic t umors. The authors conclude d , af neoplast ic th an in t he no n-neop lastic var i
ter com paring their data w ith those fro m se ants. Last ly, Sha maskin et at" reported a
lected refe rence s (C hinese/ Af rican, No rth mean age of 53. 8 years fo r periph eral variant
American , and German/ Turkish), t hat th ere COCs w ithout furthe r subc lassificat ion.
is a marked geog raph ic var iation in the rela
t ive f req uency of seve ra l odonto g en ic t u
mors. T he ameloblastomes an d ma lignant 3 .3 Gender
odontogen ic tumors in particular are not rare
in a Chinese population. Few ind ivid ual data are availab le. Acco rding
to Ho ng et al,10 the male:fem ale rat io for no n
ne oplastic (cystic) COCs (not including t he
3.2 Age od on to ma-assoc iated lesio ns) w as 1.5 :1.
Th e co rrespo nd ing ratio fo r odontoma-asso
With reference to the cl assificat ion su ggest ciated COCs 13 was 1:1.9. Kauq ars et al23 re
ed by t he present authors, info rm atio n abou t view ed 29 cases of periphe ral COCs{w ith no
the age d ist ributio n of the ind ividual COC fu rther subclassification} fro m t he literature
variants and subtypes is rath er sporadic o r and found a ge nder d iffe rence w hen com
nonexistent d ue to the small number of cas paring 10 patien ts yo un g er t ha n 40 years
es in each var iant/subtype an.d to th e fact that w ith 19 patients 40 years and olde r. Of pa
available data is most oft en pooled . In gro up t ien ts younger than 40, t he male:fema le rat io
1a th ere are, ac cord ing to Hong et al. 10 tw o was 1:0.4 . w he reas fo r t hose 40 years and
age peaks-one in the 2nd decade and o ne older th e rat io was 1:2.2. Interestingl y, 14
in t he 8t h deca de, wi th no information abou t years earlie r Freed man et al24 exam ine d 70
mean age . In g roup 1b (COCs assoc iated pati ents (64 cases from a literature survey
with odon to mas) Ho ng et al 10 fo und a sharp an d 6 cas es from their ow n files wit h no fur
peak in the 2nd dec ad e w it h a mean age of the r details) and arrived at almos t t he same
14.7 yea rs, w hich corresponds w ell wit h th e nu m bers but in reverse order: Pat ients

163
17: Calcifying Ghost Cell Odontogenic Cysts/Tumors

younge r than 4 1 years exhibited a male.te been suggested for the peripheral amelo
male ratio of 1:1.7. and patients older than blastoma (see cha pter 6).
41 were 1:0.7.

3.4 location
5. Path olog y
According to Hoffm an et al,2578.5% of COCs
arise cent rally in bone and 21.5% are ob
served in t he ging iva. Apart from these data, 5 .1 Macroscopy
specific locat ions related to cae variants
cannot be given at present. Information is not available for cacs.

5.2 Microscopy
4. Pathogenesis 5.2. 1 Histolog ic definitions
Accord ing to the 1992 WHO ctassmcanon
There has been universal agreem ent on the the coe is "a cyst ic lesion in which the ep
odontogeniC Origin of COCs since Gortm et ithenatnmnq shows a well-defined basal lay
ap2 first suggested it. However, th ere has er of col umnar celts, an over1ying layer that is
been much discussion as to the possible often many cells th ick and that may resem
histopathoqenesis of COCs. sreer'" raised ble stellate ret iculum, and masses of 'ghost'
the question of whet herthose COCs that also cel ls that may be in the epithelial cyst lining
have features of oth er odon togen ic tumo rs or in the fibrous capsule. The 'ghost' epithe
(groups 2Aaa, 2Ab u, 2AbPl develop t hese lial cells may become calcified . Dysplastic
secondarily. or whether the COCs are them dentine may be laid down adjacent to the
selves seco ndary phenomena in preexisting basal layer of the epithelium. and in some in
odontogenic tumors . s neervieter answered stances t he cyst is associated with an area of
th is Question himself by stating, -It is widely more extensive dental hard t issue format ion
accepted that those cacs which have other resembl ing t hat of a complex or a compound
features of odonto gen ic tumors develo p odonto ma."
these seconcanly," The definition used by the present authors
All centrally located Oocsere likely to orig is as follows:
inate from red uced enamel epithe lium or Lesions in which the histopathologic features
remna nts of odo ntogenic epithelium." Re necessitate a separation into th ree main vari
garding the histogenesis of the peripheral, ants : ( 1) a non-neoplastic (cystic) variant w ith
neoplastic variant (group 2Abu), two major three subtypes, (2) a benign (solid) variant
sources of origin must be cons idered. Those also with three subtypes, and (3) a malignant
lesions, which are located entirely with in the or carc inoma variant.
connective tissue of th e gingiva and are sep
arated from the surface epithelium by a band 1. A lesion characterized by a simple cystic
of connective tissue , very likely arise from structure lined by a nonproliferative. odon
remnants of the denta l lamina. whereas oth tog enic epithelium with a we ll-def ined
er lesions appear to arise from the oral sur basal layer composed of 4 to 10 cell lay
face epithelium. A similar histogenesis has ers that may resemble stellate reticulum

164
Pathology

U minal prolife rations of SMA tissue, often


<9 ex hib iting a plexifo rm patt ern. The ep i

o I thelium of th e cyst lining co ntains a large


num ber of ghost ce lls in con trast to the
transform ed ameloblastomas ep it he lial
portion, j uxtaep ithelial de ntinoid is rarely,
if ever, present. This neop lastic COC is
known as SMA ex COCo
A subtype of the neop last ic variant is a
lesion c haracte rized by epit helial prolifer
at ions from the surface gingival epithelium
Fig 17-11 coe associated w it h a complex odo n into t he lamina p ropria or proliferating ep
tom a. The toothlike structure is surro unded by it helial islands or co rds enti rely located
rem nants of cyst epithe lium {arrows} and cluste rs with in the lamina propria and separated
of ghost cells (H&E, x80 ). f rom the ora l epithe lium by a band of co n
nect ive t issue . It th us bears a str iking re
semblance to t he peripheral amelob las
toma except t hat ghost ce lls are foun d
centrally in th e ep ithe lial tumor com po
and conta in isolated or c lustere d ghost nents and juxtaepithelial d ent inoid is ad
cells th at may d em onst rate dystrophic ca l jacent to the peripheral ce ll.
c ification . A final (rare) subtype of t he neop lastic
In a pro liferative su btype the ep ithe lial variant has histo pathologic features t hat
linin g shows pro life rat ion int o t he su r vary from area to area. Some portion s re
round ing fib rous capsu le w ith the p res semble SMA-like ep ithelium , others show
ence of multiple daug hter cysts , th e ce n adenomatoid odontogenic tumorlike fea
ters of wh ic h often show extens ive ghost tures. Both are characte rized by t he oc
ce ll fo rmation. cu rrenc e of ghost cells and de nt ino id.
J uxtaep ithetial dent ino id (osteoid) may
be found in both of these coe types, in 3. Malign ant COCs (see cha pter 28 ).
part icu lar close to masses of ghost ce lls.
The p roliferat ion of t he cyst lining may also
5.2.2 Histopathologic findings
show un i- or m ult ifocal, int ralum inal act iv
ity produ cing a netlike patte rn resembling One ch aracter istic and distinctive histolog ic
a unicystic plexifo rm ame lob lastoma but feat ure inseparably tied to the COC is t he oc
co ntain ing isolated or c lustered gh ost cu rrence of so-called ep ithe lial ghost ce lls.
cells and calcification. The nat ure and co nte nt of these ce lls have
Th e com bined microscopic features of been wid ely discu ssed over the years based
a COC (non-neop lastic or cystic variant) on histomor pholo gic, co nve nt ion al histo
and a com po und (or com plex) odon toma chem ical, immunohistoc hemical, and ultra
(Fig 17-11) shou ld be c lassif ied as a cys structural (bot h t ransmission and scanning
tic ghost ce ll odontoma (see cha pter 16) electron mic roscopy) investig ations. Conse
and not as a COC variant. quentl y, various t heor ies have been p ro
po sed and recently reviewed and evaluated
2. A neoplastic( solid) lesion in wh ich the cyst by Takata et al,28 w ho also mad e extensive
lining shows both intramural and int ralu- st ud ies on the im mu noreact ivity of gh ost

165
17: Calcifying Ghost Cell Odontogenic Cysts/ Tumors

,..".:"0l3?:~~~:--7
-- , .
..7I'f- '; ~ '; - ,
" ,' " 1

, r. "",'
~" ~ -'-'-~,
I ,
' "
" _i,
, ,. .~
~t "'~ ' '...
", ,,,
til. I ,' ' , "
-;
.-,. ""."-: ; r:..,
1J:
_ ~":~
~" , ,I! I, I "
f"
,. '

';. " It;~? ~~ " \l ~ ' 1' 1

- '" t Ilt1 \
\' 1
) -i
"t-...:',1f /
I
, .
"
i

, -, -;-".:..'.c
\: , .
-.",
.... ~. ... ,..J ; ~ ~ :\
iti;~-;<1~ __~ ,

Fig 17-12 COC, type 1a,with intraepithelial ghost


cells (H&E, x60).
---
Fig 17-13 Ghost cells (shown in Fig 17-1 2) with
the characteristic lossof nuclei. Note the earlydy
......-.:....".{.'..~ ..- ,. I
.....~ I:t , ,.
i

strophic calcificationseen asfine basophilic gran


ules or small bodies. (H&E, x120),

cells using antibodies aga inst several enam with th e connective tissue wall of the cyst,
el-related proteins. evok e a foreign body reaction with the for
The ghost cells, however, have been re mation of mu ltinuc leate giant cells.
porte d to occu r in several ot her odo ntog enic In so me variants of COC, atubular dent i
lesions in add it ion to t he coe suc h as odon no id mate rial may be found in the cyst wall
tomas, ame loblast ic fibromas, amelo blastlc clos e to t he epit helial lining, adjacent to ep
fibro-odontomas , and solid / rnultic ystic ame ithelial prolife rations, and particularly in con
loblastomas.2 8 ,2 9 Furthe rmore, ghost ce lls tact with masses of gho st ce lls (Fig 17-14).
with similar hlstcmorp holcqlc app earance to W het her the d entinoid (or osteoid) mater ial,
t hose in odo ntog en ic lesions are found in so me of wh ich may become mineralized,
cra niopharyngiomas and the c utaneous cal
c ifying ep ithe lioma of Malherbe (piloma
trixom a). The mere presence of ghost ep
ithelial cells in a lesion does not, t herefore,
justify the diagnosis of eoe. Ghost ce lls are
generally described as pa le, eos inop hilic,
balloon-shaped, elliptic ep ithe lial ce lls that
have lost their nucl ei, leaving a faint outline
of t he or iginal nuclei, hence the term ghost
(Figs 17-12 and 17-13). Although the cell out " Ii.: . .. . :c ''- '' :$/ ~,
lines are usually well d efined,they may some I
; ~' 'f3 '" ' . ~;:, ; ' ~ '\" ' , " ~~' ~,.-4'l:.' , . J'
t imes be blurred so that groups of ghost cells
appeared fused . Dyst ro ph ic ca lc ific atio n
~;~~~~~~ ~ .,
i" ~ ~'),<~,, ~) , ""
.',?::: " .'~.~~:' '~-~; . .'
" , ;~ , .. <". rI ~4"
may occ ur in some of the ghost ce lls, initial r ...... ~ . , ; '."AIlIIIIl:_,I*"'jlt "',.....:-_: ~ "' .~'; ":'..~ .? ,.. i:
ly as fine basoph ilic granules and later as Fig 17-14 Dentinoid material found adjacent to
small spherical bodi es. Ghost ce lls may the epithelial cyst lining which contains ghost
break t hroug h the epithelial basement mem cells, The cyst wall harbors small aggregations of
brane (be extruded) and , when in con tact inflammatory cells (H&E, x80).

166
Pathology

shou ld be regar d ed as an infla mmatory jo rity of t hese stud ies have focused on the
(metap lastic) response to th e presence of nat ure of t he ghost cetls. " As early as 1964,2
ghost cells in th e cyst wa ll o r rep resent a tr ue Gorlin et al conclud ed th at g hos t ce lls in
ind uctive effe ct is st ill to be clarified . T here is, COCs , pi lom atrixomas, and c ran iopharyn
how ever, a general trend in the opi nions of g io mas represented a fo rm of abno rma l
recent aut hors that the fo rmer theo ry is fa keratin izatio n, a t heo ry sup ported by many
vored . aut hors ove r the years . However, most im
Takeda et al"" found melan in-eontaining m unohistochemical investigations on cytok
cells in th e epithelial islands of ameloblas eratins in th e ghost cells of COCs failed to
tomato us proli ferative COG s (g ro up 1d ). Al demonstrate positive staining fo r d iff erent
though no conclusio ns cou ld be draw n as to kinds of keratins.lO ,3 2- 3 4 Takata et af" used
the spe cific o rig in o r patholog ic significance a polyclonal ant ibody agai nst wide-spectrum
of pigmentatio n in the COGs,t he authors stat cyto keratms and found th at ghost ce lls in
ed that the detection of me lani n is not a cha r COC showed on ly fai nt o r no positivity, w hile
acte ristic h isto logic feat ure of t his t um or . adjacent "non-ghost" ep ithelia l cells we re ob
The refo re, COCs in which m elanin is fo rm ed vious ly positive. The aut ho rs co ncluded that
shou ld not be co nside red a variant of coe abe rrant keratinization seems to make a m i
as ind icated by Krame r et al." Takeda and nor co ntr ib ut ion to th e fo rmation of g host
cowo rke rs 17 have describe d the occur rence ce lls. Thus, the biologic pro pert ies of ghost
of melanin pigment in odontogenic kerato cells in eocs are d iffe rent from t hose of ker
cysts, complex odontomas , ameloblas tic fi atinocytes. Hon g et al' o exp ressed the op in
o ro-od o ntomas . odontoame lob lastomas, io n that t he characteristics of ghost cells are
and adencrnatold odontogenic tumors. Th e compatible w ith t he features of coa gulat ive
autho rs noticed th at all p igm ented odonto nec rosis of odonto g enic epithelium.
gen ic lesions, except for odonto genic kera Further , Takata et al28 show ed that am el
tocy sts, are associated w ith t he fo rmat ion of ogen in was im munolocalized to g host cells
de nta l hard ti ssues or promine nt calc ifica in all COC cases, irrespective of variant. In
tion. add it ion , enamelin, sheat hlin, and enam
Ng and Siar''? reported a case of COC elysi n we re exp ressed to varying deg rees.
(most likely g rou p 1c) in wh ich nests, co rds, Co lu mnar and stellate reticulum cells of t he
and islands of typical clea r cells w ere fo und ep ithelial cyst lining w ere negat ive for the
in the co nnective t issue wa ll of the cyst. T he enamel-related p rote ins exam ined as we re
clear cells corresponded well to similar ce lls g host ce lls in pilcmatrixornas (w hic h we re
occurring in variou s odontogen ic tumors positive fo r hair keratin). The authors con
(see chapters 5, 10, and 27). In a study of the cl uded t hat g host cell s in COCs conta in
occurrence of Langerhans cells in odonto ename l-relate d p rotei ns in the cytop lasm ac
genic cysts , Akhlagh i and Dourov" incl uded cum ulated d ur ing t he process of pat ho log ic
a case of coe (no detai ls given) , where transformat ion .
Lan gerhans cells we re detected among the
ca lcified ghost cells of t he cyst ep it heli um.
5.2.4 Ultrastruc tural findin g s
Fejersk ov and Krog h8 we re the first to show
5.2.3 Histoche mical/imm unohisto chemi
th at the u ltrast ruct ure of COC ghost ce lls
cal fin din g s
does no t reveal t he so-ca lled keratin patte rn
Us ing met hods fro m co nventio nal histo identical to th at observed in ep idermis and
chem istry to imm unocytoc hem istry, t he ma- o ral epithelia, the main difference being the

167
17: Calcifying Ghost Cell Odontogenic Cysts/ Tumors

and the sq uamo us or papillary type, w hic h


resem bles t he SMA histologically and is
found exclus ively in adults." Bernstein and
Buchino'" pointed out th at the ACP oft en
exhibits histo logic feat ures of bot h th e COC
(SMA ex COC in the nom enclature used in
t his cha pte r, and gh ost cell amelob lastoma
[GCAj acc ording to Badge r and Gamner-" ]
and t he SMA Ghost cells are a prom inent
feature of both AC Ps and GCAs. Based on a
histopathologic compa riso n of 26 cases of
Fig 17- 15 Electron micrograph showing part of AC Ps and 3 cases of GCAs, t he autho rs
an epithelial cell (lower left corner) from the cyst concl ude d t hat t he biologic behavior of t he
lining of a COC (type 1a) and an adjacent ghost tw o lesions app ears to be similar and th ey
cell (upper right corner). Note the coarse, thick should be cons idered homologous tumors.
tonotnament bundles occupying the cytoplasmof
the ghost cell (TEM, x8,OOO).

6. Notes on treatment and


coarse, thick tonofilament bundles in COCs
as opposed to t he even ly dist rib uted , fine recurrence rate
tonofuaments in a matrix cha racterizing th e
keratin pattern (Fig 17-15). These fin dings Ap propriate t reat ment forth e non-neoplast ic
were supp orted by Regezi et al2 9 who co n (cystic) variants of e oe (groups 1a, 1b, 1c,
c lude d that the ghost ce lls represented an and 1d) and the neoplastic variant of subtype
abe rrant or unusual fo rm of keratin and not 2Aba is believed to be co nservative, surgical
t rue keratin .Setomura et al'" espec ially stud enucleat ion. For t he remaining neop last ic
ied the initial calcificat ion in eoe ghost ce lls variants (2Aau and 2A b~ ), some investiga
and found that a variety of vesicles were scat tors cons ider the ir behavior and p rogn os is to
tered amon g t he tonof ilament bund les. be t hat of a SMA , meaning t reat ment must
Some vesicles con tained needlelike crystals be radical. For t reatm ent of the malig nant
wh ich were cons ide red initial ca lcif icat ion COGs or odontog enic ghost ce ll carcinoma
sites in ghost ce lls.This finding differed from (group 2B), see chapter 28.
previous reports where th e calcif ication of Rec urrence of eoes is rare. According to
ghost ce lls was found to occ ur in association Buch ner." nine cases have been reported.
with the bundles of tonoftlaments.v-" Since t he rec u rrences occu rred aft er as
much as 8 years, a follow-up period of 10
years seems advisab le.
5.2.5 The relationship between
adamantinomatous (amelobfastomatous)
craniopharyngiomas an d GOGs
It is recogn ized th at the c raniopharyngiom a
exhibits two variants: the adamantinomatous
or ciass ictype {ACP }, which is more common
and occu rs in the first two decad es of life,

168
Refe rences

References 14. NagaoT, Nakaj ima T, Fukushima M, Ishiki T. Cal


cifying odontogenic cyst A survey of 23 cases in
1_ Gor!in RJ, Pindborg JJ, Clausen FP, v ckers RA. the Japanese literature. J Maxillofac Surg 1983;
11: 174 -179.
The calCifying odontog en ic CiSt-A possible ana
lOgue of the cutaneous calCifying epithelioma of 15. Shamaskin RG . Svirs ky JA, Kaugars GE. Intra
Ma lhefbe. Ora l SUrg Oral Med Oral Patholl962; osseous and extraosseous calcifyi ng odo nt o
15;1235-1243. genic cyst (Gorli n cysf ). J Ora l Maxi llofac Surg
1989;47:562-565.
2. Gor!in RJ, Pindborg JJ, Redman AS, etet The cal
Cifying odontogenic cyst. A new entily and possi 16 . Phdipse n HP . Reichart PA, Praetories F. Mixed
ble ana logue of the cut aneous epithelioma of Mal odontogenic tumours and odontomas. coree
nerte. cancer 1964;17:723 -729. erat o ns on interrelationship. Review of the litera
tu re and presentation of 134 new case s of odon
3. Pindborq JJ, Kram er IRH. Histolog ical Typing of
tomas. Oral OncoI 199 7;33:8 6- 99 .
Odontogenic Tumours, Jaw Cysts and Ailied Le
sions , Berlin: Sp ringer-Verlag, 19 7 1. 17. Takeda Y, Suzuki A, Yamam oto H. Histopa tho
4 Kramer IRH, Pindbo rg JJ, Shear M. Histo log ical
log ic study of epithelial com pon ents in the con
nective tissue wall of un iloc ular typ e of calc ifying
Typin g of Odo nto genic Tumou rs. 2d ed. Berlin;
odo ntog en ic cyst. J Oral Pathol Mad 1990 ;19 :
Spnnqer-Vertaq, 1992 ,
108- 113 .
5. Toida M. So-called calcifying odontog enic cyst:
18. Jo hnso n A, Fletcher M, Gold L, Chen S-Y. Calci
Review and d iscuss ion on the termino logy and
fying odontoge nic cyst: A clin icopath ologic study
classification. J Oral Pathol Med 1998;2 7:49 - 52 .
of 5 7 cases with immunohistochemical evaluation
6. Preetorlc s F, Hjmting-Hansen E, Gonin RJ, Vick fo r cvtokerann. J Ora l Max illofac Surg 199 7;55 :
era RA calcifying odontogenic cyst. Range, vari 679~ 683.
ati ons and neoplastic potential. Acta Od o ntol
scaoc 1981;39:227 ~ 2 40 . 19. Erasmus JH , Thompson IOC, van Rensburg LJ.
van der Wes thuijzen N . Central caJcifying odon
7. Colmenero C, Patron M, Colmenero B. Od onto togenic cyst. A review of the literature and the ro le
genic ghost cel t tumors. J creooroeouotec Surg of adva nced imaging techniques. Dentomaxi llo
1990;18 :2 15- 21 8. fac Rad iol l 99 8; 27 :30-35.
8. Feerskov 0, Krogh J. The calCifying g host ce ll 20 . Lu Y, Xuan M, Takata T. at al Odontogenic tu
odontogenic tumo r-or t he ca lcifyi ng odonto rnors A demographic study of 759 cases in a Chi
gen ic cyst J Oral Pathol 1972;1:273-287. nese population. Oral Surg Oral Med Oral Par rot
9. Buchner A The cen tral (mtraosseous) calcifying Oral Radial Ended 1998;86:707~7 1 4 .
odontogenic cyst: An analysis of 2 15 cases. J Oral 2 1. Ng KH, Star CH. Morphometric analysis of ep
Maxillolac Surg 1991 ;49 :330 -339, ithelial components and dentinoid formation in
10. Hong SP, Eilis GL. Hartman KS. calCifying odon non-neoplastic calCifying odontog enic cyst. J Ni
tog enic cyst. A review 01 nin etytwo cases with hon Univ sen Dent 1995 ;3 7:156 -1 65.
reevaluation of their nature as cysts o r neoplasms, 22 . Lom bard i T, KUlfer R, Oi Felice R, Sams on J . Ep
the nature of g host cells, and subc lassificatio n. ithelial odontoge ni c ghost c ell t umo ur of the
Oral Surg Oral Med Oral Pat hol 199 1;72:56 -64. ma nd ibular g ing iva, Ora l On co l 199 9;35:439
11. TAkata T, Lu Y, Ogawa I, et al. Prolifer ative activi 442 ,
ty of calcif ying odontogenic cysts as evaluated by 23. Kauga rs CC. Kau gar s GE, DeBiasi GF. Ex
proliferating ce ll nucle ar ant ige n labelin g ind ex. traosseous caiClfying odontog enic cyst: Repo rt of
Patror Int 1 998 ;4 8 :8 77 ~881 . case and review of literature. J Am Dent Assoc
12, Vickers RA, Oornn RJ. Am eloblastoma: Delin 1989; 119:715-7 18.
eation of early histop athologic features of neo 24. Freed ma n PO, Lumerman H. Gee JI<. calcifying
plasia. cancer 1970;26:699-710. odcntoqemc cyst. Oral Surg Oral M ed Oral Patho l
13_ Hirshberg A, Kapl an I, Buc hner A. CalCifying 1975;40:93-106.
odont ogenic cyst associated with odontoma: A 25. Hoff man S. Jacoway JR , KroIIs SO. Intraosseous
poss ible separate entity (od ontocal cifying oooo and parosteat tumors of the jaws. In: Atlas of Tu
tcceoc cyst ). J Ora l Maxillofac Surg 1994 ;52: mor Pathology. Washington DC : Armed Forces
555-558. Institut e of Pathology, 1987:30- 34.

169
17 : Ca lc ify ing Ghost C ell Odontog en ic Cysts/ Tumors

26 . Shear M. Cysts of the Oral Reg ions. Bristol: J. 34 . Lukin maa PL, Leppenie mi A. Hietanen A. et at.
Wrig ht, 19 76. Features of odo ntogenesis and expression of cy-
tokeratms and tenasc in--G in three cases of ex-
27 . Shear M. Developm ental odo ntoge nic cysts. An
traosseo us and intraosseous ca lcifying odonto-
update, J Oral Pathol Med 1994;23 :1- 11.
gen ic cyst, J Oral Pat ho t Med 1997;26 :265 - 2 72.
28. Takata T, Zhao M, Nikar H, et al. Ghost ce lls in cal-
35. Sato mura K. Nakanishi H, Fujisawa K, et al. lnitia-
cifying odontogen ic cyst express enamel-related
proteins. Histoc hem J 2000;32 :223 - 229 .
tron of ectop ic ep ithelial calc ificatio n in a ca lcify-
ing odo ntoge nic cyst. J Oral Patho l Med 1999 ;
29 , Regezi JA, Courtney RM , Kerr DA. Keratinizat ion 28:330 -335,
in odo ntogen ic tum ors, Oral Surg Ora l Med Oral
36 C hen SoY, Miller AS Ultrastructure of the keratin-
PathoI 19 75 ;39 :44 7- 4 55.
ising and calcifying odo ntog enic cyst. Oral Surg
30 , Ng KH, Siar CH. Clear ce ll c hange in a ca lcifying Oral Med Oral PathoI 1975;39 :769 - 780.
odo nto genic cyst , Oral Surg Oral Med Oral Patho l
37 . Bad ge r KV, Gard ne r DG. T he relatio nship of
1985;60:41 7- 4 19 .
acamannnor natous cra niop haryng ioma to g host
3 1. Akh lag ~l i E, Dourov N. Langerhans cells in odo n- ce ll ameloblastom a of the jaws : A histo patholog-
togenic cysts. A retrospective study based on 14 2 ic and immunohistoc hemical study. J Oral Pathol
cases, Bull Group Int Rec h Sc i Stoma tol Odonto l Med 1997;26 :349 - 355 ,
1995 ;3 8:7 1- 76 .
38 . Bernstein ML, Buc hino JJ. T he histologic similar-
32. Yamamoto Y, Hira numa Y, Eba M, et at Calcify- ity betwee n c raniop haryngiom a and odo ntogen ic
ing odo ntogenic cyst immuno histochemical d e- lesions: A reapp raisal. Oral Surg Oral Med Oral
tect ion of keratin and involuc rin in cyst wall. Vir- Patho l 1983 ;56 :502 - 5 10.
c hows Arch A Pathol Anat Histopatho I 1988;412:
189 - 196.
33. Kakudo K, Mushimoto K, Shirasu R, et al. Calci-
fying oc ontoqe nic cysts: Co-exp ressio n of inter"
me diate filame nt protei ns, and immu no histo-
c hemical d istributio n of keratins, invo lucrin, and
filaqq rtn. Patho l Res Pract 1989;185 :891 - 899.

170
Chapter 18

Odontoameloblastoma

1. Terminol ogy from 29 cases refer red to the OOSAK bone


tumor register. ' After c rit ical revision, 18 ap
Th e odontoameloblasto ma (GAl w hich is p rop riate cases were selected fo r evaluation.
characterized as being extremely rare, was Accord ing to the 1992 Wo rld Health Orga
for merly known by d ifferent names such as nization (WHO) crlte rla," 4 cases of OAs and
adamanto-odont oma, calcified mixed od on 14 AFOs were c lassif ied. The authors were
togenic tumor, soft and calcified odontoma, unab le to find any significant differences be
an d ame loblastic odontoma. T ho ma 1 int ro tween the clinica l symptoms , age, radiogra
duced t he t erm odontoameloblastoma in p hy, and f requency of recurrences between
1970. It was cons idered by some to be yet t he two entit ies. In add ition, a dec isive histo
anot her member of the odo ntoma group, to logic different iation was impossible. The re
gether w ith the ame lob lastic fibro-odontoma fore, the authors sup po rted th e hypothesis
(AFO), until Hooker- showed that t hey are t hat the re may be only one entity.
twoseparate tumors wit h different clinical be Kau ga rs and Zussrnan n" d esc ribed a
havior . t hough previously grouped tog ether case of odontoamelobastoma in 1991 and
under t he t erm ameloblastic odontoma. c rit ically reviewed t he English literature of re
Hooker different iated the amelob lastic f ibro po rted cases, b ringing the total to 12. Ac
odo ntoma from t he ame lob lastic odontoma cep tab le cases we re selected on the basis of
and used the term amelob lastic odon toma histo logic c riteria in t he form of pub lished
for the more aggressive t umors composed photo graphs or adequate desc ript ions and
of an SMA and a complex or com po und put in th ree catego ries: unequ ivoc al amelo
odo ntoma. blastoma; co nnective t issue with mature, ho
In the lite rature, few of the reported cases mog eneous ap pearance; and fragm ents of
satisfy th e c linical and histologic crite ria to malformed calcified denta l struct ures. In re
substant iate the class if icat ion of oco nto cent years only a few poss ible cases of odon
am eloblasto ma ; t he majo rity of cases re toam eloblastomas have bee n reported.2 .5,6
ported as odontoamelob lastomas appear to
be examples of t he less agg ressive amelo
baste flb ro-od ontorna.e In fact , a num ber of
investigators in the field of odon togen ic t u
mors still q uestion the existence of the odon
toamelob lastoma. w ac hter et al" made a crit
ical attempt to differentiate betw een t he OA "German-Austrian-Swiss register for jaw tumors, Baste.
and the AFO by means of histolog ic criteria Switze rland .

171
18: Odontoameloblastoma

No. of cases

6
UJWomen
5
4 [jJ Men
4
n=1 5
3
2 2 2 2
2
1
OI I - U IJ I U IJ I U IJ I_. IJ IJ
u -~ lU-l~ <::u-<::~ ::lU-39 40-49 50-59 60 -69
~ . ~ . ~ - ~ ~ ~

Fig 18-1 Distribution of


Age in decad es
OAs according to age
and gende r.3 ,6- 6

2. Clinica l and rad io logic profile 3. Ep idemiolog ica l data

Odon toame lob lastom as have been c harac- 3 .1 Prevalence, incidence, and
te rized as slow, prog ressive ly grow ing le- relative frequency
sions with growt h character ist ics similar to
those of SMAs. They present as expansue, Odcntoa meloblasto mas appear to be ex-
cent rally destruct ive lesions. Symptoms in- tremely rare and no figures on inc idence,
clude p rogressive swe lling of t he alveo lar prevalence, or relative f requ ency are avail-
bo ne, du ll pain, changes in occlu sion, and ab le. The situat ion is com plicated even fur-
delayed erupt ion of teeth . t her by the fact t hat a nu mber of cas es
Radiograp hica lly, t he OA ap pea rs as a published und er the names amelob last ic
well-defined uniloc ular or mult ilocular radi- odontom a or odontoame lob lastoma do not
oluce ncy con taining varying amounts of ra- meet the strict histologic criteria ofthis lesion
diopaque substances. The radiopaque ma- and represent instead examples of t he
terial may be in the form of smal l particles ame loblastic fibro-odon toma.
(d enticles representing a compound odon-
tomalike app earance ) or of a larger centrally
located mass of dental hard structures w it h 3 .2 Age
t he featu res of a co mplex odontoma (wh ich
may cause divergence of roots of th e adja- Distribution of age at th e time of diagnosis is
ce nt teeth). shown in Fig 18-1 (n=1 5 ). The mean age of
15 cases was 18.8 yea rs (range , 3 to 50
years).

3.3 Gender

The male:female ratio was 2:1 in t he cases


reviewed by Kaugars and Zussmann " and

172
Pathology

5. Patho log y

3 2 5.1 Macroscopy
n = 14
No d etail ed descriptions of th e macroscop-
ic app earance are availab le.

5.2 M icroscopy
5.2. 1 Histologic defin itions
Fig 18-2 Topographic distribution of location for Both the 1992 WH05 and t he p resent au-
OAs. 4 ,6 th o rs d efine the OA as follow s:
A very rare neo plasm that inclu des odonto -
genic ectomesenchyme, in ad d it ion to odon-
togen ic ep ithe lium th at resembles an amelo-
b lastoma (SM A) in bo t h structu re a nd
1:3 in th e fo ur cas es repo rted by Wach ter et beha vio r. Beca use of t he p resence of the
al.6 Due to th e sm all num ber of represe nta- odontogeni c ectomesenchyme, ind uct ive
tive cas es, no defin ite conclus ion can be changes take p lace lead ing to t he fo rmat ion
d rawn fo r the gend er d istribut ion of OAs at of dentin and enamel in parts of th e tumor.
present.
5.2.2 Histopathologic findings

3.4 Location M icroscopy reveals p ro life rat ing odonto-


genic ep ith elium in a mature con nective tis-
Figure 18-2 shows t he d istribution of 14 cas- sue strom a, charact eristic of a SMA. The ep-
es of OAs4 ,6 th e majority of wh ich is located ithelium is arranged in islands and rosettes
in th e poste rior mand ib le (n=9). with tall,co lumnar, pe ripherally palisaded ep-
ithelial ce lls. Reverse nuclear polarizatio n, as
seen in fo llic ular am eloblastomas, may be
found . T he neop last ic odontogenic ep itheli-
um fo rms islands and co rds betwee n dys-
4. Pathogenesis plast ic dent inoid substances and enamel
(Fig 18-3 ). The often large mass es of dys-
p last ic dentin and enamel are arrange d in a
The OA is cleartyot odontogenic or igin; how- ha phaza rd pattern as in a co m p lex odon-
eve r, its relationsh ip to othe r odontogenic tu - toma, alt ho ug h rud im ent a ry teet h (as are
ma rs-the amelob lastoma (SMA) on t he on e found in compound odontomas} also may be
hand and the odontomas o n the other-is not p resent. In add it ion, a variab le amou nt of the
well understood. characte ristic ce llu la r odo ntogen ic ecto -
mesenchym e is present, wh ich g ives rise to
induction phenomena resu lti ng in hard t is-
sue formatio n. Wachter et 314 who compa red
4 cases of OAs w it h 14 cases of AFOs, found

173
18:Odomoame~b~t~

~
5.2.4 Ultrastructural findings
Stud ies on ultrastructu ral aspects of odon-
toarnerobtastomas have not been published.

6. Notes on treatm ent and


recurrence rate

Fig 1B-3 low magnifica tion of an coon- Since th e OA has been con sidered an aq-
toameloblastoma revealing odontogenic epithe- gressive lesion , most aut hors reco mmend a
lial islands and cords bordering a large mass of radical treatment as applied for arneroblas-
dentinoid material (hematoxylin-eosin, x20 j to mas. 3 ,6 In the series reviewe d by Kaugars
(Courtesy of OOSAK. Prof G. Jundt, Bas te. and zussman," three recurrences were not-
Switzerland). ed, inc ludi ng on e case in which the OA re-
c urred twice. Wachter et er- d id not record
any recurrences amon g their cases .
Kaugars and Zussma n" d iscussed the
no decisive histologic criteria to se pa rate similarity of OAs with both ameloblastomas
these two lesio ns. However, it appeared th at and odontomas. Wh ile the locatio n. expan-
SMA-like structures were more ch aracteris- sion . and recurrence rate appear to be simi-
tic fo r the ooontoarnetobtastorna. wh ereas lar to those of the SMA, the age at the time
the ecto mesenchymal component was m ore of d iag nosis is m ore comparable to that of
p rono unced in t he AFO. Ghost cells may be t he complex o d on to ma (60% in fi rst two
present in OAs. decades of life; n=15 ). Wachter et al 4 con-
side red the OA and the AFO to be one enti-
ty because of a simil ar biolog ic behav ior and
5.2.3 Histochemical/immunohistochemi-
p rog nosis. A lso. t hey c o nside red the OA
cal findin gs
(and the AFO) to be more of a hamartoma-
Among a num be r of other mixed odonto- tou s lesion tha n a t rue neoplasm. They rec-
ge nic tumors. Yamamoto at al8 studied a o mme nded the pe rformance of reg ular fo l-
case of OA by imm unoh istochemica l meth- low-up in o rder to dete ct "recu rrences" early.
ods. They fo un d positive reaction of the
odontog enic epit helium to KL-1 anti bodi es
with som e d ifferences in intensity. Cells pos-
itivefor proli ferating nuclear cell antig enwere
seen more frequently in the epithelium of the
QA and ame lo blastic fibroma. Th e aut hors
concluded that tumor cells in each odonto-
genic tumor possess cha racteristic proteins
associated with proliferat io n potential and
that am elo blastic fibromas and OAs have a
hig he r pro liferatio n pote ntial t ha n othe r
mixed od ontogenic tumors.

174
References

References 5. Kramer IRH, Pindborg JJ, Shear M. Histolog ica l


Typing of Odontogenic Tumo urs. 2d ed. Berlin:
1. Thoma KH . Oral Pathology, 6th 00. St LouIS: M0s- Springer-Verlag, 199 2.
by , 19 70 :49 7-499 6. Kaugars GE,Z ussma nn H. Ameloblasticodontoma
2. Hooker SP. Ameloblastic odontoma: An ana~ of (cocotoamecoastorre). Oral Surg Ora l Med Oral
26 cases. Ora t Surg Oral Med Ora l Pat ho i Pathol 1991 ;77 :3 71-3 73 .
t967;24:119-122. 7. Gunbay T. Odontoameloblasloma: Report of case.
3. Thompson IOC, Phillips VM. Ferreira R. Houseg o J Clin Pedetr Dent 199 3;18 :17-20.
TH. Odontomeloblastom a: A case report. Br J Oral 8. Yamamoto K, Von ada K, Yamamoto T, et al. An im-
Maxillofae Surg 1990 ;28:3 47 -349 . munohistoc hemical study of od ontog enic mixedtu-
4. Wach ter R, Remagen W. Sto ll P. Kann man XWr- mours. Eur J Cance r B Oral Oncol 1995,3 1B:t22-
scnen Ooonto-Amerobtastom uno ameromas- 128 .
ttscn em Fibr o-Odontom unt erseheiden? Dtse h
zabnarzn Z 1991 ;46:74-77.

175
Section Four

Benign Neoplasms and T umor-like


Lesions Showing Mesenchyme and/or
Ectomesenchyme

Introdu cti on t issue com pon ent co ns ists of vasc ular,


loose-textured fibrous t issue." In their ac-
co unt of t he formal genesis of benign odon-
This section covers th ree different ent ities- togenic tu mors, Re ich art and Ries2 st ress
odontogenic fibromas, odontogenic myxo- that from a histoge net ic viewp oint, cemen-
mas, and benign ce mento blastomas-which to b lasts- togethe r w it h odontoblasts--be-
are all classified in the 199 2 ed ition of the long to the ecto mesenchymally d erived cells.
World Health Organizatio n (WHO) c lassifica- Thus, t he p resent autho rs have modified the
tion.' definition of the 199 2 WHO classification for
However, from a histomor pholoqic view- the three neop lasms in th is section : lesions
point, neithe r th e odontoge nic fib roma nor originat ing from mesenchy me and/or odon-
t he odonto genic myxom a contains ty pical tog enic ecto mesenc hvme with or without
cellular ectomesenchyme wit h few de licate p resence of odo ntog enic ep ithelium.
connective tissue f ibers as is c lassic ally seen
in t he ameloblastic fibroma. The co nnect ive
tissue com po nent in th ese two neoplasms is
that of a mature, mesenchymal o r m esod er- Com ments
mal (co nnective tissue ) type. Likew ise, the
benign cementoblastom a does not inclu d e
a histomorp holo qically c haracte rist ic ec- Read ers sho uld note the terminology used
tom esenchymal component. a fact t he au- in cha pte rs 19, 20, and 2 1. During the Edi-
thors of the 199 2 W HO class ification ac- torial and Consensus Confe rence, held in
know ledg ed when t hey stated th at "the soft Ju ly 2003 in assoc iation wit h the prepa ration

177
Introduction

of t he new WHO vo lu me Tumours of the Conference was he ld du ring th e final p ro-


Headand Neck , t he fo llowing changes in ter- d uctio n of th is book, rewriting chapters 19,
m inolo gywere int rod uced forthe tumors de- 20 , and 21 to int rod uce t he new terminology
scr ibe d in the afo rementio ned chapters of was not possible.
this boo k.
Tw o variants of the odon togen ic fibroma-
the simple type and t he complex o r WHO References
type- we re rena med epithe lium-poor and
Krame r IRH, Pin dborp . Shear M. Histo log ical
epithelium-rich, respect ive ly . The ter ms Typing of Od ontoge nic Tu mo urs. 2d ed. Berlin:
myxoma or myxofibroma are unc hang ed . As Springer-Verlag . 1992.
for the ben ign ce me ntobtestorna, the w o rd 2. Reichart PA, Ries P. Co nsiderations o n the classi-
"benign" has been dropped an d it is now ficatio n of odo ntoge nic tumo urs, Int J Oral Surg
cementoblastoma. Because the Co nsensus 1983 ;12:3 23 - 333 ,

178
Chapter 19

Odontogenic Fibroma

1. Terrninol oqy a central (jaw) fib rom a ; the co nnectiv e tissue


is that of a mature, mesen chymal type and
not that of the embryo nic. ect o mesenchymal
The odontogenic fib roma (OF) is an elusive type as exemp lified by the con nective t issue
and co ntroversial tu mo r: elusive because of component of th e amelobfastic fibrom a (AFs,
its rarity and co ntroversial because of the un- cl assification g roup 1.1.2). The co nnective
certainty as to the number of di stinct types tissue of COFs varies from a relatively ace l-
that exist.' At present the term odontogenic lular, dense. fibrous type to areas of de licate
fibroma appears to be applied to various fib e rs interspersed with considerable
types of lesions. It is, however, generally am ounts of g round substance (simple type)
agr eed that topographically tw o variants can to a cellular, fib rob lastic type interwoven with
be distinguished: an intraosseous or central less cellular and often vascul ar areas (WHO
type (CO F) and an extraosseous or pe riph- type ). The latter type also co ntains foc i of cal-
eral type (PD F). This chapter deals only wit h c ified material resembl ing dysplastic ce-
the cen tral variety. More info rmation on POFs m entum, osteoi d , or dysplastic dentin.
is availab le in Gardner." Buchner at al.3 Da- The occurrence of od ontogenic ep itheli-
ley and Wysocki,4 and Siar and Ng .5 um, whethe r by c ha nce o r as pa rt of th e
According to the 199 2 World Health Or- pathogenesi s of the lesion, varies am ong
ganization (W HO) pubftcation.s the COF is COFs . In the sim ple type , remnants of odon-
derived from "Odo ntogenic ect omesen- toge nic epi thelium are seldom numerou s
chyme with or without included odontogenic and they appear as inactive-looki ng ,small, ir-
epithelium" and is th us classified wit h myxo- regular islands and cords . However, odon-
mas (odontoge nic myxoma, myxofi br om a) tog enic , inactive-looking epit helium is an in-
and be nign ce m ento bla sto mas in g ro up teg ral co mponent of th e WHO type . It may be
1.1.3. Howeve r, it wa s str essed in 19 71 7 that sparse but it is often conspicuous. The ep-
in the absence of odonto genic ep ithelium. ithelium d oes not exhibit a central stellate
the d iagnosis of odo ntogenic fibroma sho uld retic ulum o r pa lisad ing of the pe ripheral
be made "o nly if t here is good evidence that cell s, feat ures that are characteristic of the
the tumour originates from the od ontogenic active-looking e pithelial co mpo nent of the
appar atus" (the 19 92 WHO ciassmcauon" ameloblastic fibroma. These find ings may
added "with caution" to this caveat ). The support the view held by t he present authors
present authors do not agree with the WHO that the od ontog en ic epit helium in the COF
panel abo ut includ ing the odontogenic fi- does not exhi bit an aetive-loo king "ind uction
broma in g roup 1.1.3. Basicall y, the COF is response" because it is not embedded in an

179
19: Odontogenic Fibroma

ectomesenchyma l environ ment. Like w ise, the prese nce of fo ci of ca lcified co llageno us
the calcified material fo und in t he WH O type material resembl ing dysp lastic cementum,
COF is co nsidered to be metap lastically pro- osteo id (or bon e), or dysplast ic (atubular)
duced (d ysp last ic) cemento idjosteo idj dentin. As already stated, odontogen ic ep-
dentinoid, and th e prese nce of this material ithelium may be spa rse or co nsp icuo us. Not
is not aresu lt oftrue reciprocal indu ct ion phe- everyone agrees about the des irab ility of dis-
nomena. tingu ishing betwee n the simple and WH O
Rega rding group 1.1.3 in the W HO etas- types of odo ntogen ic fib roma. Handlers and
sificatio n' c-which apart from the odo nto - associates? c hallenge d the existence of the
gen ic fib roma also includes t he odon togen ic simple and WH O types of COF and , based
myxo ma {OM } or myxofibro ma and the be- on a literature review , maintained th at sepa-
nign cemen tob lastoma (BC), also ca lled ce- ration of odontogenic f ib romas into these
mentob lastoma and t rue cementoma-the two variants is inconsistent amo ng re-
present aut hors do not see any evidence fo r searchers. The autho rs cons idered the two
th e presence of odo ntogenic ec to mes - typ es as op pos ite ends of th e same t umor
enc hyme in the two latte r ent ities. In fact , spect rum .
COFs, OMs, and BCs belong to a group of It sho uld be men tioned that neith er the
lesions cha racterized by mesenchymal tis- first! nort heseco ndveditionot the WHO clas-
sue with or witho ut odontogenic epit helium. sificat ion use th e terms simp le type COF or
In 1980,Gardner" made an attempt to clar- WHO type COF; both te rms were proposed
ify the criteria by wh ich a lesion should be di- by Gardne r" and have been widely accept-
ag nosed as COF. The autho r distinguished ed. Doyle et al' 0 suggeste d the term complex
between t hree ce ntral lesions: ( 1) hype rplas- odontogenic fibroma as an alternative to the
ti c d enta l fo llicle , (2) sim ple COF, and (3) WH O type . Gard ner,11 in his recent review of
WHO type COF. The first is a well-circum- c urrent kno wledge concern ing t he CO F,
scribed mass of fibrous t issue that occ urs agreed that Doyle et at's alternat ive d esign a-
around t he crown of an unerupted tooth and tion is p robablya mo resu itab le te rm and also
has a radiologic appea ranc e similar to th at ad ds the te rm fibroblastic odontoge nic fi-
of a smal l d entigerous (fo llicular) cyst. This bro ma. Th e 1992 WH O c lassificatio n only
lesion shou ld no t be cons ide red a COF. recognizes and illustrates the WHO ty pe as
The second is a tu mo r co mposed of f i- a COF. The type resembling t he dental fo lli-
brous co nnective tissue contain ing scatte red cle (simple typ e) is included under the sub-
rests of odonto ge nic ep ithelium. Its histolog- head ing 1.1.3.2-myxoma (od ontog enic
ic ap pearance is therefore quite similar to that myxoma, myxofib roma)-i n th e 199 2 pub li-
of a dental follicle, from wh ich it is presum- cation .
ab ly derived. Th e lesion is relatively ace llular, Th e rarity of the lesion in questio n became
the fibers are often de licate, and there is a appa rent w hen, in 1994, a study of the rad i-
co nsiderable amo unt of gro und substance ologic feat ures of the COF,12 including a re-
yielding a f ibromyxoid quality. This simple view of articles p ublished in t he Eng lish lan-
type may exhibit small islands and co rds of guage literat ure, disclosed a total of only 51
odontogen ic epithelium, butthey are seld om cases . The authors, however, did not distin-
numerous. guish betwee n simp le and WH O type cases.
In contrast , the W HO type COF is a fi- Due to insufficient docume ntation in single
broblastic lesion wh ich is interwoven with case reports and reports of smaller series of
less cellular areas in w hich nume rous small COFs in the literat ure, it is not poss ible to re-
blood vessels are p resent. This ty pe shows trieve reliable d ata on cases of the simpl e

180
Epidemiological data

typ e. The present authors have been able to


trace and verify 15 cases of WHO type COF
from a literat ure survey.1 0,13-20

2. Clinical and radiologic profi le

The tumor is silent when small, and a pain-


less swe lling may anno unce its p resence . A
few patients may exper ience slight sensit ivi-
ty. The growth is slow but progressive, fre-
quently resulting in co rtical expansion. Mo-
bility of t he teeth has bee n ob served in a
Fig 19-1 A large COFthat has developed around
number of cases.
an embedded mandibular third molar. Note the
The radiographic features of t he COF are
multiloculation.
not diagnostic. It is seen as a uniloc ular ra-
diolucent area wit h we ll-defined borde rs in
approximately half of cases, some of wh ich
may show a sc lerot ic bord er. Th e larg er le-
sions show sca lloping of the margins or mul-
tiloculatio n (Fig 19-1). In a few cases t he oc-
currence of calcified material may lead to a
mixed radiolucentjradiopaque appea rance .
Like many centrally located benign lesions of
t he jaw s, the COF may disp lace teeth and
cause root resorption of adjace nt teeth. Le-
sions may be assoc iated wit h the crown of
an unerupted mo lar, premo lar, or inc isor (Fig
19-2).
Fig 19-2 A COF in a young patient occurring
around an unerupted mandibular first molar. The
differential diagnosis between a COF and a
dentigerous cyst cannot be made from this radi-
ograph.
3. Epidem iological data

3.1 Prevalence, inc id enc e , and


relative frequency spec ified Ame rica n popu lation {20,000 cas-
es).22 Such a range merely mirrors the lac k
No data are available co nce rning prevalence of a un iform def inition and the w idesp read
or incid ence. A numbe r of autho rs have in- co nf usion co nc erning t he od ontog en ic f i-
dicated relat ive frequency; over the years, a b roma. Regezi et al23 did not f ind a single ex-
wide range has been seen, from 0.7% in a am ple of t his t umor in a review of 706 odon -
Chi nese populatlon' " to 22. 8% in an un- togenic tumors. However, they reported tw o

18 1
19: Odontogenic Fibroma

No . 01 cases

s

, , LIJ
LIJ M~
3 3 n:::15
3

o I I IJ 1 IJ 1 I) IJ I I) I II IJ 1 U
"v-"... ........ 'I'" ,......,, ",

' v- '" 'v- <10 - 39 40 -49 50-59 60- 69 Fig 19-3 Distribution of 15
Age in decad es cases of WHO type COFs by
age and gender.

cases of odontogenic myxoma wit h ~3 + col


lagen," w hich may be compatib le w ith the
simple type COF. ,,
,,
: 2

3.2 Age n '" 15

Age at th e time of diagnosis rang ed from 11


to 66 years (Fig 19-3). The mean age w as 10 3
39.8 years.

3.3 Gender
Fig 19-4 Topographic distribution within thejaws
of 15 cases of WHO type COFs.
Ge nd er d istrib ution showe d th at t he
mate-temala ratio for COF is 1:2.8 (see Fig
19-3 ).

3.4 Location

The sites of COF occurrence w ithin the jaws 4. Pathogenesis


is shown in Fig 19-4 . There w ere consider
ably more ca ses located in the mandible th an
in the maxill a. giving a maxilla.mandible ratio Some authors be lieve the COF to be deri ved
of 1:6.5. Of t he mandibular lesio ns. most in- fro m the ectomesenchymal t issue of the pe
vo lved the molar and premola r ar ea s rioo ontat ligament. dental papilla, or dental
(76.9%); of the maxillary lesions, o nly th e an- follicle. It is the epithe lial component of the
terior reg ion was affected . WHO type of COF and the fact that this to

' 82
Pathology

mar does not occ ur in an extragnath ic loca eith er a desmop lastic or an odontogen ic fi
tion that p rovide the stro ngest argument for b roma. or as state d by the latter authors,
this t umor being of odonto ge nic origin . 1 "every jaw fibroma is odontogenic if it do es
Gardner! ' stated that it is possible that t he not clearly demonstrate the features (stated
WHO type COF arises from the periodontal ab ove) of a desmop lastic fibroma."
ligament, wh ile the simp le typ e is derived
from t he dental follicle, thus accountin g for
their dissimilar mic roscopic ap pearances .
Th e crite ria for d esignat ing a c entr al fi
broma as odontogen ic are still far f rom be 5. Patholog y
ing defined. It may be difficu lt, if not im pos
sible,to decide whether a cent ral fib roma has
arisen from the mesen chym e of t he jaws 5.1 M acroscopy
rather than from the odontogenic apparatus.
The presenc e of od ontog enic epithelium em The op eration spe cimen has been de scribed
bedd ed in t he tumort issue may be sufficient , as having a gray to brown ish co lor. Cutting
because these stru ctu res are rarely found in through t he tissue mass, the patho logist may
nonod ontogenic jaw lesions. How ever , notice calcified material.
some autho rs (WH O,6 Garoner'') claim that
the abse nce of odo ntog enic epith elial rem
nants do es not preclude a central fibrom a 5.2 Microscopy
from being odontogen ic. Thus, t he histoar
5.2.1 Histo logic definitions
chitecture of a partic ular cen tral f ib roma
does not p rove that the lesion is nonodonto Th e 1992 WHO classiflcation'' defines a COF
genic unless t he fo llowin g c haracteristics are as "a fibrob lastic neop lasm containing vary
found : bun dles of abunda nt colla gen fibers ing am ounts of appa rently inactive odonto
separated by sp ind le-shaped fibroblasts with genic epithelium." According to t he WHO
elong ated or ovo id nuclel'" combined with panel t his definit ion covers various typ es of
areas of de licate co llagen fibers aggregat ing lesions. "One resemb les a th ickened d ental
rntotccatturtnke oonores." and the abse nce follicle both in location and in structure; tis
of odontogenic epithe lial remn ants of ca lc i sue of th is type is referred to later unde r t he
fied mate rial. If th is morph ologic pattern heading 'Myxoma.' Another and less com
occu rs in a central fib roma that has shown mo n lesion is com posed of a more cellularfi
locally aggressive behavior, there is a con brous tissue, contain ing islands and strands
siderab le chance th at the lesion is a non of odontogen ic epithelium. This second typ e
od onto gen ic de s mop last ic fibrom a. It is, may con tain varying amo unts of hard t issue
however, possible that a ce nt ral desmo plas resemb ling dysp lastic cementum or bon e."
tic fibroma may infiltrate or expand into an The first typ e described in t he WHO clas
unerupted tooth and in so do ing be intimately sification corresponds to the simple odonto
assoc iated with its crown . Th is situ at ion genic fibroma. Th e simple typ e is the most
should not be co nside red evid ence of odo n co llagenou s variant on the histologic spec
togen ic origin but must be regard ed as co t rum of myxoma, myxofib roma, and odo nto
incid ental. genic fibroma. As po inted out by Gardner, 11
The p resent autho rs agree wit h th e idea it is important to emphas ize that the clinical
put forward by Gardner" and su pported by behav ior of th e my xoma and the simp le
Siootweg and Muller24 that a jaw fibroma is odontog enic f ib roma are different. The sirn

183
19: Odontogenic Fibroma

Fig 19-5 Simple type COF exhibiting thick colla


gen bundles with scattered. inactive-looking
odontogenic epithelial remnants
(hematoxylin-eosin [H&E], x80).
to: - ~ " "~& ~ {-il';;
..,p. ":;:,W ' -, ' ' S>"~ 1 "', 'i'.~ '
,--;. c-, ~'~~: l W,':
~"" ; :" { ';....'; ~~ _ _' r.! ~ ~,~;.,...f!~;
: :: .- ~,~. .~ ! : ::J~<J.!~',\ ' ~ '. /l!::"J,~.
-: ~;~.;.l''' '#r !r """,.';~
~ .~ .

'~' ;:5 ~~';::~:',:? :"l~- ,,;~ . ,y,.\{;f',


:~.~,

~ ,'. " ', ,'.:,;"!ii" ~,."f, , ~ 1 '. '


",.' ~ '.,.'- . .- '.'..
,' , " '-, ~ .' , '
~ "''' ~'
, ,: ' ~ "
.'~
.""~_v;;j: ',;;'
.,
"i>'"$' ,,,~
.. , - " > ~:'~ ' . 'iliI< '" ~,

'<?;': ~ ,<~;:':~ .~ :\~'~ ~2; ' '" ,.~.)'~.,;\

Fig 19-6 Fibroblastic COF(WHOtype). The odon Fig 19-7 A COF (WHO type) showing a focus of
togenic epithelium is conspicuous. In less cellu calcified collagenous and cell-rich matrix with em
lar areas there are numerous small blood vessels bedded inactive-looking odontogenic epithelial
(H&E, x50). islands (H&E, x50).

pie odo ntogen ic f ibrom a is an expansile le qu ality (Fig 19-5). It may exhibit inactive-look
sion t hat does not infiltrate t he surro und ing ing rests of od ontogenic ep it helium but they
bone , whereas th e myxoma does . Conse are seldom num ero us. Occas iona lly, nonde
quently, from a cl inical point of view, they sc ript calcifications are found.
shou ld be cons idered separate entities, al The p resent aut ho rs' de finit ion for t he
thoug h they are related histo ge netica lly. The WHO type COF is as follow s:
second type of COFthat is discussed by th e A ben ign neoplasm co mposed of cellula r
WHO panel is identica l to th e odonto ge nic f i conn ective tissue. It often occ urs in fibrob
brom a, WHO type,the term mo st workers ap last ic strands that are interwoven with less
pear to have accepted . ce llular areas in wh ich num erous small blood
Thedefinit ion used by th e p resent authors vessels are present (Fig 19-6). Foci of calci
for the simp le typ e COF is as fo llows: f ied co llag enous matrix, resem bling dys
An expans ile, noninfiltrating connective tis p lasti c cement um, osteo id (or bon e). or
sue lesion resem bling a d ental follicle. It is atubular dysp lastic d entin often occ ur (Fig
relat ively acellular, t he fib ers be ing quite del 19-7). Islands or strands of inact ive-looking
icate, and there is a co nside rab le amount of od ontoge nic epithe lium are an inte gral com
grou nd s ubstance yieldin g a f ibromyxo id po nent of th is type of COF; they are usually

18 4
Pathology

conspcuous. A Clearly defined capsule is not


encountered.

5.2.2 Histopa thologic findings


Wesley et al26 and later Watt-Smith et al27
used electron microscopy to examine a case
of WHO type COF. Watt-Smith and cowork
ers found that the fibroblastic cells exhibite d
features characteristic of both smooth mus
cle cells and fibroblasts. Myofibroblasts have
been detected in a variety of odonto genic le Fig 19-8 Area from a COF (WHO type) exhibit
sions. ing a few inactive-looking epithelial islands and
scattered pleomorphic (giant cell) fibroblasts
5.2.2.1 The COF versus the amefoblastic (H&E, x 100 ).
fibroma
It is important to stress the histoarchlteetural
differences between the ametoblasttc fibro
ma (see chapter 12) and the COF alluded to and also in a numbe r of cuta neous lesions.30
earlier. The AF is classified (by the WHO etas There is no reason to suspect that the bio
sification 6) as a neoplasm composed of pro logi c behavior of this rare histologic variant
liferating odontogenic epithelium em bed diff ers from that of other simple COFs.
ded in a cellular ect omesenchymal tissue
that resembles the de ntal papilla. The ep 5.2.2.3 COFs (WHO type) associated with
ithelial component is usually in the form of giant cell react ion
strands and islands, often cons isting of a pe In 1992, Allen et al20 reported three cases of
ripheral layer of cuboidal or co lumnar cells WHO type COFs that were associated with a
which may enclose a sma ll number of cells giant cell react ion similar to t hat seen in the
resem bling stell ate reticu lum . This di ffers central giant cell lesion (CGCL) of the jaw
considerably from th e inact ive-looking cell (see Chapter 33 ). A year later, Fowler et al31
rests found in the COF. The AFs connective published a report in which 3 of 24 cases of
tissue component is embryonic looking and COFs, exhibited an associated giant cell re
considerably more cellular than that seen in action. In one of Alien et at's cases, recur
the COF, and there is little co llagen in t he rence 14 months late r displayed both the
form of delicate fibers. COF and th e giant cell co mponents. The na
ture of these unusual lesions wa rrants further
5.2.2.2 HistOlog ic subvariant of the simple study to clarify whether they are truly COFs
COF that exhibit a giant cell reaction or whether
Gunhan et al28 reported an unusual example the od ontogenic ep ithelium and fibrous con
of a simple COF t hat exhibited numerous nect ive tissue are simply incidental findings
pleomorphic fibroblasts and an unusua lly associated with CGCLs.
large number of small calci fications. The More recently, Odell et al32 reported on 10
pleomorphic fibro blasts (Fig 19-8) were sim lesions from 8 patients with a rare and histo
ilar to those that occu r in the "qtant cell f... log ically distinctive lesion com posed of giant
broma," a soft tissue gro wth of the oral cavi celt granuloma and fibrous tissue containing
tyfirst described by Weat hers and Caltihan,29 dispersed epithe lial islands. It was not pas

185
19 : Odonto gen ic Fibroma

sible to asce rtain wh ether t his lesion was a granular ce/l odo ntogenic tumor (GCOT) is
variant of CGCl or of COF, altho ugh some sometimes app lied to lesions of th is type.
of the clinical, radiologic, and histologic fea Gardner" is of the opin ion t hat t he GCOT is
tures were more in keeping w ith CGCL. The a sep arate entity, alt ho ugh some simple
possibility that th is lesion, nam ed "hyb rid COFs (but ap parent ly not the WHO typ e) ex
CGCland COF-like lesion of the jaws" by th e hibit scatte red granular cells.
autho rs, is a new entity cannot be ruled out.

5.2.2.4 COFs (WHO type) con taining


eosinophilic droplets
Two cases of WHO typ e COFs reported by 6. Notes on treatment and
Dunlap 1 exhib ited another pec uliar histolog
ic feature. Both cases contained solita ry or recurrence rate
clustered eosinophilic hyaline droplets. The
droplets were weakly pos it ive for amy loid. A Treatment for COFs, irrespect ive of type, is
histo logically ide nti caltumorwas reported as enu c leat ion by vig orou s curett ag e. l ong
an examp le of atyp ica l calcifying ep ithelial te rm follow-up of a large series is not avail
o dontoge nic tu rnor.P'' Ho weve r, Du nlap ab le, but th e rec urrence rate is cons idered
do ubte d the latt er diagnos is for his two cas low .
es. The origin and ident ity of t he droplets was
uncertain, but similar material has been ob
served in other odon to genic tu mors and may
References
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5.2.2.5 Multiple calcifying hyperplastic
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od ontog enic fibr oma. Oral Su rg Ora l Med Oral
13. Janssen J H, Blijdo rp PA. C entral odontogen ic fi- PathoI 19 75 ;40 :235-245.
broma. A case rep ort. J Maxillofa c Surg 1985 ;' 3 :
27. w an-Smnn SR, EILabban NG, Tinkler SM. Ce rl-
236-238.
t ral od o ntog enic fibro ma. In! J O ral Maxillol ac
14. Dunlap CL, Bar ker SF, Ce ntral odontogenic fi- Surg 198 8; 17;8 7-9 1.
broma of th e WH O type . Oral Surg Oral Meet Oral
28. Gu nhan O. Gubu zer 8 , Ga rd ner OG, Dem iriz M.
Patho I1 984 ;57 :39 Q.-394.
Finci R. A ce ntral odontogen ic fibroma exhibiting
15. SChofield IDF. Central odontog enic fibroma: Re- pl eom orp hic fibrob lasts and num ero us calcifica-
port of a case, J O ral Surg 19 81 ;39:218-220. tions . Br J Oral Macnotac Surg 199 1;29:42-43.
16. Dahl EG. wonsoo SH. Haug en JG. central odon- 29. W eathers DR, Gallihan MD. Giant--cell fi broma.
togenic fibroma: Review of the Irterature and re- Qra lSu rg O ral MedOra! Pathoi 1974;37:374-384.
port of cases. J Oral Surg 198 1;39 :120- 124 .
30. Houston GD. The giant cell fibroma. A review of
17. Mallow RD.SpatZSS, Zubrow HJ . K1ineSN. Odon- 4 64 cases, Oral Surg Or al Med Oral Pat ho i
togenic hbroma with calcification. Oral Surg Ora l 1982 ;53 :58 2-58 7.
Med Oral PathOl l966;2 2:564--568.
31. Fowl er C, Tomich C. Brannon R. Houston G. cen-
18. DIl(Ql1 WA, Ziskind J. Odontoqeruc fIbroma . Oral tral odontogenic nbrorna: Clinicopathologic fea-
Surg Oral Mad Oral Pathol1956;9:813-816. tures of 24 cases and review of th e literature. Oral
Surg O ral Med Oral PathoI1993;76 :587.AbstraCl.
19. PlOcock LD , Bruce 'rW/. OdontogeOlc norco-e.
Oral Surg Oral Mad Oral Patho I1 954 ;7:30 7.J 11. 32 . Od ell EW, Lombardi T. Barren AW. Morgan PRo
Spe ig ht PM . Hybrid central giant cell granuloma
20 . Allen CM, Hammond HL, Stimson PG, Central
and central odontogenic fib rom a--like lesions of
odontogenic fibroma. WH O type. A report of three
th e jaws. Histopathology 199 7;30:165-1 7 t .
cases with an unusual assoc iated gi ant cell reac-
tion. Oral Surg O ral Med Oral Path oI1 99 2;73 :6 2- 33 . Smit h RA, Ha nsen LS , OeDecker D. Aty pical cal-
66 cifying epithelial odontogen ic tumor, J Am Dent
Assoc 198 0 ;100 :70 6-709.
2 1. Lu Y, Xuan M , Takata T. et al. Odontogenic tu-
m ors, A dem og raphic study 01759 cas es in a Chi- 34 , Gard ner DG, Radden S, Multip le calcifying hy-
nese population. Oral Su rg O ral Med Oral Pathol pe rplastic oeotartomcies Oral Surg O ral Med O ral
Oral Radiol Endod 199 8 ;86 :70 7-7 14. Patho t O ral Badict eooco 1995:7 9 :603--606.

187
Chapter 20

Odontogenic Myxoma or Myxofibroma

1. Terminology 2. Clinical and rad iologic profile


The German patholog ist Rudo lph Virc how Most OMs are first noticed as a result of a
was probably t he first to describe the histo- slowly inc reasing sw elling or asymmetry of
log ic featu res of myxo fibroma (1863 ), a l- the affected jaw. Lesions are generally pain-
thoug h lesions of t he jaws were not pa rticu- less and ulce ration of t he overlying oral mu-
larly ment ioned . In 1947 , Thoma and cosa on ly occurs w hen the tu mor interferes
Goldm an 1 first desc ribed myxomas of th e w ith th e de ntal occ lusion. Growt h may be
jaws. Since t hen t he odontog enic myxoma rapid and infiltration of neighboring soft tis-
(OM) has been a subject of cont inuous sc i- sue structures may occur. Most od ontoge nic
entific debate. Histog enesis, pathog enesis, myxomas are located intraosseou sly, but p e-
and particularly therapyof this ben ign nonen- ripheral variants have bee n d esc ribe d.v! ''
caps ulated odonto genic neoplasm have Bot h the buccal and lingual co rtical plates of
been discussed avidly. In t he 1992 Wo rld the mand ib le may oc casionally expand .
Healt h Organizat ion (WHO) crassmcattcn." Kaffe et ar' found expansion of t he jaws in
the term myxoma is used along with odon- 74% of patients. When the max illary sinus is
togenic myxoma and myxofibroma as alter- involved, the OM ofte n f ills th e ent ire ant rum.
native terms. In severe cases, nasal obstruction or exop h-
The odo ntogen ic myxom a was reviewed thalmus may be t he leadin g symp tom s, Dis-
extensively by Farman et at in 1977,3 who placemen t of tooth roots has been registered
evaluated 21 3 cases of OMs pub lished in t he in 74% of patients and roo t resorpt ion in
international literat ure. Kaffe et ar' pub lished 9.5%.4Assoc iation wit h unerup ted teet h was
an analysis of the Eng lish langu age literatu re on ly seen in 5% of OM cases reviewed.Th ere
betwe en 1965 and 1995 that included 164 appea rs to be no spec ific pred ilection of OM
cases of OMs. Smaller series of OMs- ali in- fo r any ethn ic qroup."
clud ed in the latter survey- were pub lished The radio log ic ap pe aranc e of odo nto -
by Hard er," Schm idseder et al,6 Siootweg g en ic myxomas is variab le, althoug h t he
and wnncarnor." and Peltola et al.8 In 1996, majority are cha racterized by a multiloc ular
Lo Muzio et al9 reporte d on clinical, radio- radiolucency w ith a "soap bubb le" or hon-
logic, immunoh istochem ical, and ultrastruc- eycomb ap pearance (Figs 20-1 to 20 -3).
tural feat ures of 10 cases of OMs. Kaffe et at" extensively reviewed th e radio-
logic feat ures of OM, finding a mult ilocu lar
appea rance in 53 cases (55%) and a un iloc-
ular appearance in 34 cases (36% ). Nine cas-

189
20: Odontogenic Myxoma or Myxofibroma

Fig 20-1 Panoramic radiographshowing a multilocular lesion in Fig 20-2 Soft tissue mass over-
the anterior mandible. Several of the anterior teeth are severely lying the posterior right mandi-
displaced. bular alveolar process (see Fig
2Q.3 ).

es (9%) were considered nonloculated. Cor- n - and T2-weighted images. The aut hors
relation between size and tocula rity revealed compared these find ings with those for soft
that most of the unilocula r lesions (85%)were tissue myxomas and found discrepancies
smaller than 4 em, with a mean size of 2.8 for T1- and T2-weighted signal s. A similar
em. In contrast, 74% of the multilocular le- study,12 however, found cor respondence be-
sions were larger than 4 em, with a mean size tween the MRI findings for bot h OMs and soft
of 5.7 em. These aut hors also gave a detailed t issue myxomas . Sinc e OMs may present
accou nt of the characterist ics of th e rad io- w ith a variety of radiologic features, includ-
log ic borders of OMs. In 77 cases (80% ), ing poor definit ion on plain radiographs, im-
OMs were characterized as radio lucent le- aging techniques such as CT and MAl have
sions. Twe lve lesions (12.5%) we re mixed become indispensible for reliable diagnoses.
and seven revealed radiopacities (7.5%). Ra-
dio paque lesions occurred in the maxilla with
the tumors extending into the maxillary si-
nuses. 3. Epidemiological data
The significance of co mputed tomogra-
phy (GT) and magnetic resonance imag ing
(MAl) for t he diag nosis of OMs was d is- 3.1 Prevalen ce, incidence, an d
cussed by Kawai etal. " Magn etic resonance relative frequency
imaging revealed a well-defined, w ell-en-
hanced lesion with hom ogen eous signal in- The odo ntogenic myxoma is a rare neoplasm
tensity on every pulse sequence. The lesion and rates for prevalence and incidence are
showed intermed iate signal intensity on the not available. Aegezi et al 13 found 3.1% of

190
Epidemiological data

Fig 20.3 Panoramic radi-


ograph of the lesion shown
in Fig 20-2. A munnocutar ra-
diolucency is seen invoM ng
the right angle of the mandi-
ble and part of the mandibu-
lar ramus.

641 cases of odo ntogen ic t umors were OMs. 3.3 Gender


In a recent study of 759 odontogen ic tum ors
in a Chinese po pulation, Lu etat" foun d OMs In the analysis of Kaffe et al." the male:female
represented 8.4%. The relative freq uency for ratio was 1 :1.6. Farman et al3 different iated
various geographic regions varied from 1.3% the ir material fu rther into maxill ary and man-
to 13.8%. Ade keye et al 15 stated that the ab- dibular OMs by gender: 42 .6% of maxillary
solute incid ence of OMs in t heir geograph ic OMs occu rred in me n (mandibular OMs,
region (Nigeria) could not be assessed ; how- 44 .4%) and 57.4% oc c u rred in women
ever, they estimated the OM freq uency to be (mandi bular OMs. 55.6%).
between 1% and 3% among fibroosseous
lesions.
3.4 Location

3.2 Age To pographic di stribution of o d onto g en ic


myxomas (n == 125) is shown in Fig 20-5.4
Age and gender distribution of 164 cases of Mandibu lar OMs accounted for 66.4 %, with
od on tog en ic myxomas are shown in Fig 33 .6% in t he max illa. Whereas 65. 1% of
20-4.4 Age at the time of diagnosis ranged mand ibular cases were located in the molar
from 1 to 73 years, wit h a mean of 30 yea rs; and p remolar areas, 73.8% were seen in the
75% of cases we re d etected betw een the same areas of the maxilla.
2nd and 4th d ecades.These figures are com-
parable to those of Farman et al,3 who dif-
feren t iate d between maxillary and mandi-
bular OMs as to gender and age . The mean
age at the time of diagnosis of maxill ary OMs
in men was 29.2 years (mandibular OMs,
25 .8 yea rs) and in wo men 3 5.3 years
(mandi bular OMs, 29.3 years). Harders held
the view that the OM on ly rarely oc cu rs be--
fore the age of 10.

19 1
20: Odontogenic Myxoma or Myxofibroma

No. of cases

35

so
30 []J Women
[]J Men
25 22 n = 164
22 2 1
an ta
te
15
to
10
5

0- 10 11-20 2 1- 30 3 1- 40 41- 50 51- 60 61 + Fig 2Q-4 Distribution of OM


Age in decades cases according to age and
qerxter."

4. Pathogenesis wh ich recur mo re often and may transform


into matiqnancie s."
The pathog enesis of odontogenic myxomas A comparatively w ide spect rum of cells of
has been discussed extensively du ring the origin has been pro posed for the OM since
last two decad es, and it has been argued that it was first de scr ibed . Adekeye et at" re-
the designation of the OM as an odontogenic viewed th e diffe rent argume nts fo r individual
tu mo r is uncertain. According to Lucas." t he tissues that have been cons idered as poss i-
classification of t he OM as an odontog enic b le sou rces of OMs. The dental pap illa, de n-
tumor has been justified by its frequ ent oc- tal fo llicle, and periodontal tissues have been
cu rrence in ado lescence; its association wit h im plicated as possib le "ge rm ce nte rs" of
missing or unerupted teeth; and the spo radic OMs. However, there are a numb er of argu-
p resence of odon togenic ep ithe lium with in ments against these possiblities. Ade keye et
the neoplastic, myxomatou s tissue. Ade keye at." p roposed that no st rong evidence for an
et ai,15 however, express ed the view that the odonto ge nic origin co uld be fo und exce pt
frequ ency and significance of these features that the OM may rep resent a degen erat ive
may have been overstated. The autho rs sup- form of odontogenic fib roma. These authors
posed t hat the rarity of OMs in any extrag- postu late d t hat the int raosseous ne uro-
nathi c bone cou ld be the on ly firm reason for fib ro ma, sh ow ing exten s ive my xomat ous
sug gesting an od ontogenic or igin. changes, wo uld have a numbe r of feat ures
Wh ile som e analog y betwee n th e appear- in common w ith the so-called OM.
ance of th e ep ithe lial and/o r ecto meeen- Only in recent years have ultrastruct ural
c hymalj mese nc hymal co mpo nents and a and, in parti cul ar, imm unoh istoch em ical
phase of norm al odonto genesis is apparent stud ies shed more light on t he possib le ori-
in most odon togen ic tumors, suc h an analo- gin of OMs. In an attempt to c haracterize th e
gy seems op en to several interpretation s in extracellular matrix of OMs , Sc hmidt-West-
OMS. 15 The OM seems to behave differently hausen et al!" foun d no resem blance be-
from myxomatous tumors of the long bones, tw een th e matrix in OMs and that found in

192
Pathology

normal tooth develop ment. Lombardi et at"


also did not find similar staining patt erns fo r
viment in and 8 -100 prote in in OMs com- 3
pared to de ntal follicle, dental pa pilla, and pe-
21
riodon tal ligament cells, sug gesting a non-
odontog eni c or ig in for t he t umor. Other n = 125
studies suggested that ce lls in OMs are of 3
myofibroblastic oriqint ? or that OMs are of ,,,
dual fibroblast ic-histiocytic origin.2o 29 25 ,:23

5. Patholog y Fig 20-5 Topographic distribution of location of


125 cases of OMS.4

5.1 Macroscopy
. ,
The cut sections of OM specimens ch arac-
teristically reveal a white-g ray color in t he mu-
.
( .....
,,
coid sub stanc e, wh ich will st ic k to an instru-
ment w hen to uched.
,

5. 2 M icro scopy ".,"


r. .
. . ii"
..-~ .'
.~ "

5.2. 1 Histologic definition ( , I

Both t he 1992 WH0 2 an d t he present au- '" '/ ' ;" ,.


thors use the fo llow ing def init ion for an odon - Fig 20-6 Odontogenic myxoma characterized by
togenic myxoma: abundant mucoid stroma that contains spindle-
A locally invas ive neoplasm co nsisti ng of shaped or angular cells. The amount of collagen
rounded and angular cells lying in an abun - is moderate (hematoxylin-eosin [H&E], x8D).
dant mucoid strom a.

5.2.2 Histopathologic findings


c ap illaries. In cases of myxof ib rom a, th e
Odon toge nic myxomas are locally agg res- amou nt of collagen in t he mucoid stro ma is
sive, ncn en capsufated, nonmetastas izing mo re prominent. The tlbrllshavebeen shown
neoplasms th at infiltrat e bon e marrow by silver imp regnati on to be retlc uftn." In-
spaces. Histop atho logically, t he OM is c har- f lamm ato ry infilt ratio n is rarely seen (Fig 20-
acterized by loose, abun dan t mucoid stro ma 6 ). Remnants of odontog en ic ep ithe liu m
that contains round ed, sp indle-shape d, or have oc casion ally been noted ; som etim es
angular cells. Cellular and nucle ar polymor- t hey are su rrounde d by a narrow zone of
phism is rare, as is mitotic act ivity. Usually tu- hyalinization. Th e myxom atou s component
mor ce lls are evenly spaced with in a fine fib- of OMs (Fig 20-7) has been co mpared to
rillar mu cin ous matr ix. The stroma may be p rim itiv e mesenchyme wh ich is fo und
relatively avascula r or may exhi bit de licate throughout the bod y. It has also been co m-

193
20: Odontogenic Myxoma or Myxofibroma

trix stains positively with Alcian blue, but pe-


riod ic eoo-scmrt staining may be negative.
Takahashi et al20 studied OMs immune-
histochem ically using a nu mber of anti-
. bodi es (&-100 protein. vimentm. transferrin,
ferritin , alpha-t -antichymotrypsin , alpha-1-
antitrypsin neuron-specific enolase, CK 1,
I
and ot hers).Staining patterns of spindle,stel-
,


--
.. I

.

late, and hyaline ccns suggested a dual fi-
bro blastic-hist iocytic origin .
In 1992, Lom bard i et al 18 pub lished a
Fig 20-7 Higher magnification of the tumor study in which they co mpared the staining
shown in Fig 2()-6 showing the mucoid ground patterns of OMs and human tooth germs us-
substance with little collagen in the form of deli- ing antibodi es against &-100 protein and vi-
cate fibrils. The cellsarerounded, spindleshaped, menti n. Whe reas od ontog enic myxomas
or angular (H&E,x120). were positive for &-100 protein and vimentin,
nor mal developmenta l odonto genic struc-
tu res we re positive for only &-100 protein .
Given their find ings tog ether with biochemi-
pared to th e dental papilla and the dental fol- c al results from previous studies on g ly-
licle. co saminoglycans, t he authors suggested
From the diffe rential diagnostic point of that t hese dat a contrad ict an odontogenic
view, the histopat holog ic appe arance of the origin for OMs. Moshiri et at 19 who did a sim-
OM should not be co nfused wit h that of the ilar study using S-100 protein , vimentin , and
thickened follicle of a toot h wi th del ayed actin, coul d not find a positive staining reac-
eruption. Histopathologically,thickened fol li- tion for S-100 in OMs. They suggested that
cles are characte rized by a non-neoplastic, the OM tumor cells might be myofibroblas-
myxoid, basophilic ground substance and tic. Lom bardi et al21 published a 1995 study
c om monly by islands of odontogenic ep- on immunohistochemical findings (&-100 . al-
ithelium.Odontogenic myxomas may also be pha-smooth mus cle actin , and cvtokeratin
co nfused with myxomatous degen erat ion as 19) com paring OMs and soft tissue myxo-
obse rved in fast-growing neop lasms, partic- mas. A minority of OMs (3 in 7) were posit ive
ularly fibrosarcoma s. c hondrosarc om as, for S-100 : soft tissue myxomas, norma l and
and liposarcomas. enlarged dental follicles, and int ramuscu lar
myxomas were S-100 negative. Due to the
staining patterns, t he authors had some dif-
5.2.3 HistochemicaVimmunohistochemi-
ficulty in distingu ishing between OMs and
cal find ings
myxo id nerve sheath tumors. In anoth er
Farman et al3 reviewed histochemical find- study,22 however, the auth ors were able to
ings in OMs. The ground substance of OMs distingu ish nerve sheath myxomas from oth-
has been show n to con sist of about 80% er oral myxomas using neural antigen s as im-
hyaluronic acid and 20% cho ndroitin sul- muno histoche mical markers.
phate. Tu mor cells appear to be relatively in- Rece ntly, Jaeger et al23 studied a novel
active wit h low levels of oxidative enzymes. cell line (Mix 1) of OM that retained t he mor-
Tumor cells also show slig ht alkalin e phos- phol ogic characteristics of the OM cells and
phatase activity. The myxoid intercellular rna- matrix. The cell line was charact erized as a

19 4
Noteson treatment and recurrence rate

well-differentiated fibroblast able to synthe- . . . .' .'


size different proteins (type I collagen, fi- ,.I' '. ' 0.
. ! :'" -: ".
bronectin, tenascm) of the tumor matrix. My-
ofibroblastic differentiat ion was not found in : ':,
.#0 '..
\ :. -
. '
'. ' .
,
." .
.
. . ..
' . '

this study. , . "

In summary, OM tumor cells are mes- ,: ' f~':'\..' ,


"- >
. -"
enchymal and express vimentin; occasiona l ' . ' .
positivity to 5-100 prote in and muscle- .> " : . "
.,
specific actin is found . The matrix exhibits
different proteins, mostly type I and type VI .,' ,.. ..J;~ " . . -
collagen, tenascin, fibronectin , and proteo- . .
glycans; OM tu mor cells have been charac- Fig 2D-8 Odontogenic myxoma with an area of
terized as secretory." prominent collagen component (myxofibroma).
Note the delicate blood vessels in the stroma
(H&E. x60 ).
5.2.4 Ultrastruc tural findings
An extensive st udy on the ultrastructure of
OMs was published by Gold blatt in 1976.24 mor ce lls we re spi ndle shaped with ce ll
Two basic ty pes of t um or ce lls were de- processes. Nuclei were indented with mod-
scribed: secreto ry and nonsecretory. The se- erate margination of con densed heterochro-
cretory cell type was considered the princi- matin. The cytoplas m was rich in intermedi-
pal tumor cell and resem bled fibroblasts. ate fil ame nts and variab le amou nts of
However, ultrastructural findings indicated organelles. Cells presented a prominent Gel-
an abortive collagen fibrillogenesis. In addi- gi apparatus, dilated endoplasmic reticulum ,
tion, prom inent secretory activity resulting in and free ribosomes. Banded coll agen fibrils
an excessive production of acid-mu- in the stroma were found in close contact
copo lysaccha ride matrix was noted . Gold- with t he cells.
blatt suggested the term myxob/ast tor the tu-
mor cells in the OM. The OM tumor cells
showed ma ny co mmon alit ies with fibrob-
lasts of t he dental papilla, dental pulp, and 6. Notes o n treatment and
odontogen ic fib roma, a finding wh ich wo uld
be compatible with an odontogenic origin. rec urrence rate
However, ultrastructural features we re also
similar to cells of th e umb ilical cord. There- While generally considered a slow-growing
fore, Goldblatt concluded th at or igin from neoplasm. odontogenic myxomas maybe in-
primitive nonooo ntc c eruc mesenchyme filtrative and agg ressivew it h high recurrence
cannot be completely ruled out by transmis- rates. Due to poor follow-up and lack of re-
sion electron mic roscopy (TEM) stu d ies ports, a precise analysis of recurrence rates
alone. is still missing. However, recurrence rates
La Muzio et al9 studied OMs by immu no- have been reported with an average of 25%
histochemistry and TEM. Results indicated (range, 10% to 33%).25 Treatment has varied
the tumor celts had a myonbroblasttc origin. from local excision, currettage, or enucle-
Using TEM, Jaeger at al23 found an OM tu- ation to radical resection . Recurrence is COl)-
mor cell population that consisted most ly of sidered to be d irectly related to the type of
one type of cell resembling a fibroblast. Tu- th erapy, with conservat ive surgery resuttinq

195
2 0 : O dontog en ic M yx o ma o r Myxof ib ro m a

in a higher numbe r of recu rrences. Forsmall- 9. Lo Muzio LL, Noc ini PF, Favia G, et al. Odo nto-
genic myx oma of t he jaws. A clinical, rad iolog ic ,
er OMs, t he treatment of cho ice is cu rrettage
im munoh istochem ical, and ult rastructural study ,
beca use a tumo r-free bo rder may be co n- O ral Surg O ral Med Oral Pat hol O ral Rad io l En-
firmed more easily. Frozen sections, particu- d od 1996 ;82:426- 433.
larly in larger OMs, has been recom mended 10. Tahsinoqlu M , Coloq u S, Kuralay T. Myxoma of
for ad equate co ntro l of the borders . Radical t he ging iva: A case report. Br J Oral Surg 1975;
surgery is necessary when bord ers are poo r- 13 :95- 97.
ly defined. Maxillary OMs must undergo rad- 11. Kawai T, M urakam i S, N ishyama H, et al. Diaq-
ical resect ion. As is ofte n th e case, "recu r- nostic imag ing for a case of max illary myxo ma
rence" of OMs may, in a number of cases, be with a review of the mag net ic resonance images
du e t o incom plete removal of the tumo r of myxoid lesions. O ral Surg O ral Med O ral Pathol
O ral Radio l Endod 1977 ;84 :44 9- 4 54 ,
ratherthanto true recurren ce . Radiotherapy,
elect rocautery and c hemo the rapy have oc- 12. Sumi Y, Miyaishi 0 , Ito K, Ueda M . Magnet ic res-
onan ce imaging of myxoma in the mand ib le: A
casionally been used, but th ese the rapies
case repo rt. O ral Surg Oral Med O ral Patho l O ral
seem to be ineffective, though only a few Rad io l Endo d 20 00;90:67 1- 67 6 ,
stud ies on thi s prob lem have been pub-
13 . Regezi J , Kerr DA, C ourtney RM, Arbo r A. Odo n-
lished. Several reports on surgical and pros- toge nic tum ors: Analys is of 706 cases. J O ral Surg
theti c rec onstruction have bee n pub- 19 78 ;36 :771 -77 8.
lished.2 6 - 2 8 14 . Lu Y, Xuan M, Takata T, et at. Odo nto ge nic tu-
m ors. A dem og raphic stud y of 759 cases in a Chi-
nese populat io n. O ral Surg Oral Med O ral Pethel
O ral Rad io l Endo d 1998;86 :707 -71 4.
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19 78 ;7:148-1 55 jaw myxom a a nd me se nc hyma l ce lls of tooth
germ. Path ol Res Pract 1992 ;188 :14 1-1 44 ,
6. Sc hm idse de r R, G roddeck A, Sc heun ema nn H
Diag nostic and therapeut ic prob lems of myxo- 19. Mo shiri S, Oda D, Worthingt on P, Myall R. Odo n-
mas (myxofibromas) ofthe jaws,J Maxillofac Surg toqenic myxom a: Histoc hem ica l and ultrastruc-
19 78 ;6 :28 1- 286, tural study. J O ral Patho l Med 19 92;2 1:40 1- 4 03.
7. Siootweg PJ , W ittkampf RM . Myxo ma of the jaws. 20 . Takahashi H, Fujita S, O kab e H. Im m unohi sto-
An analys is of 15 cas es, J Max illof ac Surg c hem ical investigatio n in odo ntogenic myxom a.
1986 ;14 :4 6- 5 2 J O ral Patho l Med 199 1;20 :114 - 119.
8. Peltola J, Magnusso n B, Ha ppo nen I1-P, Bo rrman 2 1 Lo mb ard i T, Loc ks C, Samso n J, ooensw. 8 100,
H. Od ontoge nic myx om a-a rad iog raphic stud y o.-sm ooth m uscle acti n and cyto keratin 19 im-
of 2 1 tumours. Br J O ral Maxillofac Surg 1994 ; m unohistochem istry in odo ntogenic and soft tis-
32 :298-302. sue myxomas. J Clin PathoI 1995 ;48 :759 -762.

19 6
Refere nces

22. Green TL. Leighty SM, Watters R. lrnmunoneto- 26 . Arcu ri MR, Tabor M, Fergason H. Treatme nt of
chem ical evaluation of oral rnyxoid lesions. Oral odontogenic myxoma of the mandible with bone
Surg Oral Med Oral Pathol 1992;73:469-471 graft and dental implant supported FIXed perter
23. Jaeger M, Santos J. Domingues M, er at. A novel d enture: a cnmcar report. J Prost het Dent
ceume that retains the morphological character- 199 4 ;72 :230- 23 2.
istics of the cells and matrix of odontogenic myx- 27. Arcuri MR , TaborMW, FergasonHW, Haganman
oma. J Oral Pathol Med 2CXXl;29:129-138. C. Odontogenic myxoma of the maxillary sinus: A
24. Goldblatt L1. Ultrastructural study of an odonto- clini cal report. J Prosthet Dentl993;70:111-113.
genic myxoma. Oral Surg 19 76 :42:206- 220 . 28. Chiodo A.A, Strumas N, Gilbert RW, Birt BO. Man-
25. Barker BF. Odontogenic myxo ma. Semm Diagn agement of odontogenic myxoma of the maxilla.
Patner 1999:4:297-301. OIo1aryn901 Head Neck Sur9 1977: 573-576.

197
Cha pter 21

Benign Cementoblastoma

1. Terminology thesia. In t he survey published by Ulmansky


at al,2 61 % of the patients had a history of
The benign cementoblastoma (BC) or true pai n. Of 15 cases of Bee rep orted by .jenc et
cemen toma w as first des cribed by Norb erg al,5 9 we re symptomatic and patien ts co m-
in 1930 . 1 It is a rare benig n od ont ogenic tu- plained of pain. Th e type of pain is usua lly
mor of ectomesenc hymal origi n. It is co nsi d- characterized as a toot hache arising in the
ered to be the only true neoplasm of ce- pu lp. A vitality test of teeth involved in the
mental origi n an d is charact erized by the process is ge nera lly positive. A Be may re-
proliferation of cellu lar cementum . Ulmansky so rb roo ts and eve n invade root canals.t In
at al 2 reviewed the internationalliterature on rare ca ses it may involve unerupted teem.s
Be and fou nd 66 bona fide cases of this neo- Rad iog raph ically, benign ceme ntobtas-
plasm in addition to five of their ow n (n - 7 1). tomas have a c haracteristic , almost path o-
Additional cases of BGs have been repo rted gnomonic appearance (Figs 2 1-1 and 21 2).
by MacDonald-Jankowski an d Wu 3 (n = 4 ), The lesio n appears as a radiopaqu e, often
Slootweq" (n = 3 ), Jelic at al5 (n = 15), Biggs rou nd mass. fused with one or several roots
and Benenati- (n = 1), Mag i at al 7 1996 (n = of the associated tooth, th us o blit erating the
1), and Piatelli at al 8 199 7 (n = 1). In 1999, EI- radiopa que details of the root(s). The opaci-
Motty9 published a short review on BGs and ty is surro unded by a thin, w ell-defined rad i-
cemento-ossifying fib romas. olucent bord er. This typ e of appearan ce was
evident in 93 .8% of the cases reviewed by VI
mansky et al.2 T he size of lesio ns reported
by Jelic et als (n = 11) varied betw een 0 .5 cm
and 5 em , with an average of 1.36 em if the
2. Clinical and radiologi c profile s- cm les io n w as exclud ed. T he aut ho rs
stre sse d th at t he spectrum of a Be's rad i-
o graph ic appearance d epends o n its deg ree
The benig n ce me ntoblasto ma. intimately as- of m ine ral izat ion. Th us. ear ly-stage BCs
sociated w ith a toot h root, generally presents generally appear more rad ioluc ent. In suc h
as a slow-growing , unilateral swelling wi th ex- cas es d ifferential d iagnoses should incl ude
pansion of the affected bone. Ulmansky at pe riapi cal inflammatory lesions. foca l (peri-
al2 recorded swelling and expansion in 70% apical ) cemento-osseous dysp lasia, central
of their cases. In contrast to most other be- giant cell lesions, odontogenic myxomas, or
nign odontogenic tumors, BCs are associat- sono/morucysnc ameloblastomas. Mature,
ed w ith pain and occasionally w ith pares- more cal c ified BC lesions may mi m ic ce-

199
21: Benign Cementob lastoma

Fig 21 -1 Panoramic radi-


ographshowinga benign ce-
rnentoblastorna at the root of
the mandibular left first mo-
lar. The central radiopaque
mass is surrounded by a ra-
diolucent zone characteris-
tic of BCs.

3. Epid em iological data

;~~
,'
3.1 Prevalence, incidence, and
re lative frequency
,
.!
. .
'
." ..
.'
11.,~
, l ,\ ,

,;
'.:;
, Since t he benign cementoblastoma is a rare
neoplasm, few ep id emi o log ica l data are
availab le. Benign cem entoblastom as make
up betw een 0 .2% and 6.2 % of odontogenic
'. .
("
.,
.' ';;'~: . ..:'
.. ,
'
turne rs.'?

3.2 Age
Fig 21-2 Periapical dental radiograph showing a T he d ist ribut io n of be nign ce mentob las-
benign cementoblastoma at the apex of the root
tomas by age and gend e r for cases pub-
of the mandibular left canine. There is only a fine
lishe d in refere nces 2 to 9 (n = 93) is show n
radiolucent rim around the periapical radiopaque
lesion. in Fig 21-3. At t he t ime of d iagnosis, t he pa-
tient's age may range from t he 1st to the 7t h
decad e. However, 46 .2% of BCs are d iag-
nosed before t he ag e of 20 years and 7 1%
befo re age of 30.
mento-
ossify ing fibro mas, osteoblastomas , odo n-
to mas, calcify ing ghost cell cysts, or ca lcify- 3_3 Gender
ing ep ithelial odontogenic t umors. Comput-
ed to m og ra phy o r magnet ic reso nance Gender distri but ion varied among d ifferent
imagi ng are usually not necessary fo r d iag- smaller series of ben ign ce me ntoblastomas.
nostic purposes. T he male:fem ale ratio of the 93 cases already
mentton eo ' "? was 1:1.2.

200
Path ogenesis

NO. Of cases
2 0 19
zo
te OJ Women
te OJ Men
n : 93
"
12
12
11
10
o 7
5
,
6
3
4

2
Fig 2 1-3 Age and gen-
der d istr ibut ion of 93
o "-'c~"'-:::~c:::'';:J.!~~L=tL:''-lc"c"'-:::'.:'''-=:L1L
0- 9 50 -59 60 -69 7 0 ~79
cases of benign cemen-
toblastom as.

mentioned in his review that the mandi bular


f irst molar and premolars may be affected in
,,, 75% of cases. The maxillary molars and p re-
molars are th e secon d most affecte d regions.
14 3 :4
i Deciduous teeth are rarely affected. Several
teeth may be invo lved, and bilate ral lesions
have been reported.

18 11
"
4. Pathogenes is
Fig 2 1-4 Top ograph ic d istribut ion of 95 cases of
benig n cernentcoestomes accordi ng to perma-
nent toot h groups.2-9 One ad d itional case not Little is known about the pathog enesis of
shown involved t he roots of a d eciduous molar. benign ce mentoblasto mas. They are od on-
tog en ic tum ors and are d erived fro m ec-
tomesenchymal cells of the periodontium ,
incl udi ng ce me nto b lasts . The be nign ce-
mentobtestorna is tho ught to evolve in three
3.4 Loca tion stag es. The first stage is c haracterized by pe-
riapical osteolysis, followed by a cem enta-
Locations of BCs according to too th grou ps blast ic stag e, and then an inactive stage of
involved are shown in Fig 21-4 (n = 95 ). The maturation and calcif ication. The BC is co n-
mand ibular permanent molars and premo- side red a neop lasm with unlimited growth
lars are most co mmonly involved , with 66% potent ial. Its etio logy is unknown, and t rau-
of cases occ urring in these regions. EI-Mofty9 ma does not seem to p lay a role.

20 1
21: Benign Cementoblastoma

. fi"

""-1' .:"'" ": .( ' ;;- \ ', t


:-(H ; .!, ~ ., . " ';" .~'
: '~ .
tv ~:~ ,
'-
' ~ ,'- , '
< -
- " "
~~" '"
...
~,/ .. ,
- . - ,

;" ~ ..:>t
~ ,""'! ,~
t~'?h;.~
~ ~1 "

i~~~\~:j';"\:""
",
"

V .:'(;;li:-.Ll

Fig 21-5 Macroscopic view of the surgical spec-


i
;1;;' ,~t,t

" ~~ !"... . ,

Fig 2 1-6 Sheets of cementum-like hard tissue


"", ; . ,~,
'-~ . ,_ /
:, .
.. '-
imen shown in Fig 21-1 . The lesion is large and with some reversal lines as seen in Paget disease.
extends up to the cementoenamel junction of the Small areas of connective vascular tissue are in-
tooth. terspersed between the cementum-like masses
(hematoxylin--eosin [H&EJ, x50).

5. Pathol ogy

5.1 Macrosco py ~iig~;~~;~~


~~-~~~:-:'~~~~~;""~" ~: i~

Macroscopi cally, the ben ign ccrn cntcotas- ~ .~"~,,,......


r_'-V~ - :""J=--~~
.__ . ' " ~'"
,~; .~ ' " ;.;.,., ~h ., ':"~ ,""It." ' ''- ' ' ':;'
~~~ j ( '~ ~ ~ ~ ..
' '"' ~
..._~~
~-

tom a appears as a mine ralized mass wh ich ~r . ,~"""'"'" -" r ~ 1).,.,: "~
~ . ~.i ... ...~ ,.if.S."!~
is fused to the root(s} of a tooth , in most cas-
}
s. : ;,1/' (. it "'?c>i ,...~1,
' ~~~ , . (. f; :V.. , '#'1 " "-';1
es invo lving the ap ical th ird (Fig 2 1-5).
tI,
' I, ' ~
" I:. s M~
I f'I y: ~ " " ,~
'I{ , ~ " ~
I " ~ ., . .~ ~ ~' ,>
_
I _ _ _
I ._
,
5 .2 Microscopy
Fig 2 1-7 The periphery of the lesion shown in Fig
5.2. 1 Histologic definition 21-6. A capsule-like condensation ot fibrous con-
Bot h the 19 92 World Hea lth Orga nization nective tissue with an abundance of active-look-
(WHO) classification 1 1 and the p resent au- ing cementoblasts is seen (H&E, x70).
tho rs def ine the Be as fo llows:
A neo plasm characterized by the formation
of sheet s of cementu m-like t issue wh ich co n-
tains a large numb er of reversal lines and is blasts. Fibrou s t issue with dil ated vessels and
unm ineralized at the pe rip hery of the mass mult inucl eated clast ic gia nt cells may be ob-
o r in the mo re active g rowth area. served betwee n the calcif ied bands. At the
perip hery of the min eralized mass, pro lifera-
tion of cemen toblasts and ce me ntoclasts is
5.2.2 Histopathologic findings
evide nt. It has bee n stresse d that in many in-
The numerous baso ph ilic reversal lines are sta nces it is diffic ult to d ifferentiate these ce lls
similar to t hose observed in Paget d isease from osteo btasts . and they may exhibit p leo-
(Figs 21-6 and 2 1-7). Ceme ntal trabec ulae mo rph ism. Inc reased mitotic activity has not
are rim med wit h plum p , activ e cem ento - been reported . The peripheral un mineralized

202
References

border of the BC corresponds to the rad i- 6. Notes on treatment and


olucent zone seen in rad iographs. Often a
correct diag nosis can be made after corre-
recu rrence rate
lating the histopathologic, clinical, and radi-
ologic features. The reco mmended treatment of choice is
Since in man y cases the cementum pro- early sur gical removal d ue to the BG's ca-
duced in the BG is ind isti ngui shable from pac ity for pe rsiste nt g rowt h, expans ion, and
bone, it may be misinterpreted as a cem en- involvemen t of adjac ent structu res . The
tifyi ng/ossifying fibrom a , a ben ign osteo- g rowth rate has been est imated to be ap-
blastoma, an osteoid ost eoma , or fib rous p roximat ely 0.5 ern per year. The tumor is
dysplasia. Cases in which osteocementum- read ily enucleated and does not recu r. "He-
like materi al is formed make th e diagnosis cu rrence" is usua lly the result of incomplete
particularty d ifficult, especially when differ- re moval. The affected tooth has been re-
entiating a BC from an osteoblastoma whi ch moved wit h the tumor in almost all repo rted
has a tendency to recur. Slootweq'' co m- cases. Biggs and Benenati.s however, de-
pared cases of BCs and osteo blasto mas and scribed a case in wh ich the tumor was sur-
conc luded that from a histo log ic view the two g ically separated from the involved molar.
lesions cannot be separated. The diagnosis
of BG is mad e easier when the lesion is fused
to the root of a tooth . Ch ron ic focal scleros- Ref erenc es
ing osteitis has also been con sid ered as a d if-
ferential d iag nosis histopatholog ica lly. Final- 1. Norberg O. Zur Kenntnis dar dysodo ntogeneti-
ly, accord ing to some autho rs, BGs may be sc hen ceec bwmste d er Kieterknochen. Wsehr
Zah nheifkd 1930;46:321-355.
mistaken for ost eosarco mas.
2. Ulmansky M. Hj0rting-Hansen E, Praetcnus F.
Haque MF. Benign cementoblastoma. A review
5.2.3 Histochemical/ immunohistochemi- and five new cases. Oral Surg Oral Med Oral
cal findings Pathol1994;77:48- 55.
3. MacDonald-Janko wski OS, Wu PC. c em ent o-
No histochemical or immuno histochemical blastoma in Hong Kong Chinese. A report of four
studies of BCs have been published to date . cases . Oral Surg Oral Med Oral Patner 1992 ;
73:760-764.
4. Slootweg PJ. Gementob lastoma and osteoblas-
5.2.4 Ultrastructural findings
toma: A comparison of histologic featu res. J Oral
No ultrast ructural studies of BGs have been Pathot Med 1992:21:3 85-389,
pub lished to date. 5. Jelic JS, Loftus M. Miller AS, Cleveland D. Benign
cementoblastorne: Report of an unusual caseand
analysis of 14 add itional cases, J Oral Maxillofae
Surg 1993;51 :1033-1037.
6. Biggs JT. Benenati FW. A case report. Surgically
treating a benign cementoblastoma while retain-
ing the involved tooth . J Am Dent Assoc 1995;
126:t288-t 290.
7. Magi K, Bela! E. Kana A. Otake K Benign ee--
mentoblastoma. Case report. Aust Dent J 1996;
4 1:9- 11.

203
2 1: Be nig n Ce mentob lasto ma

8. Piatelli A, Oi A lberti L, Scara no A, Piatelli M. Be- 10. Lu Y, Xuan M, Takata T, ot at. Odo ntogenic tu-
nig n ce mentob lastoma assoc iated with an un- mors. A dem og raph ic study of 759 cases in a Ch i-
erupted third molar. Oral Onea l 1998,3 4:2 29- nese pop ulation. Oral Surg Oral Med Oral Pathc l
23 1 Oral Rad iol Endod 1998;86 :70 7- 714.
9 , EI-Mofty S. Cemen to-ossifying fibroma and be- 11. Kramer IR H, Pind borg JJ. Shear M. Histolog ic
nig n c eme ntoblasto rna. Semin Diaq n Pat ho l Ty ping of Odo ntogenic Tumors 2d ec. Berlin:
1999 ;16:302- 30 7, Spring er-Verlag, 1992.

204
Section Five

Malignant Epithelial Odontogenic Neoplasms

Introduct ion to Odontog enic Type 1 Primary intraosseous carci noma ex


Carcinom as odontogenic cyst
Typ e 2 A. Malignant ameloblastoma
B . Ameloblastic ca rcinoma, arising
During the past 20 years considerable con- d e novo, ex ameloblastoma, or
fusion has existed about the definition and ex odontogenic cyst
classification of malig nant od ontogenic car- Type 3 P rimary intraosseo us carcinoma
cinomas, in pa rticular the d efinition of the pri- arising d e novo
maryintraosseous sq uamouscellcarcinoma A. Nonkeratiniztn q
(PISC, o r sometimes PIOC) and its variants, B. Kerati nizing
as we ll as the d ifferen tiatio n between malig-
nant amerobtastomas and amerobrastrc The autho rs also di scu ssed so me of th e
carcinomas. T he nosology of malignant neo- pro blem s associated with the definition and
plasms derived fro m odontog enic ep ithe li- classificatio n of odo ntoge nic ca rc inom as.
um has therefore varied conside rably. In They po inted out tha t there is lack of histo-
1982, Elzay' pro posed a mod ificatio n of the log ic delin eatio n, as d emonstrated by th e
first World Health Organ izatio n (WHO) c las- fact that tumo rs co nsisting exc lusively of co n-
sification which ap peared in 19 7 1 2 and sug- vent ional we ll-diffe rentiated ameloblastoma
gested a classification of p rimary (de novo ) in the primary tum or and in metastases have
PISC an d PISC ansinq ex amelob lasto ma in bee n cl assified as malig nant amelo blas-
add ition to distin guishing between a well -dif- to mas. Furt her, classificatio n is co mplicated
ferentiated variant (ma lig nant ameloblas- by the fact t hat some PISCs may reveal ar-
toma, type A) and a poorty diffe rent iated vari- eas that are histoloqicanysimilarto malignant
ant (amelo blastic ca rcinoma, type B). ameloblasto mas (tha t is they have no mor-
In 1984, Slootweq and M Qlle rJ suggested phologic features of malignancy). Ther efore,
the following subclassifica tion of PISC: it is possibile that the same lesion may have

205
Malignant Epithelial Odontogenic Neoplasms

been cl assified as a ma lignant ame lob las- Ed ito rial and Con sensus Co nf ere nce in
t om a (ex hibit ing mo rp ho log ic feat ures of Lyon (IARC/WH O) in J uly 20 03 in associ a-
classic ame loblastomas) o r as a PISC in t he tio n with th e preparat ion of th e new W HO
absence of metastas is. In add itio n, matters vo lum e "Tumours of t he Head and Neck".
have been comp licated by the use of the term T o fu lly apprec iate th ese changes w ith
malignant ame lob lastoma fo r cases showing spec ia l emphas is on the interp retati o n of
ame lob lastomatous fo ci with a m o re a n- c hapters 22 to 26 of t he present book, the
aplasti c co mponent and exh ibiting a more lo- read er is st ro ng ly advised t o co nsu lt t he
ca lly dest ructive patt ern in comparison to WHO volum e on "Tumou rs of the Head and
con ventiona l ame loblasto mas. Neck" , cha pte r 6.
Waldron and Mustoe" s ug geste d a re-
vised c lass if icatio n of t he p rimary int ra-
osseo us ca rcino mas . In 199 9, Eversole" re-
References
vised the class ificat ion of ma lig nant ep ithelial
odo ntog en ic neo plasms based o n mo re re- 1. Elzay RP. Primary intraosseous carcinoma of the
cent pub lications. jaws: Review an update of odontogenic carcino-
In th is classif icat ion Everso le int rod uces mas. Oral Surg Oral Med Oral Patho l 1982;54:
an ent ry unde rt he nam e of malign ant (metas- 299- 303.
tasizing) ameloblastoma . Th is tumor is not in- 2. Pindborg JJ, Kramer IRH. Histologic Typing of
c lud ed in t he 199 2 WHO clas sificatio n," Odontogenic Tumours, Jaw Cysts and Allied Le-
sions. Berlin: Springer-Verlag, 1971 .
which uses t he term malign ant ame lob las-
toma as the eq uivalent of Everso le's am eto- 3. Siootweg PJ, Muller H. Malignant ameloblastoma
orarnelobtasticcarcmoma.OralSurgOralMed Oral
blastic carci nom a.
Pathol 1984;57:168- 176
The present aut hors co nside r Eversole's
c lassification to be the most appropriate on e 4. WaldronCA, MustoeTA. Primaryintraosseous car-
cinoma of the mandible with possible origin in an
unti l mo re d eta iled info rm at io n on path o- odontogenic cyst Oral Surg Oral Med Oral Pathol
gen esis, biolog ic p rofi le and behavior be- 1 9 8 9;67: 7 1 6~ 724
comes evident.T hus, the Eversole cl assific a- 5. Eversole LA. Malignant epithelial odontogenic tu-
tion forms t he basis of the fo llow ing cha pters mours. Semin Diagn Pathol 1999;16:31 7- 324
o n m alignant epi the lial odonto g enic neo- 6. Kramer IRH, Pindborg JJ, Shear M. Histological
plas ms w ith t he ch ang es in c lassification Typing 01 Odontogenic Tumours. 2d ed. Berlin:
and t erminolo gy agre ed upon during t he Springer-Verlag, 1992.

206
Chapter 22

Metastasizin g, Malignant Am eloblastoma

1. Termin ology 2. Clinical and radiologic profile


The solid/ m ulticystic ameloblastom a (SMA) Gene rally, ameloblasto rnas that ma y metas-
of the mandible an d max illa is an epithelial tasize do not have any spec ific cl inical fea-
odonto genic t umo r, th e biologic profile of tures. In the ir review, Reichart et all fo und
which has recently been reviewed by Reic h- swelling , pa in, de layed toot h erupt ion, ulcer-
art at at 1 The relative frequency of amelo- atio n, and toot h mobility to bethe m ost com-
blastomas varies between 11 % and 92%.1 m on sym pt oms (see chapter 5). The re are,
Only 0.02% to 0.7% of ge neral pathology however, a number of factors th at appe ar to
biopsies are amelo blastomas. Ametobtas- contri bute to a potential metastatic sp read ,
lomas are generally cons idered benign , al- including duration of the neoplasm, extent
though they are locally invasive and have a and size of the initia l tumor, initial ty pe of sur-
high recurrence rate depending on the type g ery (co nservative versus rad ical th erapy),
of initial surgical treatment. 1 As such, they multiple recurrences and respective surgical
share a number of featu res with the basa l ce ll interventions, and use of rad iatio n or chemo-
carcinoma of skin. both in biologic behavior th erapy. An analysis of the ca ses reviewed
and histopatholog ic features. In rare cases, by A mae rally et al 6 revea led th at a cases
an ameloblasto ma ma y und ergo malignant (33%) had evidence of metastasis within 6
transformation (becoming an amelobtastic years of d iagnosis, a sho rter period fro m ini-
carcinoma; see c hapter 23) . Lik e basal celt tial tumo r to metastatic disease th an th e 10
carcinomas of skin , SMAs may- in rare in- years and 4 m onths reported by Ueda at al.5
stances- metastas ize. Em ura- was probably A lso, repeated surg ical intervention w as not
the first to describe metastasis to local lym ph always a pro m inent feature in the histo ry of
nodes. m etastasizi ng , m alig nant ameloblast o ma
Vorzimer and Perla3 men ti on ed metasta- (M AJ. Se ve n pati ents (2 9 %) had on ly tw o
sis of ameloblastoma to t he lun g for the first cou rses of surgery, and in nine the re was no
time in 1932. Oth er review s of metastasis evid ence of the primary tumo r at th e time
have been published by La uq hlin," Ueda et metastasis occurred, indicating that uncon-
al,5 Amee rally et al,6 and Henderson et al.7 trolled local d isease is not always a prereq-
Malignant behavior is present in about 2% of uisite for d istant sp read."
SMAs.B The most common site of metastasis is the
lu ng . Fro m the analysis of Am eerally et al,6 it
appeared that 75% of the cases evaluated
had lung metastasis, incl udi ng ruler lymph

207
22: Metastasizing, Malignant Ameloblastoma

nodes; 25 % involved bones. includi ng skull , reso nance imagery (MRI) are needed for ad-
vertebrae, and fem ur; 18% cervical lymph equate diagnosis in such cases.
nodes; 11% liver; 10% bra in; and 3.5%, oth-
er nodes. spleen, and kidn ey. Henderson et
al7 recently reviewed 41 cases of MAs wit h
metastasis to the lung. For this specific loca-
tion , the time from d iagn osis to the detecti on 3. Epid emiological data
of metast asis rang ed from 3 mo nths to 31
years, with a med ian d isease-free interval of
9 to 12 years . Pulm o nary metastases a re 3 .1 Prevalenc e, incidence, and
most commonly found bilaterally and w ith rel ative frequ ency
multiple nodules." Lung metastatic disease
may so metime s man ifest clin ically as suba- Malign ant ameloblastomas are rare. and on ly
cute resp iratory obstruct ion o r dysp nea." but about 65 cases have been described in the
in the majority of cases thorax rad iog rap hy literatu re, the majority (75%) of wh ich devel-
(co mputed tomography, mag neti c res o- oped pu lmonary metastasis. Compared to
nance imagery) will reveal only metastases. amelobta stic carcinomas. how ever, they
Subma nd ibular or cervica l lymph nodes may seem to be mo re common (see chapter 23 ).
be palpated or d iagn osed by sonoq raphic Due to its rarity, no details o n prevalence. in-
techniques. Duffey et a!9 analyze d cases of c idence, o r relative freq uency for th e MA
MAs with metastasis to cervical lymph nodes, have been published to date.
and retrieving nine cases from the literature
and adding one of the ir own. The t ime from
first presentation to t he d etection of metas- 3.2 Age
tases was a mean of 11. 7 years (n ~ 7) wit h
a range of 2 to 24 years. Five of nine patients The mean age of 65 cases of MAs- based
had addi tional d istant metastases. on 43 cases reviewed by Laughlin,' 7 cases
In rare cases, the meta static ameloblas- by Ueda et a[,5 11 cases by Ameerally et al,6
toma may be asso ci ated w ith hyp erca l- and single cases reported by Duffey et al,9
ce mia.'? In the case report by Harada et al,1 0 Sug iyama et al." Wei r et al,12 and Witterick
it was elevated to 12 .8 mgjd . the inorganic et at's-was 34.4 years wit h a range of 5 to
phosphate level was 2.2 rnq/o. and the al- 74 years. Fig ure 221 shows the age distri-
kaline phosphate level was 170 U. The hu- bution of MAs in this sam ple.
mora l hypercalcemia is co nsidered to be the
result of osteolytic facto rs such as a trans-
formi ng growth facto r or parath yroid-like 3.3 Gender
substanc e. Substa nc es secreted by t he
metastatic ame loblastoma have also been The female.male ratio fo r the sam e sample
considered.'? (n = 65 ) was 1:1.2 (see Fig 221).
Rad io logi ca lly, MAs ca nnot be d isti n-
gu ished from their nonrnetastasizinq coun-
terpart s. Since metastasis often occurs on ly 3.4 l o c at ion
after one to several local recurrences of the
tumor. rad iog rap hic interpretation of the p ri- Of 43 cases reviewed by Lauqhlin," 38 were
ma ry site becomes mo re and mo re diffic ult. located in t he mandible and 5 in the ma xilla
Computed tomog raphy (CT) and magn etic (7.6: 1). Henderson et al 7 reviewed cases of

208
22: Metastasizing, Malignant Ameloblastoma

to be of hem atogen ous spread. The fact that 5. Patho logy


lung metastas is of MAs is most often found
bilaterally and w ith multiple no du les lends
sup port to th e id ea of a hem atogenous 5.1 Macroscopy
spread .This is also supported by the fact that
diftu se'yscatt eredtumor toci are often found No detailed description s en the gross pathol-
bilaterally, and clusters of t umor ce lls are ogy of resected s pecimens of mali gnant
com mo nly observed in th e su rro und ing ameloblastomas have been published in the
blood vessels. literatu re. However, it may be assumed that
Lymphat ic spread of ma lign ant t umor the macroscopy of MAs do es not differ from
ce lls is generally a well-accepted route of that of co nventional amelo blastom as.
metastasis. Eisenbe rq."' how ever, question- Cranin et at" d esc ribed a massive granu-
ed th is mod e of spread for MAs. She con- lar cell ameloblastoma with metastasis. Th e
sidered it very unlikely that a lymph node c ut su rface of t he resec ted speci men re-
metastasis co uld reside in an indolent or dor- vealed t he tu mo r to be pa rtially so lid and par-
mant state from the t ime of initial th erapy to t ially cyst ic.
clini cal presentation of lymph node involve-
ment, w hich in the case that she discu ssed
was 17 years. Eisen be rg p roposed t hat in 5 .2 Microscopy
so me cases the lymp h node tu mor may rep-
5.2.1 Histologic definitions
resent neop lasia occurring in con junction
wit h th e phenomenon of heterotopia. This The 1992 World Healt h Organ ization (WHO)
th eory wo uld imply that od ontogenic ep it he- c lassi f ication 16 us ed t he t erm malignant
lium may become trapp ed in Iymphoid tissue ame loblastoma t o d escribe a t u mor t hat
during embryogenesis and late r unde rgoes today would qu alify as an ameloblast!c car-
beni gn neop last ic t ransformation to an cinoma. The MA was ne it he r de fined nor
ameloblastoma in sit u.This would also imply commented on in the WHO classification.
t hat the p rocess was rnultrtocal from the be- The def inition used by th e p resent autho rs
ginning, so that th e jaw tu mor and the tumor is as follow s:
in the lym ph nod e bore no direct relationship A neopl asm in wh ic h both th e primary and
to one anoth er. Such a hypothesis wo uld (in metastatic growth s are c haracterized histo-
some cases of lymph node involvement of log ic ally by benig n, innoc uous-appearing
MAs) accou nt for why, afte r long periods of SMA t issue components that lac k any fea-
time, a single (metastatic) lesion arose dis- tures of malignancy .
tant from t he prim ary tumor location but wit h-
in its gene ral anatomic region. As SUCh, t he
5.2.2 Histopathologic findings
presence of an amelob lasto ma in a lymph
node may not be based on lym p hat ic or Altho ugh a variety of histologic amelob las-
hematogenous spread but may rep resent toma su btypes are known , in MA cases, plex-
anothe r (ectopic) p rimary lesion. More cases iform histopatho logic typ es p revail, wit h 80%
of MAs have to be stud ied to bett er unde r- of metastatic lesions being either mixed or of
stan d th e pat ho genetic and path ologi c t he pure plexiform type (see chapter 5). De-
p rocesses of the SMA and its capab ility to spite the fact th at most MAs are of the p lexi-
metastas ize. fo rm type (Figs 22-2 and 22-3), it is not pos-
sib le to predict metastatic potential. Further,
instances of metastasis have arisen from sol-

2 10
Notes on treatment and recurrence rate

Fig 22-2 Metastasizing/ malignant ameloblas- Fig 22-3 Malignant ameloblastoma (lung metas-
tomaof predominantly plexiform type.Thetumor tasis) from the same patient shown in Fig 22-2.
isthat of a SMA in a fibrous stroma(hematoxylin- Note how clearly the classic appearance of a be-
eosin [H&E], x60). (Courtesy of Professor J.J. Sci- nignameloblastoma is retained (H&E,x60).(Cour-
ubba, Baltimore, MD.) tesy of Professor J ,J. Sctubba, Baltimore, MD.)

id invasive variants of ame lob lastomas rath er 6. Notes on treatm ent and
than from the unicystic type. In very rare cas-
rec urrence rate
es the MA may be associated wit h ftbrosar-
coma {malignant mixed tumor)."?
Ueda et at" stud ied the tumo r do ubling Adeq uate initial surg ica l t reatm ent of the pri-
time of t hree m etastatic nod ules of MA. lnthis m ary neo plasm p lays t he most imp ortant role
case, vo lume doubling t ime was constant in th e prevention of posto pe rative m etasta-
among indivi d ual nodul es fro m 129 days to s is. Rad ica l resect ion w ith prima ry rec on-
201 days. The semilog g raph revealed a rel- struction of mandi bul ar amelo blastom as has
atively parallel slop e of tumor growth, ind i- become the most accepted therapeutic con -
cating that th e nodu les were slow g rowing. cept.
It has been stated t hat patients wit h a tumo r Several modalities for the treatme nt of pu l-
doubling time of 45 days or less had a sig- m onary metastasis of MAs have been used,
nificantly reduced survival expectancy after but little has been published on these meth-
surgical treatment of metastasis of the lung. ods. Th e most co mmon treat ment of choice
is su rgery, althoug h rad iatio n and chem o-
therapy also have been described . Current
5.2.3 Histo chemicaVimmunohistochemi-
strateg ies sup po rt the use of chemothera py
cal findin gs
and rad iat io n fo r palliative t herapy and an ag-
The malignant ame lob lastoma has not been gressive surg ical app roach for t reatable le-
studied by immuno histoc hemist ry. sio ns.? Surgical tre atment con sists of local
excis ion o r lobectomy. Co mputed to mo gra-
p hy-gu ided fine-need le aspi ration or biopsy
5.2.4 Ultrastructural findings
techn iques may be used in preope rative his-
Stud ies on th e ult rastruc tu re of m alig nant tologic/cytolog ic d iagnosis. Mu lt iple metas-
ameloblastomas have not bee n pub lish ed in tases may on ly be removed if sufficient pu l-
the English literature. mon ary reserve is maintained.

211
22: Metastasizing , Malig nant Am eloblastoma

Radiat ion t he rapy ha s s ho w n h ig h rec u r- Ref er en ces


re nc e rates." Lauqhlin" recommended rad i-
at io n o n ly f or ino p e ra b le m etast ati c les io ns . 1. Reichart PA, Philipsen HP,SonnerS . Ameloblas-
toma: Biological profile of 3677 cases. Eur J Can-
Eliasso n et at" d isc ussed t he lim itat ions of
cer B Oral Oncol 1995;31B:86- 99.
c he mot he ra py in detail . C he m ot he ra py has
2. Emura M, A case of metastatic ameloblastoma.
bee n s ho w n to hav e a pall iat ive eff ect a nd
Jpn J Surg 1 92 3 ;24:7 6 0 ~7 64.
may in some cases red uc e the s ize of th e t u-
3. Vorzimer J, Perla D, An instance of adamantino-
mor, b ut bas ed on t he ir rev iew o f M A s a nd
maof the jaw with metastasis of the right lung. Am
lu ng m et astasis, Henderson et a l7 co u ld not J Pathol 1932;8:445-453.
se e a ro le fo r c hemot he ra py as a p rim a ry
4. Laughlin EH. Metastasizing ameloblastoma. Can-
t reat m e nt of MAs.
cer 1989;64:776- 780.
The med ia n di s eas e-f re e Interval bet w ee n
5. Ueda M, Kaneda T, Imaizumi M, Abe T. Mandibu-
in it ia l p res e ntatio n an d t h e occu rrence o f
lar ameloblastoma with metastasis to the lungs
met astasis of M A w as 9 years in t he rev iew and lymph nodes:A case report and review of the
by Lauqhlin." Of th e 43 pat ients he st u d ied, literature. J Oral Maxillofac Surg 1989;47:623-
19 (44.2%) w e re known to hav e d ied of the 628.
t u m o r a nd/or met ast asis . T he t im e from ini- 6. Ameerally P, McGurk M, Shaheen O. Atypical
t ial di agnosis t o t he detect io n of p ul monary ameloblastoma: Report of 3 cases and review of
metastasis rang ed f ro m 3 mo nt hs to 3 1 the literature. Br J Oral Maxillofac Surg 1996;34:
235- 239.
yea rs, with a m ed ia n d isease-f re e p e riod of
9 to 12 years . T he m edia n su rviv a l ti m e afte r 7. Henderson J, Sonnet JR,Schlesinger C, Ord RA.
Pulmonary metastasis of ameloblastoma: Case
t reat m e nt of th e p rim a ry t u m or ra ng ed fro m
report and review of the literature. Oral Surg Oral
1 1 to 14 yea rs. Afte r t he d iagnosis of m etas- Med Oral PathoI 1999;88:170- 176,
tasis , median s u rviva l ra ng ed from 3 m o nt hs
8, Houston G, Davenport W, Keaton W, Harris St.
to 5 years? T he lo ng est s urviva l t im e re cord - Malignant (metastatic) ameloblastoma. Report of
ed afte r t he appearance of m et astatic d is- a case, J Oral Maxillofac Surg 1993;5 1:1152-
ease was 25 years." 1155.
A s w it h many ot he r malignant odo nto- 9. Duffey DC, Bailet JW, NewmanA.Ameloblastoma
gen ic neop lasms, k n ow led ge a nd experi- of the mandible with cervical lymph node metas-
e nce is st ill li m it ed in case s o f m ali gnant tasis, Am J Otolaryngol 1995;16:66-73 .
ame lo b last o m as . The refo re, He nd e rso n et 10. Harada K, Kayano T, Nagura H. Enomoto S.
al" reco mme n d ed cont in ued report ing of Ameloblastoma with metastasis to the lung and
associated hypercalcemia. J Oral Maxillofac Surg
suc h cases t o f u lly u nd erstand t he mecha-
1989;47:1083-1 087.
n is m a nd opt im a l treat m en t m et hods fo r
11. Sugiyama M, Ogawa I, Katayama K, Ishikawa T.
MA s .
Simultaneous metastatic ameloblastoma and thy-
roid carcinoma in the cervical region: Report of a
case. J Oral Maxillofac Surg 1999;57:1255-
1258.
12. Weir M, Centeno BA, Szyfelbein WM. Cytological
features of malignant metastatic ameloblastoma:
A case reportand differential diagnosis. Diagn Cy-
topathot 1998;18:125- 130.
13. wrttenck IJ, Parikh S, Mancer K, Gullane PJ. Ma-
lignant ameloblasto ma. Am J Otolarynqol
1996;17:122- 126.

212
Refere nc es

14. Eisenberg E. Malignant (metastatic) ameloblas- 17. Tanaka T. Qhkubo T,JujltSuka H, et at Malignant
toma: Report of a case. J Oral Maxillofac Surg mixed tumor (malignant amelob\asl:oma and ft-
1983;51 :1156- 1157. brosa rco ma) of the rredna . Arch Pathollab Med
1991 :115:84-87.
15. Cramn AN, Bennett J, Solomon M, Ouarcoo S-
MassivegranuJarceil ameloblastoma WIth metas- 18. Eliassen MAH , Roy MJ. TenholderCMF. Diagno-
tasis: Report of a case. J Oral MaXJllofac Surg sis and treatment of metastatic ameloblastoma
1987;45;800-804. Metastatic ameloblastoma. South Med J 1998:
82 :1165 -1168.
16. Eversole LA. Malignant epithelial odontogenic tu-
mors. Semin Oiagn Pathol 1999; 16:317-324.

2 13
Chapter 23

Ameloblastic Carcinoma
(Primary, Secondary [Dedifferentiated]
Intraosseous; Secondary [Dedifferentiated]
Ext raosseous)

1. Terminology tu re and o ne of their own. Sm all ser ies of AC s


we re rep orted by Lau et al 8 (tw o case s) and
Carcinomas der ived from am elo blastom as tntante-Cossto et al 9 (thr ee cases). Sing le
have been c lassified a number of ways, in- case re po rts w er e pub lished by Siootw eg
cluding malign ant ameloblastoma, emeto- and MUller,lO An dersen and Banq,! ' Lee et
otesttc carcinoma, metastatic ameloblas- al,12 Bruce and .rec ksc n." Ing ram et al,14
toma. and pn'mary intra-alveolar epidermoid and Sim ko et ai." Recently, Cox et a116 d e-
carcinoma. ' The te rm ame/ob lastic carcino- sc ribed a case of arneloblasttc ca rci noma
ma (AC) wa s introduced by Shafer in 1974. 2 with malignancy-assoc iated hypercalcemia;
The World Health Organization (W HO) etas- a peripheral AC was report ed by McClatchey
sittcationsot 19 7 13 and 1992 4 do not include et at'": and Kao et apa described th e case of
this term in the section on odontogenic car- a n o dontogen ic carci no ma with d ist ant
cnornas. metastasis which, accord ing to tne histology,
In 1987 , Co rio at at' reported eight cases could pro bably also represent an AG.
of ACs from the U.S. Armed Forces Institute
of Pathology (Washingt o n DC ). These au-
thors classified ameloblastlc carcinomas as
"any ameloblastoma in which there is histo- 2. Ciinical and radiologic profile
logic evidence of malig nancy in the primary
or the recurrent tumo r, reg ard less of whet her
it has metastasized." T he ameloblastic car- Co mmon c linical sig ns and sympto ms of
cinoma is c urre ntly defined as a malignant ameloblastic ca rc ino mas inc lud e swe lling,
epithelial odonto genic tumo r that histo log i- pain, trism us, and dysphonta." Rapi d g rovvth
cally has ret ained t he feat u res of a me lo- of the tumo r is another impo rtant cl inical find-
blastic d iffe rentiatio n, yet also exhib its cyto- ing . Men ta l nerve paresthesia may also oc-
logic features of mahq nancy.s Primary and cur." In cas es of maxillary AGs the most fre-
secondary (dedi ff erentiated) int ra- and ex- qu ent c linical co m p laint is a ma ss in the
traosseous AC vari ants have bee n described c heek, b ut other clinical findi ngs suc h as
in the literature. pain, anesthesia of the infraorb ital nerve. and
In 1991 Nagai at al6 reviewed the literature a fistu la in the palate have also bee n noted.
on amelobrasnc carcinomas and found 46 In rare cases 16 an AG may occu r with ma-
cases, but features of ind ividual cases were lign ancy-associated hypercalcemi a. Hyper-
not shown. Lolac hi at a1 7 repo rted on 3 4 cas- calcemia is co nsidered a metabolic compli-
es of ACs from the Eng lish lang uage litera- cation of mal ignancy and is divided into two

2 15
23: Ameloblastic carcinoma

No. of cases

5 I'JJ """"'"
4 01 "'"
4 n= 24

3 3
3

2 2 2
2

0 1 __ I_ Y!_IJ_~Ju l_ !JIIJ !J I l l IJ IIJ !J Ill IJIIJ IJ Fig 2 3- 1 Age and


u- s 1O- HI 20-~ ;jQ-3~ 4 0-49 SO-59 60-69 70-79 80 +-
genderdistribution of
Age in decades
24 cases of amelo-
blasticcarcinomas.

variants : humora l hyperca lcemia of matlq- bone and may extend into the neighboring
nancy and local osteolytic hypercalcemia. soft tissue: patho logic fractures mavoccur."
Not more than four cases of MAHG-associ- Axial and coronal CT scans may reveal cor-
ated ACs have been reoorteo." tical thinning, perforations , and soft tissue in--
Principally, am eio brasnc carcino mas may vasion.
arise de novo,ex ameloblastoma, or ex odon-
togen ic cyst. Most ACs are thought to have
arisen de novo, with a few cases of malignant
transformat ion of amelobtastornas being ap-
parent. Such was t he case descr ibed by Cox 3. Epidemiological data
et at" in wh ich mult iple rec urrences of a
mandibular ameloblastoma oc curred w ith
the eventual developm ent of an amelob last- 3.1 Pr ev al ence, incidence, an d
tc carcin oma in the same site as the previ- relative frequency
ous ly d iagn osed ameloblasto ma. Arnelo-
blastic carci nomas have been reported to Cases of amelobtasttc carcinomas are rare
metastasize to the lungs and to distant sites; and no details on prevalence. incidence, or
however, in other cases with extend ed fol- relative fequency are presently available.
low-up, metastasis has not been observed, Com pared to t he metastasizing , malignant
regardless of the malignant histopatholcqv.' ameloblastoma, however, the AC seems to
Radiologically , amelobtastic carcinomas be more common (2 :1).6
may resem ble SMAs. but in most cases they
present as m.ocnned radiolucencies. Foci of
radio pacities, probably due to dystrophic cal-
cification, have also been observe d. Otten le-
sions present with perforation of the cortical

216
Pathology

3.2 Age both central (intraosseous) and pe rip heral


(extraosseous) variants have bee n de-
The age distribution of 24 cases of ACs ' .6-1 8 sc ribed . An amefoblasnc carcinoma origi-
is shown in Fig. 23-1. Amelob lastic carcino- nating from the ging ival or alveolar mucosa
mas mainly affect the etderty, but the age ep ithelium is very rare. Peripheral ACs may
range is 15 to 84 years. arise de novo and as dedifferentiated ACs
from preexisting ben ign pe riphera l amelo-
blastomas.
3.3 Gend er Histomorphoqeneticauy, tw o different AC
entities may be recoqnized. One is charac-
The marefemate ratio of 24 AC ceeeew-" terized by lesions that initially demonstrate
was 1.4:1 (see Fig 23-1). the morphology of a SMA but dedifferentiate
over time. Dedifferentiation may occur spon-
taneously or be related to surgical proce-
3.4 Loc ation dures that become necessary due to recur-
rences of the primary tumor or therapeutic
The topog raphic distributi on of 24 cases of radiat ion.The second entity comp rises those
AC,8-18 is shown in Fig 23-2; the majority of ACs th at have malignant cytologic features
cases we re fo und in the mandible . de novo. Am ong the cases of ACs reviewed
by Slootweg and Mull er,lO the re were tw o
cases in which the metastasis exhibited a
less differentiated pattern than the primary
t umor. In nine cases, the pr imary t umor
4. Path og ene sis and metastasis exhibited ded ifferentiation. In
14 cases , the primary amelo blasto ma had
The pathogenesis of ameloblastic carc ino- undergone anaplastic transformation but
mas is not cle ar. They may orig inate ex metastat ic disease was not present or, if pres-
ameloblastoma or ex odontogenic cyst, and ent, was not histologically proven.

5. Path ology
l'
,
- - 4-----4-\
: 5.1 Mac ros copy
5 ,,: 0
n =24 Few descript ions of t he macrosco pic as-
pects of ACs have been pu blished. Cox et
,
,, al16 de scribed a large AC specimen meas-
4 :, 0 uring 17x16x 13 cmandweighing 1,875 g.
3- - ---'- The internal portion of the tumor was tan-yel-
7' low wit h a necrotic and friable appearance:
several large cystic spaces were noted with-
Ag 23-2 Topographicdistributionof 24 cases of in t he necrotic area. In anothe r case.?the cut
ameloblastic carcinoma. Asterisk indicates that surface of the tumor was gra y-w hite and
no specificlocation was given. smoot h with a cent ral cystic area.

217
23: Ameloblastic Carcinoma


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"...t: ~~ , 't..__c: ~\<! ilt _, ~ , ~

Fig 23-3 Islandsand cords of highlycellularodon- Fig 23-4 A higher magnification of the AC in Fig
togenic (ameloblastomatous) epithelium in a ma- 23-3. Nuclearenlargement and hyperchromatism
ture fibrous stroma. Peripheral palisading is not of the ameloblastomatous component are evi-
obvious (hematoxylin-eosin [H&E], x80). (Cour- dent (H&E, x160).
tesy of DOSAK, Professor G. Jundt, Bas!e,
Switze rland.)

5. 2 Mi crosco py reverse n uclea r polarizati on; pe rip he ral


palisading and po larizat ion are not always
5.2. 1 Histologic definitions
clearly evident. Th e stellate reticu lum within
The WHO class ificatio n of 19924 did not use epit helial islands is often condensed and hy-
the term ameloblastic carcinoma. However, perceuutar. present ing a less ord erly pattern.
the autho rs described th is entity under the The c haracteristic differentiating features are
name malignant ameloblastoma, thus caus- nuclear enlargement with granular stippled
ing considerable con fusion (see chapte r 22). nu cle op las m, n uc lear hyp erc hromatis m,
The defi nit ion used by the present authors mild p leomo rp hism, an inc reased nuclear
is as follows: cytoplasmic ratio, and increased mitotic ac-
A neoplasm in w hich the histologic patt ern t ivity w it h abnorma l forms of mitoses (Fig
of a SMA has been retained in t he primary 23-4 ). Mitotic figures may attain a cou nt of 2
growt h in the jaw s and/o r in any metastasic to 5 per high-power field." In some cases, in-
growth, yet also exhibits cytolog ic featu res of dividual ce ll ke ratinization and keratin pearl
malignancy. form at ion may be seen. Necrosis and dys-
tro ph ic calc ifications also may be observed
in some of t he ep ithe lial islands, histolog ic
features not usually cha racteristic for amelo-
5.2.2 Histopathologic findings
blastomas. Different histologic patterns may
The AC is compose d of islands and cords of be noted w ithin t he malignant component
ameloblastomato us odontogenic ep ithelium high ly d iff erent iated squamo us ce lls or a
in an infilt rative pattern with in a stro ma of ma- more basaloid , poo rly differentiated variety.'
ture fibrous tissue (Fig 23~ ) . The ep it helium The co nnective tissue is usually com posed
may reveal a single oute r layer of amelo- of mat ure col lage n fibers with occasional in-
blastic ce lls of co lumna r to cu bo idal sha pe flammatory ce lls, hemorrhag e, an d/or he-
whic h exhibit a tend ency for palisading and mosiderin pigment.

218
Notes on treatment and recurrence rate

In rare cases , arnelobfastic ca rcinomas negative for these markers, as well as for vi-
may reveal clear cell differentiation. These tu- mentin. desrnin, actin, and factor VIII.The en-
mors demonstrate tumor islands with pe- tire tumor was negative for carcinoembrvon-
ripheral palisading of columnar or cuboidal ic antigen (CEA).
cells with reversed nuclear polarity. Prom i- Mueller et al 19 studied the DNA ploidy of
nent clear cells may be observed within fol- amelob lastomas (SMAs) and amelo blastic
licular epithelial islands. The clear cell com- carcinomas. Of the primary SMAs, 14 (82%)
ponent may be misinterpreted as a salivary were di plo id; 3 of 5 recu rrent amelo blas-
gland clear cell adenocarcino ma, a mu- tomas were dfplotd. No sig nificant differ-
coepidermoid ca rcinoma, or a metastatic ences in ploi dy bet ween pr imary and
neoplasm. Although only a few cases of the recurrent ameJoblastomas or among plexi-
clear cell variant of AC have been desc ribed, form , follicular, or acant homatous amelo-
they seem to have an aggressive clinical blastom a variants were demonstrated. Of five
course. ACs, four were aneuploid; ploidy did not cor-
Bruce and Jac kson 13 have drawn atte n- relate sign ificantly with th e incid ence of
tion to the difficulty in differentiating between metastasis. Aneuploidy seems to be more
the histologic appearance of the primary in- common than ploidy in ACs and may be re-
traosseous squam ous cell carcinoma and garded as a strong predictor for malignant
the AC. In this context, Corio at all stated that potent ial.
~ Although the primary intra-alveolar carcino-
ma (PISC) and the ameloblastic carcinoma
5.2.4 Ultrast ructural findings
exhibit some clinical differences, their histo-
logical features are similar enough to sug- Ultrastructural studies on arneloblastic car-
gest a histogenetic relationship. It is possible cino mas have not been published to date.
then that the primary intra-alveolar carci no-
ma (PISC) may rep resent simply a less dif-
ferentiated, usually non-keratinizing form of
ameloblastic carcinoma, both lesions being
derived from odontogenic epithelial rem- 6. Notes on treatment and
nants."
In a few cases, fine-needle aspiration cy- recurrenc e rate
tology has been app lied for the initial diag-
nosis of AC.14 The rarity and unusual biologic behavior of
ACs make it difficult to develop effectivetreat-
ment protocols. However, the clinical course
5.2.3 Histoch emical/immunohistochemi-
of th ese tum ors is aggressive with extensive
cal findings
local destruction. The t reatment of choic e is
Systematic histochemical or immu nohisto- radical surgery w ith neck dissection. 13 Some
chemical studies have not been performed autho rs have recom mended preope rative ir-
with tissues derived from ameloblastic carci- radi ation to decrease tum or size, but t his
nomas. Lau et alastudied th eir two cases for seems to be of only limited value.'! The re-
the presence of cyto keratins and showed sistance of ACs to radiotherapy has been de-
that the amelobtastom atous areas of the ACs scribed , but the significance of chemothera-
reacted strongly with antibodies directed py as a form of treatment is not clear."
against cvtokeratins CAM 5.2 and AEl and Loca l recurrences and metastasis to the
AE3; the basaloid and spindle cells were neck and lung seem to be common. t- and

219
23 : Ame loblastic Ca rc inoma

questions as to the mod es of metastasis of 8. Lau S, Tide man H. Ameloblastic carcino ma of the
jaws, A repo rt of two cases Oral Surg Oral Med
ACs have been raised. Aspiration of malig-
Oral Path o l Oral Badio l Ende d 1998;85 :78- 8 1,
nant cells int o t he lung, hematog enous
spread, and spread via lymphatics have all 9. Infante-Cossio P, Hernand ez-Guisado JM , Fer-
nandez-Mac hi n P, et at Arneloblastic carcino ma
been p roposed . Three of seven cas es re-
of t he maxilla : A report of 3 cases. J Oral Maxillo-
ported by Corio et at' had recurren ces w it h- tao Surg 1998;26 :159 - 162.
in 1 year. Pat ients w it h ACs in w hom bot h the
10. Sioot weg PJ, MOiler H. Malig nant ame loblasto ma
primary tumo r and metastasis revealed de- o r arnelo blastic carcin oma. Oral Surg Oral Med
differentiation died wit hin 2 years afte r metas- Oral Patho l 1984 ;57:168- 17 6.
tests."? Patients w it h maxillary ACs seem to 11. And ersen E, Bang G. Arneio blast!c ca rc inom a of
have an even more serious proqn osis.F the maxilla. J Maxillofac Surg 1986; 14:338- 340.
Survival of pat ients with ACs has to be 12. Lee L, Maxym iw WG , Wood RE. Ame lob lastic ca r-
evaluated over a long period of time due to c inoma of th e maxilla m etastatic to th e mand ible.
the possibility of rec urrence and th e appear- Cas e report, J Cranio maxillofac Surg 1990 ;18:
ance of local and distant metastasis. 24 7-2 50.
13 . Bruce RA, Jackso n IT. Ame lob lastic carcin o ma.
Repo rt of an aggressive case and review of th e lit-
erature. J c rano maxmorac Surg 1991 ;19 :267-
2 71.
References
14 . Ingram EA, Evans M L, Zitsch RP. Fine-needle as-
piratio n cyto logy of am elo blastic carcino ma of the
1. Corio RL, Go ldblatl Ll,Edw ardsPA, Hartm ann KS.
maxilla: A rare tumo r. Diaq n Cytc pat hc l 1996;14 :
Arneloblastic ca rc ino m a: A clinicopat holc qic
249 -252.
study and assess me nt of eig ht cases. Oral Surg
Oral Med Oral PathoI 19S7 ;64 :57 0-5 76. 15 , Simko EJ , Branno n RB, Eib ling DE. Arnelo blastic
carc ino ma of th e mand ib le. Case report. Head
2. Shafer WG, Hine M K, LevyBM.A Textb ook ofOral
Nec k 199 8;2 0 :65 4 - 659 ,
Patho logy . 3r d ec . Philadelph ia: w e Saunders,
1974 :254 . 16. Cox DP, M uller S, Carlson GW, Murray D, Amelo-
b lastic carc ino ma ex ame lo blasto ma of th e man-
3 , Pind bo rg JJ, Kramer IRH. Histolog ic Typ ing of
dible w ith mal ig nancy-assoc iated hypercalcemia.
Odo ntoge nic T umo rs, Jaw Cysts, and Allied Le-
Oral Surg Oral Med Oral Patho l Oral Rad iol En-
sio ns Ber lin: Sp ringer-Verlag , 197 1.
dod 200 0;90 :7 16 - 722.
4 K ramer IRH, Pind borg JJ, Shear M . Histo log ical
17. Mc Clatch ey KD, Sullivan MJ , Paug h DR. Periph-
Typing of Odo ntogenic Tum ours. 2d ed. Berlin:
eral ameicotasuc ca rc inoma: A case repo rt of a
Sp ringe r-Verlag, 1992.
rare neo plasm. J Oto laryngol 1989;18 :109- 111.
5 Eversole LR, Ma lignant epithelial odo ntoge nic tu-
18. Kao SY, Po ng BY, Li WY, et at. Maxillary odonto-
mo rs. Sem in Diagn PathoI 1999 ;16 :3 17 - 3 24 .
genic carc ino ma w ith d istant m etastasis to axil-
6 , Nagai N, Takeshita N, Nagatsuka H, et al. Amelo- lary skin, b rain, and lung : Case repo rt. Int J Oral
blastic carcinoma: Case repo rt and review . J Oral Maxnlotac Surg 1995 ;24 :229- 232.
Pethel Med 199 1;20:460-463.
19. M ueller S, DeRose PB, Co hen C. DNA plo idy of
7, Lolac hi CM , Shash i K, Madan M D, Jacob s J R. am elob lastom a and ame lo blastic carc inoma of
Am eloblastic carcinom a of the maxilla. J Laryngol th e jaws. Analysis by image and flow cvt ornct ry.
Oto l 1995 ;109 :10 19 - 1022 , A rch Pathol Lab M ed 1993;11 7 :1126-11 31 .

220
Primary Intraosseous Squamous Cell Carcinoma
(Solid)

1. Terminology Primary intraosseous squamous cell car-


cinomas are rare. Elzay" reviewed the litera-
According to Morrison and Deeley.' the cen- ture in 1982 and found 12 cases. Ohtake et
tral squamous cell carcinoma of the jaw was al? published a series of 28 cases of central
first described by Loos in 1913. In 1948, carcinomas in 1989 without clearly separat-
Willis2 suggested the term intra-alveolar epi- ing solid PISCs from cystogenic PISCs. Suei
dermoid carcinoma, and Shear' later revised et al" reviewed the literature on PISCs in
this to primary intra-alveolar epidermoid car- 1994, describing 39 cases from 24 publica-
cinoma. Pindborg et af suggested the term tions; however, details of individual cases
primary intraosseous carcinoma, which was were not shown." The most recent and com-
accepted by the World Health Organization prehensive review of PISCs is that of Thomas
(WHO) classification of 1992. 5 et al.? who included one case of their own for
Primary intraosseous squamous cell car- a total of 29 cases. The cases described by
cinoma (PISC or PIOC) must be differentiat- Bridgeman et al 10 in 1996, Kaffe et al!' in
ed from other odontogen ic carci nomas, 1998, and Ide et al 12 in 1999 were not in-
such as malignant ameloblastomas and car- cluded in the cases reviewed byThomas and
cinomas arising from odontogenic cysts. coworkers. The latter case 9 is of interest be-
Squamous cell carcinomas (SCCs) involving cause it was suggested that the tumor may
the jaw as an infiltration from the gingiva, alve- have originated from reduced enamel ep-
olar ridge, floor of the mouth, or maxillary si- ithelium.
nus or via -metastases have to be excluded.
The primary intraosseous squamous cell
carcinoma has been described , often incor-
rectly, under a variety of names, which in-
clude primary epithelial tumor of the jaw, car- 2. Clinical and radiologic profile
cinoma of the jaw, central epidermoid
carcinoma of the jaw, intra-alveolar carcino-
ma, intra-alveolar epidermoid carcinoma, Persistent symptoms like postextraction
central squamous cell carcinoma of the jaw, pain, toothache, periodontal disease, or peri-
primary odontogenic carcinoma of the jaw, coronitis were the presenting complaints re-
intramandibular carcinoma, central mand- ported by Thomas et al.? The diagnosis of
ibular carcinoma, primary intra-alveolar epi- PISC was delayed, mainly because the den-
dermoid carcinoma, and primary intra-alveo- tal problems were given top priority and the
lar squamous cell cercinoine" underlying disease was missed. Othersymp-

221
24: Primary Intraosseous Squamous Cell Carcinoma (Solid)

No. of cases

10
I...--V Women

8
8 [JJ Men

n=29
6

o ,. . . ,. . . ,. . . Id ,...... Id '..... ,...... Id ,...... ,...... k"

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89


Fig 24-1 Age distri
Age in decades
bution of 29 cases of
PISCs.9

toms were swelling, pain, and sensory dis 3. Epidemiological data


turbances. Since persistent pain and swell
ing of the jaw seem to be important present 3.1 Prevalence, incidence, and

ing symptoms of PISCs, this diagnosis has to relative frequency

be considered in all cases where initial den


tal treatment has failed. The diagnosis of Primary intraosseous squamous cell carci
PISC is difficult, and an infectious etiology nomas of the jaw arising de novo are more
may often (wrongly) be considered. Once the rare than cystogenic PISCs (see chapter 26).
histologic diagnosis of PISC has been made, Thomas et al? reviewed the English language
metastatic disease has to be ruled out. Prin literature in 2000 and found 29 acceptable
cipally, the investigation of the primary tumor cases. While there may be a few more cases
should include a chest radiograph to exclude hidden away in the internationall iteratu re,the
lung metastasis. PISC still appears to be an extremely rare
The radiographic features of PISC were re odontogenic lesion. Rates of prevalence, in
viewed by Kaffe et al." ' Osteolytic bone cidence, and relative frequency are not cur
changes are characteristic. The margins of rentlyavailable.
PISC lesions are poorly defined, diffuse, and
irregular in most cases.
3.2 Age

Primary intraosseous squamous cell carci


nomas commonly occur in elderly patients.
According to the review of Thomas et al," the
mean age of patients with PISCs (n = 29) was
53 years with a range of 4 to 81 years. Fig
ure 24-1 shows the age distribution of these
cases.

222
Pathology

and remnants of the dental lamina in the gin-


giva. Eversole 13 suggested that future stud-
ies should focus on disturbances in cell cy-
cling , proto-oncogene expression, and
tumor suppressor gene mutations to gain a
better understanding of the pathogenesis of
malignancy. To study the pathogenesis of
PISCs, however, is particularly difficult be-
23 3 cause of their rarity.

Fig 24 -2 Topographic distribution of 29 cases of


PISC,9 5. Pathology

5.1 Macroscopy

3.3 Gender Details on the macroscopic appearance of


PISCs have not been published.
Of 29 cases of PISCS,9 20 were men and 9
women; the male:female ratio is 2.2:1. The
male predominance is in agreementwith pre- 5.2 Microscopy
vious reviews.6 ,11
5.2. 1 Histologic definition
Both the 1992 WHO classitication'' and the
3.4 Location present authors define the PISC as follows:
A sq uamous cell carci noma arising with inthe
The distribution of PISCs according to loca- jaw, having no initial connection with the oral
tion is shown in Fig 24-2. The majority of 29 mucosa, and presumably developing from
cases were located in the posterior mandi- residues of odontogenic epithelium.
ble. Six cases occurred in the midlines of the
maxilla and mandible, three in each jaw.
5.2.2 Histopathologic findings
Some of the reported cases of PISCs have
revealed histologic features of squamous cell
carcinomas which were indistinguishable
4. Pathogen esis from SCCs of the oral mucosa. In such cas-
es, a definitive diagnosis may be impossible
without reliable clinical and radiographic
, The etiology and pathogenesis of PISCs are data. Primary intraosseous squamous cell
unknown. However, the cells of origin are carcinomas may reveal a distinct odonto-
odontogenic epithelial cells consisting of the genic pattern with basal-type cells forming
reduced enamel epithelium , the rests of alveoli or arranged in a plexiform pattern with
Malassez in the periodontal ligament and in palisading of the peripheral cells. The nuclei
the alveolar bone subsequent to tooth loss, of these cells are often oriented away from

223
24: Primary Intraosseous Sq uamo us Cell Carci noma (Solid)

5.2.4 Ultrastructural findings


-:- ~: ' ~".
Rusk in et al 14 pu b lished e lectron mi cro-
g rap hs of PISCs wi th th eir tw o case
repo rts.The histo log ic d iagnosis of well-dif-
~
....( ,,-, ferent iated SCC was s up po rted by ultra-
structural find ings. The sq uamous ep ithelial
"
cells revealed prom inent d esm osomal co n-
nect ion s and large irreg ular nuclei with
;., .... -4 - prominent nuc leoli.
,:t,
Fig 24-3 Primary int raosseous sq uamous cell ca r-
cinoma exhibiting irreg ular islands of wen-ont er-
entiated SCC (hematoxylin-eosin, x40). (Courtesy 6. Notes on treat me nt and
of OOSAK, Professor G. Jundt, Baste, Sw itzer-
land.) rec urrence rate

Of the 29 cases evaluated by Thomas et al,9


14 were treated with surgery as the primary
the basement me mb rane. Squamous meta- modality. Seven patients received combina-
p lasia and kerat iniza tion , as o bserved in t io n therapies (surgery and radiotherapy,sur-
acant ho mato us arnelo btastomas. m ay be ge ry and c hemotherapy, etc ). Out of 14 pa-
seen. In a few cases, foc i of ce nt ral necrosis t ient s treated surgic ally, 11 underwent
or d egeneration withi n the epi thelial islands hemimand ib ulectomy in conjunctio n with a
have been o bserved. Since t he histo log ic rad ical or modif ied radical nec k d issectio n.
cha racteristics of PISCs are not pathog no- Ten (34.5%) of 29 patients had lymph node
mon ic, a diagn osis can be made o nly if t here metastasis.
is no evidence of the tumor arising fro m c t. Rad ical sur gery rs accepteo as the p rimary
ther the oral mucosa or fro m an odontog enic mode of thera py for PISCs. Involvement of
cyst. Serial section ofthe main speci men has the lym ph nod es requ ires bloc k resection
been recommend ed toexciude other orig ins co mbined with t he excisio n of the prtrnarvtu-
of SCCs. Further, PISC has to be d ifferenti- mo r.
ated fro m metastatic tumo rs and from pri- The p rog nosis fo r patients with PISCs is
mary int raosseous muc oe pid erm oid ca rci- d ifficu lt to d etermin e because of the small
nomas (Fig 24-3). nu mber of repo rted cases, the d iff erent treat-
me nt modalities, and the variab le follow-up
time (fro m 5 to 60 months in the review by
5.2.3 HistochemicaVimmunohistochemi-
Thomas et aI9). The 5-year surv ival rate of pa-
cal findings
tients with PISCs has been rep orted as be-
No detailed histoch emica l or immuno histo- twe en 30% and 40 %.3Of the 12 patients eval-
che mical studies of PISCs have been pu b- uated by ElzaY,6 40% had a 2-year survival.
lished. To et al 15 stated that involveme nt of the lymph
nod es did not affect the prognosis, as is the
case fo r oral SCCs. In add itio n, it was noted
that patients with a delayed d iagnosis seem
to have a poo r p rognosis.

224
References

References 9 Thomas G, Sreeratna KT. Balan A. Ambika K. Pri


mary intraosseous carcinoma of the mandible-a
case repo rt and review of the literature. Eur J Surg
1. Mor rison R, Deeley TJ. Intra alveo lar carcinoma Oneal 2000 ;26:8 2-86 .
of the jaw : Treatment by supervoltag e rad iother
apy. Br J R<ldiOI 1964:35:32 1-326. 10, Bridg eman A, Wiesenfe id D, Buchanan M, at al.
A primary Intraosseous carcinoma of the antenor
2. Willis RA. Pathology of tumors. Lo ndo n: CY Mos. maxilla. Report of a new case. Int J Oral Maxillo
by,1948:310-316. rae Surg 1996;25:279-28 1.
3. Shear M. Pnmary intra-alveolar epidermo id carci 11. Kattc I, Ardekian L, Pelec M, at al. Radiologica l
noma of the Jaw. J Pethel 1969;97:645- 651. features of primary intraosseo us carcinoma of the
4. Pind borg JJ , Kramer IRH. Histolo g ic Typing of jaw, Analysis of the literature and report of a new
Odo ntoge nic Tumours, Jaw Cysts and A llied Le case, Dento maxillolac Radio I1998;27 :209-21 4.
sions. Berlin; Spn nger.Yenag, 1971. 12. Ide F, Shimayam8 lF, Horie N, Kaneko T. Primary
5. Kramer IRH, Pindborg JJ. Shear M. Histologica l intraosseo us ca rcino ma of the mand ible w ith
Typing of Odontogenic Tumours. 2d ed. Berlin: probab le origin fro m redu ced enamel epithe lium,
Springer.Venag, 1992. J Oral Pathol Med 1999 :28:420-422.
6. Elzay RP. Primary intraosseous carcino ma of the 13. Eversole LA. Mal igno.nt epithelia l odo ntogen ic tu
jaws . Review and update of odontogenic carci mars. Semin Diagn Patbor 1999: 16:317-324.
no mas. Oral Surg Oral Med Oral Pathoi 1982; 14. Rusk in JO. Cohen OM, Davis LF. Primary intra
54:299-303. osseous carcinoma: Report of two cases. J Oral
7. Ohtake K, Yokobayashi Y, Shingaki S, et al. Cen Maxiliofac Surg 1988;46:425-432.
tral carc inoma of the jaw . A survey of 28 cases in 15. To EHW. Brown JS. Avery 85. Ward -Booth RP.
the Japanese literature. J Craniomaxillofac Surg Primary intraosseous carc inoma of the jaw. Three
1989 ;17:155-161 . new cases and a review of the literature. Br J Oral
8. Suei Y, Tanimoto K, Taguchi A, Wad a T. Primary Maxillofac Surg 1991 :29 :19 - 25.
intraosseo us carcinoma: Review of the literature
and d iag nost ic c riteria . J Oral Maxiliofac Surg
1994;52:580- 583 .

225
Chapter 25

Primary Intraosseous Squamous Cell Carcinoma


Derived from Odontogenic Cysts

1. Terminology of PISC ex odo ntog eni c cyst. In t heir ac


companying literat ure review. the authors
fou nd 3 1 we ll-documented cases in which
In rare cases, primary intraosseou s squa transition betw een the norma l cyst epith eli
mous cell carcinomas (PISCs) may arise from um and the sq uamo us cell carcino ma was
the epithelial lining of odo ntogenic cysts. Ei demo nstrated histologically.
ther nonk eratini zing or odonto genic kerato
cysts now termed keratinizing cystic od onto
genic tumor (KCOT ) (see c hapte r 26) may be
the origin of PISCs. The total number of re
ported cases of PISCs ex odontoge nic cysts 2. Clinical and rad iologic profi le
is difficu lt to determine because d iagnostic
criteria have been missing. The fact that a
number of cases have been published as Clinical sympto ms are nonspec ific and in
possible or prob able cases of PISCs ex odo n c lude pain and swelling . Cases in which the
togenic cysts is a clear indication that it is mand ible is affected may involve expansion
sometimes difficult to prove conclusively that of the co rtical plates. Cervical lymphadeno
a PISC has developed from the lining of a pathy has also been reported. Parest hesia or
cYSt.' 2 Eversole et al3 critically reviewed t he anesthesia is uncommon but may occu r af
literature on PISCs ex odontogenic cysts and te r local invasion oft he inferior alveolar nerve.
accepted 36 cases, of which 33 we re ex Rad iologi cally, PISCs ex odo ntoge nic
cluded because of insuffic ient data. In 1989, cysts are nonspecific and are c haracterized
Waldron and Mustoe'' added another 13 cas by a radiolucency surrounded by a relatively
es that had been published since 1973 and we ll-defined radiopaqu e border (Figs 25-1
added their own probable case. Schwimmer and 25-2 ).
et ar' summarized the c linical data of 56 pre
viously reported cases in addition to a case
of their ow n. As early as 1975, Gardners stat
ed that to estab lish t hat the malignancy was
primary in the cyst, one must demonstrate
thetransition ofthe epithelial lining of the cyst
to carcinoma in situ and to invasive carcino
ma. Recently, Berens et al6 pu blished a case

22 7
25: Primary Intraosseo us Squa mo us Cell Carcinoma ex Odontogenic Cysts

Fig 25-1 Panoram ic ra


diograph of a40-yea r~ l d
man with a well-defined
cystic lesion in the left
maxilla. A tentative diag
nosis of rad icular (resid
ual) cyst was made. The
patient did not return for
treatment.

Fig 25-2 Pano ramic ra


diograph of the same le
sion shown in Fig 25-1 af
ter 2 years. The border of
the enlarged radiolucent
lesion was ill defined.
Histopathology revealed
a PISC ex odontoge nic
cyst.

3. Epidemiological data 3.3 Gender

Of 5 1 cases of PISC ex odontogen ic cysts,


3.1 Prevalence, incidence, and 33 .9% were wom en and 66 .1% were men
relative freq uency w ith a ma le:fema le ratio of 1:1.8 4

The PISC ex odo ntoge nic cyst is rare. Inci


dence has been esti mated at 0.3 1% to 3%.7 3.4 Location
Other estimates say th at one case per million
popu lation may occur." Of 56 cases of PISC ex odontog enic cysts,"
42 (80.3%) cases were located in the man
di ble and 14 (19.7%) in the maxilla . The ra
3.2 Age tio of mandi bular to maxillary lesions was 3:1.
In the review by Berens et al,6 19 cases were
The median age of 56 rep orted cases" was located in the mandible and 9, including their
57 years, w ith a range of 4 to 90 years; 5.4% own case, we re max illary lesions (mandi
occ urred in the first two decades, 25.0% in ble:maxilla ratio, 2:1).
the 3rd to 5th decades, and 69.9% in the 6th
to 8th decad es. Data for a detailed age dis
tribution are not read ily available.

228
Pathology

4. Pathogenesis 5.2.2 Histopath ologic findings

Primary sq uamo us ce ll carcinomas may


The pathoge nesis and etiology of PISC ex arise from a variety of cysts. Schwimmer et
odontogenic cysts is unknown . Long-stand al" reviewed 56 cysts associated with PISC
ing chronic inflammatory changes have been ex odont ogenic cyst and found the majority
proposed as possible pred isposing factors (37.5%) of cysts to be of the inflammatory
of malignant transform ation of the epithelial residual type, 17.8% were keratinized resid
lining of the cyst, but this cannot be sub ual cysts, 19.7% were follicular cysts, and
stantiated. Some reports have emph asized 17.8% were apical or lateral radicular cysts.
that keratinization of the cyst epithelium may The remaining 7.2% of the cysts were not
be associated with a higher risk of transfo r classified. Eversole? do ubted that the lateral
rnatiorr' (see chapter 26). periodontal cyst was place of orig in for
PISCs.
Dysplastic changes of the stratified squa
mo us epith elium are common and include
pleo morp hism, inc reased mitotic activity,
5. Pathology dropping off of bulbous rete ridges, hyper
chro matism, and cellular crowd ing. Sec
ondary squ amous epithelial changes such
5.1 Macroscopy as pseu doep ithelio matous hyperplasia,
acanthosis, and hyperkeratosis also may be
Detailed reports on the macro scopic ap observed (Figs 25-3 to 25-7). Foci of invasion
pearance of PISC ex odontogenic cysts have of the cyst epithelium may be evident in ear
not been published. The cystic nature of the ly cases of PISCs. In advanced cases, solid
lesions, however, is evident in all cases. tumor islands may invade the fibrous cyst
wall and alveolar bo ne. Most carcinomas
arising from cyst epithelium are well or mod-
5.2 M icroscopy
5.2. 1 Histologic definition
No particular definition for PISC ex odo nto
genic cyst has been pub lished by the World
Health Organization (1992). However,the ba
sic criterion for the diag nosis of this type of
lesion is that the transition between normal
cyst epithelium and squamo us cell carcino
ma has to be demo nstrated histologically.
Thus, the present authors use the following
definition :
A squamous cell carcinoma arising from the Fig 25-3 Nonkeratinizing odontogenic cys t
epithelial lining of an odontogenic cyst. (residual type) with carcinoma in situ of the ep
ithelial lining. Onlya slight inflammatory reaction
is seen in the connectivetissue wall (hematoxylin
eosin (H&E], x80). (Courtesy of Professor J.J. Sci
ubba, Baltimore, MD.)

229
25: Primary Intraosseous Squamous Cell Carcin oma ex Odo ntogenic Cysts

- . ~.~~~ , .~-.) 'j"': '".,'t'1;:.~. : ' P:.~"'"~f (:'~~ 4


~t; ;;, ::.~J" ~~, ,'.~.:~,','
, - . ~ . ro.j, ,l'./' ....,
t.~'.:A),d:!~~~;:tl.;~., o: ~'" :;: ~''l'''~,~y }'i~
(,'' .~ "
:~...."
"i::~;"''' ''~"' :' '\' .; {.-:r,.!l'~ ,e-:'JI' .',;0; ;' ',.~ ~
:'Ir:~" "lrt.;,.i\.i '-':, ~~: . :, ~ . ,';.~r:~
~
f ...
o:-. ,~ " ., .
~~~;"'(~~~l~ ;j:~t-.i....(/.,rt< S~~~~~.;~:~~rt~~. ~;trl'' J
,

.'. ""-~'.';:' "' ~. ~..,....~"'~l.'.,.:(,


.~~ .; I,o ...~~~.. ", ~ -e.' , ~.~"t~' ... '1
' ~tf'~~-" ~ ~"'''\' ,,"~.~-.;,..1~
:-~~~,
)l:~ : . t':/, ,,,,?'-'Y- ' r:..?';';.:tI
\j''~101':l~~ .' " ';' :4*-~ :-; ~->~~ '~#""'
'' ' l''..r'. ,.. ... ~'
" .<. :. :.' :-
, . _ ._ ~ " ~ ~~

Fig 25-4 Higher magnification of a different area


r~~~~iti
~.>
i?! -: ,,,,,. ...,,,,1i!i:
,.<,. ~{:.,t./.~1..r'":::-",-,;:,,"'.":.....
Fig 25-5 Epithelial lining of a nonkeratinized cyst
..-~C" . '"
~ '!. ~'b: .. .... ..
"':';-;"00 :."\.. I &oi....

of the cyst lining shown in Fig 25-3. Notice severe exhibit ing infiltrative squa mo us cell carci noma
ep ithe lial dysplasia with nucle ar hyperchrom a arising from cyst epithelium (H&E,xSO). (Courtesy
tism, cellular polymorphism, and loss of intercel of Professor J.J. Sciubba, Baltimore, MD.)
lular cohesion. The basal mem brane is still intact
(H&E, x120). (Courtesyof Professor J.J. Sciubba,
Baltimore, MD.)

'~'fJ"i !!te"' ''' '''''

~ ~
Fig 25-6 Squamous cell carcinoma arising from
the reduced enamel epithelium of a retained tooth

Fig 25-7 Another area of the same lesion shown
in Fig 25-6. The well-differentiated squamous cell
(H&E, x60). (Courtesy of Professor P.J. Siootweg, carcinoma IS evident (H&E, xSO).
Utrecht, The Netherlands.)

erately well dlfte rentlated.? T he fibro us cap 5.2.3 Histochem ical/ imm unohistochemi
sule of th e cyst may be t hickened as a result cal findings
of chronic inflam mat io n. W hen histological
ly evaluating an odo ntogenic cyst fo r t he oc Primary inl raosseo us sq uamous cell carci
currence of prima ry ma lignancy, ot her pos nomas arising from non keratin izing odonto
sib ilities-suc h as t he invasio n of the cyst genic cysts have rarely been st ud ied with
lining from an adjacent p rimary or metastat spec ial staining met hods. Recently, McDon
ic carci nom a a nd cyst ic de ge nerat ive ald et al'? fo und a squamous ce ll carcino ma
ch anges t hat have occurred in a primary or ex odontogenic cyst to be p53 po sitive.
metastatic ca rcinoma-m ust be exc luded.

230
Refe rences

5.2.4 Ultrastru ctural findings References

No studies on the ultrastructure of PISC ex 1. Hamp l PF, Harrigan WF. Squamous cell carcinoma
arising from an odontogenic cyst: Report of case.
odontogenic cysts have been pub lished in
J Oral Surg 19 73;31 :359- 362.
the English language literature.
2. Waldron C, Mustoe T A. Primary intraosseous car-
cinoma of th e mand ible with prob able origin in an
odontogenic cyst. Oral Surg Oral Med Oral Pathol
1989;67:71 6- 724.
3. Everso le LR, Sabes WR, Rov in S. Aggressive
6. Notes on treat me nt and growth and neoplastic potential of odon to genic
cysts. Cance r 1975;35:270-28 1.
recur rence rate
4. Schwim mer AM, Aydi n F, Morrison SN. Squamous
cell carcinoma arising in residual odo ntogenic cyst.
Since odo ntoge nic cysts with PISC cannot Report of a case and review of literature. Oral Surg
be differentiated clinically and radiographi- Oral Med Oral PathaI199 1;72:218- 221.
cally from conventional cysts, most of them 5. Gardne r AF.A survey of odontogenic cystsand their
areenucleated at first-stage surgery.Afterth e relationship to squa mous cell carcinoma. J Can
Dent Assoc 1975;3:161-167.
histopathologic diagnosis has been estab-
lished the treatment of choice for the PISC 6. Berens A, Kramer JF, Kuettner C, et at. Entstehung
eines Plattenep ithelkarzinoms auf dem Bode n ei-
ex odontogen ic cyst is radi cal surgery.
ner odon togene n Zyste. Mund Kiefer Gesichtschir
Treatment has varied , however, depending 200 0;4:330- 334.
onthe degree of invasion noted at biopsy and
7. Fanibunda K, Soames JV. Malignant and prema-
the prese nce or absence of lym ph node lignant change in odontogenic cysts. J Oral Max-
metastasis. Larger lesions require mandibul - morae Surg 1995;53:1469- 1472.
ectomy, maxillectomy, or partial resection of 8. Otten J-E, Joos U, Schill i W. Karzinomentste hung
the affected jaw with lymph node dissection auf dem Bode n des zystenbildenden odcntoqenen
to radical neck dissection. Epithels. Disch Zahnarztl Z 1985;40 :544-54 7.
The 2-year survival rate of patients with 9. Mc Donald AR, Progrel A, Carson J, Regezi J. p53--
PISC ex odontog enic cysts varies among d if- posit ive squamou s cell carcinoma originating from
ferent studi es'' from 53% to 80%. Figures on an odontogenic cyst. J Oral Maxnrotac Surg
recurrence rates have not been indicated in 1996 ;54 :216 -2 18.
the majority of reported cases.

231
Chapter 26

Primary Intraosseous Squamous Cell Carcinoma


Derived from Keratinizing Cystic Odontogenic
Tumor

1. Terminology the norm al epithelial lining to invasive carc i


nom a.
Primary intraoss eo us sq uamous ce ll car ci
nomas (PISCs) ex keratinizing cystic odon
togenic tumors (KCOTs) are very rare wh en
compared to PISCs arising from other odo n 2. Clinical and radiologic profile
togenic (no nke rat iniz inq) jaw cyst s (see
chapter 25 ). Befo re 199 2, on ly 6 case s of
PISCs arising from KCO Ts had been de Since there seem to be less than a doze n ac
scribed.' Add itional cases were published by ce ptable cases of PISCs ex odontogenic
Yoshida et al,2 Dabbs et al,3 Hennis et al," keratocysts in t he English language litera
and Foley et al.5 Cases of sq uamous cell car ture, specific clinical and radiographic crite
cinomas (SCCs) arising from KCOTs in pa ria of these tu mors are still unclear and may
tients w ith Gorlin syndrome have been de not be very d iffe rent from those of PISCs ex
scribed by Ramsd en and Bar rett" as well as odonto ge nic cysts (see cha pte r 25) (Figs
Moos and Renni e." Herbener et al8 reported 26-1 to 26-3).
a case of juxtaposed KCOT and squamous
cell carcinoma. Althoug h some morpholog
ic similarities betw een the KCOT and the tu
mor were observed, definitive evidence of a
common origin was not de mons trable.
To qualify as a PISC, there must be no ini
tial connec tion with the oral muc osa, overly
ing skin, or antral or nasal mucosa. The pos
sibility that th e PISC represents a metastas is
from a distant primary tumor must be ruled
out by physical and radio grap hic (computed
tomograp hy and magn etic reson anc e im
agery)examination,and the subse quent c lin Fig 26-1 Panoramic radiograph of a 13-year-old
ical course. As with the PISC ex odonto gen ic boy with a displaced maxillary right third molar.
cyst,the only c riter ion th at proves that a squa The borders of the floor of the maxillarysinus are
mous cell carcinoma has arisen from a KCOT indistinct. (Courtesy of Professor W. Wagner,
isthe dem onstration of direct transition from Mainz, Germany.)

233
26: Primary Intraosseous Squamous Cell Carc inoma ex KCOT

Fig 26-2 Axial CT scan (same as Fig 26-1 ) show- Fig 26-3 Corona l CT scan showing destruction
ing destructio n of the right posterior maxilla. of the right maxillary sinus with a homogeneous
(Courtesy of Professor W. Wagner, Mainz, Ger- radiopaque massfilling the entiresinus.(Courtesy
many.) of Professor W. Wagner, Mainz, Germany.)

No. of cases

10
OJ Women
8
OJ Men
6 n ",,1 4

2
oj
0-9
ro OTTI ro llimJLU
10-1 9 20 - 29 30-39 40 -49 50-59 60-69 70-79
OJ OJ
80 +
Age in years

cases associated wit h Gorlin's syndro me Fig 26-4 Age distri-


juxtaposed KCOT and sec but ion of 14 cases of
PISC ex KCOTs.

3. Epid emiologi cal data 3.2 Age

3.1 Prevalence, incidence, and Figure 26-4 shows the d istribut ion of 14 cas-
relative frequency es of PISC ex KCOTs. A ltho ug h th e sam ple
is sm all, cases te nd to invo lve mainly elde rly
Since t he num ber of well-docume nte d cas - patients.
es of PISCs ex KCOTs is extremely small, no
f igures on prevalence, in ciden ce, o r relative
f req uen cy are available.

234
Pathology

suggested that keratin metaplasia, followed


by epithelial hyperplasia and development of
epithelial dysplasia of cyst epit helia, were the
sig nif icant events in the development of
SCCs in odontog en ic cysts. It was also sug-
n = 14 ge ste d th at cyst linings that reveal kera-
3 tin ization we re at g reater risk for deve lop-
ment of SCCs. Furth ermore , w hile there are
several we ll-doc umented cases in wh ich a
KCOT and an SCC are juxtaposed ," it was
not possible to determine w hetherthese rep-
resent ma lignant transfo rmation withi n the
cyst or co llision of tw o pathog enetically dis-
Fig 26-5 Topographic distribution of 14 cases of
tinct entities. As w ith PISC in odo ntoge nic
PISC ex KCOTs.
cys ts, the re is a relative dearth o f pat ho-
genetic information for PISC ex odo ntogenic
kerato cysts. The same (unknown) tactors
that lead to transfo rmat ion of cyst epithelium
in non keratinizing cysts may also be relevant
3.3 Gender for KCOTs.

The male:fema le ratio of tu mors in 14 pa-


tients was 1.3:1. These are our ow n (non-
pub lished ) data prepared for this book.
5. Pathology
3.4 Location
5.1 Macroscopy
Figure 26-5 shows the to po graphic distri bu-
tion of 14 cases. Two cases involved th e en- No detailed desc riptions of the macroscop-
tire mandi ble. ic aspects of PISC ex KCOTs have been pu b-
lished .

5.2 Microscopy
4. Pathogenesis 5.2. 1 Histologic defini tions
No spec ific def inition of PISC ex KCOTs was
Althoug h the ep itheliu m of the KCOT seems pro posed by the Wor ld Health Orga nization
to have a high er mitotic activity than that of (WHO) c lassification of 199 2, 10 althoug h th e
other odontog enic cysts, th ere is litt le evi- odo ntogenic keratocyst-as it was kno w n un-
dence that the KCOT is assoc iated With ma- til now-as an entity was define d as "a cyst
lignant change more often than any other arising in the tooth-bearing areas ofthe jaws,
type of odontogen ic cyst. In fact, the poten- or posterior to the mandibular third mo lar,
tial for malignant transfo rmation in KCOTs and characterized by a th in fibrous capsule
seems to be quite low. Browne and Gouch? and a lining of kerati nised stratified epitheli-

235
26: Primary lntraosseo us Sq uamo us Cell Carcinoma ex KCOT

um usually about five to eight cells in thick- 5.2.2 Histopatho logic findings
ness and generally w ithout rete rid ges."
The definition of PISC ex KCOT used by In o rd er to co nfirm a histo logic diag nosis of
the present authors is as follows: "A squ a- PISC ex KCOT, th e histo log ic crit eria of the
mou s cel l carcino ma arising from t he ep- KCOT and t he trans itio n of t he normal cyst
itheiial lining of a keratinizing cystic od onto- ep it he lium of KCOT to SCC have to be
genic tumor." demonstrated. The PISC ex KCOT may de-
velop fr om pa rak eratin ized o r o rtho kera-
tinized cyst ep it he liu m . Mi ni c 1 claim ed to
have desc ribed t he f irst case of PISC ex
KCOT fro m ort hok erati nized cyst epit heli-

1//: >~ : I~ ' 'l \ 't ~ II: ' ':'; -~l' I

~-"""" /~'~

~:' .";~\;J7f. ,i~~: . .~


,,:~;)L~~~.lb,.~
Fig 26-6 KCOT with infiltrating large islands of Fig 26-7 Higher magnification of the tumor In Fig
we ll-d iffe rent iated sq uamo us cell ca rc inomas 26-6 showing infiltrating large and small, pre-
(same patient shown in Figs 26-1 to 26-3)(hema- dom inant ly well-d iffe rentiated sq uamous cell car-
toxylin-eosin [H&E), x50). cinoma islands (H&E, x80).

.0, .4 '" .7''"':....li;i


-
~r : :' :; ' :;~.S:,1 ~M9:tl~~~~<:!.~ ~,
J- ..., "'~~
.''fiI!'!. @ii~
lti
\ -:'. '1,
~'" t ~~

~t~t. ' ~; ; :~' i. '~ : :t,,,,,: ~..:..:.,:.....:


, t: ,(-:;i~~
,.;,'J. ~f!. ::'J .''.J.
~"}. ~~ t ~,,;:
'r.;::f'ii , ~,, '
_ _
,~ ,:-'
<~~~~
..
:
~::;-. - .
~~
<_'-',;Jo-. - J:- ..
:::& ,:,1;., e.{::~:':t:r fi"""'f;;fi.lt ~ y ~ ~ ..-' ' ~'~
f~~;~
~ -r-:,
r
[1~I-":fi,lJ:; ;:{~:~,.Iii~ \ ' ., ~ " -:: ~' ~~
;,~' .''''1; " '.' ~'':t . t "
.', ~1\f,'
~,y~ ,~"!":''j. , ,,~,, ..., 1\ , - "." , ~ ~ :
'.:?P},'(, l 'r. "" "" '~ ?j.:.a" ~j", . '-{- - , '"
- A '.: 'f :-\' ~';" ~~""',t- . "J..., .; ', .. -" - .\
~&:\ ' i ' l """ ~" \o.,~
~ . ~.,.. ~ .t-
_ '\ .,. 'ti~iJ! t{," .ls.$" .... { ~11. ': ': _ a ~ ......
~ ,;~ ...,~

~~~~b;
7:1 ' ,
:~~;:;
~*-'Ii1' ,~
: :\'~)1~i:.:~~ t?~:~~"
, "" .-." . , ;"",.. ." t : !~!1I:l:fI~~
- . ' , ".' ,C '

iii. ,"" ..i~


' . ~ ' , ~ '..~:," "~-,,",-. [,,'.. '_'':1';.
... ', " ' " . .'
. ... , .".. ' ,....:-,..'.
~
tf~a1,
\")1'. /'.. "..
,;.. '::- ' : ,::,\~~ :...( .
....,'~ >l~.,
Fig 26-8 Squamous cell carcinoma ex KCOT. Fig 26-9 Higher magnification of the transitional
The transition zone betw een the cyst lining of the zo ne revealing squamo us cell carcino mas that
KCOT and several Islands of the SCC is clear have arisen from the cyst lining of the KCOT (H&E,
(H&E, x25). (Courtesyof Professor P.J. Siootweg, x60). (Courtesy of Professor P.J. Siootweg,
Utrecht, The Nethertands.) Utrecht, The Netherlands.)

236
References

urn.' Epit helial dysplasia of varying d eg rees 6. Notes on treatment and


are oft en fou nd. Histo pathol ogic feat ures of
rec urrence rate
cystog enic SC Cs parall el t he prog ress ive
changes from dysplasia to SCC t hat typical-
ly occur in p recancerous lesions of the oral The tr eatm ent of c ho ice fo r th e PISC ex
mucosa." It is of further interest th at metas- KCOT is radical surg ery w ith nec k d issect io n
tasis to cervical and submandi bul ar lymp h of lym ph nodes. Due to t he sma ll num ber of
nodes occurs in up to 50 % of repo rted cas- cases of PISC ex KCOTs, no relevant infor-
es of PISC ex odont ogenic cysts; indeed , an ma ti o n o n rec urre nce rat e, freq uen cy of
enlarge d lymph nod e may be t he initial pre- metastas is, or pro g nosis are available. Lon g-
senting sign of a cystogenic SCC (Figs 26-6 term follow-up, as w ith pat ients with oral ca n-
to 26-9 ). ce r, is mand atory.

5.2.3 HistochemicaVimm unohisto chemi-


References
cal findings
No histoch em ical or im m unoh istoch em ical 1. Minic AJ. Primary intraosseous squamous cell
carcinoma arising in a mandibular keratocyst. Int
studies have been pu blished o n the PISC ex
J Oral Maxillotac Surg 199:2 1:163- 165.
KCOT. However, Hig h et al'2 exam ined the
2. Yoshida H, Onizawa K, Yusa H. Squ amous cell
DNA content of a KCOT and th e sub sequ ent
carcinoma arising in association with an ortho-
SCC. Using flow cyto met ry,they were able to keratinized odo ntogenic keratocyst. Report of a
show a pro min ent, abnorm al DNA stemline case. J Oral Maxillafac Surg 1996:54:647-65 1.
in the KCOT, w hic h was also p resent in th e 3. Dabbs OJ, Schw eitzer RJ, Schweitzer LE, Mantz
subseq ue nt SCC. F. Squamous cell carcinoma arising in recurrent
odontog enic keratocyst: Case report and litera-
ture review. Head Neck 1994;16:3 75-378 ,
5.2.4 Ultrastructural findings
4. Hennis HL, Stewart WC, Neville S, O'Connor KF,
Herbener et al8 stud ied th e ult rastructure of App le OJ. Carcinoma arising in an odon togenic
keratocyst with orbital invasion. Doc Ophthalmol
a KCOT and a juxtaposed SCC . At t he ultra-
199 1:77:73- 79.
structural level, so me of t he ce lls observed in
5. FoleyWL, Terry BC, Jacoway JR. Malignant trans-
both the KCOT an d t he SCC had a remark-
formation of an od ontogenic keratoc yst: Report
able resem blance to ame loblasts of devel- of a casco J Oral Maxillofac Surg 199 1;49:768 -
opin g t eet h a nd am elo b last-like cells of 77 1.
amelo biastoma. The aut ho rs saw so me indi - 6. Ramsde n RT, Barrett A. Gor tin's synd rom e. J
cations of a possible relat ion ship between Larynqol Otal 1975:89:6 15- 629.
the KCOT and SCC, but t heir observations 7. Moos KF, Rennie JS. Squamo us cell carcinoma
were not sufficient to suppo rt a conc lusio n arising in a mand ibular keratocyst in a patient with
of a shared orig in. Gor lin's syndrome. Br J Oral Maxillofac Surg
1987:25:280- 284.
8. Herbener GH, Gould AR, Neal DC, Farman AG.
An electron and optical mic rosco pic study of jux-
taposed odon tog enic keratocyst and carcinoma.
Oral Surg Oral Med Oral Pathol 1991 ;7 1:3 22 -
328.

237
26: Prima ry Intraosseous Squamo us Ce ll Ca rcinoma ex KCOT

9. Browne RM, Gough NG. Malignant chang e in the 11. Everso le LR, Sabes WR, Rovin S. Aggressive
epithelial lining of odon togenic cyst s. Cancer growth and neop lastic potential of odontogenic
1972;29: 1199- 1207. cysts. Ca nce r 1975;35:270- 28 1.
10. Kramer IRH, Pindborg JJ, Shear M. Histo logic 12. High AS, Quirke P, Hume WJ. DNA-ploidy stud-
Typing of Odontogenic Tumors. 2d ed. Berlin: ies in a ke ratocyst unde rgoing subseq uent ma-
Springer-Verlag, 1992. lignant transformation. J Oral Pathol 1987;16:
135- 138.

23 8
Chapter 27

Clear Cell Odontogenic Carcinoma

1. Terminology orbital region, and base of the skull, as well


as regional lyrnph node metastasis. The pa
tient died of the disease after 15 years. The
In 1985 , two gro up s of research workers aut ho rs labe led th ese cases clear ce ll
(Hansen et a!' and Waldron et a1 2 ) described ameloblastoma (CCA) and co ncluded that
a total of five cases of an agg ressive, intra th e two lesio ns should properly be cons id
bony neo plasm of putative odontogenic ered malig nant (clear cell) ameloblastomas
oriqin. All cases were characterized by a bi (MCCAs). In a later personal co mmunication
morphic ce ll popul ation cons isting of poly with Gard ner' Wald ron suggested that the
gonal cells and clear cells. The presence of CCOT and the MCCA rnay be part of a
clear ce lls in various odo nto ge nic tumors histopathologic spectrum and not separate
should not be surprising because th e dental entities.
lamina is thoughtto be a commo n origin,and In 1995, Eversole et al5 analyzed 17 cas
the remnants of these odontogenic cell rests es of CCOTs and MCCAs (8 cases from the
are reported to co ntain clear cells as one of literature and 9 cases from their own files, in
their co mponents." cluding an evaluation of the long-term follow
In the thr ee cases pub lished by Hansen et up of th e 3 cases initially reported by Hansen
al.' there were no local or distant metastatic et a!') and co nclud ed that CCOTs exhibit
foci. The authors were therefor