Documente Academic
Documente Profesional
Documente Cultură
Philipsen
Odontogenic Tumors and Allied Lesions
Odontogenic Tumors
and Allied besions
616 .9'923 14
All rig hts reserved. This book or any part thereof may not be reproduc ed,
stored in a retrieval system, or t ransm itted in any for m or by any
means, electronic. mec hanical, p hotoco pying, o r othe rwise, without the
wr itten perm ission of the pub lisher.
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
Introductio n 177
Contents
Section Six: Malig nant Ectom esenc hyma l Odo ntogenic Neoplasms
Introduction 333
Introduction 365
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
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
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
22
References
23
Chapter 3
25
3: Early Norm al Odo ntogenesis
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>
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.
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.
28
Disintegration of the denta l lamina complex
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
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
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
.>,
,
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)
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
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
35
4: Use of Rad iography in Diagnosing Odontogenic Tumors and Allied Lesions
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
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
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
42
Chapter 5
SolidjMulticystic Ameloblastoma
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.
44
Epidemiological data
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
--- O . 5 --~
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;
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
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
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
55
5: So lid / M ult icystic Amelo blasto ma
References 16. Coleman HG, Altini M, Groenev eld HI. Nuc lear
orga nizer regio ns (AgNORs) in od ontogenic cyst
and amelob lastom as. J Oral Pathol Med 1996;25:
1. CusackJW. Report of the amp utation of portions
436-44 0.
of the lower jaw. Dublin Hasp Rec 1827;4:1- 38.
17. Do Ca rmo MAV , Silva EG. Argyroph ilic nucleolar
2. Broca PP. Rec herc hes su r un nouveau grou pe de
organize r regions (AgN ORs) in arnelo blastornas
tu meurs designees sous Ie nom d'odo ntomes.
and adenomatoi d odonto genic tu mou rs (AOTs).
Gaz Heb d Sci MOd 1868:5 :70-84.
J Oral Pat hol Med 1998:27:153- 156.
3. Malassez L. Note sur la patnoqen ie des kystes
18. Yamamoto G, Yosh itake K, Tada K, et al. Granu-
dentaires d ites periostiq ues, J Co nn Med Prat
lar c ell amelo blastoma. A rare variant. Int J Oral
(Paris) 1884 :7:98- 99: 106- 107:115- 116.
MaxillofacSurg 1989;18: 140-1 4 1.
4. Ma lassez L. Sur Ie role d es de bris epitheliaux pa-
19. Hartman KS. Granula r-cell ame loblastoma. Oral
rade ntaires. Arch Physiol Norm Patho l 1885:5:
Surg Oral Med Oral Pathol 197 4;38:241-253.
309 -340 and 6:379-449.
20. Narvarrette AR, Sm ith M. Ultrastruc ture of granu-
5 . Ivy RH, Chu rchh ill HR. The need of a sta nd ard-
lar cell ameloblastoma. Cancer 1971;27:9 48 -
ized su rg ical and pathol og ica l classificatio n 01the
955.
tumors and a nomalies of de nta l origi n. T rans Am
Assoc Den t Seh 193 0 ;240 - 258 . 21. Ta ndler 8 , Ross i EP. Granular cell ame lob las-
6. Baden E. Termino logyof the ame lob lastoma : His- to ma: Electron micros cop ic obs ervations. J Oral
PathoI 1977;6: 40 1-4 12.
tory and current use. J Oral Surg 1965;23:40 -49.
22. Kumamoto H, Ooya K.l mm unohistochemical and
7. Partriella VM, Rogow PN, Baden E, Williams AC.
ultrastructu ral investigation of apop toticcell death
Gigantic amelob lastoma of the mand ible : Report
in gra nular cell ameloblastoma . J Oral Pathoi Med
of case. J Oral Surg 197 4;32:44-49.
200 1:30:245- 250.
8. Ueno S, Nakam ura S, Mushimoto K, Shlra su R. A
23. Altini M, Hille JJ, Buchner A. Plexiform gra nular
clinicopatho logic study of ameloblastoma. J Oral
c ell odontogenic tumo r. Oral Su rg Oral Med Oral
Maxillofac Surg 1986;44 :36 1- 365.
Pathol 1986 ;6 1:163- 167.
9. Reichart PA. Philtpsen HP, Son ner S. Ameloblas-
24. SiarGH, Ng KH, Chla TY. Co mb ined granular cell
toma: Biologica l prof ile of 3677 cases. Eur J Can-
ame loblastoma and plexiform granular cell odon -
cer B Oral Oneal 1995;31B:86-99.
togen ic tu mour. Singapore Dent J 1990 ;15:35-
10. Larsson A. Alm eren H. A me loblastoma of the 37 .
jaws. An analysis of a consecu tive series of all cas-
25. Siar CH, Ng KH. Unu sual gra nular ce ll odo nto-
es repo rted to the Swedish Cance r Registry dur-
ge nic tu mor. Report of two undescribed cases
ing 1958- 1971. Acta Pathol Micro biol Scand [A]
with features of granular ce ll ameloblastoma and
1978 :86:337 -349 .
plexifo rm gran ular cell odontogenic tumor. J Ni-
11. Shear M, Sing h S. Ag e-standard ized incidence han Univ Sc h Dent 1993:35:134- 138 .
rates of ameloblasto ma and dent igerous cyst on
26. Mi rch andani R, Sciubba JJ. Granular cell lesions
the Witwatersrand, South Africa. Commu nity Dent
of t he jaws and oral cavity; A cli nicopatholog ic,
Oral Epidemio l 1978;6:195- 199.
im munohistochemical, and ultrastructu ral study.
12. Gardner DG. Critique of the 1995 review by Re- J Oral Maxillo!ac Surg 1989:4 7:124 8- 1255 .
ichart et al. of the biologic profile of 3677 amelo-
27 . RO hl GH, Akuamoa-Boateng E. Granular cells in
blastomas . Oral Oneal 1999;35:4 43- 449.
odo ntoge nic and non-odontogenic tum ours. Vir-
13. Sma ll lA, Wald ron CA. Am elob lastomas of the chows Arch A Pathoi Anat HistopathoI 1989 ;4 15:
jaws. Oral Surg 1955;8:28 1-297. 403-409.
14. Bade n E. Odontoge nic tum ors . Pat ho l An nu 28. Sand ra F, Mitsuyasu T, Nakamura N, et at Im-
197 1:6:487-509. munohistoc hemical evaluation of PCNA and Ki-
15. Krame r IRH, Pindborg JJ, Shear M. Histo logical 67 in ameloblastoma. Oral Oncol 200 1;3 7:193-
Typing of Odontogen ic Tumours. 2d ed . Berlin : 198.
Spring er-Verlag, 1992. 29. Pindborg JJ. Odo ntog enic tum ors. In: Pathology
of t he Dental Hard Tissue. Co pen hagen: Munks-
gaard, 1970:367-428.
56
Refe ren ce s
30. Altini M, Siabbert HD, Johnston T. Papilliferous 43. Kumar D, Mulligan ME, Levine AM, Dorfman HD.
keratoameloblastoma. J Oral Pat hol Med 199 1; Classic adamantinoma in a 3-year-old. Ske letal
20:46 - 48. Radial 1998;27:406-4 09.
31. Siar CH, Ng KH. "Combined ameloblastoma and 44 . AguirreA, Takai Y, Meenaghan M, etal. Lectin his-
odontogen ic keratocyst" or "keratinizing amelo- tochemistry of arneloblastomas and odontogen ic
blastoma ." Sr J Oral Maxillofac Surg 1993 ;3 1: keratoc ysts. J Oral Patho l Med 1989;18:68 -73.
183- 186.
45 . Saku T, Shibata Y, Koyama Z, et al. Lectin histo-
32. Said-Al-Naief NAH, Lumerman H, Ramer M, et al. chemi stry of cystic jaw lesions: An aid for d iffer-
Keratoameloblastoma of the maxilla. A case re- ential d iagnosis betw een cystic amelob lastoma
port and review of the literature. Oral Surg Oral and odo ntoge nic cysts. J Oral Pathol Med 199 1;
Med Oral Pathol Oral Rad iol Endod 1997;84 : 20: 108 - 113.
535-539 .
46. Vedtofte P, Pindborg JJ, Hakomori S. Relation-
33. Wilson D, Walker M, Aurora N, Moore S. Amelo- ship of blood group carboh ydrates to differentia-
blastoma wit h mucous ce ll d ifferentiation . Oral tion patterns of normal and pathological odonto-
Surg Oral Med Oral Patho l Oral Radial End od genic epithe lium . Acta Patho l Microbiol lmmunol
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
and mucous metaplasia in the epithelial linings of ameloblas to mas from odontogen ic cysts based
radicular and residual cysts. J Oral Pathol Med on expression of bloo d cell carboh ydrates . Oral
1995;24 :309- 3 12. Su rg Oral Med Oral Pathoi 1988 ;66:480 - 482
35. Kuhn A. Ube r ene Kom bination von Adamanti- 48. Yam ada K, Tate moto Y, Okada Y, Mori M. Im-
nom mit Harnanqiorn als zent rale Kieferge- mu nostai nin g of invo luc rin in odonto genic ep-
schwu lst. Dtsch Msch r Z 193 2;50:49-5 6. it helial tu mor and cysts. Oral Surg Oral Med Oral
Pathol 1989;67:564- 568.
36. Van Rensburg LJ, Thompson 10C, Kruge r HEC,
Norval EJG. Hemangiomatous amelob lastoma: 49. Mori M, Yamada K, Kasal T, et al. Immunoh isto-
Clinical, radio logic, and patho log ic feat ures. Oral chem ical expression of ame logen ins in odo nto-
Surg Oral Med Oral Pathol Oral Rad iol Endod genic epithelial tum ours and cysts. Virchows Arch
200 1;9 1:374-380. A Pathol Anat Histopathol 199 1;418 :319-325.
37. Lucas RB. A vascular ameloblastoma . Oral Su rg 50 . Saku T, Okabe H, Shimokawa H. Immu nohisto-
Oral Med Oral PathoI 1957:10;863- 868. chemical demonst ration of ename l prote ins in
odo ntoge nic tumo rs. J Oral Pathol Med 1992 ;21:
38. Fischer B. Ube r ein prirnares Adamantinom der
113 -1 19.
Tibia. Z Pathopsych 1913;12:422-433.
51 . Snead ML, Luo W, Hsu DD-J, et al. Human amelo-
39. Czerniak B, Rojas-Coro na RR, Dorfm an HD. Mo r-
blastoma tumors express the ame logenin gene.
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-
brous dysplasia. Canc er 1989;64:23 19- 2334. tern s of exp ression of intermed iate filaments in
ame lob lastoma and human fetal toot h germ. J
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
bones-a reactive proce ss of adamant inoma tous 53. Heikinheimo K. Cell growth and differentiation of
tissue. J Cancer Res Clin Oncol 1992;18: 152- develop ing and neo plastic odo ntogen ic tissues.
156. Turku, Finland : University of Turku, 1993. Disser-
tation.
41. Hazelbag HM, Van de n Bro ek LJ, Fleuren GJ,
Taminiau AH , Hogendoo m PC. Distribution of ex- 54. Salo T, Kainu lainen T, Parikka M, Heikinheirno K.
tracellular matr ix com ponen ts in adamanti noma Expression of lam inin-5 in ameloblas to mas and
of long bone sugge sts fibrous-to-epithelial trans- human fetal teeth. J Oral Pathol Med 1999;28:
formation. Hu m Pathol 1997;28:183- 188. 337 -342 .
42. Sweet DE, Vinh TN, Devaney K. Cortical osteofi-
brous dysplasia of long bone and its relationship
to ada manti noma. A clinicopathologic study of 30
cases. Am J Su rg Pathol 1992; 16:282 -290 .
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
tion of osteolytic cytoki nes and adhesion mole- 19 72 ;108 :173 -1 76.
cules in ameloblasto mas. J Ora l Pat hol Med
68. Mince r HH , McG in nis J P. Ultrastructure of three
19 98 ;27:496- 5 00.
histo logic variants of the amelo b lasto ma. Cancer
56. Kim J , Yook JI. Immu nohistoc hem ical study o n 19 72 ;30:1036 - 104 5.
proli fe rat ing ce ll n uc lear antigen exp ression in
69. Hod so n JJ. Obse rvations o n orig in and natu re of
ameloblastom as. Eu r J Cancer B O ral O neo l
the ada mantino ma with special refe ren ce to cer-
1994;306: 126 - 13 1. ta in m uco-ep id erm oid variat io ns. Br J Plast Surg
57. Fun aoka K, Aris ue M , Kabayashi I, et al. Im- 19 57; 10:38-5 9.
muno histochem ical detectio n of p roliferating ce ll
70 . C utler LS. Intracyt op lasm ic de smosomes in hu-
nuclear antigen (p e NA) in 23 cases of am elo-
man ora l neopl as ms. Arc h O ral Bioi 19 76;21 :
b lasto ma. Eur J Cancer B Oral Onco ! 1996 ;3 2 8 :
22 1-2 26.
328 -332.
71. Takeda Y, Kikuc hi H, Suzuki A. Hyaline bodies in
58. Piattelli A , Fioron i M, Santi nelli A, Rubi ni C. Ex-
am e lob lasto ma: Histolog ical and Ultrastructu ral
p ressio n of p ro liferating c ell nuclear antige n in
ob servatio ns. J Ora l Pathol 1985;14:639 -643.
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-
toma with myofibroblastsand intracellula r sept ate
59. Chen J , Aufd em orte TB, J iang H, et a l. Neoplas-
junctio ns. Ca ncer 1980;45 :2858 - 286 3.
tic o d on tog en ic ep ithe lia l ce lls exp ress b on e
sialo p rotein. Histoc hem J 1998;30: 1- 6. 73. Sm ith SM, Ba rtov SA. Am elo bla stom a w ith my-
ofibro blasts: First rep o rt. J Oral Patho l 19 86;15:
60 . Gao YH, Yang LJ, Yamagu c hi A. Im mu nohi sto-
284 - 28 6.
che m ical d em onstration of bo ne morphog enetic
prot e in in odo ntog enic tum o rs. J Oral Patho l Med 74. Niiz tma M. Tissue cu lture of an am e lob lastom a. Z
1997;26:27 3 - 277 . Ze llforsch Mikrosk Anat 195 7;46 :127-1 3 8.
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.
mu nohis toc hemi cal dem o nstratio n of bcl-2 pro- Am J Anal 1956 ;99:3 5 1-3 89.
tein in ame loblastoma. J O ral Path ol Med 199 7; 76. Yasuda K, Sato m ura K, Nagayama M. Behaviour
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,
e lectro n mi croscope. J Osa ka Univ Den t Sch d iagn osis an d treatment of ame lo blastoma. In:
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
ture of the sim p le amel ob lastoma. Acta Patho l Mi- Saunders, 199 4:3 01 - 31 4.
cro biol Scan d 196 1;5 2:140 - 154. 79. Feinb erg SE, Ste inbe rg B. Surgical ma nagement
65 . Kim SK. Nasjleti CE, Weathe rbee L. Fine structur e of am elob lastoma. Cu rrent status of the literature.
of cell types in an amelob lasto ma. J Ora l Patho l Oral Surg Oral Med Oral Pal hol 1996;8 1:
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
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
Fig 6-3 Distribution ot 135 cases of PAs by age (in decades) and gender.
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.
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
66
References
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.
69
7: Desm op lastic Ame loblasto ma
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).
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).
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
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
77
8: Unicystic Ameloblastoma
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
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
.
~=:::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
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
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~------------------.
87
9: Squamous Odontogenic Tumor
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.
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
n = 28
3.4 Location
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).
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
92
Chapter 10
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).
94
Epidemiological data
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
96
Pathogenesis
No. of cases
n=50
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).
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 . .. ,( "
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 .
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
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
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
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
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.
111
11: Adenomatoid Odontogenic Tumor
112
Pathology
113
11: Adenomatoid Odontogenic Tumor
References
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
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
121"
12: Arneloblastic Fibroma
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
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
~---..,
'\$4~' ; ~'f)
' ~";
r',.,'" :~,.-;-'.:;0.~~, " '
~>-_. ':; - ~~> '.." ;'f;;..: ,r.- i;I " " - - ,~
o
" ' .~
' \ , ./. :
- \'
c . ' ,-, -,
..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).
125
12: Ameloblastic Fibroma
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
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.
130
Pathology
5. Patholog y
5.1 Macroscopy
3 4
131
13 : Ameloblastic Fibrodentinoma
13 2
Chapter ~ 4==-================::J
Ameloblasti c Fibro-odontoma
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.
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
134
Pathology
No. of cases
ac
31
30
20
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
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).
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.
3.3 Gender
4
3
13
20'
ve
20
3.4 location
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
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
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.
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.
4. Pathogenesis
9 .8 --f ~ ~ 2U
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).
152
Refere nces
153
Chapter 17
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.
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
157
17: Calcifying Ghost Cell Odontogenic Cysts!Tumors
158
Terminology
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-
159
17: calcifying Ghost cell Odontogenic CystsfTumors
Type 2Abn
Type 2Aaa
160
Clinical and radiologic profile
16 1
17: Calcifying Ghost Cell Odontogenic Cysts/Tumo rs
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
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"
,. '
- '" t Ilt1 \
\' 1
) -i
"t-...:',1f /
I
, .
"
i
, -, -;-".:..'.c
\: , .
-.",
.... ~. ... ,..J ; ~ ~ :\
iti;~-;<1~ __~ ,
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
168
Refe rences
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
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
~ . ~ . ~ - ~ ~ ~
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
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
173
18:Odomoame~b~t~
~
5.2.4 Ultrastructural findings
Stud ies on ultrastructu ral aspects of odon-
toarnerobtastomas have not been published.
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
175
Section Four
177
Introduction
178
Chapter 19
Odontogenic Fibroma
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
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.
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
' 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 19-6 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
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.
186
Refe re nc es
9. Handlers JP, Abrams AM, Melrose RJ. Danforth 22. Bhaskar SN. Synopsis of Oral Pathology. 5th eo.
R. Central odontog enic fibroma Clinicopatho- St . Lo uis: CV Mosby. 1977259
logic features of 19 cases and review of the liter-
23. Beqezr JA. Kerr DA Courtney RM. Odontogenic
ature. J Ora l Maxi llofac Surg 1991 ;49:46-54.
tumors: A na lysis of 706 cases. J Oral Surg
10. Doyle JL Lamster lB . Ba de n E. Odontogenic fi- 1978:36:771-778.
broma of the complex (WHO) type. Report of six
24. Slootweg PJ, MOller H. Central fibroma of the jaw,
cases. J Oral Maxillofac Surg 1985 ;43 :666 -674.
odontogenic Of desmoplastic. A report of five eas-
11. Gardner 00. Central odontogenic fibroma cur- es with reference to ditterential diagnosis. Ora l
rent concepts. J Oral Patho l Mad 1996;25:556- Surg Oral Mad Oral Pathol1983;56:61-70.
56 1.
25 . Fisker AV, Philipsen HP. Desmoplastic fibroma of
12. katte I. Buchner A Rad io logic feature of central the jaw bones.mt J Oral Surg 1976;5: 28 5-29 t .
odontogenic fibro ma . Ora l Surg Oral Meet Oral
26 . Wesley RK, Wysoc ki GP, Mintz MM . The ce ntral
PathoI 1994 ;78:81HI18.
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
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
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
192
Pathology
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.
,
193
20: Odontogenic Myxoma or Myxofibroma
.
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
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.
References
15 , Ad ekeye EO, Avery BS, W illiams H K, Edwards
M B. Advanc ed central myxoma of th e jaws in
Tho ma KH , Go ldman HM . Central myxoma of the
Nige ria. Clinical features, treat ment and patho-
jaw , J Oral Surg O rthod 1947;33 :53 2.
ge nesis. J O ral Sur9 1984 ;13 :177 - 186.
2. Kramer IRH, Pind bo rg JJ, Shear M . H isto log ic
16, Lucas RB , Pathology of Tumo urs of t he Oral Tis-
Typ ing of Od o ntogenic Tumours. 2d ed. Be rlin:
sues. 2nd ed . Lond on and Edinb urgh: Churchill
Springe r-Verlag , 1992 .
Livingstone, 19 72 :156-1 63 .
3. Farman AG, Nort je CHF, GrotepassFW,et al. Myx-
17. Sc hm idt-West hausen A M, Becker J ,Sc huppa n D,
ofib ro ma of th e jaws . Brit J Ora l Su rg 19 77 ;
Burkha rdt A, Reic hart PA. Odo ntoge nic myxo-
15:3- 18.
rna-cnaract enzauo n of t he extrace llular matrix
4. Kaffe I, Nao r H. Buc hner A. Clinica l and radio log- (ECM) of the tumour stroma. Eur J Cancer B O ral
ical features of odo ntoge nic myxo ma of the jaws, Onco I 199 4;30B :377 -380.
Dento maxillofa c Rad io I 1997 ;26 :299 -303.
18. Lo m bard i T, Sams on J, Be mard J-P, et al. Co m-
5. Hard er F, Myxomas of th e jaws . Int J O ral Surg parat ive im m unohistoch emical analysis between
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
199
21: Benign Cementob lastoma
;~~
,'
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.
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"
;" ~ ..:>t
~ ,""'! ,~
t~'?h;.~
~ ~1 "
i~~~\~:j';"\:""
",
"
V .:'(;;li:-.Ll
" ~~ !"... . ,
5. Pathol ogy
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
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
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
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
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
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)
2 15
23: Ameloblastic carcinoma
No. of cases
5 I'JJ """"'"
4 01 "'"
4 n= 24
3 3
3
2 2 2
2
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
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
.,- _
' /
l;; oIll.
~'Jt . ..~
~.. -"'r. ".. ...
'Cl p ;.r9
go,
. , ~ ,.~...
' .... T .. .~ ," ' ' ' h !r"
",, ~" ~, ..' ~j'P . ' , ' . ..,.. o<~~-'~
"" l\l~ . , ... r~B4 .~ ~ o" i!O! ",Jl '4
I
l l,~P'~wt,':~
li: . V(;r~ ' '':'~~ .t'':.: ~~'
!'if.o. ~ j~ .. r , ,,~~
. ~'D t Q 't,O;oi(~~ 'lI!f,~N f l}l 4i' ~
,.-~,~fle., '"'" "'.. 5t ill(I1ltO
t'.'J - -
-
,
' '',.,f.<-
""~
to u ~ . ""
<l ,lj "" .. .... j)
i" n'"" .~ ..
;.- t'1b~ .$~~ $ _ ~ .:':. ~' ~ 0_
~ ~ .. . ""CI "
lIIVlI~ " f
u;~e~: ~ ~t ' ,i'"" ~!tt't" ~
"
"...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.)
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)
221
24: Primary Intraosseous Squamous Cell Carcinoma (Solid)
No. of cases
10
I...--V Women
8
8 [JJ Men
n=29
6
222
Pathology
5.1 Macroscopy
223
24: Primary Intraosseous Sq uamo us Cell Carci noma (Solid)
224
References
225
Chapter 25
22 7
25: Primary Intraosseo us Squa mo us Cell Carcinoma ex Odontogenic Cysts
228
Pathology
229
25: Primary Intraosseous Squamous Cell Carcin oma ex Odo ntogenic Cysts
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.)
~ ~
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
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
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
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
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-
~-"""" /~'~
~~~~b;
7:1 ' ,
:~~;:;
~*-'Ii1' ,~
: :\'~)1~i:.:~~ t?~:~~"
, "" .-." . , ;"",.. ." t : !~!1I:l:fI~~
- . ' , ".' ,C '
236
References
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
239
27: Clear Cell Odontogenic Carcinoma
Based on the histologic find ings and the tu and mo bility of th e teeth is often present. In
mor 's clinical behavior, Dr Rick c hoseto des ede ntulous pat ients, a poorly fitting denture
ignatethe lesion a clear cell odontogenic car may be an early sign of tum or presence. The
cinoma. CCOC occurs as a cent raltumor in eitherjaw,
Odontoge nic tumors co ntaining a sign ifi whereas the CCA/MCCA may in extremely
cant number of clear ce lls are rare, They are rare cases be located in the gingival soft tis
represented by the clear cell variant of the sues (periph eral variant descr ibed by Ng and
calcifying ep ithelial odontogenic tum or (CC Siar 21 ).
CEOT, see chapter 10), th e clear cell amelo Radiographically, the CCOC app ears as a
blastoma (CCA/MCCA), and the c lear cell poorly delineat ed uni- or mu ltilocula r radi
odo ntoge nic carcinoma, A relatio nship, if olucen t lesio n that occu rs w ith prominent
any, betwee n the latter two entities is an in bone destruction. Divergence of roots with
teresting and controversial issue, and it has or w ithout root resorption is common. Nair et
yet to be fully elucidated. Piattelli et al7 was al ' 8 found that in its initial stages th e CCOT
the first to theorize that the CCOC is a dis may resem ble early periodontitis that fails to
tinct and separate entity and not a clea r cell resolve in spite of period ontal therapy. The
variant of the ame loblastom a (MCCA). In th e CCA/MCCA has the same radiog raphic ap
review by Eversole et al,5 however, the au pearance as that of its benign cou nterpart,
th ors evaluated on ly th e po ol ed data re the solid/ rnulticystic ameloblastoma.
garding CCOCs and MCCA s w ithout differ
entiating between the two.
T he present authors ana lyzed th e tota l
number of available cases of CCOCs and
CCAs/ MCCAs at th e end of 2000, and it 3. Epid em iolog ical data
seemed that on the basis of dem ograp hic,
clinical, and histologic features, th e tumors
co uld be di vid ed into 26 cas es of 3.1 Prevalence, in c idence, and
CCOCS -' 8 and 9 cas es of CCAs/MC relat ive f requ ency
',5,7
CAS, ' 9-25 It must be stressed that the avail
able data are still too few to allow defin itive In a demogra ph ic study of 759 cases of
co nclusions as to w hethe r the lesion s are odo ntoge nic tumors in a Ch inese pop ula
separate entities, tion, Lu et al26 found tha t th e relative fre
qu ency of CCOTs was 0.3%. This is the only
data available as yet.
240
Epidemiological data
No . of cases
10
OJ Women
8
OJ Me'
6 n =26
5 5
4
n = 21
3.3 Gender
241
27: ClearCell Odontogen ic Carcinoma
5.1 Macroscopy
~~~:1{J~~t~~~~~~:::~~~~~~~'~~~;:~~~~~~~
Macroscopic features of CCOCs or CCAs/ ~ ' ' .'.... ~;...-: -" ;o''' '::. . i' ;..--iJ fi t ~ ..~ ~:~ '~"""' ;;-~~
MCCAs are rarely described. Hansen et a!' ~~~ t;!!j{~;~~~~'~ ~.; ~ri:~::~~~~~~~
~~:;,t-I t...,~-" ~~.,..: ~~'"a .c.. ~-::_ .I~:~- ~~""'i
.
found that sections of surgical spec imens of ~~}_;~:~~U ~ : ~ ~. '~. "!-~~~~~~
;f..
::if .,.,~....,,;,..." --~ "",." .~ ' '''~ '~ " . ..... ;~ Itt ~ ..... ~-- ~. "1~~
CCOT d isclosed a hom ogenous, pinkish (.(~~.~ !': ;'::;_ . --:' ~t ;'~:..:: '.~...~. r~~ \\~.~_~t :;
gray or white, solid (often glistening) tumor ::..... . ~,
...
r...;,, :.. ;...~.J-.....:.-'
...
..., -~ ..-:; ~ -
_:...:.~:::-;~ . - ~ \;i.~ .'*
.... ':Jli;: - . ..... .
~ i~~
.' -..-......
~_ . , -.~ :::"!'l
242
Pathology
of CCOC has island s th at are almost excl u- present authors believe that the CCOC and
sively of the clear cell phenotype. the CCA/MCC A co nstitute separate tumors.
A defin ition of the CCA/M CCA was not Future studies of larger numbers ofthese two
contained in the 1992 WHO class.fication .?" tumors may reveal w hether they should be
The present autho rs use the fo llow ing defi- viewed as entit ies or variants of a biologic and
nition: histopathologic spectrum.
A malignant neoplas m showing areas con-
sistent with a diagnosis of a fo llicular amelo -
5.2.2 Histopathologic findings
blastoma in wh ich varying numbers of tumor
Islands show periphera l palisad ing of c ub- T he diagnosis of CCOC is based on histo-
oidal and cy lindrical cells w ith reversed nu- patholog ic findi ngs as outlined in the pre-
clear po larity (directed away from the basal ceding section . Tumors with clear cells im-
lamina). A pro minent clear cell co mponent is pose ser ious pro blems for different ial
present within the fo llicula r nests replacing diagnosis since clear cell tumors in the head
the stellate retic ulum (Fig 27-4). The stroma and nec k region can originate from a num-
IS composed of dense, fibro us connective ber of sources, including salivary glands
tissue w ith hyalinized areas. (c lear ce ll m ucoepidermoid carcinomas,
The CCOC was considered an entity in clear cell acinic cell carcinomas, clear cell on-
Eversole 's 1999 class ification of odonto- cocytomas, and epit helia-myoepithelial car-
genic carcnornas."? Eversole dist ing uished cinomas, to name a few), other odontogenic
between th ree histo path ologic patterns, of t umor s (such as the c lear cell variant of
whic h the firs t tw o correspon ded to the CEOT), and metastatic renal clear cell carci-
present authors' definition. Eversole's third nomas (hyperneph romas) .Clear cell nests or
pattern co rrespo nded to what the present islands may be a prominent featu re in devel-
authors call clear cell ame loblastoma/m alig- opmentallateral periodo ntal cysts and in the
nant clear ce ll ame lob lastoma. T hus , the gingival cyst of the adu lt." The problem of dif-
ferential diagnosis of clear cell tumors of the
head and neck was reviewed by Everso le3 1
and Maiorano et al.32
Several authors have noticed the occur-
renc e of hyalinized or partly hyalinized stro-
ma in both CCOC S 6.14 and CCAs/MC-
CAs.'9.2o Miyauchi et al ' 5 and Kumamoto et
al 17 fo un d eosino philic hyaline deposits
(remin isc ent of amy loid -lik e g lob ules in
calcifying epithelial odontoge nic t umors)
formed In direct contact w ith th e epithelial
nests in their reported cases of CCOCs. How-
ever, these de posits did not stain w ith Con-
go red. The authors suggested it is possible
t hat the CCOC is capable of epit helioec-
Fig 27-4 GGA/MGGA follicular (SMA-like)tumor tom esenchymal ind uction, a view the pres-
island with peripheral palisading of cuboidal and ent auth ors do not support.
columnar cellsthat have reversed nuclear polari- The patho logist wi ll probably find the di-
ty. The stellate reticulum has been replaced by agno sis of CCA/M CCA less difficu ltthan that
clear cells (H&E, x150). of CCOC . Histolog icall y, typical SMA-lik e
243
27: Clear Cell Odontogenic Carcinoma
(fo llicular) structures with palisading of the Muramatsu et al ' 2found that the foci of some
peripheral cylind ric cells and reversed nu- ce ils w ere 8-100 protein positive and sug-
clear polarity, co mbined w ith cen tral areas of gested thatthese might be Langerhans cells.
clear cells w here a stellate reticulum wou ld Eversole et al 5 reported to have found mod-
be expect ed, are cha racteristic feature s. Th is erately intense pos itivity for 8-1 00 protein
clear cell differentiation in a SMA was first and cyto keratin, more so in the polygonal
noticed by Waldron et al.2 Both the pr imary cells than in th e clear cells. De Aguiar et al20
and metastatic foc i are characte rized histo- found pos itivity fo r only cytokeratin s 14 and
logically by be nign, innoc uo us-ap pearing 13 in their case of CCA/ MCCA. Cytokeratin
tum or islands, w hich lac k any featu res of 14 is one of th e major cyto keratins of nee-
matlqnancy.>? This is in co ntrast to the plastic cells in SMAs.33
malig nant ep ithe lial odontogenic tumor, in
Eversole's classif icatiorr'?called ameloblast-
5.2.4 Ultrastructural findings
ic carcino ma, that histologically retains the
features of amelo blastic di fferent iation yet Eversole et al28 gave ultrastructural descrip-
also exhib its cytologic features of ma lignan- tions of tissue samples from a case (at the
cy. tim e d iagn osed as CCO T) reported by
Hansen et at.' They found the presence of
abun dant glyc ogen rosettes in the cytoplasm
5.2.3 Histochemical/immunohistochemi-
oft he clear cells. No well-develop ed Golgiap-
cal findings
pa ratus , free t onofilaments, or secretory
Histochem ically, clear cells in both CCOC s granules were observed, suppo rting the the-
and CCAs/MCCAs show identical react ions. ory of a nongl and ular epithelial origin. Annu-
Studying fresh-frozen tumor sect ions, Ever- late lamellae were frequ ently present in the
sole et al26 found that the cytoplasm in clear cytopl asm, as were Iysosomes. Many ceils
tum or cells of CCOTs (C COCs) exhibits had ce ntrioles o r m icr otubul e or gan izing
promin ent d iastase-d ig est ed PAS-positive centers adjacent to the nuc lei. Desmosomes
granules. Bot h for malin-fixed and fresh - linked adjacent tum o r cells . Th e plasma
frozen sections failed to di sc lose cyto plasmic me mbranes were often convoluted, with in-
alciano philia. Thes e findings were confirmed terdig itating mic rovilli. These findings were
by Miyauc hi et al. ' 5 Further, Eversole et al28 generally co nfirmed by Fan et al 8 and
foun d that enzyme histochemical reactions Miyauc hi et al. 15 However, Fan et al8 d id not
disc losed diffuse granular positivity for acid find conspicuou s cytop lasmic g lyc oge n;
ph osph at es, no nsp ec ific este rase, an d rather the cytoplasm was c haracterized by
NADH diaphorase, but the cells we re nega- sparse organ elles. Maiorano et aj32 pointed
tive for alka iine phosphatase. out th at clear ce lls most ofte n result from fix-
lmmunohistoc hemi cally, several authors ation artifacts and glycog en storage ; in some
have exa mi ned tu m or ti ssue from instances they may be a reflection of pecu-
CCOCS8.1 2.15.17 and CCAs/MCCAs.2o How- liar functional states of the tumor cell or may
ever, the immunohistoc hemical features of result from a lac k of organelles. Guilb ert et
CCOCs are still unclear. Most autho rs agre e al,23 w ho exami ned the ultrastructu re of a
that tumo r cells stain diff usely and intensely CCA/ MCCA , found the cytoplasm of the
positive for CK 19, epitheli al membrane anti- clear ce lls to be rich in glycoge n and lyse-
gen (EMA ), and filagg rin but are negative for so mes.
8-100 protein, glial fibr illary acid ic pro tein, in- In 1994, Mi lch g rub et al 34 described a
volucrin, virnentin, and smoo th muscle actin. un ique salivary g land tum or w hic h they
244
N otes on treatme nt and recurre nce rate
called hyalinizing clea r cell carci noma nosis with no evidence of metastasis or re-
(HCCC). This tu mor, most frequently occur- currence.
ring in women in minor salivary glands (par- The present authors do not support the in-
ticularly at the base of the tongue or palate) terpretation of Berho and Huvos's findings.
is composed of nests or solid sheets of uni- The demographic data of their cases exact-
formly clear cells and others with weakly ly match those of CCOC cases. The histo-
eosinop hilic cytop lasm. The clear cells have logi c crite ria as well as the immunohisto-
a polyhedral ap pearance, round nuclei, In- chemical profiles of the HCCCs also fit those
conspicuous nucleoli, and no nuclear atyp- of CCOCs. The disagreement with Berho
ia. The cytop lasm is filled with PA& positive, and Huvos's view may be explained by the
diastase-sensitive glycogen granules but is fact that they only referred to 5 out of the 15
devoid of mucin. reports on CCOCs available at the time of
Immunohistoch emistry shows the expres- their report. It should be add ed that recur-
sion of epithelial markers-cytokeratin, EMA, rence and metastat ic d isease may occur
and occasionally carcinoembryonic antigen more than 5 years after initial diagnosis,30so
(CEA)- but an absence of myoepithelial de- follow-up periods of 14 and 17 months do
terminants-S-l 00 prote in, actin, and vi- not rule out metastat ic potential.
mentin. Ciusters of tum or cells in HCCCs are
separated by broad bands of PA& positive,
hyalinized fib rous stroma that may undergo
myxoid or hyaline degeneration. The stroma
may hence resemble amyloid but it is nega- 6. Notes on treatment and
tive for Congo red. Althoug h capable of
lymph node metastasis, the HCCC appears recurrence rate
to behave in a less agg ressive fashion than
other malignant clear cell tumors of the sali- The reason forthe change in nomenclature--
vary glands. Occurrences of this t umor in in- fro m CCOT to CCOC-is to be found in the
traosseous jaw locat io ns was recently re- continued follow-up of t he t hree cases ini-
ported by Berho and HUVOS35 in tw o wom en, tially reported by Hansen et a!' and reviewed
66 and 53 years of age. One tumor arose in by Eversole et al5 10 years later. One of the
the mandible, the other in the maxilla. The three patients, a 74-year-old woman with an
authors we re aware of the close resem- ante rior maxillary tum or, develop ed wide-
blance between HCCCs and CCOCs spread local extension and regional lymph
(CCOTs) and did not believe that their cases node and pulmonary metastasis. Death oc-
satisfied the histologic criteria for CCOCs. curred 7 years after the initial diagnosis. In a
Both cases reported showed an overgrowth second case involving the anterior mandible
of a heavily hyalinized stroma (not illustrated of a 4 1-year-old wom an, multiple recur-
in the article). The authors further claimed rences with regional and distant metastasis
that the characte ristic perip heral arrange- resulted in death 15 years after the initial di-
ment of the polyhed ral cells seen in CCOCs ag nosis. In both these cases, the original di-
were not found in their HCCCs. Lastly, they agnosis did not allude to malignancy and the
found the immunoh istochemical prof iles of primary treatm ent co nsisted only of curet-
their cases to be more in keeping with the tage. Cases with a favorable outcome were
one described for HCCCs than fo r that of usually treated by radical resection at the
CCOCs. Both patients exhibited good health time of initial surgery, whereas some of the
14 and 17 months, respectively, after diag- cases that involved multi ple recu rrences,
245
27: Clear Cell Odontogenic Carcinoma
metastasis, and d eath were initially treated 9. MillesM . Doyle JL. MesaM ,Raz S. Clearcell od on-
by loc al enucleation and c urett ag e. tog enic ca rcinoma wit h lym p h nod e metas tasis.
Oral Surg Oral Med Oral PathoI 1993;76:82-89.
Of the nine rep o rted cases of CCAs/M C-
CAs, o nly two did not sho w rec urren ce-one 10. Nik ai H, M iyauch i M, Lju in N. A case of clear cell
od ontog enic tum or. Tr Soc Patho l Jpn 1993; 82:
pe rip heral variant w ith a 5-year tollo w-up?'
127, A bstract.
and o ne case of a 14-year-old boy fo llowed
for 15 years n Th e rem ainin g cases sho we d 11. Sadeg hi EM, Levin S. Clea r ce ll odontogen ic car-
c ino ma of the mand ible: Repo rt of a case , J Oral
multip le recurrences w ith and w ithout lymph Maxillofae Surg 1995;53:613-6 16.
node m etastasis.21,22
12. Muramatsu T, Hasturnoto S, Inn oue T, et al. Clear
Thus, early aggress ive surgery is clearly cell odontogenic ca rc ino ma in the mand ible: His-
the th erapy of c ho ice and a close fo llow-up tochem ica l and imm unohistoc hemical observa-
for seve ral years is mandatory. t ions w ith review of the literature. J Oral Pathol
Moo 1996;25:51 6- 521.
13. Vesper M , Wilck T, Dona th K, Sc hmelzle R. Hel-
References Izelliges odontogenes Karzinom in Verbindu ng
mit ein em Plattenep ithelka rzinom. Fallbericnt uno
1. Hansen LS, Everso le LA, Green TL . Powell NB. Lit eratu rubersic ht. Mund Kiefe r Gesichtsch lr
Clear cell odontogenic tumor- a new histologic 1998;2:270- 274.
variant with agg ressive pote ntial. Head Neck Surg 14. Yam amo to H, Inu i M , Mod A, Tagawa T. Clear cell
1985;8:115- 123. od ontog enic ca rcinoma, A case report and liter-
2. Wa ld ron CA , Sma ll IA, Silve rma n H. Clear ce ll ature review of odo nto genic tumours with clear
ame loblas to ma-an odontoge nic ca rcino ma. J ce lls. Oral Surg Ora l Med Oral Pathol Oral Radiol
Oral Maxillof ac Surg 1985;43:707- 717. Endod 1998;86:86- 89.
3. Wysocki GP, Brannon RB , Co lone l L, et al. Histo- 15. Miyauch i M, Ogawa I, Takata T, et al, Clear cell
genesis of the lateral pe riodonta l cyst and the gin- odontogenic tumour: A case with induction of
gival cyst of the adu lt. Oral Surg Ora l M eet Oral d ent in-like struct ures. J Ora l Patho l Med 1998;
PathoI 1980;50:327- 334. 27:220- 224.
4. Gardner QG. Some current concepts on t he 16. Ku mam oto H, Kawamura H, Ooya K. Clear cell
pa thology of ame lob tastomas. Oral Su rg Oral odontogenic tum or in the mandible: Repo rt of a
Mad Ora l Pathel Oral Radiol Endod 1996;82: case wit h an immunohistochemical study o f ep-
660-669. ithelial ce ll mar kers . Pathollnt 1998;48:6 18- 622.
5. Everso le LR. Duff ey DC. Powell NB . Clear cell 17. Kuma moto H, Yamazaki S. Sate A. et at Crear cell
o d ontogen ic ca rc inoma. A clinicopathologic odonto ge nic tumo r in the mand ible: Report of a
analysis. Arc h Oto laryngol Head Nec k Su rg 1995; case with duct-like appearances and den tinoid in-
121:685-68 9. duction. J Oral Pathol Med 2000;29:43-47.
6. Bang G, Koppang HS, Gilhuus-Mo e 0 , et al. Clear 18. Nair MK , Burkes EJ, Cha i-LJ-Dom O. Rad iograp h-
cell odon toge nic ca rcino ma: Rep ort of three cas- ic man ifestation of clear ce ll odo nto genic tum or,
es w ith pu lmonary and lymph nod e metastases. Oral Surg Oral Med Oral Pathol Oral Radio ! En-
J Oral Pathol Med 1989;1 8:1 13- 118. dod 2000;89:250- 254.
19, M ad A, Escut ia E, Carrera M , Peric ot J . Clear cell
7. Piattelh A. Sesen na E, Tnsit P. Clear cell odonto-
genic ca rcinoma. Report of a case wit h lym p h ameloblastoma or odo ntogenic car c inoma. A
nod e and pu lmonary metast ases. Eur J Cancer B case rep ort. J Cranfomaxitlofac Surg 199 5;23:
OraIOneoI 1994;308:278-280. 387-390.
8. Fan J, Kubota E, Imam ura H. et al. C lear cell odon- 20. de Aguiar MCF, Gomez RS. Silva EC, de Araujo
tog enic carc inom a. A case repo rt with mass ive in- VC. Clear-eell ameloblastoma (clear-cell odonto-
vasion of neighboring organs and lymph nod e genic car cinoma ). Report of a case. OralSurg Oral
me tast asis. Or al Su rg Oral M ed Ora l Pathol Med Oral Pathol Oral Radiol Endod 1996;81 :
1992;74:768- 775. 79-83.
246
Re fere nces
21. Ng KH, Siar CH. Peripheral ameloblastoma with 29. Kramer IRH, Pindborg JJ, Shear M. Histological
clear cell differentiation. Oral Surg Oral Med Oral Typing of Odo ntogenic Tumours . 2d ed. Berlin:
PathoI1990;70:210 - 213. Springer-Verlag. 1992.
22. Muller H, Slootwe q P. Clear cell differentiation in 30 . Eversole LA. Malignant epithelial odontogen ic tu-
an amelob lastoma. J Maxillofac Surg 1986;14: mors. Semin Diagn PathoI 1999:16:317 - 324.
158- 160.
3 1. Eversole LR. On the differential diagnosis of clear
23. Guilbert F, Auriol M, Chomette G. Una forme rare cell tumour s of the head and neck. Eur J Cancer
c 'eplmetlorna primit if de la mandibule : Le ca rci- B Oral Oncol 199 3;29B:173- 179.
a
nom e odo nto qeniq ue ceuutes claires . Etude
32. Maiorano E, Altini M, Favia G. Clear cell tumors of
cliniqu e et mo rp hologique. Rev Stom atol Chi r the salivary gland s, jaws, and oral mucosa .Semin
Maxillo!ae 1991 ;92:2 77 -2 80.
Diaqn PathoI 199 7;14:203- 212.
24. Oduk oya 0, Arole O. Clear-cell amelo blastoma of
33. Vigneswaran N, Whitaker SB, Bud nick SO, at al.
the mandible (a case report). Int J Oral Maxillofac Expression patterns of ep ithelial differentiation
Sur9 199 2;21:358 - 359 .
antigens and lectin-bind ing sites in amelobla s-
25. Duffey DC, Bailet JW, Newman A. Amelob lastoma tom as: A comparison with basal cell carcinomas.
of the mand ible with ce rvical lymph node metas- Hum Pathol 1993;24:49- 57.
tasis. Am J Otolarynqol 1995;16:66- 73.
34. Milchgrub S, Gnepp DR, Vuitch F. et a1. Hyaliniz-
26. Lu Y, Xuan M, Takata T, et al. Odon togeni c tu- ing clear cell carcinom a of salivary gland. Am J
mors. A demographic study of 759 cases in a Chi- Surq PathoI 1994;18:74- 82.
nese popu lation. Oral Surg Oral Med Oral Pathol
35. Berho M, Huvos AG. Central hyalinizing clear cell
Oral Radio l Endod 1998;86:707 - 7 14.
carcinoma of t he mand ible and the maxilla. A clin-
27. Reichart PA, Philipse n HP, Sonner S. Ameloblas- icopat hologic study of two cases with an analysis
to ma: Biological profil e of 3677 cases. Eur J Can- of the literature. Hum PathoI 1999;30:101 -1 05.
cer B Oral Onool 1995;3 1B:86-99.
28. Eversole LR, Belton CM, Hansen LS. Clear cell
odont oge nic tum or : Histoc hemical and ultra-
structural features. J Oral Pathol 1985;14:603-
6 14.
247
Chapter 28
249
28: Ghost Cell Odontogenic Carcinoma
OJ Women
OJ Men
n=18
0-9 10-19 20-29 30-39 40-49 50-59 60-69 70 + Fig 28-1 Age and
Age in years gender distribution of
18 cases of GCOCs.
3.1 Prevalence, incidence, and T he GCOC occurs more com mon ly in the
relative frequency max illa than in the mandible with a ratio of
2:1.
Because of the extre me rarity of this tumor,
few data are availab le as yet. Lu et al4 men -
tioned that the GCOC appears to be more
common in Asians than in other races, al-
though t he true pre vale nce re ma ins un- 4. Pathogenesis
known. In a demographic stud y of 759 cas-
es of odontoge nic tumors in a Ch inese
population , Lu and co wo rkers ? fo und a rela- The origin of the GCOC is not fu lly known .
tive frequency of 0.4% for the GCO C. Ho we ver, Lu et al" stated that the im-
munophenotype of the ma lignant cells sup-
ports an ep ithelial or igin. T hree patterns of
3.2 Age deve lopment seem likely." Most common ly,
the tumor histo logically presents de novo but
Distribution of age at the time of diagnosis with a benign COC and a ma lignant epit he-
fo r the 18 reviewed cases (Fig 28-1) shows lial component presen t in the same lesion,
that 55 .6% occur in the 4th and 5t h de cades. Less commonly, the GCOC occurs after the
Ages ranged fro m 13 to 72 years with a mean recurrence of a ben ign COC , It is unc lear
age of 3 7.3 years (women , 43 .8 years; men , whether t hese two patterns rep resent the
34.8 years). same process but with temporally dist inctde-
velopment. A third pattern is the GCOC aris-
ing fro m ano the r odontog enic tumor such
3.3 Gender as an SMA In all cases , however, a typ ical
ben ign COC can be identified either adm ixed
The male :female ratio for the 18 cases was or sep arate from the ma lignant cell and irre-
2.6:1. (See Fig 28-1). spective of the developmental pattern .
250
Pathology
25 1
28 : Ghost Cell Od on togeni c Carcinoma
252
Section Six
253
Chapter 29
255
29: Ame loblastic Fibrosarcoma
Fig 29-1 Lateral oblique radiograph of the left Fig 29-2 Patient shown in Fig 29 -' at age 16
mandible of a 13-yea r-old boy show ing an am eto- years. The patient presented w ith a large intrao-
blastic fibroma . The first mandibular molar is im- ral soft tissue ma ss in the left ma ndible. Radi-
pacted, andthe second molaris missing. The AF ographically, most of the previous defect has
was en ucleated. been replaced by bone and the third molar has
develo ped . Alveolar bone destruction is evident
mesially to the crown of the third molar. The his-
tologic diagnosis was AFS.
ceration and bleed ing, as well as paresth e- smallest was 4 x 4 x 3 cm and the largest was
sia of the lower lip, were also reported. These 7 x 6 x 4 cm.
findings were in agreement with those of AI- involvement of the cervical or subm andi-
tini et al,2who evaluated signs and symptoms bular lymph nod es in cases of AFS seems to
of cases of ameloblastic sarcom as (AFSs, be uncommon . Among 49 AFS cases, only
AFDSs, and AOSs). Swelling was observed 1 case with histologic do c umentation of
in all cases, and pain was a frequent com - metastasis involving the lung, liver, and me-
plaint. Mobility of the teeth, a freque nt find- diastinallymp h nod es was reported."
ing in malignant jaw neoplasms, was seen in Radiog raphi cally, rad iolucencies with ir-
some cases. regular and indistinct margin s are character-
Since 44 % of AFS cases arise in previously istic (Figs 29-, and 29-2 ). Large rad iolucen-
benign ameloblastic fibro mas, the history of cies w ith a mu ltil ocu lar appe aranc e and
patients with an AFS must be taken with great gross expansion and th inning of the co rtical
care in order to classify the neop lasm as de bo ne may be seen. In cases where radio-
novo or as transformation from AF to AFS. in pacities are obse rved with in radiolucent
this co ntext, the recurrence rate of AFs has areas, a d iagnosis of ameloblastic tibro-
been regarded as important; it has been re- dentin osarcoma or arneloblastic fibro-
ported to be as high as 18.3%.' 8Frequent re- odontosarcoma is likely. Park et al9 exam-
curren ces and multip le surgica l interventions ined the ir pati ent using com puted tom o-
have been considered possible suppo rting gra phy (C'T) sca ns. These showed a well-
factors of malignant transformation. defined heterogeneous mass of soft tissue
Dallera et al8 reported measurements of dens ity and a thin enhancing capsule in the
th e tum ors in t heir five AFS patients. The subm andibular area. Radionucleotide bone
256
Epidemiological data
3. Epidemiological data
3.3 Gender
No. of ca ses
14 13
[JJ Women
12
[JJ Men
10 n =49
8 7
6 5 5
4 4
4 3
1 1
257
29: Amelob lastic Fibrosarco ma
24 2
8' 5. Pathology
5.1 Macroscopy
Fig 29-4 Topographic distribution of 49 cases of
AFSs.7 - 16 Asterisk indicates AFS wit ho ut spe cific
location in maxilla or mand ible. The macroscopic findings of resected spec-
imens were described by Eda et al20 and
Dallera et al8 in detail. The specimens were
tender but solid and whitish at the cut sur-
faces. The buccal and lingual co rtices of the
mand ible were extrernely thin'?Dallera et al8
4. Pathogenesis described the specimens as tough and rub-
bery; some calcified sp icules of bone were
detected. Cortical plates were focally perfo-
The pat ho genesis of t he amelo blastic fi- rated , thinned, or destroyed. In other cases,"
brosarcoma has not bee n fully estabiished. the cut su rface of the tumo r was soft and pale
Out of 36 cases of AFS, 13 had a previous with a few hemorrhagic areas; in so me parts,
diagnosis of AF according to data com piled a capsule was detected.
by Muller et al.? Thus, in a number of cases,
gradual transformation of an AF to an AFS
has been documented over time. The differ- 5.2 Microscopy
ence in the mean age at the time of d iagno-
5.2. 1 Hist olog ic definitio n
sis for AF (15 to 22 years" ) and AFS cases
(24.9 years)supports a stepwise pro gression Both the 1992 WHO classification 1 and the
of a benign to a malignant neop lasm as op- present autho rs define the AFS as follows: "A
posed to a de novo malignancy. Several in- neoplasm wit h a similar structure to amelo-
vestigators have tried to correlate AFS de- blastic fibroma , but in which the ectomes-
velop me nt with the stag es of de veloping enchymal co mponent shows the features of
teeth histologically. In one case, Yamamoto a sarcoma."
et al5 observed two characteristic features at
the epithelium-ectomesenchyme interface:
5.2.2 Histopatholog ic findings
epithelium that was surrounded by both a
cellular stroma and a cell-free zone, and a few The histopathology of the AFS is character-
aperiodic fibrils arranged near the basal lam- ized by a consistent appe arance in which a
ina. The authors interpreted these findings malignant ecto mesenchymal component is
as corresponding to the early bell stage of mixed with a benign epithelial odo ntoge nic
odontog enesis. Chomette et al'9 have sug- co mponent. The malignant ecto mesenchy-
258
Pathology
Fig 29-5 Ame loblastic fibrosarcom a exhib iting Fig 2 9-6 Islands of am eloblastic ep ithelium, one
stran ds of amelob tastic epithelium in a malignant of wh ich shows rnicrocystic dege neration. The
ectomese nc hymal t issue of variable ce llularity sarco matous ecto me senchymal compon ent is
and polymorphism (hematoxylin-eosin [H&E], hypercellular (H&E, x60).
x100),
mal component cons isten tly takes up more seen in pleomorphic malignant fibrous histi-
than 70% of the tumor area compared t030% ocy1oma, have occasiona lly been desc ribed
bythe odontog enic aolthelium." T he ben ign in AFS cases-"
epithelial component shows budd ing and Col lagen is usually present on ly in small
slender cords, usually only two layers t hick, amounts. In some cases, a homogeneous,
composed of sma ll polygonal epithe lial cells. eos inop hilic material is fou nd in t he ec-
In addition, epithelial Islands and nests w ith tomesenchymal compone nt su rround ing
the same histopat ho log ic appea rance as the ep ithe lial Islands. Ame lob lastic fibrosar-
ameloblasticfibromasare evident. Columnar comas typically display the greatest density
or cuboidal ep ithelia l tumor ce lls resembling of ectomesenchymal malignant tumor cells
preameloblasts are arranged at the periph- around the ep ithe lial islands. In some cases,"
eryin a palisading pattern. The nucle i are hy- areas of osteo id matrix have been identified
perchromatic and are po larized away from in a lacelike pattern between the malignan t
the basement membrane; the cytoplasm is ectom esenchyma l cells; th e authors inter-
clear and vacuo lated (Figs 29-5 and 29-6). preted this as evidence of an osteogen ic sar-
Polyhedral cells resem bling stellate reticu- com a-l ike appearance. Both be nign and
lum-li ke epithelia l cells are seen in the ce n- malign ant gia nt ce lls may occasionally be
ter ofthe epithel ial islands . No mitoses or ma- found . The vascular component is usually in-
lignant cytoloq ic features are detected in the conspicuous. T he ma lignant compo ne nt
epithelial component. T he ectomesenchy- may reveal different grades of maligna ncy
mal comp onent of the neoplasms shows a from low to hig h.
marked incre ase in cellularity. The fibroblast- In some cases of AFS,11, 13 cor ds of odon -
like cells are pleomorph ic, rounded, or fus i- togenic ep itheli um have been ob served re-
form and display increased, sometimes atyp- sem bling those seen in odontoge nic fibro-
ical, mitotic activity. Cy1ologically, these cells mas rat he r than ameloblasti c fi brom as.
show hyperc hroma tic nuclei and scant cyto- T hese cases of odontoge nic fibroma-li ke
plasm. Cells w ith ma rked po lymorphism, as sarc omas were cl in ica lly aggressive or
259
29: Ameloblastic Fibrosarcoma
caused death.21 Slater" considered these columnar cells revealed positive staining for
cases to be possible nonodontoge nic sar- tissue po lypeptid e antigen . The spindle-
comas arising adjacent to "normal" gingival shaped fibrob lastic cells were positive for vi-
odo ntogenic epithelium. mentin, Sano et al ' 2 assessed the growth po-
Of furthe r interest is thatthe epithelial com- tentia l of amelo blast ic fibros arco mas in
ponent of the AFS eventually becomes less relation to ameloblastic fibrom as (AFs) and
promi nent and may d isappear altog ether af- related lesions by MIB-1 immun ohistochem-
ter local recurrences. Park et al? repo rted a istry. Positive reactio ns for MIB-1 were ob-
case of highly malignant AFS which revealed served in the nuclei of tu mor cells in both the
that sheets of more anaplastic and poorly dif- epit helial and ecto mesenchyma l co mpo-
ferentiated cells were not associated with the nents . Labeling ind ices were co nsidered
benig n odo ntogenic epit helium. w hereas higher in the ectomesenchymal comp onents
less anapla stic mesench ym al tissue was in the AFS and in AFS with later recurrence.
closely associated with it. The authors sug- The labeling ind ices of ecto mesenchymal
gested that the anaplasia of mesenchyma l components were significantly different be-
tissue correlates with the degeneration of be- twee n the nonrecurrent AF and the amelo-
nign odontoge nic epithelium and that the blastic fibro-odonto ma and AFS. The authors
loss of benign odontogenic epithelium re- concluded that evaluation of the growth po-
sults from an overgrowth of the malignant tential in AFS and related lesions could help
mesenchymal portion of the lesion. in understanding tumor aggressiveness and
in selecting appro priate surgical proced ures.
Mu ller et at? perfo rmed a DNA ploidy
5.2.3 Histoche micaVimmunohistochemi-
analysis of the ir patients with AFS. Measure-
cal findings
ment of DNA ploidy by flow cytom etry or im-
Leider et al17 studied their cases by histo- age analysis has been considered useful in
chemical methods using Wilde r reticu lum distingu ishing benign from malignant neo-
stain. Masson trichrome stain. alcian blue plasms and providing an objective means of
stain fo r mucopolysaccharides, and Mowry histologic grading. In their study. four of five
colloidal iron technique for acid mucopoly- cases were diploid. as were three cases of
saccharides with and without hyaluronidase AFS which were used as controls. Although
d igestion. The find ings were compared to there is a relationship between increased his-
cases of AFS and nonodontogenic fibrosar- tologic grade and DNA aneuploidy for many
comas. Staining characteristics of the mes- histo log ic types of sarcomas, the authors
enchymal component did not reveal any dif- were unable to demonstrate this association
ference between the different neo plasms. with their AFS cases.
Chomette et al'9 found that, compared to
classic fib rosarcomas. a high level of alkaline
5.2.4 Ultrastructural findings
phosphatase and adenosinetriphosphatase
(ATPase) activities was present in cases of The ultrastructure of amelob lastic fibrosar-
AFS. com as has been studied by several research
Yamamoto et al5 found that keratin could groups.s,9,20.22 Yamam oto et al5 observed
be demo nstrated in the columnar and poly- two cell types- columnar and polyhedral- in
hedral cells of the epithelial component. The the epithelial component. The columnar cells
intensity of the staining reaction was not uni- had slightly enlarged oval nuclei located api-
form; the polyhed ral ce lls were more in- cally with in the cells. The cytop lasm showed
tensely stained. The basa l part of some small processes and infoldi ng tow ard the
260
Not es on treatment a nd recurrence rate
basal lamina; the nu mber of mitoc hondria enuc leation or curettage of AF, wid e local ex-
was moderately increased. The Golgi app a- cision ens uring co mplete removal may be
ratus appea red less well develop ed . Roug h warranted in viewofthe high recurrence rate.
and smooth en doplas mic ret icu lum were Regardless of therapy, a patient w ho has un-
seen; the number of glycog en granu les was dergone thera py for an AF must be fo llowed-
moderately increased. Tonofilaments were up by regu lar c linical and radiog raphic ex-
well preserved, revealing typica l arrange- ams for at least 10 years."
ments in bundles. Desmosom es were also The vast majority of authors recom mend
detected . The po ly hed ral ce lls d isplayed radi cal extensive surg ery for ameloblastic fi-
large amounts of ton ofilaments and g lyco- brosarco mas, usually necessitating partial or
gen granu les. The mese nc hymal sp ind le- total mand ibu lect om y or maxillect omy. In
shaped, fibroblast-like cells showed irregular some recently pub lished cases, postsu rgical
nuclei with one ortwo nuc leoli and a variable radiotherapy! " or adjuvant chemotherapy
amount of heteroch romatin. Some lipid g ran- with cycl oph osph ami de, vinc rist ine, and
ules and filam ents w ith focal co ndensation coxorub icin? we re adm iniste red. In the latter
were also observed. The authors interpreted case, chemotherapy and subsequent radio-
their ultrastru ctur al find ings as features of thera py were ineffective.
sarcom as. The ultrastructural study by Metastasis see ms to be rare in AFSs; of 49
Chomette et al' 9 de mon str ated clear cells AFS cases.' there was only 1 case wit h his-
with nu merou s microfilaments, sec reto ry tologic docume ntation of metastasis to the
cells, fibrob lasts, and myofibroblasts, In ad- medi astin al lym ph nod es, lung, and liver.
dition to these pleomorphic cells, ma ny pe- Mu ller et al 7 suggested that routi ne neck dis-
culiar granular ce lls with numerou s lysoso- section for AFS would therefore not be indi-
mal bodies were also found . cate d.
Rec urrences with adequate ly document-
ed follow-up occurred in 20 of 49 ad equate-
ly treated patients," Tw o- and 5-year survival
rates are not available, but 20.4% of patients
6. Notes on treatme nt and w ith AFS died w ithi n 2 to 19 yea rs."
The prognosis for the AFS seems better
recurrence rate tha n that for othe r fibrosarcomas of th e oro-
facial region. Due to the fact that metastasis
The info rmatio n available con ceming treat- is rare in AFS cases and survival seems to be
ment, course, and prog nosis of the AFS is compa rably good, some auth ors 16.23 have
limited du e to the paucity of cases reported. theorized that the AFS may be con sidered a
When conside ring treatm ent modalities, one low-g rade fibr osarco ma . Prein et al 24 sug-
must keep in mind that an AFS may develop gested that th e AFS be considered "semi-
trom a preexisting AF or AFO, or it may arise malignant "; they pro posed calling the AFS a
de novo. Since 36% of review ed cases arose "proliferative ameloblastic fib roma."
in previously ben ign amelob lastic fibro mas,"
some aut hors have suggested that arnelo-
blastic fibromas be treated more radically to
prevent recu rrences and poss ib le transfor-
mation to AFSs. Muller et al7 supported this
view based on the data they acc umu lated on
amelo blastic f ibrosarcomas; "Rath er th an
26 1
29: Amel ob lasti c Fib ros arc oma
9. Park HR, Shin KB, So MY, et al. A highly malig- 22. Takeda Y, Kaneko R, Suzuki A Arneloblastic f i~
nant arneloblastic fibrosarcoma. Report of a case. brosarcornas in the maxilla, malignant transfor-
Oral Surg Oral Med Oral Pathol Oral Radiol En- mation of ameloblastic fibroma. Virchows Arch A
dod 1995:79:478-481 . Pal hol Anal Histopathol 1984;404:253- 263.
10. De Oliveira Nogueira T, Carvalho YR, Blume r 23. Reichart PA, Zob l H. Transformation of amelo-
Rosa LE, et al, Possible maligna nt transformation blastic fibroma to fib rosarcoma. Int J Oral Surg
of an ameloblastic fib rom a to ame loblastic f i- 1978:7:503- 507.
brosarcoma: A case report. J Oral Maxillofac Surg 24. Prein J, Rem agen W, Spiess l B, Schatrcth U.
1997 :55:180 - 182. Ameloblastic fibroma and its sarcomatous trans-
11. Tejima Y, Utsumi N, Suzuki S, FUjita K, Takahashi formation. Pethel Res Pract 1979 ;166:123- 130.
H. Arnelobla stic fibrosarcoma arising de novo in
the maxilla. Pathol lnl 1997 ;47:564 - 568.
12. Sano K, Yoshida S, Nimo iyma H, et at Assess-
ment of growt h potential by MIB-1 immunohisto-
chemistry in arnelob lastic fibroma and related le-
sions of th e jaws compared with ameloblastlc
fib rosarcom a. J Oral Patnol Med 1998;27:59-63.
262
Chapter 30
263
30: Ameloblastic Fibrodentin osarcoma and Fibro-odontosa rcoma
occlusal trauma. Mobility of the teeth and/or age at the time of d iagnos is of patients with
tissue proliferation thro ugh extraction soc k- AOSs reported by Altini et al" (S IX cases, age
ets were noted in some cases. The growth unknow n for one ) was 21 years. The patient
rate was usually moderate, although rapid described by Takeda et alBwas a 23-year-old
growth was also reported. Clinically, region- man, and that reported by Phillips et all was
al lymph nodes did not show signs of a 29-year-old man.
metastatic involvement.
Radiog raphically, the AFDS and AOS
have to be differentiate d from th e ame lo- 3.3 Gender
blastic fibrosarcoma (AFS) by the presence
of radiopaque foci in an otherwise radiolu- Both patients wit h AFDSs were men.3 .4 Of the
cent lesion. In the two cases of AFDSs de- six AOS cases reported by Altini et al," two
scribed to date the mandibula r lesion was ir- were men and four were women.
regular but relatively well circumscribed in
one case," The other case revealed a large
mu ltilocular rad io lucency containing an 3.4 Locat io n
unerupted molar and a radiopaq ue mass at
the lower border of the mandib.e." Amelo- In both AFDS cases, the large lesions were
blastic odontosarco mas have a similar radi- located in the mand ible.3,4 In the six AOS cas-
ographic appearance with irregular or well- es, the lesions were ali located in the mandi-
defined margins and fo ca l radiopacit ies ble; of these, five were in the posterior man-
within a radiolucent area. Computed tomog- d ible ."
raphy (CT) and magnetic resonance imagery
(MRI) help to define the lesions in more de-
tail.
4_ Pathog enesis
3. Epid emiological data
The etiology/ pathogenesis of the AFDS and
AOS is un kno w n. As in am elob lastic fi-
3 .1 Prevalence, incidence, and br osa rco ma, however, th e lesions may
relative frequency t heo ret ic ally occur as a sync hrono us or
metac hro nous proces s at th e site of an
Both the AFDS (two accepted cases) and the ameloblastic fibroma or amelob lastic fibra-
AOS are exceedingly rare malignant odo n- odo nto ma. in some c ases, the malignant
togenic tum ors. Therefo re, no figu res o n proc ess deve lo ps from a benign lesion
prevalence, inciden ce, or relative frequency (ameloblasnc fibro-odontoma) which recu rs
are available. and becomes malignant.' 1,12
Slater2 discussed the tenm ame /ob lastic
odontosarcoma and co nsidered the notion
3.2 Ag e of a "maligna nt tooth," as suggested by the
wo rd odomose rcome, disturbing. The AOS
The AFDS patients were two men, ages 27 term resulted from the obse rvation that an
and 25 years.34 The case reported by Breg- odo ntoge nic sarcoma can arise from an an-
ni et al'o was a 32-year-old man. The mean tecede nt arneloblastic libro-odonto ma, and
264
Pathology
265
30: Arn e lob lastic Fib ro dentinosa rco rna and Fib ro-od o ntosarco rna
266
Refe rences
9. Thoma KH. Oral Pathology . 4 th ed . St. Lou is: CV 12. How ell RM. Burkes EJJ. Maliqnant transformation
Mosby, 1954 :1234-1 235, of ame lob lastic fibro-odontoma to ameloblastic fi-
brosarcoma. Oral Surg Oral Med Ora l Pathoi
10. Bregni RC, Taylor AM , Garcia AM. Ameloblastic
1977 ;43:391 -40 1,
fibrosarco ma of the ma nd ible: Report of two cas-
es and review of th e literature. J Oral Pathol Med 13. Eda S, Saito T, Mo rimura G, et al. A case of amelo-
200 1;30 :3 16- 320, blastic fib rosarcom a. with an elec tron-mic ro-
sco pi c obse rvat ion. Bull To kyo Dent Coli
11. MOiler S, Parker DC, Kapadia SB. et al. Amelo-
1976;17:11- 25.
blastic fibro-sarcoma of the jaws. A clinicopatho-
logic and DNA analysis of five cases and review
of the literature with d iscussion of its relationship
to arnelo blastlc fibroma. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1995;79:469- 477 ,
267
Chapter 31
Odontogenic Carcinosarcoma
The 1992 World Health Orqanization (WHO) with hyperchromatism and moderate nu-
classification 1 of odontoqe nic tumors de- clear polymorphi sm. Slater" considered
fined the odontogenic ca rc inosar co ma the mitotic rate of the epithelial co mpo-
(OCS) as "a very rare neoplasm, similar in pat- nent to be similar to that of the malignant
tern to ame lo blastic fibrosarco ma, but in ecto mese nch yma l tissue com ponent
which both the epit helial and the ectornes- (Figs 31-1 and 3 1-2).
enchymal co mponents show cytolog ical fea- Slater 2 furt her pointed out th at a carci-
tures of malig nancy." No further com ments nosarco ma lacking th e ameloblastic fibro-
accomp anied this def inition and no exam- ma-like pattern could still be recognized as
ples of the histopathology of the OCS were odo ntogenic if the epi th elial co mponent
given. resem bled that of an amel obl astoma . He
In 1999, Slater2 stated that "such a tumour considered a tum or of this type to be a sar-
has not been reported as yet, to t he best of comato id carc ino ma arising in an arnelo-
my knowledg e." A literature search in 200 1
did not reveal any case reports or mentions
of this neoplasm.
In his review, however, Slater 2 presented
a case of OCS from his own files:
A 55-year-old man living in Saud i Arabia
had an 8.0 x 6.2 x 5.0 cm tumour of th e
right mandibular bod y and ramus excised
by hem imand ib ulectomy. Histolog y re-
vealed an amelo blast ic fi bro ma-like
pattern with strands and cords of od onto-
genic epithelium separated by hypercel-
lular fibrous co nnective tissue. The ame-
loblastomatous c omp onent di spl ayed
Fig 31-1 Odontogenic carcinosarcoma with ir-
peripheral large cells with crowd ed large
regular epithelial sheets and islands character-
hyperchro matic nu clei; mitotic fig ures
ized by cell ular atypia and increased mitotic
were observed among these large basa- activity. In this field , the ectomese nchymal co m-
loid ce lls as well as among plump cells in ponent is predominantly fibrous and poor in cells
the central stellate reticulum area. The sar- with malignant features(hematoxylin-eosin [H&E],
comatous co mpo nent showe d closely x75). (Courtesy of Professor J.J. Sciubba, Balti-
packed mitotically active polygonal cells more, MD.)
269
3 1: Odont ogenic Ca rcinosarco ma
_,~{I,I;."'
.. Ci
l~oJ:"~.F/ . .#fj,;bj,:';~';~ ~:P ,~~ ' ~;~~"t , ,~I ~.:"~'t! ~t11
. .., , ~ ~,'... <> ." , " " ... ""
<>~ ,d "~~""';'~ :" :"',r~~~-:' .\ " " \ \-"~ 'G'W () ' ,<~ "''''' ..7 .' 1~ f
..
, . ' ." '
~ "'. -~~~'~<.J"'
do-~">;.~ ~. ....~,"':..~-..";;,~,!>.
",~ "' 'j,,1''i; 'I.' \,"' ,,, ~~_.
~,>..
... .. :--, ,.. _ :;.~....--~-.:!-, ,. "t , "~,,,," _ _<"~:;'''' l' ~ -' ' ' 'Ii
.~~ ~":1:.:.._
.....JV~\~;.
.... '\....., ,;- ;\~ i
.,.........
~ ... I
At the Consensus Conference held in Lyon
~r~;~~tN~t~;~fill~(~!~i~f~~
(IARC/ WHO) inJuly 2003 in conjunction with
th e preparation of chapter 6 (odo ntogenic tu-
mors ) for the fort hcoming WHO volume Tu-
!1.;;t :: /$~:'f.'t;.~~~,~:?,:~fr:::l::~~
~~ ~~ :~;~ t..(,!-l;~;'~; iZ3_~i.~ -,..-~. !.~~", ~:~') .~. \~:"~
mours of the Head and Neck , it was unani-
mously d ecided not to incl ude the
\t\~\t.' ~"qi- -:- ....::" ~~-;: "' . ~ j:,~~q ~~-<l'.; :~~;;"~ :/'...J>.f':.0 .. j>
1
lW\. !X L . ~_ ~ ..~1'-. ;'3-"" _~~ , . ~ . ~ '~B...... ~.-:-..." ,,: "J;;." t.~ od ontog en ic ca rci nosarco ma in th e new
e> "'~; ' ''' "f " t: ~ .;.,~_,,. . -, ":-: ..'..,;. " '..,.$;: .:. ~:\: .i'j-i<-.4 , ';~y;
. ~ " dO , ',,-, . i ....-,. ~. "'!. ,. .: ~_, t ... ,. -i" ~" ~, S -:~;, _~"~_ ( ,,"',,,: .....4.-4
_ .. -; -:t,~
~ _,,_ f .~. ;.!
WHO classification due to the present lack
Fig 31 -2 Areaof an OCS exhibiting only the ec- of substant iated evidence.
to mesenchymal component w he re spind le-
sha pe d fibro blasts arranged in w hirled co nfigu-
rations show distinct sarcomatoid features (H&E,
x75). (Courtesy of Professor J .J. Sciubba, Balti- References
more, MD.)
1. Kramer IRH, Pindborg JJ, Shear M. Histologic Typ-
ing of Odontogenic Tumou rs. 2d ed. Berlin;
Springer-Verlag, 1992.
blastoma (a variant of ameloblastic sarcom a)
and not an ameloblastic ca rcinosarcoma, 2. Slater LJ. Odontogenic sarcoma and carcinosar-
coma. Semin Diagn PathoI 1999;16:325- 332.
Sarco matoid carc ino mas or ca rcinosarco-
mas have been reported as malignant mixed 3. Tanaka T, Ohkubo T, Fujitsuka H, et al. Malignant
mixed tumor (malignant ameloblastoma and fi
tumors (malignant amelob lasto mas and fi- brosarcorna) of the maxilla. Arch Pethel Lab Med
brosarco mas) and as odontogenic carc ino- 1991 ;11 5:84 -87.
mas with sarcomatous pro llferation .P"
4. Yoshida T, Shingaki S, Nakajima T, et al. Odonto-
It seems evident that a con sensus as to genic carcinoma with sarcomatous proliferation. A
the definition of this obviously extremely rare case report. J Craniomaxillofac Surg 1989;17:
tumor must be arrived at and cases of OCS 139- 142.
must be published before co nclusions abo ut
thei r etiology and biologic behavio r ca n be
made.
270
Section Seven
Intro duction to Neoplast ic of the dental follicle, which also gives rise to
the periodonta l ligament. Cementoblasts
and Non-neo plast ic Osseous synth esize an organic matrix-cementoid-
Lesion s w hich is deposited on th e dentin d uring
odo ntogenesis. Calcified cementum is most-
ly avascular. The apical third of the root may
The term fibro-osseous lesions refers to sev- inco rporate cementoblasts. Inthe normal pe-
eral lesions representing a d iverse process riodontal ligame nt , it is common to find
in which the normal bone architecture is re- round, strongly basophilic, calcified masses
placed by fib ro blasts and collage n fibe rs known as cementicles, which are produced
containing variable amounts of mineralized in that location. Lesions derived from ce-
material. The term is not a specific diagno- mentob lasts may be either neoplastic or dys-
sis, indicating only a broad group of several plastic.
entities. Although there is no completely sat- One of these groups is the cemento-os-
isfactory classification, it is generally accept - seous lesions. These are non-neoplastic le-
ed that benign fibro-osseous lesions in the sions of the jaws and include a variety of le-
oral and maxillofacial regions can be d ivided sions characterized histopathologically by
into three categories: t he benign fib ro-os- the presence of cementum-like tissues. The
seous neoplasms, the non-neoplastic fibrous World Health Organization (WHO) classifica-
dysplasias, and react ive (dysp lasti c) le- tion of 19714 used the unifying concept of
sions.1- 3 cementomas to group together lesions con-
taining ceme ntu m-like tissue, thus forming a
Cementu m is a mineralized dental hard tis- co mplex group of lesions wit h ill-defined
sue covering the root surface of teeth. It is characteristics. Therefore, in this classifica-
avascular and may present a structural simi- tion both neoplastic (benign cementoblas-
larityto woven bone. Cementoblasts are con- tomas, cem enta-ossifying fi bromas) and
sidered to be de rived from ectomesenchyme non-neop lastic lesions (periapical cemental
271
Introd uction to Neoplastic and Non-neo plastic Fibro--osseous Lesions
272
Chapter 32
Ossifying Fibroma
273
32 : Ossifying Fibroma
ripheral odo ntoge nic fibro ma, and ca lcifying tend erness in 5 1% of patients:the remaining
fib rob lastic granu loma) is react ive in nature 49 % were asym ptomatic. Ho wever, th e clin-
and is not the extraoss eous counte rpart of ical presentation is variabls.!? Small lesions
the COFB are often discovered inc identally. Bilateral
and multiple COFs have been re ported.l"!"
If untreated , lesions may become large and
cause considerable cos met ic and functional
pro blems.
2. Clinical and radiologic profile Rad iographi cally, Eversole et al5 fo und
that the 64 COF cases they exam ined were
all we ll-defined u nilocu lar, ro u nd , or oval
In an analysis of 75 cases of COFs in an Amer- structures (Fig 32 -1). Larger tum ors may
ican population, Su et al9 ide ntified a slow- have a m ultiloc u lar radiog rap h ic appear-
growing, bu ccoling ual jaw expansion or mild ance . Macfr onald-Jankowsk i' " described
Fig 32-1 Radiograph showing a well-defined, Fig 32-2 Mixed radiolucency and opacity in the
unilocular COF in the edentulous leftmandibular edentulous area distal to the mandibular left se c-
area of a 45 -yea r-old man. Small radiodensities ond pre molar.
(arrow) are seen in the lower part of the radiolu-
cency.
Fig 32-3 Radiographic stages of a COF. A: Mixed radiolucency/ radiopacity in the periapical mandibu-
lar right molar region. B: The same tumor after 7 years. The radiopacities have increased significantly
with age.
274
Epidemiological data
No . of cases
45
39
40 DJ Women
35
30 27
DJ Men
n = 157
25
20
19
16
15 3
10
5
o .LL-l.LJL.L.J.u.L....I.-'L.JL.L.J.u.L....I.--"-..JL..L"-~=.--"-
0- 9 10 - 19 20-29 30- 39 40 -49 50 -59 60-69
Age in years
Fig 32-4 Age distribution
of 157 cases of COFs.
three stages in the radi ographic ap pea rance examined by Everso le et al 5 were associ ated
of the CO F. The initial ap pearance is radi- with t he c row ns of im pacted t eet h and 35 %
olucent, w hich t hen becom es pro g ress ively of th e tumor s we re detected in ede ntulo us
radiopaque as t he stroma m ineralizes (Figs areas.
32-2 and 32- 3). Eventu ally, the ind ivid ual ra-
diopac ities coal esce to th e exte nt that t he
matur e lesio n may appear sc lerot ic . The au-
thor also present ed a sum mary of t he radi o- 3. Epidemiolog ica l data
logic featu res in 177 rep o rted cases of COFs
from th e literat ure and his own f iles,9,10,14,15
demonst rat ing that 42 % we re radi olu cent, 3.1 Prevalence, incidence, and
24% were radio paq ue, and 34 % had a m ixed relative frequency
appearan ce. The pr esenc e of a w ell-defined
margin was held by Sc iubba and Younal' Ptc No data on these aspects of CO Fs are avail-
be a co nsiste nt and reliabl e rad io log ic mark- ab le.
erfo r CO F.
Su et al9 report ed th at the averag e lesio n
diameter w as 3.8 em, w it h a range of 0 .2 to 3.2 Age
15 em in 54 case s of CO Fs. A majority (93%)
of COFs failed to demonstrate an association Based on pooled, comparabl e d ata retrieve d
with the tooth apex b ut oft en ca used di ver- fro m th ree repo rts on CO Fs (n ~ 157),5.9.15
gence of the involve d roots. Root reso rption 79 .6% of t umo rs we re d iagn osed before 40
was not a co m mo n f ind ing . Th is raises doubt yea rs of age, and 58.6% before 30 years of
as to wh ether th e CO F orig inates in t he peri- age (Fig 32- 4). Th ere is a d istinct peak in th e
odontal ligament. Su et al also notice d t hree 3 rd decade for women, wit h case s in men
different patt ern s of radi ographic bo rders: a oc cu rring slig htly earlier. Th e mean ag es for
defi ned lesi o n w it hout a sclerot ic bo rder patients in t he c ited stud ies5,9,1 5were 36 , 32 ,
(40%), a w ell-d efined lesion wit h a sclerotic and 30 year s, respectively. A mean age of
border (45%), and a lesio n wit h an ill-<Jefined 3 9 was found in a stu dy of 20 Hong Ko ng
border (15%). No ne of t he 64 case s of CO Fs C hinese patients (all w om en) ."?
275
32: Ossifying Fibroma
5. Pathol ogy
5 .1 Macrosc o py
276
Pathology
Fig 32-7 COF with hypercellular stroma (right) Fig 3 2-8 lrr equl ar c em entum-like structu res,
and a combination of bo ne trabecu lae and ce- some of which exhibit fringelikeosteoid rims. The
mentum-like spherical structures (left). (H&E, fibrous stroma in this COF is of variable cellulari-
x80). ty (H&E, x80).
biopsy procedure. A fibro us ca psule was A be nig n osteogen ic, well-demarcated neo-
identified in 44% of the lesions. plasm composed of calcified material and a
fibroblastic stroma, whic h may be very cellu-
lar (Fig 32-6). The calcified com po nent is
5.2 Microscopy usually a combi nation of bon e trabeculae
and strongly basoph ilic cementum-like struc-
5.2. 1 Histologic definitions
tures with variable osteoblastic rimm ing (Figs
According to the 1992 World Health Orga- 32-7 and 32-8). Osteoclast-like giant cells
nization (WHO)classification,4 a COF is a "de- and occas ional an eury sm al bone cav ity
marcated or rarely enc apsulated neoplasm com pon ents c hara cteri zed by sinuso id
consisting of fibrous tissue co ntaining vary- blood spaces may be present.
ing amounts of min eralized material resem-
bling bone an/or cementum."
The definitio n used by the present autho rs
is as follows:
277
32: Ossifying Fibroma
5.2.2 Histopathologic findings fiber patterns in the hard tissue elements, in-
clud ing woven bon e tra be culae, lamellar
In their 75 cases of COFs, Su et al ' ? found bo ne t rabeculae, ovo id-curvoid deposits,
three histologic subtypes. Thefirst and most and anastomo sing curvedj linear trabeculae.
co mmon subtype has an equal amount of
calcified mate rial and fibroblastic stroma.
The calcified structures consist of both sep-
arate and retiform bony trabeculae with a
prominent osteoblastic rim and occasional 6. Notes on treatment and
osteoclasts. Round ed or lobulated cemen-
tum-like bodies may be scattered throughout recu rre nce rate
the lesion and may cons titute a major co m-
ponent, such as in a cementifying fibroma. Surgical curettage or enuc leation are th e ini-
The conn ective tissue cons ists of sheets of tial treatm ent of choice for most small COFs.
spind le-shaped, fibroblastic, or stellate cells In the absence of a reliable d iagnostic or
with focal areas of storiform pattern (a typ i- prognostic predicto rto indicate the potential
cal radiograph would show a well-defined of COF for aggressive behavior or th e likeli-
mixed radiolucency and radiopacity). hood of recurr ence , periodic clin ical and ra-
The second and least com mon subtype of diographic follow-up should be pursued. For
COF is cha racterized by predo minantly stori- larger tumors or a sudden growth spurt con-
form cellularity inthes troma co ntaining scant noting agg ressive behavior, en bloc resec-
separate osteo id or bony trabeculae, often tion should be considered as secondary de-
without osteoblastic rimming. Some cells in finitive therapy. If the tumo r is only partially
the storiform pattern exhib it stellate or round- rem oved, co ntinued growth does not nec-
ed nuclei which may resemb le potential os- essarily follow. Nevertheless, Eversole et al5
teoblasts, and dense co llagen f ibe rs are repo rted a 28% overall recurrence rate fol-
sometimes interming led with t he sto rifo rm lowing curettage in 22 patients with a mean
pattern (a co rresponding radiograph is main- follow-up period of 38 months.
ly radiolucent).
The third subtype of COF represents a
combination of the first two, which are each
seen in different areas of large lesions. It is
important to stress that the COF is a sharp ly 7. Juvenile oss ifying fi broma
dem arcated lesion. The hard tissues of the
tumo r do not fuse with the surrounding bone,
except occasionally in limited areas ." This is The juvenile ossifying fibroma is a well-de-
a significant feature in d istingu ishing a COF fine d clinical and histologi c entity that has re-
from a fibrous dysplasia, in which it is co m- cently been separated from other central fi-
mon to find that the metap lastic bon e of the bro-osseous lesions, includi ng the COF-' It
lesion fuses d irectly to the bord ering cortical is described in the WHO classification" as "an
bone. actively grow ing lesion consisting of a cell-
Eversole et al5 assessed the histolog ic fea- rich fibrous strom a, cont aining bands of eel-
tures of a series of 64 cases of COFs using lularosteoid without osteob lastic rimming to-
both light and polarization microscopy. The gether with trabeculae of more typical woven
use of polarized light enab led the authors to bone. Small foc i of giant ce lls may also be
study and differentiate between fou r different present, and in some parts there may be
278
Re fere nces
279
32: Oss ify ing Fibroma
11. Wei-Yung Y, Pederson GT, Bartley MH. Multiple 19. Su L, Weathers DR, Waldro n GA. Distinguishing
familial ossifying fibromas: Relationsh ip to other features of focal cemento-osseous dysplasias and
osseous lesions of the jaws. Oral Surg Oral Med ceme nto-ossifying fibromas. I. A pathologic spec-
Oral PathoI1989:6 8:754- 758. trum of316 cases. Oral Surg Oral Med Oral Pathol
12. Hauser MS Freije S, Payne RW. Timen S. Bilater-
199 7;84:301 - 309.
al ossifying fibroma of the maxillary sinus. Oral 20. Fu YS, Perzin KH. Non-epithelial tumours of the
Surq Oral Med Oral PathoI1 989 :68 :759-763. nasal cavity, paranasal sinuses and nasopharynx:
13. Sakoma T, Kaw asaki T, Watanabe K. Concurrent
A clinicopat holigic study. II.Osseous and fibre-os-
seous lesions including osteo ma, fibrous dyspla-
cementifying and ossifying fibromas of the man-
sia, ossifying fibroma, osteoblastom a, giant cell
dible. Report of a case. J Oral Maxillofac 8 urg
t umour and osteos arco ma. Cancer 19 74;33:
1998;56 :778- 782.
1289-1 305.
14. Eversole LR, Merrell PW, Strub D. Rad iog raphic
21. Hyams VJ, Batsakis JG, Michaels L. Tumours of
characteristics of central ossifying fibroma. Oral
the uppe r respiratory tract and ears. Atlas of Tu-
Surq Oral Med Oral PathoI 1985;59:522-527.
mours Pathology, 2d ser., fascicle 25. Washing-
15. Sciub ba JJ , Younai F. Ossifying fibroma of man- ton, DC: Armed Forces Institute of Path ology,
d ible and maxilla: Review of 18 cases. J Oral 1988:18 1.
Pathol Med 1989:18:3 15- 328.
22. Johnson LC, Yousef M, Vinh TN, et aJ. Juvenile
16. Summerlin D.J, Tom ich CEo Focal ce mento-os- active ossifying fibroma its nature dynamics and
seus dysplasia: A clinico path ologic study of 22 1 origin. Acta Otolaryngo l Suppl 1991 ;488:1- 40.
cases. Oral Su rg Oral Med Oral Pat hol 1994 ;
23. Williams HK, Maugham C, Speight PM. Juvenile
78:6 11-620.
ossifying fibroma . An analysis of eight cases and
17. Anand SV, Dabey WW, Cohen B. Tumo urs of the a comparison with other fibro-osseous lesions. J
jaws in West Africa: A review of 256 patients. Br Oral Pathc l Med 20 00;29:13-18.
J SUr9 196 7;54:90 1- 9 17.
24. Adler C-P, Neuburger M,HergetGW. Psamm6ses
18. Slootweq PJ. Maxillofacial fibro-osseous lesions: Desmoosteo blasto m des rechten Oberk iefers.
Classification and differential diagnosis.Semin Di- Fallbericht und Differenzialdiagnose einer selte-
aqn PathoI 1996:13:104- 112. nen Turnor entitat . Mu nd Kiefer Ges ichtschir
200 1;5:150-154.
280
Chapter 33
Fibrous Dysplasia
281
33: Fibrous Dysplasia
282
Clinical and radiologic profile
283
33: Fibrous Dysplasia
Mac fronald-Jankowski'P d id extensive gerprint bone pattern pathogno mon ic for FD.
study on the rad iologic features of 93 cases Displacement of the maxillary sinus co rtex,
of FDs, and found 5% of the affected areas alteration of the lam ina du ra to the abnormal
to be radiolucent and 95% to be of a ground- bone patte rn, and na rrowing of t he peri-
glass appearance. The shape of mandi bular od o ntal ligament space were also d istin-
growths was ovoid in 9 1% of patients and guishing rad iologic features.
multilocular in 9%. Expansion of the lower W hile t he typ ical plain fi lm and CT
border of the mandible in a buccolingual di- c hanges (Figs 33-4 to 33-7) of fibrous dys-
rection was seen in 100% of patients, as was plasia have been well described in the litera-
antral involvement in maxillary cases. Dis- ture, findi ngs with MRI and co ntrast-en-
placed teeth were seen in 4 1% of the evalu- hanc ed MRI have rarely bee n rep ort ed.
ated cases. Casselmann et al ' 6 studied MRI sig nal char-
Othe r radi og raphic fi nd ing s t hat have acte ristics on T1- and T2-weig hted images
been described in FD cases are loss of lam- and a gadolinium-enhanced T1-we ighted
ina dura and d isplacement olthe inferior den- spin ec ho sequ ence in five patients with cran-
tal nerve canal. While some researchers con - iofacial FD. Low to intermediate signal inten-
sidered an upward displacement olthe canal sity was usually seen in t he largest pa rt of the
to be unique for FD, others found a marked affected areas on both spin echo sequences.
do wnward dis placement of t he infer ior Smaller region s of hyperintensity on T1-
alveolar nerve ca nal." Petrikowski et al ' 5 and T2-weighted imag es and intermediate
co mpared rad iog raphi c featu res of FD, signal intensity throughout a growth on T1-
osteogenic sarc omas, and osteomyelit is. weig hted images were also seen. All areas
Compared to osteog enic sarcomas and os- we re enhance d, but only tw o became hyper-
teomyelitis, the authors fo und sup erior dis- or isointe nsive co mpared to fat. High levels
placement olthe mand ibular canal and a fin- of clinical and patho log ic activity may cor-
Fig 33-4 CT scan of an enlarged extended max- Fig 33-5 CT scan show ing unilate ral en large me nt
illary alveolar process. of the mandibie.
284
Epidemiological data
relate with high signal intens ity on spi n echo 3. Epidemiological data
performed normally and w ith en hance ment.
Varying signal intensity, includin g highe r in-
tensity on T2-we ighted images, is explained 3.1 Prevalence, incidence, and
by the comp lex histology and high levels of relative frequency
metabolic activity of FD.t6
Bone scintigraphy of beni gn jaw lesions, Figures on prevalenc e and incidence fo r the
including FDs, has been performed."? Ab- monostotic and po lyostotic variants of FD
normal scintigrams w ere fo und in all FD cas- have not been published to date. Generally,
es,as well as in patients in who m the disease MFD is considered to be uncommon and
was con sidered to be inactive. In addition, it PFD is a relatively rare oisease.? In their re-
hasbeen shown that scintigraphy cannot be view of FD, Eversole et al' found MFD in 74%,
used to d ifferentiate between FD and os- PFD in 13%, and c raniofacial FD in 13% of
teomyelitis." patients.
The rad iog raphic ap pearance of jaw
growths co mpared to those of other bones
of the skeleto n in both the monostotic and 3,2 Age
polyostotic variants of FD have been d is-
cussed by Gibson and Middlemiss.! " Since the FOs through out the patient' s life-
time persist (if bone is not surgically remod-
elled), the onset of the disease is often diffi-
cult to estab lish. Mc Donald -Jan ko ws ki,13
w ho studied nine series of FD w hich includ-
ed all th ree variants, recorde d 61 cases in
w hich the age of the patient at the time of di-
Fig33-6 Three-dimensional reconstruction of the Fig 33-7 Denta CT scan showing the thickening
mandible as seen in Fig 33-5. Note the irregular of the lower border of the right mandible.
surfaces of both the buccal and the lingual corti-
cal plates.
285
33: Fibrous Dysplasia
Percentage of cases
42
" ae aa OJ Craniofacial
dysplasia
fibrous
39
36
33 30
[JJ Polyostotic fibrous
30 dysplasia
~.~ nl.
27 24 ~ Monostotic fibrous
24 dysplasia
21 is
18
15 tz
" 12
12
9
6 Fig 33-8 Agedistribution
3
a of FD (monostotic, poly-
0 -10 11 - 20 21-30 31-40 4 1-50 51- 60 60+ ostotic, and craniofacial
Age in years variants) accord ing to
Eversole et al.'
286
Pathology
gorized as a benign unencapsulated neo and the present auth ors classify FO as fol
times exhibit aggr essive behavior; the same lesion occ urring mainly in young subjects,
activating mutation causes pituitary adeno usually in the maxilla, and showing replace
ma, whi ch is a neoplasm; and high levels of ment of the normal bone by a cellular fibrous
287
33: Fibrous Dysplasia
5.2.2 Histopath ologic findin gs glomera te structures. Th ese are consid ered
by some researc hers to be more represen-
The histopath ologi c features of FD vary w ith tative of cement um than bone. Anothe r fea-
the d uration of disease and stage of devel- tu re that is generally not observed elsewhere
opment. Fibrou s dysplasia rep laces normal in th e skeleton of patients with FD but which
bo ne with a ce llular, fibrous tissue co ntain- may occur in the jaws is lamellar bone bor-
ing irreg ularly shape d bony trabeculae. The de red by osteo blast s.
trabeculae consist of imm atu re, non lamellar In cases w here biopsy spec ime ns do not
(woven) bo ne w ith out osteoi d rim s o r os- co ntain sur rounding tissue, the evaluation of
teoblasts (Fig 33-9). Early of FD gro wths are the FD border ca nnot be mad e. In suc h cas-
cha racterized by a fib roblastic tissue w hic h es, the obse rvation that fibro us dysp lasia
Is richly cellul ar, ofte n revealing a w ho rled shows a rather unifo rm ap pea rance w ith a
pattern wi th little bon e. T he t rabec ular constan t ratio of bon e t o fib rou s tissue
arrang em ent has been co mpared to the ap- throughout the ent ire area may be helpful in
pea rance of Chinese c haracte rs and , there- diag nos is and ciassification.
fore, is ofte n refe rred to as "Chinese charac- Nor ma lly, there are no differences in the
ter trab ec ulae" (Fig 33- 10). Affected bon e histo logic ap pea rance of MFD and PFD cas-
usua lly fuses wit h the adjacent nonaffected es. Ho wever, there ma y be a hig he r inci-
bo ne, w hether co rtical or ca nce llous. As FD d ence of lam ellar bon e in MFD.21
progresses, the amou nt of lam ellar trabecu- The diff erentia l diagnosis of fibro-osseous
lae inc reases. These trabec ulae are slender les ions, includ in g fibrous dysplasia, has
and tend to run parallel to eac h other. They been discus sed by a nurnbe r of aut horities
lie very ciose together in a moderately ce llu- for several d ecad es. ' 2. ? '2.2' Slootweq ' " de-
lar fibrou s stroma. The te rm osseous keloid sc ribed the differential diagnosis of maxillo-
has sometimes been used fo r this typ e of le- fac ial fibro-osseo us lesions and compared
sion. Monostot ic FD of the jaws may exh ib it the histopatholog ic features of fib rous dys-
varying amounts of sp herical, amorp ho us plas ia, cernerrt o-ossifyinc fi bromas, and fo-
calcifications and curved/ linear, round, cal- cal cementa-osseous dysplasia (focal and
c ified trab ecul ae which tend to form co n- fl or id) . Fibrous dy sp lasia , as has already
,: . .,..
~ - :J. ,-
~~~4J1Y, '\t~
.,
:A1'.}
Fig 33-9 Irregularly shaped trabeculae of woven Fig 33-10 Higher magnification of a "Chinese
bone in a cellular, slightlyvascular fibrous tissue character" trabecula (H&E, x120 ).
stroma (hematoxylin-eosin [H&EJ, x80 ).
288
Notes on treatment and recurrence rate
been discu ssed, is characterized by evenly co ncluded that the diagnosis of FD is not a
distributed islands of woven bo ne th at fuse histo logic or ultrastructural problem. On the
with surroun d ing bo ne. Th e presenc e of other hand , he pointed out that the d ifferen-
lamellar bone and osteoblastic rimming does tiation of fibr o-osseous lesions using cyto-
not exclude the diagn osis of FD as would be logic characte ristics is not possible because
the case for lesions occ urring outside the fibroblasts, osteo blasts, and osteo clasts are
maxillofac ial bon es. Cemento-ossifying fi- identical in all th ese lesions.
bromas are encaps ulated or well demar-
cated (see c hapte r 32). A broad range of
mineralized material is found in ce mento-os-
sifying fibromas; wove n, as well as lamellar,
bone may be found in addition to rounded 6. Notes on treatment and
cell-poor particles of cementum-like materi-
al. Juvenile and psammomato id COFs are recurren ce rate
subtypes with cel lular stroma showing mi-
totic activity. Cemento-oss ifying fib romas Clinical manag eme nt of and therapy for FD
may resemb le wel l-differe ntiated osteosa r- of the facial skeleton and jaws may be a ma-
comas but it also may be more ce llular and jor problem, especially when assoc iated with
have a high er number of mitoses than os- g ross fac ial d isfigu rement. In most cases,
teosarcomas, Focal cemento-osseous dys- however, FDtends to stabilize and essentially
plasia (see c hapte r 34) has histopathologic stops enlarging when skeletal maturation is
features similar to those of COFs but witho ut reached . Small lesions , particularly those of
demarcation. the mand ible, may be surgical ly resected .
Due to the d iffuse natur e and large size of a
number of lesion s, particularly those of the
5.2.3 Histochemical/immunohistochemi-
maxillary co mplex, extensive surgical proce-
cal findings
dures may be necessary. The treatment of
Systematic histoch emi cal or imm unohisto- choi ce is principally surgica l, dependin g on
chemical studies of fibrous dysp lasia have th e size and consistency of the lesion. Sur-
not been reporte d in the literatur e, gical recontouring and surgi cal redu ction of
the dysp lasia to an acceptable con tour with-
out co mp lete rem oval is usually recom -
5.2.4 Ultrastructural studies
mended.
Ultrastructu ral studies of FD have not been Cam illeri23 suggested t hat su rge ry for
reported in the literatur e. Howeve r, Donath 22 craniofac ial FD is indicated at any age if im-
studied so me fibro-osseous lesions of th e portant functions are threatened; defo rmity
jaws, includi ng fibro us dysp lasia, by electron becomes substantial; or co mplications such
microscopy. Ultrastructurally, FD tumor cells as obstru ction and infection of paranasal si-
are of the osteo blast type and possess only nuses, dental malocclusion , or severe epis-
short fragments of rough endo plasmic retic- taxis de velop , During surger y on active-
ulum, a pro minent Golgi ap paratus, mito- phase FD, excess ive bleeding may occ ur.
chondria, an d free ribosomes. Co llag en Reliable data on the incidence of co ntin-
fibers attach to the bone surtace at right an- ued growth (no recurrence) after surgical re-
gles. Newly form ed osteocytes exhibit a few duction of FD of the jaws are d ifficult to de-
organelles but contain free riboso mes and lit- term ine ,24 bu t it has been est imated that
tle rough endop lasmic reticulum. Donath 22 between 25% and 50% of patients will ex-
289
33: Fibrous Dysplasia
perienc e some regrowth afte r a surgic al re- 4. Lich tenstein L, Jaffe HL . Fibrous dys plasia of
co nto uring pro cedure. Since regr owth after bone. Arch Pathol 1942;33:777- 8 16.
surgical red uct ion seem s to be more co m- 5. Pritchard JE. Fibrous dysplasia of the bones. Am
mo n in younger individuals, surge ry shoul d J Med Sci 1951; 222:3 13 - 332.
be delayed as long as pos sible .i" 6. Dahlgren SE, Lind PO, Lindbom A, Martensson
Frac tu res an d int raosseo us infect io ns G. Fib rous dysp las ia of jaw bon es. Acta Oto-
laryng oI 1969:68:2 57- 270.
have been described in patients with FD.25
Infection is related to the sclerotic and avas- 7. Wald ron CA, Giansanti JS. Benig n nbrc-osseous
lesions of the jaws: A cl inical-radiologi c-histolog-
c ular natur e of mature FD and may result in
ic review of sixty-five cases. Oral Surg Oral Med
the developm ent of osteom yelitis. Oral PathoI 1973;35:190-20 1.
In rare cases, malignant transformation of
8. Daramo la JO, Ajagbe HA, Obisesan AA, Lagun-
fibrous dysplasia may occur, resulting in os- daye sa, Oluwasanmi JO. Fibrous dysplasia of
teosa rco ma. Yabut et al26 reviewed the liter- th e jaws in Nigerians. Oral Surg Oral Med Oral
ature of maligna nt transformation in patients Patho I 1976;42:2 90- 300.
wit h FD. While most of the diagnoses of 83 9. Awange DO. Fibrous dysp lasia of the jaws: A re-
patients we re made in childh ood, malignan - view of lite rature. East Afr Med J 1992;69:205-
cies d eveloped during the 3rd to 4th decades 209.
of life. Approximate ly 0.4% of FD cas es were 10. Obwegeser HL, Freihofer HPM, Horejs J. Varia-
estimated to unde rgo malignant transfo rma- tion of fibrous dysplasia in the jaws. J Maxillofac
Surg 19 73;1:161 - 171 .
tion. Local irradi ation is considered to be a
main ca use for malign ant change; however, 11. Yoon J H, Kim J, Lee CK, Choi J. Clin ical and
only 23 of 83 patients received irrad iation, histopathological study of fibro-osseous lesions
of the jaws. Yonsei Med J 198 9;30: 133- 143.
showing that thi s is not a prereq uisite fo r ma-
lignancy. Th e prog nosis for sa rco mas is 12. Siootweg PJ, Muller H. Different ial dia gnosis of fi-
bro-osseous jaw lesions. A histolog ical investiga-
poor, w ith a mean survlval time afte r diagno- tion o n 30 c ases . J Cr aniomaxillofac Surg
sis of 3.4 years.26 1990 :18:2 10 - 2 14.
13. MacD ona!d-Jank owski D. Fibrou s dysplasia inthe
Patients with FD sho uld be evaluated peri- jaws of a Hong Kong popu lation: Radiog raphic
odically, both clinically and rad iogra ph ically, presentation and systemat ic review. Dentomax-
fo r gro wt h and the late develop ment of pain illotac Rad ial 1999;28 :195- 202.
and swelling which may ind icate possib le 14. Coh en MM , How ell RE. Etiology of fibrous dys-
malignant ch anges. plasia and McCune-Albright syndrome. Int J Oral
Maxillofac 8urg 1999;28:36 6- 37 1.
15. Petrikowsk i e G, Pharoah MJ, Lee L, Grace MAG.
Radiog raphic diff erentiation of osteogen ic sarco-
m a, osteomyelitis, and fibrous dysplasia of the
References jaws. Oral Surg Oral Med Oral Pathol Oral Radial
Endod 1995:80:744- 750.
1. Eversole LR, Sabes WR, Ravin S. Fibro us dys- 16. Casselmann JW , De Jonge I, De Clercq C, Hont
plasia: A nosologic prob lem in the di agnosis of f i- GO. MRI in craniofacial fibrous dys plasia. Neuro-
bre-osseous lesions of the jaws. J Ora l Pethel radiology 1993; 35: 234-237.
197 2:1:189- 220. 17. von Wo wern N, l-ijartinq-Hansen E, Edeling GJ.
2. Waldron C. Fibro-osseous lesions of the jaws. J Bone sci ntigraphy of ben ign jaw lesions. lnt J Oral
Oral Maxlllof ac Surg 1985;43 :249- 262 . 8u rg 19 78;7:528-533.
3. Lich tenstein L. Polyostotic fibrous dysplasia. Arch 18. Gibson MJ, Midd lem iss JH. Fibrous dysplasia of
Surg 1938;36:874- 898. bo ne. BrJ Rad ioI197 1;44 :1-1 3.
290
References
19. Lathc uwer C, Brocheriou C. Sarcoma arising in ir- 23 . Camilleri AE. Craniofac ial fibr ous dysplasia. J
radiated jawbones. Possible relationship with pre- LaryngolOtol 1991 ;105:662.
vious non-ma lignant bone lesions. Rep ort of 6
24. Waldron CA. Fibro-osseous lesions of the jaws. J
cases and review of the literature. J Maxillofac
Oral Maxillo!ac Surg 1993;5 1:828-835.
Surg 1976;4:8-20.
25. Pierce AM, Sampson WJ, Wilson DF, Goss AN.
20. Kramer IRH, Pind borg JJ , Shear M. Histolog ical
Fiftee n-year fo llow-up of a family with inherited
Typing of Odo ntoge nic Tumou rs. 2d ed. Berlin:
craniofacial fibrous dysplasia. J Oral Maxillofac
Springer-Verlag, 1992.
Surg 1996;54:780 - 788.
21. Siootweg P. Maxillofacial fibro-osseous lesions:
26. Yabut SM, Kenan S, Sissons HA et al. Malignant
Classification and differential d iagnos is. Sem in Di-
transfor mation of fibrous dysp lasia. Clin Orthop
aqn PathoI 1996 ;13:104- 112.
1988;228 ;28 1.
22. Donath K. Ultrastrukturpatho logie de r 'fibro-os-
saren Kiefert asio ne n." Dtsch Z Mund Kiefer
Gesichtschir 1986;10:218-224.
291
Chapter 34
293
34 : Focal Cemento-osseous Dysplasia
(COFs); ceme nto blasto mas; cerne nto-os- Familial occ urrence of FocCODs has been
seous dysplasias with single, multiple, and descrlbed.l " They have also been observed
florid subtypes. In their study, no cases of in assoc iation with Crouzon syndrome and
FocCODs were found. Slootweg 12 reviewed acanthosis nlqricans.! " In the last 20 years,
maxillofacial fibro-osseous lesions,their clas- several additio nal case reports of FocCODs
sificatio ns, and d iffere ntial d iagnoses. He have been pub lished.15 - 17
suggested dividing FocCODs into focal and
florid variants.
294
Epidemiological data
295
34: Focal Cemento-osseous Dysplasia
No. of cases
180 168
n =420
160
140
120 115
100
80
60 47 51
40
.=
201 ~ 14 8 Fig 34-3 Age distri-
oL Oi IiJ FlJ
2
bution of 420 Foe-
10 -19 20 -29 30- 39 40-49 50 -59 60 -69 70 - 79 80 +
COD cases.v" No
Age in years
gender distribution
was available.
3.3 Gender
296
Pathology
5. Pathology
4. Patho genesis
5.1 Macroscopy
The pathogenesis of FocCODs is largely un- The macroscopic aspect of FocCODs has
known, but gender, age, ethnicity, and loca- been characterized as quite specific 4 .5 Dur-
tion seem to be of significa nce. Generally, ing surgery, t he oral/ rnaxil.otaclal surgeo n
FocCODs seem to occ ur predo minantly in will usually be able to remove only small, grit
the mandible of black middle-aged wom en ty hemorrhagic fragments of tissue that are
and are con sidered to be of periodontal lig- curetted with some d ifficulty. Su et al5 clear-
ament origin. ly showed that 92.5% of FocCOD specimens
The developm ent of FocCODs is charac- consisted of multiple small fragments of tis-
terized by three stages which have spec ific sue, whereas 88% of COFs were large intact
radiog raphic and mo rpholog ic appea r- speci mens.
ances. Pathogenetically, the first stage is
characterized by proliferation of a cellular fi-
brous connective tissue. During the second 5 .2 M icroscopy
stage, bone and/or cem ent um is formed
5.2. 1 Histologic definition
within the fibrous tissue, giving the lesion a
characteristic rad iolucentjrad iopaqu e ap- Both the 199 2 WHO classification 1 and the
pearance. The final stage of maturation is present authors define the FocCOD as fol-
characterized by continuous progressive for- lows:
mation of bone and/or cementum. A narrow A non-neo plastic lesion affect ing the peri-
rim of connective tissue usuaily surrounds apical tissues of one or more teeth and with
the hard tissue masses. histologic features similar to those of the le-
Generally, the comm on circumstances in sio ns of th e ce me nto-ossifying fibro ma
which excessive cem entum may be formed gro up, but without a sharpiy defined margin.
297
34 : Focal Ceme nto-osseous Dysplasia
.":,,;,rr-- ~
:; .', > ~ (; :i/ :'::,>7'" Li~
Co
~
' :~ " \. . " "",', fI., ~
':\,"" ., ,~....:'r.' :::\.,,'...'\.' !'
,y ,,"'
' '''''.' ", . .. ' ' . .' ;:'"'
';,' .)" , , 1;1 J'",< -:'>' . 1; t''r H !le,u. !
" ' I' >.. I,
b' '.
,:.' i, _ ,>,<_
, "" ; _ , I\.-
y. . ' . I~ ''\l ,
.. ~ "":
~
'.
. _ ,, -::;5
i,'-::':' r. . ~,-:',-~ - -'y~ , :,.,;.,.;
/
. ~;.'.):~~.
,v
""
~!..: ~}. ,;~:
"
Fig 34-5 Photomicrograph of a FocCOD. The Fig 34-6 Intermediate-stage focal cernento-os-
per iphe ry of the lesion is characterized by dense seous dysplasia, Irregular islands and cementicle-
fibrous tissue w ith sma ll, new ly for med islands like structures with basophilic reversal lines are
of cement o-osseous t issue (he matoxylin-eosin embedded in a dense. collagenous tissue (H&E,
[H&E], x60). x100).
298
R efe re nc es
authorities have sugg ested gro up ing Foe- mon ito r the process of calcification and the
COOs and florid cernento-osseou s dys- possible developm ent of a florid cernento-
plasias together, either as PCD with subtypes osseo us dysplasia. Baden and Saroff "? de-
(focal and florid)" or as cern ento-osseous sc ribed complications that may arise in cas-
dysplasia w ith subtypes(single , multiple, and es of Foc CODs associ ated w ith ch ro nic
f1orid).2 period ontitis. Since ceme ntum and osteoce-
Summeriin and Tomich" stated th at PCD mentum are avasc ular and the fibrous com -
and FocCO D are "clos ely related, if not iden- po nent decreases in the later stage of Foc-
tical cond itions" and co nclude d that "peri- COD development, the overall decrease in
apical cernento-osseous dysplasia and focal vascul arization may result in tissue ischemia
cemento-osseous dysplasia are the same pred ispos ing to necrosis, sequestrum for-
process." T hey also co ncl uded thatthese "fo- mation, and osteo myelitis. Deep periodontal
cal lesions may be the initial manifestation of curettage in cases of periodo ntitis, open-flap
the more generalized co ndition-the well-rec- surge ry w ith recontouring of bo ne, and elim-
ognized condition called florid osseo us (ce- ination of intrabony poc kets all expose the
mento-osseous) dysplasia." No histop atho- hard tissue masses and may predispose the
logic d ifferen ce s w ere observed betwe en patient to nec rosis and seco ndary infection.
"conventional" PCD and FocCOD,s
5.2.3 Histochemical/immunohistochemical
finding s References
Stud ies using histochemical and immuno-
1. Kramer IRH, Pind bor g JJ , Shear M. Histologic
histoc hem ical methods have not bee n pub- Typing of Od ontogenic Tum o urs. 2d ed . Berlin:
lished to date. Sp ringer-Verlag, 1992.
2. Ack erman n GL,Altini M .Th e cemento mas-a clin-
ico patho lo gical reap praisal. J Dent Assoc S Afr
5.2.4 Ultrastructural findings
1992;47:187- 194 .
Electron microscopic studies of FocCODs 3. Neville BW, Albe nesius RJ , Charlesto n SC . Th e
have not been pu blished in the literature. prevalen ce of be nig n fib ro-osseo us lesions of pe-
riod onta lligament o rigin in blac k women : A rad i-
ograp hic survey. Oral Su rg Oral Med Oral Patho l
1986;62:340-344.
4. Sum merlin W , To mic h CEo Foca l ce rnento-os-
6. Notes on treatment and seo us dysplasia: A c linicopatho logic study of 221
cases . O ral Su rg Oral Moo Oral Pathol 199 4;8:
recurrence rate 61 1-62 0.
5. Su L, Weathers DW, Wald ron GA Disting uishing
Correct d iagnosis of FocCO Ds is most im- feature of focal ce me nto-osseo us dysplasias and
portant. Diag nosis is based on clinical and cem ento-ossifying fibrom as. I. A patholog ic spec-
radiograp hic features. As soon as the diag- trum of3 16 cas es. Oral Surg Oral Med Oral Pathol
Oral Radi al Endod 199 7;84 :301 - 309.
nosis of FocCOD is clinically confirmed , the
need for treatme nt-particularly endo dontic 6. Su L, Weath ers DR, Wal d ro n GA Distinguishing
treatment-is eliminated . Patients w ith Foc- featu res of fo ca l ce me nto-o sseous d yspl asia and
cemento-ossifyin g fib romas. II. A c linical and ra-
COOs sho uld be followed up regularly, and d iologica l sp ectru m of 3 16 cases. O ral Su rg Oral
vitality test s of involved teeth sho uld be per- Med Oral Patho l Oral Radio! End ed 199 7;84;
formed . Occa sio nal rad iog raph s should 540-549 .
299
34: Focal Ceme nto-osseous Dysp lasia
7. Broph y TW. A treatise on the diseases, injuries 14. Suslak L, Olista B, Gertz man GB, et al. Cro uzon
and malformations of the mouth and associa ted syndrome with periapical cementat dysplasia and
parts. Oral Surgery 1915:867 - 87 1, P. Blakinsto n aca nthosis nigricans: The pleiotropic effect of a
and sons. sing le gene? Birth Defects 1985;2 1:127- 134.
8. Fontaine J. Periapical fib re-osteoma o r cemen- 15. Ward RM. Periapica l ceme ntal dysplasia: A case
toma. J Can Dent Assoc 1955; 2 1:10. report. Dent J 1989;89:53-54.
9. Zegarelli E, Kutsc her AH , Napoli N, et al. The ce- 16. Smit h S, Patel K, Hoski nson AE. Periapical ce-
mentom a-a study of 230 patients with 435 ce- mental dysp lasia: A case of misd iagnosis. Br J
mentomas. Oral Surg 1964 ;17:2 19. Dent 1998;185:122- 123.
10. Bade n E, Saroff SA. Periapical cem ental dyspla- 17. Long JE, Gordy FM, McG innis JP, Kro lls SO. Case
sia and periodontal d isease. A case report with re- presentation. Periapical ceme ntaI dysp lasia. Miss
view of t he literatu re. J Periodontal 1987;58: Dent Assoc J 1999;55:28- 29.
187 - 191 .
18. Wi lcox LR, Walton RE. A case of mistaken identi-
11. Tanaka H, Yoshimoto A, Toyama Y, et at. ty: Periapica l cem enta! dysplasia in an endod on-
Periapical ce mental dysplasia with multip le le- tically treated tooth. Endod Dent Traum atol 1989;
sions . Jnt J Oral Max illofac Surg 198 7;16 : 5:298-30 1.
757 - 763.
19. Taki S, Tonami N, Taki J, et at Intense acc umu-
12. Slootw eg PJ. Maxillofacia l tibro-osseous lesions: lation of Tc-99m MDP and Ga-67 in multiple pe-
Classification and differ ent ial d iagnos is. Sem in riapical cemental dysplasia. Ann Nucl Med 1995;
Diagn Patho I1996;13:10 4- 112, 9:2 43- 24 5.
13. Thak kar NS, Horner K, Sloan P. Familial occur- 20. C handler NP, Love RM , Su ndq vist G. Laser
rence of periapical ceme nta! dysplasia. Case re- doppler flowmetry. An aid in di fferential diagnosis
port . Virchows Arcnfv A Pathol A nat 1993;423: of apical radiolucencies. Oral Surg Oral Med Oral
233 -236. Pathel Oral Radia l Endod 1999:87:61 3- 6 16.
300
Chapter 35
30 1
35: Florid Cementa-osseous Dysplasia
normalities, and there are no d isturbances in consid ered in cases of infected lesions.
the blood c hemistry of affected pati ents." Schneider and Mesa" disc ussed the distin-
The florid cemento-osseous dysplasia is es- gu ishing features of both lesions in detail.
sentially a benign non-neopl astic lesion. The blood c hemistry of patients with FCODs
The first case of "gigan tifo rm cementoma" is essentially normal. In most cases, patients
was probably reported by Agazzi and Belloni do not have a familial history of the d isease.
in 1953 .9Since then one large series of 107 There are, however, reported instances of
cases," a small series of 7 Japanese patients fam ilial invo lvem ent in Italian, Frenc h, Scot-
with FCODs 10 and several case reports-! ' -12 tish, American, Finnish, and blac k African
have been pub lished. The latt er incl uded farnilies.!" Althou gh in th e major ity of cases
one case of FCOD with concomitant simple the mode of ge netic transmission is unclear,
bone cysts." Coleman et al!" desc ribed a Young et ai' S we re able to demonstrate in
case of familial FCOD in a black family in their stud y of 55 fam ily members from five
Afr ica and reviewed the literature on th is con- generations that FCOD appears t o be inher-
dition. ited as an autosoma l do minant trait with vari-
able phenotypic exp ression. The autosomai
domi nant mo de of transmi ssion was also
found in the family rep orted by Co leman et
2. Clinical and radio logic profile el. 14 Young et al 15 sug gested that familial
FCOD be regarded as a separate form of the
disease, because some dif fere nces between
The cli nical features of FCOD are character- the fa milial and nonfamilial variants were not-
istic for the different clinicopathologic vari- ed . Fami lial FCOD affec ts both me n and
ants of the disease, whi c h include solitary, wo men, som e as early as 6 years of age. Ex-
multiple, florid, and periapical acc ord ing to ce pt for the fa miiy rep orted by Co leman et
Ackermann and Altlni." The "classic" FCOD al, 14 all cases of fa milial FCOD wer e ob served
is cha racter ized by sym metric bony hard in white patients. Lesions were reported to
swelling of the jaws , ofte n involving all fo ur be florid, involving large areas of the jaws.
quadrants. The masses may become large The growth rate in familial FCOD seems to
and caus e considerable facial deformity, of- be rapid , affecti ng th e mandibu lar symph-
ten the on ly patient com plaint. There may be ysis.A numberof cases were associated with
spac ing of th e maxillary and mandibular an- multiple unerupted teeth. Assoc iated SBCs
terior teeth w ith some deg ree of d isplace- have not been record ed in patients with fa-
ment. Teeth assoc iated w ith areas of nonin - milial FCOD. 15
fect ed FCOD are usually vital. Symptom s
suc h as pain or drainage are m ostly assoc i- As in FocC OD (see c hapter 34), t he radi-
ated with exposure of the sclerotic calcified og rap hic appearance de pends on the de-
masses in the oral cavity. This may occ ur as gree of maturation of the lesions. Although
a result of alveolar atr ophy under a denture proliferative, immature FCOD lesions appear
or afte r extractio n of teeth in the area in- rad iolucen t, late r stages of maturation are
volved. Clinically, purulent discharge or fis- c haracte rized by dense radiopaque masses
tu la formation may occur as secondary phe- of ceme nto-osseous material usually located
nomena , and ce me nto-osteomyelitis w ith in the tooth-bearing, posteri or mandible or
seq uest ration may occasionally devel op . maxilla. On panoramic rad iog raphs, FCODs
From the differential point of view , c hronic appear as diffuse, lobular, irregularly shaped
diffuse sc lerosing osteo myelitis has to be rad iop acit ies. In som e cases, lesions are en-
30 2
Clinical a nd radiologic profile
meshed within poo rly defined areas of de- FCODs revealed a range of 8 to 46 HU, indi-
creased rad iodensity and have a "ground- cating a fluid conte nt. Beylouni et al.5 found
glass"appea rance. The size of FCOD lesions axial CT scans to be of use in visualizing the
varies betwee n 0.5 and 10 ern" (Figs 35- 1 buccolingua l aspect s of the lesions demo n-
and 35-2). If the lesion is infected , a radiolu- stratin g the relation ship of FCOD lesions to
cent border is often d iscernible. In cases of root apic es and cort ical plates in the buc-
FCOD associated with SBC, multiple rad i- co lingual dimensions. Vertical and panoram-
olucencies with well-demarcated, scalloped ic reconstructions may reveal further details
borders and buccal expa nsion may be ob- on the relationsh ip of FCOD to the apices of
served."? Amorphous de nse rad iopac it ies roots and to the canal of the inferior alveolar
may be seen cen trally or at the apices of nerve. Three-dimensional reconstructi ons
teeth. enable an anatomic study of the bone sur-
The use of computed tom og raphy (CT) face. Due to hig h-grade imaging, these au-
and three-dimensional imaging has been de- th ors were able to avoid biopsy of the lesions.
scribed in som e cases of FCOD.5 ,10,15 Ariji et They also considered dental imaging helpful
allO fou nd CT to be very useful in the diag- in differentiating fibro-osseous lesions fro m
nosis of FCOD. The Hounsfield units (HU) of odon tomas , in which the HU for enamel is
high-density masses were mo nitored in sev- highe r than thatfor cementum. In so me cas-
en patients with FCODs and ranged from 77 2 es, sci ntigraphy with Tc-99m showed in-
to 1587 HU with a mean of 1337.4 HU. Cyst- creased uptake of the radionuclide in the af-
like spaces observed in four patients with fected regions of the jaws.
303
35: Florid Cemento-osseous Dysplasia
No. of cases
,
35 []] women
31
30 28 DJ Men
n = 107
25
20
16
15 13
10 8
6
5
O~
10- 19
~
20 -29
u, I Ill" I Ill" I Ill"
30- 39 40- 49 50- 59 60 -69
fll
70 - 79 Fig 35-3 Age and gen-
Age in years
der distribution of 107
cases of FCODs'
The d ifferen tial d iagnoses of FCOD in- pathology labo ratories and many cases re-
clud e polyostotic fibrous dysplasia, c hronic main und iagn osed , the tr ue inc ide nce may
sc lerotic osteo myelitis, Paget disease, Gard - be much high er. On ly a few cases of FCODs
ner synd rome, and other ce m ento-osseous associated w ith SB C (see c hapt er 39 ) have
dyspla sias. bee n reported,s10,13
3 .2 Age
3. Epidemiolog ica l data
The age d istribution of 10 7 cases of FCODs'
is shown in Fig 3 5-3. The age rang e of pa-
3.1 Preva lence, incidence, and or tients was 19 to 76 years.The majority of cas-
re lative f requency es occurred in the 6th and 7th d ecades. The
mean ag e of 7 Japan ese patients with
Flor id ce mento-osseous dys plasia has long FCO Ds w as 5 1.3 yea rs (rang e, 43 to 65
been considered a rare dise ase. However, re- years).' ? The ag e rang e at the time of diag-
ce nt studies based on more precise d efini- nosis for cases of fami lial FCOD varied con-
tions and c lassifications of ce mento-osseous sid erab ly amo ng th e d ifferent fam ilies re-
dys plasias" have show n this is not th e case. ported.!"
T he incid ence of FCOD is un known. Shear
and Rach an is 16 rep ort ed th e age-speci fic
mor b id ity rates for FCO D in the Witw ater- 3.3 Gender
srand area of South Africa from 1965 to 1974
as being 0 for w hite and black men, 0.46 for The study by Ac kerm ann and Altini" showed
black women, and 0.2 1 for white women per that 103 of 107 patients were wom en with a
million po pulation per year. Sinc e th ese fig- male :fe male ratio of 1:26 (see Fig 35-3). Of 7
ures wer e based on specime ns se nt to Japanese pat ien ts w it h FCO Ds, 6 were
304
Pathology
women.10 Of 34 cases of fami lial FCODs, 20 however, must be cons idered only as a com-
occurred in women and 14 in men, revealing plication of FCOD. The periodontal ligament
a different pattern than th at of the noninher- has been consi dered the tissue of origin of
ited variant. FCOD by most aut horities, but som e re-
searchers have specu lated that FCOD may
originate from rem nants of cementum left in
3.4 Location th e bone after extractio n."
The etio logy of FCOD with SBC differs
Florid ce me nto-osseous dysplasia is o nly from that of SBC aione. While SBC, accord -
found in the tooth-bearing regions of the jaws ing to some aut hors, develops after in-
and is far more co mmon in the posterior re- tramed ullary hemo rrhage following a trau-
gions. In one study." 78% of the lesions biop- matic injury, Higuchi et al8 assumed that
sied were located in the mandible. Of the pa- cystic changes occur after the development
tients studi ed by Ackermann and Altin i," 59% of FCOD. Melrose et al? suggested that dis-
had a single lesion, whil e the remainder had orderly bone production might result in ob-
multiple lesions (29%; two to five lesions in structed drainage of interstitial fluid and thus
one or more jaw quad rants) or florid lesions lead to cyst or cavity formation. Th is as-
(12%; d iffu se invo lvement of pe riapical su mption was based on micro scopic obser-
and/or alveolar bone in more than one quad- vations of increased num bers of dilated cap-
rant). Multiple and florid lesions occurred sig- illary vessels in FCOD lesions.
nificantly more frequently in black patients
and were unusual in patients from other eth-
nic groups .
5. Path ology
3.5 Ethnic distribution
305
35: Florid Cemento-osseo us Dysplasia
!.?,.... ~' .i . '. :<'1 " " ""'} ''-A'':' "'j: .~''I.'~f'~'';~ "::. '1
;:;};(
~, ~: . ".,; ~.~G
'\>~ -:. "~~"'-C;()("
"--.., :, ', ' ..I~ 'f". .i:Y
..". . , , ),v ' " ""{..,, J .>
.-!"-
J{ ';. ~~"r"-.. J' I .~'>
,..,. " . ,' ("", "1
., ."x~.~;;::{i'/~
." ....I."Y" J , -"".
,,/'-'A"
~. . ': . .;.~ ,,:1":~~:~;~~ '\ v, ." ~_' ' . l
~ "" ' ~i. :~::
-.,~~ '.: l r::; - 4:.. ,,/,;;A:.. J::, j~" \'. : ~, ~ .~::/~:t<, ,!-:::
..,J \ I A
\ t '.. y .. d1,.. .... " \ , <,
.~;_!?j:~tj~~~
,.., , , "" \ ' . " , :0.:. ,
-, iii," ' - '. v
1.<....
'~~l'dJ":~",r
,,-J> t ~ ..). ..........
~('".:~~,,~'\ _,
,.J:...,<\ r
' , '~\ :.L \1,,,:- _
... , ~ " . .
Fig 35-4 Micrograph showing an early FCOD le- Fig 35-5 Laterdevelopmental stageolthe FCOD.
sion characte rized by round ed glo bu les and ir- Globules and trabeculae are now partially fused
regu lar trabeculae of cem entu m in a ce llular fi- (H&E, x120).
broblastic stroma (hematoxylin-eosin [H&E).
x120).
.... -.
..-' -;~.t,.~
\.'j,.~ ~;- - ~.,., .
...,,,- " - .. ~, '
' ~ ,::.~:. :,,*'i)'''';'; ~ "' .... -- - ,
.. /..,
'w~
,,~._~- -.--
'""-'. ';.':,.-..al
]l~.t .'
'. -"
.... ,(;f ~;... r , "" .~t ~ I" '/ 1.
,, .J~
> ): : ,.". ~-~~/ ~>?<~. :: ' ' ,,.:...".. ':. ~ ' cP1.'.
) \
""-,.",; ,. ,'"..
:' J
""' '<"..... . '
, - r '" . -- / .\
\
t1~~"'~J;" .: ,fj( ..
t'l-~$""~' "'; ~r&; ' ::~ \~
c.':f~;. ' . . '1'~.
\~" . '"' ..
<. ';
c"r .... ' ' .".
kJ. "'~,r .r. 1
0
.': .
' ,V ~"t ~' ; .. /;
,
~. ~~,
,, ~. ~~ / -,,-
. . 'r";'-
"t . . or
.
~ . \ "'.
..- :'t~ <-J',, ,."
"-Jii: -,
.. ,' ' .' .~ ,
'."J ' .'
t
i.~
~~
--'
/
,.iC ~,
.
.
'.~'
.
<. - (' , g;
"
" , '\\0 ,)
/
.-. ;---.....
'( i " ,1
,
.. ... .' ,,') ('</'~) \ .
"-~., '.. ....1. : y ' . . ,.
......... .". , ~.. .... ~ ;'~~ 1' t .,~>'" ', __<,
." ~. ...... :. ,i,;
'
Fig 35-6 Late mature stage at the FCOD. Coa- Fig 35-7 Paget disease. Note the similarity be-
lescence and fusion of cemental material is near tween FCOD in Fig35-6 and the pagetoid globu-
completion. Note the basophilic resting lines lar osteosclerosis here (H&E, x120).
(H&E, x160).
5.2.2 Histopathologic findings filled in, resulting in fusion oft he globu les into
so lid sheets. Fusion of cement um to sur-
Histopathologically, early-stage lesions are rounding bone or inc lusio n of bone in glob-
characterized by rounded globules or irreg- ules of cementum does not usually occur.
ular cementum trabeculae of varying size in The basophilic resting lines may represent
a cellular fibroblastic stroma. Some cas es the boun daries of the or ig inal cementum
may show a proliferative co mponent at the co mpo nent ." Maturation of the lesions
periphery of the lesion . Th is component co n- seems to occur at the center wit h prolifera-
sists of ce llula r fib ro us tissue conta ining tion and an increase in size at the periph ery
rounded globules and/or ce ment um trabec- unt il the lesion "burns itself out :' Of the cas-
ulae. Ackerman and Altini" also observed es stud ied by Ackerm ann and Altln i," 54%
that the bo ne around globules of ceme ntum showed signs of infection. resorption , necro-
306
Note s on treatment and recurrence rate
sis, and sequestration. These fin dings were 5.2.4 Ultrastruct ural finding s
more frequent in cases with out a pro liferative
component (Figs 35 -4 to 35-6). T he te rm Ultrastructural investigations of FCODs and
pagetoid globular osteosclerosls .i" which oth er non-neoplastic bo ne lesions of the jaws
should not be used to describe FCOD, de have not been publish ed to date. Mincer et
scr.bes similar histologic features in Paget al20 published ultrastruct ural features of scle
disease (Fig 35-7). rotic ceme ntal masses which occu rred in the
Cases of familial FCOD reveal asimilar his mand ibl e of a 52-year-old black wo man.
tologic appearance as th at of th e nonhered They ob served villose cell processes ("cyto
itary variant. Melrose et al / found that most plasmic filop odia"), tight junctions, and nu
cases exhibited a mixture of cementum-like mero us 7.5 to 10 nm intracytop lasm ic fila
material and irreg ular trabec ulae of bon e, ments occupying a co nsiderable portion of
with some trabeculae rimmed by plump os the ceil. While the authors interp reted these
teoblasts and oth ers showing active resorp filaments as contrac tile elements, Bu rk
tion with apposed mu ltinucleated osteo ha rdt'? arg ued th at it seems unlikeiy that
clasts. cells in cemental masses should be equip
In cases of FCOD with co nco mitant SBC, pe d fo r iocomotion. He interpreted the vi
the histo patho logic features are identical to mentin-positive filame nts as a cytoskeleton.
those of FCODwitho ut SBC .The "cavity wall " In recent years, it has been stressed by a
consists of a thin, loose fibrou s co nnective number of authorit ies that more ultrastruc
tissue layer without epithelial lining as is char tural (and immunohistochemical) stud ies are
acteristic for SBC. needed to clarify the nature of immature and
Of considerable importance is that in the mature calcified structures, which have been
proliferative phase of FCOD histopathologic designated "ce mentum-like," "osteode ntin,"
features may overlap with those of PCD and and "dysp lastic dentin."
cemento-ossifying fibroma." In fact, several
biopsies of one lesion may reveal diffe rent
histologic patterns, some of wh ich may be
taken for a ceme nto -ossifyin g fibro ma. In
such instances, differentiation may de pend 6. Notes on t reatm ent and
more on clinical and rad iog raphic appear
ance than on histoloqy." recurrence rate
307
35 : Florid Ceme nto-osseous Dysplasia
by some authors 15 who believe that partial re 7. Me lrose RJ, Abrams A M, M ills BG. Florid osseous
dysplasia. A c lin ical-patho log ic study of th irtyfour
section of the involved jaw bone may be in
cas es. Oral Burg Ora l Med Oral Patho l 1976;41:
d icated in some cases. 62-82.
Infection of FCOD may occ ur after expo
8 . H ig uch i, Y, Na kam ura N , Tash iro H . C linico
sure of the avascular sclerotic cernento-os path olog ic study of cem ent a-osseo us dysplasia
seous masses d ue to trauma. In such cases. prod uc ing cysts of the ma nd ible. Ora l Burg Oral
cemento-osteomyelitis with necrosis and se Med Oral Pathol 1988;65:339-342 .
questration may occ ur. Seq uestrectom y and 9. A gazzi C, Be llo ni L. Gli odontom i du ri d ie mas
surgical debridementlo remove infected and cella r]. A rc h Ital Ot o l Rino l La ringo l 1953;64:
necrotic tissue is the treatment of choice. Sys 3-102 .
temic antibiotics should be ad ministered to 10. Ar iji Y, Ar iji E, Hig uchi Y, et al. Flo rid cernento-os
avoid the spread of infection. How ever, the seous dysplas ia. Rad iog raph ic st udy wi th special
emphasis o n co m puted to mo g rap hy. Oral Burg
avascular nature of FCODs makes the use
Oral Med Oral PathoI1994;78:39 1-396.
fulness of antibiotic adm inistration question
able since delivery to the infected site may 1 1. Ong 50T , Sia r CH. Flo rid cernento-osseous dys
plasia in a yo u ng Ch inese ma n. Case rep ort. Aust
not be sufficient. Dent J 199 7;42:404 - 408.
Simple bo ne caviti es associated with
12. M iyak e M, Nagahata S . Flori d cem ent o-osseous
FCOD ofte n manifest act ive enlarg ement dysplasia . Report of a case. Int J Oral Maxillotac
and do not always respon d to surgical inter Surq 1999;28:56- 57.
ventions. ln some cases, however, SBCs may 13 . M iyau ch i M, Ogawa I, Takata T, et al, Florid ce
"heal" spontaneously. In these cases, the ra m ente-osseous dysplasia with conco mitant sim
diographic appearance of the mineralized pl e bon e cysts: A case in a Japanese w oman, J
tissue may be abnormal.7 Oral Pathoi Med 1995;24:285- 287.
14 . Co lem an H , Altin i M , Kieser J, Nisse nba um M. Fa
m ilial florid cem e nto-oss eo us dysplasia- a case
repo rt and review of the literature. J Dent Assoc
S Atr 1996;51 :766- 770.
References
15. Young 5, Ma rko w itz R, Sulliva n S, et al, Familial
1. Pindbo rg JJ , Kramer IRH. Histologic Typing of gigantifo rm ce mento ma; C lassi ficatio n and pres
Od o ntogen ic T um ou rs. Jaw Cysts and All ied Le entatio n of a large pedi gr ee. Oral Surg Oral Mad
sio ns. Berlin: Springer-Verlag . 19 71 . Oral PathoI 1989 ;68:740 - 746,
2. Kram er IRH, Pindborg JJ, Shear M. Histological 16, She ar M, Rach ani s CC . Epid emiology of odonto
Typing of Odontogeni c Tu mours. 2d ed. Berlin: ge nic lesions in So uth Af rica. J Dent Assoc S Afr
Sp ring er-Verlag, 1992. 1979;34:685- 688,
3. Waldr on CA Fibro-osseous lesions of the jaws. J 17. Olkarin en K , Alt o nen M, Hap pon en A-P. Gigan
Oral Maxillofac SUr9 1985;43:249 -262. tifo rm ce me ntoma affecti ng a Ca ucasian family.
Br J Oral Maxi llofa c Surg 1991 ;29; 194- 197.
4 . A ck erm ann GL, Alti ni M. Th e ce me nto mas-a clin
ico pathol ogi ca l reap p raisal. J De nt Assoc S AfT 18 . Musella AE, Slater LJ. Fam ilial flo rid osseous dys
1992;47:187- 194, p lasi a: A case repo rt . J Ora l Maxillofac Surg
1989 ;47:636- 640.
5. Be ylo un i I, Farge P, M azoyer J F, Coudert JL. Flo rid
corn o nto osseous dy splasia . O ral Bu rg O ral Med 19. Burk hardt A. Denti n formatio n in so-ca lled 'fibre
Oral Pathol Oral Radial End od 1998;85 : 70 7 os teo-c ementa l" lesio n of the jaw: H istolog ic, elec
711, tron microscop ic , and im munoh isto chemi cal in
vest igati o ns . Oral Bu rg Oral M ed Oral Pathoi
6. Schneider t.O, Mesa ML . Differences between 1989;68:729 -738.
flo rid osseous dysplasia and c hro nic di ffuse scl e
ros ing os teomye litis . Ora l B urg Oral M ed Oral 20 . Mincer HH . Mc Ginnis J P, WyattJR. Ultrastructure
PathoI1 990;70 :308-31 2. of sclerot ic cemental masses. O ral Burg Oral Med
Oral PathoI 1977 ;43 :70- 8 1,
308
Chapter 36
Cherubism
30 9
36: Cherubism
interval betwee n D4S127 and the telomere t he underlying fib ro-osseous st ructures.
of 4p. Withi n this region , a strong candidate Since these deformities may be of varying
is the gene for fibroblast groW1h facto r re severity, a g rad ing syste m has been pro
ceptor-3 (FGFR-3). Mutations in th is gene posed ":
have been implicated in a diverse set of bo ne Grade 1: involvement of both mandibular
developme nt disorders.18 In a recent study ascend ing rami
of craniosynostosis and cherublsrn.!" how Grade 2: involvement of both mandibular
ever, the FGFR-3 gene was excluded as a ascendin g rami and both maxil
possible candidate. lary tuberosities
Grade 3: massive involvement of the en
tire maxilla and mandible except
the condylar processes
Grade 4: same as Grade 3 with involve
2. Clinical and radiologic prof ile ment of the orbits, causing or
bital compression.
A number of de ntal abnormalities have
Cherubism is characterized by bilateral en been reported. The fibro-osseous lesions
largement of the mandible and maxilia with may cause pre mat ure loss of decid uous
bone loss and replacem ent with fib ro-os teeth. Agenesis of the second and third mo
seous lesional tissue. In rare instances , ribs lars of the mandible-and the maxilla, when
or long bones may be affected also. The involved- is regularly observed. Displace
spectrum of the disease can range from the ment of teeth with delayed eruption is also
unilateral subc linical involvement of the jaws seen. Resorption of roots may occu r in se
to extreme bilateral expansion. The most vere cases.
com mon site is the mand ibular angle . The Cervical lymph node enlargement may be
lesions may spread to involve the retromolar present in 45% of cases and contributes to
areas and ascending rami. In more severe the full-faced appeara nce. Lymph nodes en
cases, the coronoid processes may expand large before the age of 6 years, dec rease in
so severely as to oblite rate the mandibular size after 8 years, and are rarely enlarged at
notch. The condyle is only rarely involved, 12 years. The increase in size is produced
and most patients can open their mouths ad by reticuloendothelial hyperplasia with fibro
equately. sis. Due to the cum ulative enlargement of
Maxillary lesions (60%) usually start in the the submand ibular lymph nodes and the ex
tuberosity and involve the maxillary alveolar pansion of the mand ible, the tongue may be
processes, resulting in the development of a d isplaced , affecting speec h, mastication,
narrow V-shaped palate. The antralfloor may swallow ing, and respiration. Cherubism is
be thickened. In severe cases, the antrum not present at birth. Facial swelling first ap
may be completely obliterated. The anterior pears between the age of 14 months and 4
wall of the maxilla may becom e enlarged and years and progresses until the age of 12 to
protrude forward. The lower eyelid is pulled 15 years (Figs 36-1 to 36-3). Typically, the
down , prod ucing the characteristic Heaven earlier the lesion appears, the more rapidly it
ward "gaze." Orbital compression with im prog resses. The fastest groW1h occurs over
paired vision and pro ptosis may occur in the first 2 to 3 years with a slowing down af
some cases. ter the patient reaches the age of 5 years.
The facial deformit ies in cherubism are GroW1h of the posterior mandible and maxil
due solely to enlargement and expansion of la stops first, whereas the anterior mandible
3 10
Clinical and radiologic profile
may cont inue to g row for some time. Clini in acceptable lim its and surgical interven
cally, cherubism may beco me qu iescent tions are unnecessary or limited. Cases of
without treatment and may decrease in size extensive bone destruction resulting in an es
at 20 to 30 years, although th e jaws may re thetically monstrous appearance or severe
main somewhat large. functional disturba nces may occas ionally be
In the vast majority of cases, the cha rac observed . In add ition, aggressive forms of
teristic maxillofacial deformities remain with- cherubism have been descri bed. ' 9.2o
31 1
36: Cherubism
Laboratory findi ngs in cherubism are not (se ru m ca lc ium , parathyro id hormone,
diagnost ic. Serum calcium, phosphorus, parathyro id-related hormone, calcito nin, al
and alka line phosphatase may be elevated kaline phosphatase) ; however, urine analysis
or normal. However, elevated values in chil of pyrid inium and desoxypyridinium cross
dren are not unusual and are associated with links, hydroxyproline, and calcium in relation
the physio log ic growth of bones. Southgate to urine creatinine to assess bone resorption
et al' 2confirmed that the biochem ical profile showed values at the upper end of the nor
in fou r ch ildren with cherubism was normal ma l range .
3 12
Epidemio logical data
Radiog rap hically, th e lesions co nsist of bism. Usi ng ste reophotographic assess
multiloc ular radiolucencies w ith distinct bo r me nt, the c hanges of facial swe lling may be
ders divided by bon y trabeculae (Figs 36-4 mon ito red and co mpa red w ith th e norm .
to 36-6). Expansio n of the cortical plates as Bone sc int ig ram s have reveal ed low ra
sociated with marked thinning is also see n. dioactivity- so-called co ld areas- in so me
The co rtica l plate s may be pe rfo rat ed . cases of cherub tsrn."?
Chan ges usu ally beg in posteriorly and
spread anteriorly. Mand ibu lar lesions may
reveal caud al d isp lacem ent of the inferi or
alveolar nerve canal, and the lesion may in
volve the alveo lar process, th e mandi bular 3. Epidem iolog ica l data
angle, and the ascend ing ramu s. Lesions are
usually found bilaterally. Teeth may be dis
placed or unerupted , or they may ap pear to 3.1 Prevalence, incid en c e, and
be floati ng in the cystlike spaces. Root re relative frequency
sorptio n m ay be observed as we ll. Radi
ographically, maxi llary lesions are similar to Che rub ism is a rare disease . Unti l 20 00, ap
those of the mandible and are located pri pr oximat ely 28 0 ca ses had been de
marily in the tuberositi es. The maxillary si scribed.! " Figures on incidence and preva
nuses, wh ich are small in children , may be lence have not been published to date.
completely obliterated. Occ lusal films may
reveal a "soap-bubble" appearance. 3 .2 Age
The bilateral extended osseo us destru c
tion changes with age. Whereas trabec ulae Ch erub ism manifests in early child hood, usu
aresparse during the growth phase,the num ally at 14 months to 5 years,18 and becomes
ber and thickness of the septa increase and more marked until puberty. At this time the
the lesion becomes m ore rad iopaque whe n fibro-osseous lesions begin to regress, but in
the patient reaches 8 to 12 years of age . Dur many cases c herubism may persist through
ing this phase th e lesio n may take on a out life. Data for the c reation of a "co nven
ground-glass appearance . By 20 to 30 years tional" age distributio n are not available.
of age, the lesion c hanges to a granular tex
ture. Cystic spaces, how ever, may still be 3 .3 Gender
present at age 70.
Alt ho ugh convent ion al radi og raph y is Me n are affected tw ice as freq uent ly as
helpful in th e diagnosi s of cherubism, co m wo me n, and there is no ethnic dominance.'
puted tomography (CT) is superior for mak
ing th e diagnosis and determ ining the de 3.4 Location
gree of severity. In particu lar, CT may provide
a realistic Spatial picture ofthe lesion , ITSsite , While the mandible seems to be involved in
extent, and structure, thu s show ing some as all cases , the maxilla is affected in only 60%
pects that otherwise would not be dem on of cases. Lesions are usually bilate ral, al
strable d ue to superimposit io n and t he th ough un iiat eral cases have been repo rt
anatomic co mplexity of the jaws.10 ,2 1 ed. 22 Lesions start to develop posteriorly and
Three-dime nsional reconstructions of the extend ante riorly du ring the disease proc ess.
lesions may be helpful in planning surgical
interventions in mo re severe cases of cheru
3 13
36: Cherubism
3 14
Pathology
Fig 36-7 Early active lesion with high cellularity Fig 36-8 A mo re mat ure lesion w ith formation of
and giant cells ina vascular fibrous stroma (hema- new bone trabeculae (H&E, x60).
toxylin-eosin [H&E], x60).
comes more fibrous, and there is a decrease phatases, ATPase, and leucine amino-
in the numb er of giant cells; new bone may pept idase-were tested. These auth ors were
be formed (Fig 36-8 ). Remnants of odonto- able to characterize three stages in the mor-
genic epithelium are so metimes scattered phologic evolution of cherubism. The first
throughout. This particular findi ng has been (osteolytic) stage is characterized by an os-
Interpreted as supporting the odontogenic teolytic "granul oma " with numerous giant
origin of cherubisrn." Th e enlarged lymph celis and a high level of acid phosphatase ac-
nodes usually reveal reticuloend oth elial hy- tivity. The seco nd stag e shows repair with
perplasia, fibros is, and c hro nic inflam ma- pro liferation of highly active fibroblasts and
tlon.' an increase in leucine aminopeptidase ac-
Morph ologically, cherubic lesions are sim- tivity. The third stage exhibits osteogenesis
ilar to th ose observed in giant cell lesion, fi- as a sign of bony restoration with high alka-
brous dysplasia, and hyperparathyroidism. line ph osphatase activity. It was co nclud ed
Therefore, t he d iagnosi s of cherubism tha t histologic and histoenzymolog ic find-
should never be based on microscopic find- ings may indi cate wh ether involution or pro-
ings alone but should include anam nestic, gression of the disease should be expected.
clinical, and radiographic findings (eg, early Burkhardt and Berthold 25 found histiocyt-
onset of the disease, a positive family histo- ic ch aracteristics in both mononuclear and
ry, absence of other bone patholo gy, histo- multinucl ear cells by demonstrating alpha-1-
logic pictur e). trypsin, alpha-1-antitrypsine, and lysozyme.
Staining for lysozym e was muc h more
marked in giant cells than in mononuclear
5.2_3 Hisl ochem icaVimmun oh isl och emi-
cells. The mononu clear cell elements were
cal findings
id ent ified as fib rohi st iocytic with marked
Cherubic lesions have only rarely been stud- sig ns of activity; the multinuclear giant cells
Ied systematic ally by histochemical or im- were of the osteoclastic type, although it was
munohistoche mical methods. Chomette et thou ght possible that they might assume an
al24 stud ied t hree cases of cherubism by intermed iate po sition betw een mature os-
histoe nzymologic methods. Oxidat ive en- teoclasts and histiocytic giant celis (mak ing
zymes-i nclud ing acid and alkaline ph os- th em preosteoclastic). Since findings in gi-
3 15
36: Cherublsm
ant cell granulomas are almost Identical, the po rted that of 10 patients with cherublsm
autho rs sugges ted a relationship betwe en who had rece ived radiation therapy (25 Gyl,
the two types of lesion. a fibro sarcoma developed In 1 patient and 5
othe rs had growth distu rbances of the jaws.
Becau se t here are few funct ional distur-
5.2.4 Ultrastru ctural find ing s
bances, tr eatment Is usuaily based on the
Chomette et al24 and Burkhardt and Bert- rate of tumor progression, the extent of In-
hold 2s stud ied biops y specimens of cheru- volvement, and the psycho log ic state of the
bism by transmissio n electro n microsco py. pat ient. Most authors recommend deferring
Chomette et al24 found three types of cells: treatment until after puberty, which makes It
giant cells, ovoid cells, and fus iform cells. GI- difficult to evaluate nontreatment. The gen-
ant cells had features of osteoc lasts and re- eral view of the surgica l treatmen t Isto follow
vealed several pale nuclei with marginated the pat ient and perfo rm biopsies, surgical
heterochromatin. The cytopl asmic mem - correcti ons, and removal of ectop ically Im-
brane showed regular microvillus-like pro- pacte d teeth .' 3 Early surg ical Interventions,
jections and som etimes revealed Irregula r on the ot her hand, often result in prompt re-
larger cytoplasm ic processes. The cyto- currence and aggravatio n of the lesions. In
plasm contained numerous mitoc ho ndria 2000, von Wowern 13 showed that surgical
and well-develope d cisternae; there w erefew treatme nt d id not provoke growt h of lesion-
Iysosomes. Ovoid cells were simllar to young al tissue In any of 22 cases obse rved over a
fibrob lasts. Elongated cells were similar to period of 36 years.
osteoblasts . In young pat ients, the lesions are vascu-
Burkhardt and Berthold 2S also revealed a lar, and b lood loss may be considerable
number of d ifferent cell types. Mon onuclea r when treated su rgically. In one case, 26 vas-
fibroblastic/fibrocytic spi nd le-shaped cel ls cular transformation occu rred after surgery.
and abu ndant rough endoplasmic reticulum In cases w here treatment is necessary In a
we re most co mmon . Othe r cel l types in- young patient, so me authorities have pro-
cluded myxob last-Iike cells, myofibrob lasts, posed radical treatment rather than conser-
cells of histiocyte-macrophage different ia- vative curettage to avoid mu lt iple recur-
tion, osteoblasts, and angloblasts. On aver- rences and repeated surgical Interventions.
age, 15 nuclei per giant cell were found. Other authors have proposed curettage of
the lesions, while stili others have suggested
unilateral surgery and comparatlvefollow-up.
Contouring procedu res after age 20 are usu-
ally satisfactory In terms of facial esthetics.
6. Notes on treatment and Calciton in,which Is used as an antiresorptive
agent to prevent osteo porosis In postmeno-
recurrence rate pausal women, has recently been discussed
as a possib le med ication for cheruo lsrr."
Treatment of cherublsm Is not uniform or The prognosis for che rublsm Is generally
stand ardized . Cherublsm usually Is self-lim- goo d, since the d isease gradually regresses.
Iting and regressive, alt hou gh agg ressive The first signs of Imp rovement may be ob-
cases have been oescnbec ." Rad iation served In the maxilla; lesions In the mandible
t herapy Is absolute ly contraindicated be- may progress until age 20. After 30 years of
cause of severe sequelae suc h as osteora- age, few traces of the d isease are stili de-
dionecros is and osteosarco mas. Peters 3 re- tectable, especially In the mandi ble.
3 16
Referen ces
3. Peters WJ. C heru bism: A study of twenty cases 16. Pina-Net o JM , More no AFC, Silva LR, et al. Cheru-
from o ne fami ly. Oral Surg O ral Med Oral Pathol bisrn, gingival fi bro matosis, ep ilepsy, and men tal
1979;47:307- 3 11. defic iency (Ra mo n syndro me ) wit h juvenile
rheu mato id arthrit is. Am J Med Gen et 198 6;25:
4. Zachariades N, Papanicolaou S, Xypolyta A, Con- 433-44 1.
sta ntinidis J. Cherub ism. Int J Oral Su rg 1985;
14:13 8-145. 17. Ouan F, Gro mp e M, Ja kobs P, Poovich B. Spon-
taneous d eletion in the FMR 1 ge ne in a patient
5. Zo harY, Granskord A, Shabt ai F, Ta lmi Y. Fibrous with fragile X syndrome an d cherubism. Hum Mal-
dysp lasia and c he rub ism as a hered itary fa milial ec Genet 199 5;4:168 1- 1884.
d isease. J Cra nio maxillofac Surg 198 9;17:3 40 -
344. 18. Ma ng io n J, Ra hm an N, Edkins S. et al. The gene
for cherubism maps to chromosome 4p16.3. Am
6. Kaugars GE. Niamtu J III, Svirsky JA. Cheru bis m : J Hum Genet 19 9 9;6 5:15 1-1 5 7.
Diag nos is. treatme nt, and co mparison w ith cen-
tral g iant ce ll granulomas a nd giant ce ll tumors. 19. Tim osca GC, Galesanu RM . Co tutiu C, Grig oras
Oral Surg Oral Med Ora l Pat ho l 1992;73:3 69 - M . Ag gr essive form of c herubism : Report of a
3 74. case. J Oral Maxillofac Su rg 2000;58: 3 36-344.
7. Marek PA, Kudryk W H. Cherubism. J Otolaryngol 20. Ayo ub A F, &Motty SS. Ch e rubism : Report of an
1992;2 1:84 - 8 7. aggress ive case a nd review of the literature .J Ora l
Ma xillo! ac Surg 19 93 ;51 :70 2- 70 5.
8. Vaillant JM, Romain P, Divans M. Cheru b ism .
Find ings in th ree cases in the same fami ly. J Cran- 2 1. Bianc hi SD, Bocca rdi A , Mela F, Romag no li R. The
iomaxil lofac Su rg 1989;17:3 4 5- 349. co m p uted tom ographic appe aranc es of cneru-
bism . Skeletal Rad ioI 1987 ;16 :6- 10.
9. Penfold CN, McCu llag h P, Eveson JW, Ramsay
A. Giant cell lesion complicat ing fibro--osseo us 22. Reade PC. McKellar GM. Radd en BG. Unilateral
con d itions of the jaws. Int J Oral Maxillofac Su rg ma nd ibu lar che ru bism: Brief review and case re-
1993 ;22 :158- 162. po rt. Br J Oral Ma xillo fac Surg 1984 ;22 :189- 194.
10. Hitomi G. Nishi de N, Mitsu K. Ch erubism. Diaq- 23 . Krame r IRH. Pind borg JJ, She ar M. Histological
nests imagi ng and review of the lite ratu re in Japan. Typi ng of Od ontog en ic Tum o urs. 2d ed . Be rlin:
Oral Su rg Oral Med Oral Pat ho l 199 6;8 1:6 23 - Sprinqer-Verlaq. 199 2.
6 28. 24 . Cho me tte G, Auriol M, Gu ilbe rt F, Vai llant J M.
11. Valiathan A, Orth MS, Prashanth VK. Cheru bism: Cheru bism. Hist oenzymol ogi cal and ultrastruc-
Presentation of a case. A ng le Orthod 1997; 67: tu ral stu dy. J Oral MaXlllo!ac Su rg 1988 ;17:21 9 -
237- 238. 223.
3 17
Chapter. 37.
319
37: Central GiantCell Lesion (Granuloma)
320
Epidemiological data
No. of cases
40
39
33 OJ Women
30 LIJ Men
n= 192
19 20
20
14 13
9 9
10
Fig 37-4 Age and gen- 0 -9 10 - 19 20 -29 30-39 40-49 50-59 60 -69 70+
der distribution of 192 Age in years
cases of CGCLs,8,12, 13,1 5
321
37: Central Giant Cell Lesion (Granuloma)
age of 30 at the time of diag nos is. The avail- from the literature and found that , contraryto
abl e data do not allow calc ulati on of th e wh at was previously reported , 50 % of lesions
mean age for thes e patients. w ere located in the posterio r areas of the
jaws. However, their tabulated data showed
that 43% of cases were located in the maxil-
3.3 Gender lary and mandi bular molar regio n, mandibu-
lar ramus, and co ndy le area; 54% were lo-
There is a female predominance fo r CGCLs, cated in t he ante rior (inc iso r, canine, and
with 62.5% of all cases occurring in wo men premolar) regions (Fig 3 7-5). Thu s,their data
(see Fig 37-4). The male:female ratio varies, actual ly ag ree w ith tho se of previous au-
accord ing to age group, from 1:1.5 to 1:3. A thors' ,11,16 that the ante rior area of the jaws
female pred ominance w as noted in every is most co mmonly involved.
dec ade of life with the exce ption of th e 1st
(male:female ratio, 1:0.7 ). The freq uency of CGCL occurrence in asso-
c iat io n w ith the cro w n of an imp acted,
unerupte d , or developing tooth varies be-
3.4 Location tween 10% and 19%.8,1 2,13 This probably re-
flects that the greatest percentage of these
Pooled data on tumor location were collect- lesions occurs in young patients.
ed from the same sources as those used for
age and gende r.8,12.13.1 5 The total numbe r
of cases for wh ic h location was reported was
129. All four studies showed almost identi-
cal numbers forthe distribution of lesions be- 4, Pathogenesis
tween the maxilla and mand ible. T here is a
c lear mandibu lar pred om inance, with be-
tween 70% and 75% of the lesions being lo- Perhaps the most widely held view is that the
cated there. Kaffe et al ' 2 pooled dat a from initial CGC L is an endosteal hemorrhage. In
their own 18 cases w ith 62 cases collected 196 2 (stil lthe "repa rative era"), kramer" stat-
ed th at if the process is co nce rned with re-
pair fo llow ing hemorrhage, then the repair
fo llows a peculiar pattern complicated by re-
peated new hemorrhages. El-Labban.P who
3" studied ce ntral giant cell lesions ultrastruc-
9 tual ly 35 yea rs later, de monst rated that
Kramer was right in his statement. The ma-
n = 80 jo rity of vessels showed intravascular fibrin
7' thro mbi and endothelial ce ll damage, with
ga ps in the cell wa lls. Piasma, erythrocytes,
and fibrin we re see n subend othetially. EI-
Labban and Lee19 had previously shown ev-
idence of fusion between myofibrobl asts and
giant cel ls and postulate d t hat giant cells
Fig 37-5 Topographic distribution of 80 cases of form and inc rease in size through this fusion.
CGCLS.12 Sing le asterisk ind icates ramus and In EI-Labban's 1997 report ,18she noted that
co ndyle ; do ub le aste risk ind icate s maxillary sinus. one of the gaps in a vessel had been sealed
322
Pathology
Fig 37-6 Characteristic cellular components of Fig 3 7-7 Features of metabolically active giant
the CGCL: stromal cell population co mpnsmq ce lls in a CGCL with multiple vesicular nuclei,
spindle-shaped fibroblast-like cells with oval nu- each containing a distinct nucleolus. Note the
clei and macrophage-like cellscontaining round, fresh hemorrhage (H&E, x1 80).
chromatin-dense nuclei. Aggregations of multi-
nuclea r giant cells are distributed betwee n the
stromal cells and often found near or evensituat-
ed inside (arrow) thin-walled vascular channels.
In the upper left corner, an immature oste oid tra-
beculum can be seen (hematoxylin-eosin [H&E],
x80).
by a giant cell. The autho r sugg ested that 5.2 M icro scopy
the presence of the gia nt cell close d the gap
5.2. 1 Histologic definitions
and stop ped hemorrhag ing. More informa-
tion pertaining to the pathoge nesis ofCGCLs Accord ing to the 1992 World Health Orga-
appears later in the chapte r. nization (WHO) c lassitication.Ytho CGCL is
"an intraosseous lesion con sisting of more or
less fibrous tissue con taininq multiple foci of
hemorrh age, aggregations of multinucleat-
ed giant cells, and som etimes trabeculae of
5. Pathology wove n bo ne forming within the septa of more
matur e fibrou s tissue that may traverse the
lesion ."
5.1 M acroscopy The definition used by the present authors
is as follows:
The surgical spec imen consists of a soft, An intraosseous lesion consisting of a stro-
spongy, redd ish to brownish friable tissue of mal ce ll popu lation adm ixed with multinu-
varying size. Since the vascular tissue bleeds c leated giant cells and distributed in a col-
very easily,the spec imen is often coated with lagenous tissue. The stromal cells may be of
fresh or coagulated blood. at least tw o typ es: one resembles (myo)fi-
brobl asts, oval or spin dle-shaped with a ci-
gar-shaped nuc leus exhibiting sparse chro-
323
37: Central Giant Cell Lesion (Granuloma)
matin; the oth er resembles macr ophages unevenly distr ibuted th rougho ut , whereas
wit h smaller round nuclei exhibiting dense numero us evenly distributed giant cells are
chromatin (Fig 37-6 ). Foci of fresh hemor- present in practically every field of the neo-
rhage, hemosiderin g ranules, and thin- plasm. In a study of 10 cases of each of the
walled vascularspaces are common finding s two lesions, Abrams and Shear22 confirmed
(Figs 37-6 and 37-7). Bone format ion with Lucas' statement but concluded that a few
producti on of immature osteo id trabe culae giant cell lesions of long bones had giant
is found in a high percentag e of cases. cells that were as small as- if not smaller
than- those in jaw lesions. In addition, giant
cells of the jaw lesions contained significantly
5.2.2 Histopatholog ic find ing s
fewer nuclei than those of the long bone le-
The stromal cells project between the giant sions. The authors further concluded that
cells in swirls, with herringbone and storiform some giant cell lesio ns of long bones are
focal patterns. The agg regations of giant morph ologically indistinguishable from giant
cells show great variations in size, mo rpho l- cell lesions of the jaws and vice versa. It is
ogy, and the number of nuclei. possib le, therefore, that some jaw lesions are
Morphologically, the giant cells are of for- GCTs and that some giant cell lesions out-
eign body type or osteoc last-like. The stain- side the jaws are CGCLs. Lastly,Abrams and
ability of the cytoplasm varies fro m light ba- Shear22 sugg ested that if a giant cell lesion
soph ilia to marked eosinophilia; variations contains giant cells in which the product of
may occur within the same giant cell. Some length and breadth exceeds 1500 ~m2 , the
cells contain big ovoid and lig htly stained nu- diagnosis of GCT should be con sidered. Gi-
clei with prominent nucleoli and sparse chro- ant cell lesio ns (g ranuloma s) are likely to
mat in. Othe r cells contain small, da rkly have areas of less than 1500 ~ m 2 .
stained nuclei of irregular shape. Cytoplas- Franklin and colleagues23 also studied 10
mic vacuoles of different sizes containing ery- cases of each lesion. Unlike Abrams and
throcytes, iron-posit ive hemoside rin gran- Shear,22 they found that the giant cells in the
ules, and leukocytes are frequently found. GCT were smaller than those of the CGCL,
Mitotic figures are rarely present. In many in- but they agreed that there were more nuclei
stances, the giant cells show a definite rela- in the cells of the GCT.
tionship to vascular channels. The function Auclair et al,6 using a semiauto matic im-
of the multinu cleated giant cells that typify age analyzer, stud ied various parameters for
these lesions is still controversial, although 50 giant cell profiles from each of 42 GCTs
most investigators believe that the origin of and 49 CGCLs. They showed that the mean
these cells is related to the fusion of strom al size (area and volu me) of the giant cells in
cells with either macrop hages or (myo)fi- the GCTs was larger than that in CGCLs, but
broblast-like cells (see the section on ultra- there was a great degree of overlap between
structural findings in this chapter). the two lesions so t his feature should not be
used to establish a diagnosis. The authors
The size, number of nuclei, and distribution foun d , in ag reem ent with Ab rams and
of the prom inent and mysterious multinucle- Shear22 and Frankli n and coworkers." that
ated giant cells has been compared in both the number of giant cell nuclei was signifi-
jaw lesions and lesions in other bones. Lu- cantly greater in GCTs than in CGCLs, but
cas- " stated that the giant cells in jaw lesions overlap amo ng lesions was again marked.
are often smaller than those in giant cell tu- The aut hors conclude d that GCTs and
mors of long bone. Cells in jaw lesions are CGCLs represent a continuum of a single
32 4
Pathology
disease process modified by the age of the eluded that it is not yet possible to predictthe
patient, the site of occurrence, and possibly behavior of CGCLs from known histologic,
other facto rs. imm unop henotypic, or pro liferation parame-
ters.
5.2.3 Histochemical/immunohistoch emi-
Lim and Gibbins26 fo und no significant dif-
cal find ings
ference in staining pattern between CGCLs
Whittak er and Wald ron'' fo cused on the and giant cell tumors of long bone when us-
quantitative AgNOR differences of oral giant ing a panel of monoclonal antibod ies. Ac-
cell lesions. The study identified a signifi- cord ing to the authors, the most significant
cantly higher number of AgNORs in the nu- finding was that the blood vessels at the pe-
clei of both the monon uclear cells and the riphery of the CGCLs stained intensely with
multinuc lear giant cells of recurrent/aggres- endothel ial cell mark er factor VIII- related
sive lesions as opposed to nonrecurrent/ antigen , Ulex europaeus 1 lectin, and Obend
nonagressive lesions. The authors conclud- 10 in contrast to the striking lack of reactivi-
ed that, with some limitations, AgNOR quan- ty of the blood vessels deeper in the lesion,
tification may correlate with clinical behavior. closer to the multinuc leated cell agg rega-
The histogenesis of the multinucleated giant tions. The authors interpreted these find ings
cells remain controversial, and evidence can as a result of an absence of a mature func-
be found to sup po rt macrophage, osteo- tional microvasculature in the deep areas of
clast, and fib ro blast origins. Tiffee and the CGCLs.
Aufdernorte -" used marke rs specifi c for
macrophage lineage (1-ACT) and factor XII- Regezi,27 in a d iscussion of the article by
la antibod ies. For detection of osteoclast Tiff ee and Aufde mo rte, spec ulated that fi-
characteristics, the authors used an enzyme brob lasts are the cells of primary importance
unique to this cell type-tartrate-resistant acid in CGCLs, and th roug h their cellular prod-
phosph atase. It was show n that the giant ucts, th ey recru it and/o r indu ce monon u-
cells were neither macrop hages nor osteo- clea r ce lls to become mu ltinuclear g iant
clasts, but appeare d to represent a precur- cells. The reactive giant cells seem to be
sor cell of the g ranulocyte/macroph age line most closely related to osteoclasts. Regezi
that has not been fullycharacterized and pos- also believed that CGCLs represent benign
sesses features of both macro phages and neop lasms, or possibly abnormal reparative
osteoclasts. processes , and proposes that the lesional fi-
brob lasts are dysfunctional and express or
O'Malley et al2 found in their stu dy of ag- overexpress inapprop riate cytokines and/o r
gressive versus nonaggres sive CGCLs that g rowth factors. Lastly, Regezi suggeste d
mononuclear cells, not giant cells, were in that ap plication of modern molecular meth-
cell cycle. The CGCL represented a hetero- ods sho uld provide the next level of infor-
geneous pop ulation of cells in wh ich fibro- mation on the biology of CGCLs.
blasts (some with myofibroblastic differenti-
ation) were the dominant cell type (80% of
the mononuclear cells) and probably com- 5.2. 3. 1 Giant eel/lesions and hyperparathy-
prised the proliferative compartment. Macro- roidism
phages app eared to playa secondary role, Virtually iden tical lesions to CGC Ls have
similar to that pro posed for theirrole in giant been repo rted in pat ients with hyper-
cell tum ors of long bone.25 The autho rs con- parathyroidism. The so-called brown tum or
325
37: Central Giant Cell Lesion (Granuloma)
is a well-doc ume nted feature of t his en Further, the mononuclear round cells were
docrinopathy. This lesion, when occ urring in interpreted as being macrophages or their
the oral region, can easily be mistaken for a de rivatives. Finally, positive staining for his
typical CGCL. However, some features like tiocytic memb rane antigens suggested that
the presence of multiple lesions, multiple re the giant cells may be derived from stromal
currences, or loss of the lamina du ra around macrophages.
teeth in the involved area would be unusual Cohen et al3 1 transplanted tissue subcu
for a typical CGCL. Should these features be taneously from three CGCLs into nude mice,
present, additional studies of serum chem and t he xenog rafts were harvested at 3, 5, 8,
istry should be undertaken, inciuding meas and 13 weeks. One of the most striking fea
uring ionized calcium and parathyroid hor tures of the harvested xeno grafts was the ear
mone levels measurement of the N-terminal ly d isappearance of giant cells, a finding that
pe ptide is the reco mme nded method. It agreed with the in vitro study by EI-Mofty and
should, however, be pointed out that a brown Osdoby,29 suggesting that these cells prob
tumor is not a comm on sequela of hyper ably represent an end-stage process in cel
parathyroidism. Rosenberg and Guralnick,28 lular d ifferentiation. Ultrastructural observa
in a study of 220 patients with this condition, tio ns showed that th ese ce lls cou ld be
found that only 4.5% had clinically apparent ide ntified as myofibroblasts bot h in the orig
giant cell lesions. inal lesional tissue and in the xenografts. The
most promin ent stromai cells in th e graft
were those that resembled myofibroblast,
5.2.3.2 Gianf cell lesions in vitro and as and these cells were lying in close apposition
xenograffs to giant cells. The authors suggested that
EI-Mofty and Osdo by-" showed in their tissue CGCLs of the jaws contain a high proportion
culture study that the giant cel ls and of myof brob last-like cells which fuse to form
macrophage-like cells in CGCLs had a limit giant cells.
ed life span in culture and survived for up to
2 and 5 weeks, respectively. The spindle
shaped mono nuclear cells, however, co n 5.2.3.3 Aggressive and nonagg ressive
tinued to proliferate and were still actively gianf cell lesions
g rowi ng 10 mo nths afte r isolation. The In 1986 and 198 7, two gro ups of investiga
observation that the giant cells were unable tors9,10 focused on the correlation between
to perpetuate themselves suggested t hat the histologic features and clinical behavior
these cells might represent a fully differenti of jaw lesions in an attempt to determine
ated end ce ll. The ab ility of the sp ind le whether there are histologic differences be
shaped mononuclear cells to undergo active tween lesions that de monstrate agg ressive
proliferation, as demonstrated by the ir mitot behavio r and t hose t hat d emonstrate a
ic activity in vivo and their continuous repli nonaggressive clinical cou rse. Chuong et
cation in vitro, is analogous to that of their al,9 in their study of 17 cases of giant cell le
co unterparts in GCTs of long bones.P? sions, defi ned nonagg ressive lesions as
Based on their histoc hemical and electron tho se ch aracterized by the absence of or
microscopic observations, the authors sug minima l symptom s, slow growt h, the ab
gested thatthe spindle-shaped cells were not sence of root resorption or cortical perfora
typical fibroblasts and that they might be my tion, and a low recurrence rate. The authors
ofibroblasts, which is in agreement with ul noted that giant cells in agg ressive lesions
trastructural findings by EI-Laban and Lee.' 9 showed a higher relative size index than
326
Pathology
those in nonaggressive lesions and that g i were seen in nonaggressive lesions (60%
ant cells in recur rent lesions had a high er size and 77%, respectively) as compared with ag
index and higher fractional surface area. It gressive ones (40% and 67%, respectively).
was noted , however, thatthese histologic dif Six of the cases behaved in a markedly ag
ferences we re not as read ily apparent as the g ressive manner (presenting with pain or
differences in biolog ic behavior. paresthesia, co rtical perforation, and root re
With the use of co mpute r-aide d image sorption), and th e histologic features were
analysis, Fica rra et al' ? stud ied 32 cases of th ose co mmo nly acce pted for "true" giant
giant cell lesions with the same criteria for cell tumors of long bones. The authors ex
clinical behavior as those of Chuang et al." pressed the o pinion that if the slides from
Statistically sig nifica nt d iffere nc es in the th ese cas es were examined by an experi
number and fraction al surface area of giant ence d orth opedic pathologist with the "false"
cells were found whe n comparing ag gres information that the tissue came from a le
sive and nonaggressive lesions. The analy sion in th e epi physis of a long bone, a diag
sis was perform ed without knowledg e of the nosis of GCT woul d be made. The authors
clinical co urse and w as successful in pre favored the concept that giant cell lesions of
dicting the c linical co urse in 70% of the ag the jaws and giant cell tumors of th e extra
gressive lesions and 82% of the nonagg res gnath ic skeleto n are not separate entities but
sive ones. As mentioned earlier, Auc lair et represent a co ntinuum or a single disease
al6 used similar cyto metric method s an d process.
were unable to find any sign ificant histolog It seems, how ever, that a subset of jaw le
ic differences betwee n 5 cases of recurring sions clearly falls within the histologic profile
giant cell lesions and 20 that did not recur. accepte d fo r g iant ce ll tumo rs, and co n
In 30 CGCLs of the jaw (10 patients with versely,some long bo ne lesions Show the his
aggressive and 20 patients with nonagg res tologic features widely accepted for giant cell
sive lesions), giant ce ll nu clear DNA was lesions of the jaws. Giant cell tumors of long
quant ified by computer-aided image analy bones are considered to be locally aggres
sis.32 DNA content was th en used to predict sive, with recurren ce rates of up to 60 % after
clinical behavior and outco me. The authors curettage.33 .3 5
concl uded that cytom etric measurement of
giant cell nuclear DNA co ntent is not useful
as a predicto r of c linical behavior (agg res 5.2.3.4 CGCL associated with central and
siveness vs non aggressiveness) of these le peripheral odontogenic fibroma-like lesions
sions. The auth ors suggested that futu re in Recently, two reports36,37 described a rare,
vestigations mig ht focu s o n the role of intraosseous, hyb rid lesion with the com
stromal ce lls in determining the biologic be bined histologic features of a giant cell lesion
havior of CGCLs of the jaws. and a central odo ntogenic fib roma. Histo
logically, zones of typical gia nt cell lesions
Whitaker and waldro n" used d iscr iminant lay in a fibro us stroma co ntaining islands,
analysis to study a total of 14 2 cases of cen strands , and c lusters of odo ntog enic epithe
tral giant cell lesion s of the jaws in an attemp t lium. Osteo id trabec ulae w ere present in 5
to cor relate histologi c features with c linical of th e 10 lesions reported by Ode ll et al.37 Al
behavior. When co mparing agg ressive ver th oug h these features cannot be attributed
sus nona ggressive lesions, the presence of co nclusively to a variant of either giant cell Ie
more irregular-shaped giant cells, as we ll as sions of the jaws (or aneurysmal bone cysts)
a greater pro po rtion of smaller giant cells , or central od ontogenic fibromas, the clinical
327
37: Central Giant Cell Lesion (Granu loma)
features are slightly more sugg estive of a gi- 5.2.3.6 Giant eel/lesions of the distal
ant cell lesion. extremities
Giant cell lesions have been described in the
Ficarra et al3 7 reported an unusual case in small tubular bones of the hands and feet
which a patient,who 10 years earlier had mul- (see Panico et a1 42 ) with similar, if not identi-
tiple occurre nces of CGCLs of the left maxil- cal, clinical behavior and histology to those
la, developed multifoca l peripheral odonto- of CGCLs of the jaws. Initially,this lesion was
genic fibromas (WHO type; see cha pter 19), called a "giant cell reaction." Panico et al42
one of which was associated with a giant cell described five cases in young and middle-
lesion. The autho rs suggested that this find- aged adults (range, 16 to 41 years), three in
ing was just coinc idental or alternatively t hat the foot and two in the hand. The correct di-
the two lesions were someh ow related . agnosis of this lesion is important because a
conservati ve treat ment approach IS suffi-
cient, even in cases that recur . Compared
5.2.3.5 Noonan-like/multiple giant cell with the GCT, the CGCL lacks foci of necro-
lesion syndrome sis, has clustered rather than dispersed os-
Central giant cell lesions of the jaws are usu- teoclast-like giant cells, and exhibits foci in
ally solitary lesions. The occu rrence of syn- w hich there is osteob lastic rimm ing of tra-
chrono us, multiple lesions with the cha rac- becu lar osteo id. Immunohistochem ically,
teristic histology of the CGCL is uncommon. the authors de monst rated expression of both
A syndrome has recen tly been defined in vimentin and actin in the stromal spindle
which patients exhibit pheno typ ical features cells. Panico and coworkers'< found histo-
of Noonan syndrome and multi ple giant cell logically that the CGCL and the solid and
lesions.3gA D Alt hough this syndrome was classic aneurysma l bone cyst have many
first described more than 100 years ago, the identical features, explain ing why the two le-
first accurate study was not published until sions may be related morphologically with
1963.4 1 Comm on oral features of the Noo- on ly quant itative histologic differences. A
nan syndrome include micrognathia, a high- possible relations hip betw een aneurysmal
ly arched palate, dental maloc clusion, de- bone cysts and CGCLs of the jaws is dis-
layed toot h erupt ion, bifid uvula, and (in rare cussed in chapter 38 .
, cases) a cleft palate. In addition, patients ex-
hibited multiple giant cell lesions of the jaws.
In the case reported by Betts et al,"? a 14-
5.2.4 Ultrastructural findings
year-old boy had four separate mu lti locu lar
lesions of the maxilla and mandible. One and Several authors have stud ied the ultrastruc-
a half years after surgery,t he patient retu rned ture of the cell populations in CGCLs of the
with a new mand ibu lar lesion as well as an jaws. And ersen et a!'" found two types of gi-
intraosseous, osteolytic proc ess of the mid- ant cells (I and II), of which type II- dominat-
dle phalanx ofthe left index finger. All lesions ed by an electron-dense cytoplasm and a
were giant cell lesions. large numbe r of vacuoles and d ilated cister-
Although there are pheno typical similari- nae-was cons idered an aging or degener-
ties between these patients and patients with ating cell. Clusters of stroma l, fibroblast-like
Turner syndrom e, Noonan syndro me does cells were found in close contact with giant
not appear to be the result of a chromosome cells, the distan ce between cell memb ranes
abno rmality as in Turner syndrome. being approximately 10 to 20 nm. The pres-
ence of lami na densa- like mat erial sur-
328
Pathology
rounding these cells sugge sted that they are tasis via hematogenou s seed ing. Further,
pericytes and prec ursors to the giant ce lls. the authors suggested that a new variant of
EI-Labb an and Lee19 studi ed CGCL stro- g iant ce ll lesion may exist whic h dem on-
mal and giant cells and fou nd that th e great st rates mu ltifocality; they ca lled this entity
majority of stromal cell clusters were fibro- "craniofacial giant cell dysp lasia."
blast-like cells or myofibroblasts rich in roug h The occ urrence of multiple central giant
endoplasmic reticu lum and co ntaining fila- cell lesions is rare, with only 17 cases having
ments sim ilar to th ose of smooth muscl e been reported in the literatu re, acc ordi ng to
cells. Many of these cells were closely ap- Miloro and Quinn 4 4 In the d ifferential diag-
posed to giant cells and often showed evi- nosis, it is essential to rule out other giant cell
dence of fusion and continuity between their lesions that present with similar, if not identi-
plasma membranes and those of the giant cal, histologic features as th e CGCL. These
cells. In another study, EI-Labban 18 found includ e th e brown tumor of hyperparathy-
that approximately 75% of vessels found in roid ism, cherub ism, and t he aneurysmal
CGCLs co ntained multiple fibr in thro mb i or bone cavity. To do cument tru e multifocality,
intravascular fibrin deposits. Th ese vessels th e following facto rs must be considered .
were lined with damage d end othelial cells First, involvement of only one bone (eg, bi-
with som etimes large gaps between them . lateral mandible) might sugg est that the oc-
The end othelial cells showed an absence of currence of mu ltiple lesions may merely rep-
basal lamina, especially in areas wh ere plas- resent contiguous lesions (ie, ch erub ism)
ma, fibrin, red cells, or gia nt cells were in separated by an area of normal bone. Sec-
close proximity to the outside of th e;r plasma ond, the presence of synchron ous involve-
memb ranes. The gaps between the cells led ment would strong ly support the concept of
to extravasation of red cells and leakage of multifocality, wh ereas repo rts of metachro-
large amoun ts of plasma, which were altered nous occurrence co uld potentially represent
to fibrin within the tissue. recurr ences due to seeding or inco mplete
surgical excision . Third, many surgeons and
pathologists believe that multiple giant cell
5.2.4.7 Multifocal central giant cell lesions lesions do not exist in the absence of hyper-
of the maxillofacial skeleton (craniofacial parathyroidism or a familial history of cheru-
giant cell dysplasia) bism. Miloro and Quinn44 conc luded that no
Smith et al43 presented the case of a 4 1-year- previous single case repo rt has proved to be
old woman with a large mu ltilocu lar rad iolu- a true synchronous occu rrence of multifoca l
cency of the right mandibular angle, ramus, central giant cell lesion. Thus, the authors
and con dylar neck. A biopsy showed ce n- believed th at th eir report might represent th e
tral giant cell lesion. Nine years after her ini- first doc umented case in the literature. The
tial resection, the patient presente d with a 3 7-year-old woman presented with a large,
large lesion involving t he left sinus, left nasal multilocular , mixed radiolucency/ radiopaci-
bon e, and orbital floor. A seco nd , much ty of the posterior left maxilla and a smaller
smaller lesion was present in the right maxi1- multilocular mixed lesion in the anterior man-
larysi nus. A workup for hyperparathyroid ism dible.
showed normal values. The lesions proved There are few case reports d iscussing the
histologically to be CGCLs. Based on the associatio n between giant cell lesions and
appearance of new giant cell lesions 9 years othe r benign lesions of the jaws such as fi-
after resection of the original lesion, th e au- bro us dysplasias, ossifying fibromas, Paget
thors raised the question of possible metas- disease, and odo ntogenic fibromas. Ardek-
329
37: Central Giant Cell Lesion (Granuloma)
ian et al45 added to this list of co nditions with ment seems to be a factor in the frequ ency
their report of a 38-year-old woman with a bi- of recurrence. In Whitaker and Waldron's
lateral, mandibular giant cell granuloma. Her study ,the mean age for patients who demon-
medical history indicated neurofibromatosis st rate d one or more recu rrences was 20
and amputation of her right leg due to the years, whereas the mean age of the 26 pa-
disease. Blood tests gave no indication of tients who were followed and d id not show
hyperparathyro idism. recurrence was 28 years. Alth ough the au-
thors were not able to gath er accurate data
on lesion size as a factor in recurrence, they
had the distinct impression that lesions larg-
6. Notes on treatm ent and erthan 3.0 cm attheirg reatest diameter were
more likely to recur than smaller ones.
recurrence rate
330
References
9. C huong R, Kab an LB, Kozake wi ch H , Per ez- 22 . Abrams B, Shear M. A histological comparison of
Atayde A. Central giant cell lesions of the jaws: A the giant cells in the central giant cell granuloma
cl inicopatholog ic study. J Oral Maxillofac Surg of the jaws and the giant ce ll tumor of long bone .
1986;44:708- 7 13. J Oral PathoI 1974 ;3 :2 17- 223 .
10. Ficarra G, Kaban LB,Hansen LS. Gia nt cell lesions 23 . Franklin CD, Craig GT, Smith CJ. Quant itative
of the jaws: A clinico-patholo gic and cytometric analysis of histolog ical parameters in giant cell Ie-
stud y. Oral Surg Oral Med Oral Pathol 1987;64: slons of the jaws and long bones. Histopathology
44- 49. 1979;3 :511- 522.
11. Wood NK, Goaz PW. Differential diagnosis of oral 24. Tiff ee JC. Aufdem orte TB. Markers for mac ro-
lesio ns. 4th ed. St. Lo uis: M osby-Year Book, pha ge and oste oclast lineages in giant cell lesions
199 1:39 3- 395. of the oral cavity. J Oral Maxillofac Surg 1997;
55 :1108- 1112.
12. Katte I, Ardekian L, Taic her S, Littner MM, Buch -
ner A. Radiologic features of central giant cell 25. Abe Y, Yonemura K, Nishida K, Takagi K. Giant
granuloma of the jaws. Oral Surg Oral Mad Oral cell tum or of bone: analysis of proliferative ce ll nu-
Pathol Oral Radio! Endo d 1996 ;8 1;720 -726. clear ant ige n antibo dy and cell cu lture proce-
d ures. Nippo n Seikeigeka Gak kai Zass hi
13. Bodner L, Bar-Ziv J. Rad iographicfeatures of cen-
1994 ;68:407- 414.
tral giant cell granulom a of t he jaws in ch ildren.
Pediatr RadioI1 996 ;26:1 48- 151. 26. Lim L, Gibbins JR. Immunohistochemical and ul-
trast ructu ral eviden ce of a modified microvascu-
14. Austin LT, Dahlin CD, Royer OR. Giant cell repar-
lature in the giant cell granuloma of th e jaws. Oral
ative granulom a and related co ndit ions affecting
Surg Oral Med Oral Pathol Oral Radial Endod
the jawb ones. Oral Su rg Oral Med Oral Pathoi
1995; 79 :190- 198.
1959;12:1285- 1295.
27. Regezi JA. Markers for macrop hage and osteo-
15. Andersen L, Fejerskov 0 , Philipsen HP. Oral gi-
clast lineages in giant cell lesions of the oral cav-
ant cell granulomas. A clinical and histolog ical
ity. J Oral Maxtlotac Surg 1997;55: 1112-1 113.
stud y of 129 new cases. Acta Pat hol Mic rob ial
Scand 1973 ;8 1:606-61 6. 28. Rose nberg EH, Gu raln ic k WC . Hyp erparathy-
roid ism: A review of 220 proved cases with spe-
16. Cohen MA, Hertzanu Y. Radi ologic features, in-
cia l emphasis on findings in the jaws. Oral Surg
cl uding those seen with com puted tomog raphy,
Oral Med Oral Pathol 1962; 15(suppl 2):84.
of central giant cell granuloma of the jaw s. Oral
Surg Oral Med Oral Patho I 1988;65;255-26 1. 29. EI-Mofty SK, Osd oby P. Growth behavior and lin-
eage of isolated and cultu res cells derived from
17. Kramer IRH. Central giant cell reparative granu-
giant cell granuloma of the mandible.J Oral Patho J
loma of the jaw s and related lesions. In: Ora l
1985;14:539-552.
Pathology in t he Child. New York: International
Academy of Oral Pathology, 1963 :48-58. 30. Troise GO, DeLust ig ES, Gallardo H. Mitosis in tis-
sue cultures of giant cell tumors of bone. Oncol-
18. El-Labban NG. Intravascular fibrin thrombi and en-
ogy 1973 ;28:193.
doth elial cell damag e in central giant cell gran u-
loma. J Oral Pathol Med 199 7;26:1- 5. 3 1. Coh en MA, Grossman ES, Thompson SH. Fea-
tures of central giant cell granuloma of the jaws
19. El-Labban NG, Lee I<YV. Myofib roblasts in ce ntral
xenografted in nude mice. Oral Surg Oral Med
giant-cell granuloma of t he jaws : A n ultrastructur-
Oral Pat hoI 1988;86:209- 21 7.
al study. Histopathology 1983;7:90 7-91 8.
32. Eckardt A, Pog rel MA, Kaban LB, Chew K, May-
20. Kramer IRH, Pind bo rg JJ, Shear M. Histolog ical
all BH. Central giant cell gran ulomas o f the jaws.
Typing of Odonto genic Tum ours. 2d ed. Berlin:
Nuclear DNA analysis using image cyto metry. Int
Springer-Verlag, 1992.
J Oral Maxillofac Surg 1989;18:3- 6.
2 1. Lucas RB. Pathology of Tumours of the Oral Tis-
33. Sch ajowicz F. Giant cell tumor of bone (osteo-
sues. 2d ed. Londo n: Ch urchil l Livin gsto ne,
clastoma). J Bone Surg 1961 ;43A:1- 29.
1972 :244.
34. McDonald OJ et al. Giant cell tumor of bone. J
Bone Jo int Surg 1968;68A:235- 34 2.
331
37: C en tral Gi ant Ce ll Lesion (G ranulo m a)
35. Sanerkin NG. Malignancy, aggressiveness, and 43 . Sm ith PG, Ma rrog i AF, Delfino JJ. Mu ltifocal cen-
recurrence in giant cell tu mors of bone. Cancer tral giant ce ll lesions of the maxillofaci al skeleton:
1980;46:1641 - 1649. A case report. J Oral Maxillo fac Surg 1990;48:
300-305.
36. Allen eM, Hamm ond HL, Stimso n PG. Central
odon togen ic fibroma, WHO type. A report of three 44. Miloro M, Quinn PD. Synch ronous ce ntral giant
cases with an u nusual associated g iant cell reac- ce ll lesions of the jaws : Repo rt of a case and re-
tion. Oral SUr9 Oral Med Oral Pathol 1992;73 : view of the literatu re. J Oral Max illof ac Surg
62 -66. 1995;53:1350 - 1355.
37 . Odell EW, Lombardi T, Barrett AW, Morg an PR, 45. Ardekian L, Manor R, Peled M , Laufer D. Bilater-
Spe ight PM. Hybrid centra l giant cell granu loma al ce ntral giant ce ll granulom as in a patient with
and central odontogenic f ibroma-like lesions of neurofib romatos is: Report of a case and review
the jaws. Histop atholoqy 1997:30:165- 171. of the literatu re. J Oral Maxi llofac Su rg 1999 ;
57 :869-87 2.
38 . Fica rra G, Sap p J P, Eversole LA. Mu ltiple pe rip h-
eral odon to genic fibroma, World Health Orga ni- 46. Harris M. Central giant cell gran u lomas of the jaws
zatio n type, and central giant cell granulo ma. A regress with c alciton in the rapy. Br J Oral Maxillo-
case report of an unus ual assoc iation . J Oral Max- fac Sur9 1993;3 1:89- 92.
illofac Surq 1993;51 :325- 328.
47 . Pogrel MA, Reg ezi JA , Harris ST, Go ldr ing SA.
39. Cohen MM Jr, Gorlin RJ. Noonan-like/m ultiple g i- Cal cito nin treatment for cent ral giant ce ll granu-
ant cell lesion syndrome . Am J Med Gene t 1991 ; lomas of th e ma ndib le: Report of two cases. J Oral
40:159- 166. Maxillafac Surq 1999 ;57 :848- 853.
40. Betts NJ, Stewart JC , Fonseca RJ. Sco tt RF. Mul- 48. d e Lange J, Rosen berg AJ, van den Akker HP,
tip le centra l giant ce ll lesio ns with a Noo nan-like Koole R, Wirds JJ, van den Berg H. Treatment of
phenotype. Oral Su rg Oral Med Oral Patho l cen tral giant c ell granu loma of the jaw wit h calci-
1993;76:60 1-607. tonin. Int J Oral MaxiIJofac Surg 1999;2 8:372 -
376.
41. Noonan JA, Ehm ke DA. Assoc iated no nca rdiac
ma lform ation in ch ildren w ith congenital heart dis- 49. Kermer C, M illesi W . Watzke 1M . Loc al infection
ease. J Pediatr 1963;63 :468- 470. of co rticosteroids for ce ntral giant cell granuloma:
A case report. Int J Oral Maxillo tac Surg 1994;
42. Panico L, Passeretti U, De Rosa N, D'Anto nio A,
23 :366-368.
De Rosa G. Giant c ell reparative gran uloma of the
d istal ske letal bo nes. A repo rt of five cases w ith
im m un ohistoc hemical find ings. Virc hows A rch
1994;425:31 5- 329.
332
Section Eight
333
Chapter 38
1. Termino logy ant cell tum ors, to mention but a few de-
sc riptions. Currently, a primary form of ABC
(w hich may be vascular, solid, or mixed ) for
The aneurysmal bone cavity (ABC), first rec- wh ich no preexisting lesion is idenfified is dis-
ogn ized as a d isti nct path ologi c entity by tin guished from a secondary form that results
Jaffe and Lichtenstein in 1942,1 is an intra- fro m well-recog nized pred isposing bo ne le-
osseous, osteolytic lesion w hich has been re- sions such as giant cell lesions, cho ndro b-
ported to affect mainly the metaphysial re- lasto mas, osteoblastomas , and fibrous dys-
gion of long bon es and vertebrae. The distal plasias. Kershisnik and Batsak is'' stated th at
femur and proximal tib ia are the most com- ap prox imately 30% of ABCs are secon dary
mo n sites. and that these are fo und most often in long
Only 2% of ABC lesions are foun d in the bon es and rarely in th e jaws. Kramer et al,?
head and neck region,two thirds ofthese be- in t he 199 2 Wo rld Health Organization
ing located in the jaw , where they appear ini- (WHO) classification of odontogenic tu mors,
tiallyto have bee n recognized by Berni er and used the te rm hybrid lesions for th e seco nd-
Bhaskar.f Desp ite its recog nition, the lesion ary form of AB C.
remains a relatively uncommon finding in the The term most co mmonly used, aneurys-
facial bones. ABCs of th e jaws are rare: 64 mal bone cyst, is unfortunate in that th e le-
cases (60 cases from the literatu re and 4 new sio n has noth in g t o do wit h vascul ar
cases) that fulfilled the c linical and radiolog- aneurysms. It is also not a tr ue (epithelialized)
ic c riteria sugg ested by White' were report- bo ne cyst but rath er a lesion characterized
ed by Kaffe et al." Kalantar Motamedi5 de- by blood-filled spaces of different sizes sep-
scribed the AB C as a giant cell lesion with a arated by co nnective tissue septa. The bony
fibro us co nnective ti ssu e stro ma, various cavity contains trabeculae of bone or osteoid
amo unts of bone and osteo id, nu merous cav- tissue and osteoc last-like giant cells.
ernous channels or blood sinusoids, and no
ep ithelial or endothelial lining . The autho r
claimed to have traced a total of 78 report ed
cases of maxillofacial AB Cs in th e interna-
tional literature up to January 1997.
Prior to 1942, ABCs we re report ed in the
literat ure as ossifying hematomas, hem or-
rhagic osteomyelitis, osteitis fibrosa cystica,
expansile hemangioma, and aneurysmal gi-
335
38: Aneurysmal Bone Cavity (Aneurysmal Bone Cyst)
336
Epidemiological data
No. of cases
20
20
17 LrJwomen
15 OJ Men
n =64
337
38: Aneurysmal Bone Cavity (Aneurysmal BoneCyst)
4. Pathog enesis
338
Pathology
5.2. Microscopy
5.2.2 Histopathologic findin gs
5.2.1 Histologic definition s
The above defin ition used by th e present au
The 1992 WH O c lassificatio n? stated t he thors covers a typ ical primary ABC. In con
ABC w as "a ben ign intr aosseous lesion , trast, so me solid areas of the secondary form
charact erized by blo od-filled spaces of vary of ABC may have the appearance of fibrous
ing size assoc iated with a fib roblastic tissue dysp lasia, giant cell tumor, cemento-ossify
cont ai ning mu lt inucl eated giant ce lls, os ing fibroma, or other benign jaw tumors and
teoid, and woven bone." co nd itions. A rarely reported find ing in ABC
is th e occur rence of mitotic figures. De Dios
The definition used by the present autho rs et al23 found that 82% of c ranial and facial
is as foll ows: ABCs co ntained 1 to 3 mitotic figu res per 10
A benign intraosseous lesion characte rized high-power fields. Atypical mitosis was not
by large and sma ll cavernous channels (Fig seen. The autho rsstressed, howe ver,thatthe
38-4), the walls of which are not muscu lar or presence of mitotic figures sho uld not be
Fig 38-4 The same ABC shown in Fig 38-1 char Fig 385 ABC with more solid areas of tissue re
acterized by cavernous channels and loosely tex sembling those seen in central giant cell lesions
tured stroma with osteoclast-like giant cells of the jaw. Osteoid trabeculae are indicated byar
(hematoxylin-eosin [H&EJ, xSO). rows (H&E, xSO).
339
38: Aneurysmal Bone Cavity (Aneurysmal Bone Cyst)
Treatment of the ABC is generally directed 1. Jaffe HL. Lic htenstein L. Solitary unica me ral bone
cyst w ith em p hasis on the roe ntgen p icture, the
toward co mplete removal of th e lesion. This pathologic appea rance and patho ge nesis. Arch
may prove difficult at times. particularly if the Surg 194 2;44: 100 4 - 102 5.
lesion is multilocular and divided by multiple 2. Bernier JL, Bhaskar SN. Aneu rysm al bone cyst of
bony septae. A multitud e of treatment modal the ma ndible. Oral Su rg Oral Med Oral Pathol
ities have been reported (they have included 19 58;1 1:101 8-1028.
simpl e curettage, cryotherapy , resecti o n, 3. Wh ite SC. Comp uter aided d ifferential diagnosis
bone grafting, and no treatm ent). Block ex of oral radiograph ic lesions. Dentom axillofac Ra
cision or resection is usually reserved fo r re d ioI 19 S9 ;18 :53-59.
current cases or for secondary forms of ABC, 4. Kaffe I, Naor H, Calderon S, Buch ner A. Radio
wh ere t he associated lesion necess itates logical and clinical features of aneu rysmal bone
suc h treatment. Evidence from aspi ration, cys t of the jaws. Dentomaxillo fac Radi al 1999;
28:167 - 172.
CT scans, carotid arteriography, and opera
tive findings confirms th at maxillary ABCs are 5. Kalantar Motamedi M H. A neurysmal bone cysts
of the jaws: Clinicopatholog ic al feat ures, radi
relatively avascular. beio nging to th e "Iow
agraph ic evaluat ion and treatm ent analysis of 17
pressure" group of lesions. Conseq uently. cases . J Craniomaxillofac Surg 1998;26:56- 62.
th ey are besttreated by conservative surgery.
6. Ker sh isnik M, Batsa k is J G . Aneu rysmal bone
usually using an intraoral approach." Pro cysts of the jaws. Ann Otol Rhinal Laryngo11994;
vided that preoperative aspiration and inci 103 :164 - 16 5 .
sional biopsy have been undertaken as pre 7. Kramer IRH, Pindborg JJ, Shea r M . Histo logical
cautionary measures, there is no indication Typing of Odontog enic Tum ours. 2d ed. Berlin;
for preope rative ligation of majorv essels,and Sp ringer-Verlag, 199 2.
340
References
8. Eveson JW, Moos KR, Macd onald DG. Aneurys- 18. Svensson B, Isacsson G. Benign osteoblastoma
mal bone cyst of the zygom atic arc h. Br J Oral associated with an aneurysmal bone cyst of the
Surg 1978;15:259 - 264. mandibular ramus and con dyle. Oral Surg Oral
Med Oral PathoI1 993;76:433-436.
9. Farman AG, Nortje CJ, Woo d RE.l n;Oral and Max-
illofacial Diagnostic Imaging. St. Louis: CV Mos- 19. Szendro i M, Arato G, Ezzati A, et at Aneurysmal
by, 1993:2 28- 238. bon e cyst: Its pat hoge nesis based on angier
1D. Revel MP,Vanel D,Sigal R,et al, Aneurysmal bone graphic, immun oh istochemical and electron mi-
croscopic stu dies. Pathol Oncol Res 19 98 ;4:
cysts of th e jaws; CT and MR findings. J Comput
277- 28 1.
Assist Tomogr 1992; 16:84- 86.
20 . Yarrington CT, Abbot J, Raines D. Aneurysmal
11. Matt BH. Aneurysmal bone cyst of the maxilla:
bone cyst of the maxilla. Association with giant
Case report and review of the literature. Int J Pe-
ce ll reparative gr anulo ma. Arc h Oto laryngol
diatr OtorhinolaryngoI1993:25:217- 226.
1964:80:313- 3 17.
12. Leithner A, Windhager R, Lang S, et al. Aneurys-
mal bone cyst. A population based epidem iolog- 2 1. Hillerup S, l-ljartinq-Hansen E. Aneurysmal bone
cyst-simple bone cyst, tw o aspects of the same
ic study and literature review. Clin Orthop 199 9;
pathological entity. Int J Oral Surg 19 78 ;7:16 - 22.
363:176- 179 .
22. Shear M. Cysts of the Oral Regions. 3d ed. Oxford
13. Farole A, Manalo A, Iranpour B. Lesion of the tem-
poromand ibu lar jo int. J Oral Maxillofac Surg and Boston: Wright, 1992;179-186.
1992;50 :510- 5 14. 23. De Dios AMV, Bond JR, Shives TC, et al. Aneurys-
mal bone cyst. A clinico patholog ic stu dy of 238
14 . Bataineh AB. Aneurysmal bon e cysts of the max-
cases. Cancer 1992;69:292 1-293 1.
illa: A clinicop athologic review. J Oral Maxitlofac
Surg 1997;55:1212-1 2 16. 24. Sciot R, Dorfman H, Brys P, et al. Cytog enetic-
morph ologic co rrelations in aneurysmal bone
15. Waldron CA. Bone pathol ogy. In: Neville, Damm,
cyst, giant cell tumor of bone and combi ned le-
Allen, Bouq uet. eds.Oral and Maxillofacial Pathol-
sions. A reportfrom the CHAMP study group.Mod
ogy. Philadelphia: WB Saund ers, 199 5;4 59 -461.
PathoI2000: 13:1206- 1210 .
16. Pindbo rg JJ, Hiertinq -Hansen E. Atlas of Diseases
25 . Biesecker JL, Marcowe RC, Huvos AG, Mike V.
of the Jaws. Munksgaard, 1974;144 - 145 .
Aneurysmal bone cysts: A clinicopatholog icst udy
17. Carmichael F, Malco lm AJ, Ord RA. Aneurysmal of 66 cases. Cancer 19 70 ;26:615 -62 5 .
bone cyst of the zygomatic bo ne. Oral Surg Oral
26 . Gingell JC, Levy SA, Beck erman T, Tilghaman
Med Oral PathoI 1989 ;68:558 -562.
OM.Aneurysmal bone cyst. J Oral Maxillofac Surg
1984 ;42:527- 534.
34 1
Chapter 39
343
39: Simple Bone Cavity
gual co rtical ptates." but significant expan- rad iograp h. The cha racteristic scalloping, a
sion of the jaw is unusu al. feature first noticed by Waldron,' gives the
The SBC appears radiologically as a well- appearanc e of t he root ap ices "hanging"
defined unilocular, roughly oval radiolucen- within th e SBC cavity. Root resorption is not
cy within th e alveolar process, and it is fre- a co mmon findin g, and the lamina dura is
quently a chance radiographi c finding (Fig identifiable in most cases. In the past, the
39-1). It is located above and often in front scalloped perip hery in com bination with the
oft he mandibular canal, in contrastto th e lin- occasional oc cur rence of bony septa has
gua/ mandibular bone depression (see chap- been interpreted as a multilocular, radiolu-
ter 40), which is typically situated below and cent lesion, which can lead to an erroneous
often behind the canal. Bilateral or multiple diagnosis. In the radiographi c review of 44
lesions may occ ur (Fig 39-2). Based on trac- cases of SBCs by Co pete et al,3 the authors
ings of the peripheral border of 4 4 cases of searche d fo r th e "fallen fragm ent, or trabec-
SBCs, Copete et al3 identified four shapes for ula, sign." This sign, whi ch is seen in uni-
this lesion: cone (64%), oval (16%), irregu lar cameral bone cysts of long bones In associ-
(16%), and round (4%). The authors found ation with pathologic fractur es, represents a
that 22 (50%) had a sclerotic margin ; the bor- fractur ed co rtical fragment that has separat-
der seallopped around the roots of adjacent ed and is suspe nded in the bone cavity by
teeth in 68% of cases, a feature that may lead fluid. The fallen trabecula sign co uld not be
to the lesion being diagnosed on a bitewing ident ified in any of th e 44 rad iographs of
344
Epidemiological data
SBCs (of the jaws), Trauma -related rad io- 3.2 Age
logic signs were identified in 11 cases (25%),
with hairline, nondisplaced fract ures being Except for classic cases of SBCs diag nosed
noted in 5 cases, duri ng the 2nd decade of life, the age of pa-
t ients ranges from 2 ' 5 to 75 years." Figure
39-3 shows the age distribution in three re-
ported series of SBCs (Hansen et ai,16 Mat-
sumura et al,17 and Howe2,3). All three re-
3. Epidemiological data ports concu r in the finding of a major peak
in the 2nd decade of life (58,7%, ' 6 64.7%,17
and 75.4%2,3 of cases), In their 67 reported
3.1 Prevalence, incidence, and cases, Kaugars and Ca le" found a mean age
relative frequ ency of 24,3 years (range, 9 to 68 years); an even
lower mean age, 18.0 years (range, 2,5 to 51
The solitary bone cyst is not a common le- years), was found among 94 cases retrieved
sion if measured by th e number of reported from the literature, MacDonald-Jankowski,9
cases in the literature, The estimated num- in his study of 20 SBCs in 14 Hong Kong Chi-
ber of cases published as of the year 2000 nese patients, found that the mean age for
was around 250. No data on prevalence, in- men was 19.8 1,5 years and for wom en,
cide nce, or freq uency exist. It makes no 40.6 11,7 years. This difference in age be-
sense to indicate percentages based on the tween the sexes, which may be difficult to ex-
total numb er of jaw cysts (as is occas ionally plain, is statistically significant.
do ne in the literature), since t he SBC is a
pseudocyst or intrabony, nonepithelialized
cavity with no relationship to conventional, 3 .3 Gender
odontogeni c, or nonodontogenic ep ithelial
jaw cysts. There is a considerable diffe rence in male:fe-
male ratios between series of reported cas-
es, Inthe review by Kaugars and Cale,Bthere
No. of cases
50 46
Howe
(n= 61)
Fig 39-3 Age and 40 37
33 Hansen et at
gender distribution (n=63)
of SSGs combined 30
Matsum ura at e!
from three stud- (n= 51)
ies, 2,3,16,17 The d is- 20
tributio n is al most
10
identical in all three
studi es, with a
promi nent peak in 0- 9 10- 19 20- 29 30-39 40-49 50-59 60 - 69 70+
the 2nd decade of Age in yea rs
life.
345
39: Simple Bone Cavity
was an equal gender distributio n in both their tramedullary hemo rrhage with failure of ear-
iiterature survey and their own sampl e. How- ly organization of the hemato ma, low-grade
ever, if patients 30 years of age or older infection , cystic degeneration of bone tu-
(25.4%)were singled out, the male:female ra- mo rs, local alteration of bo ne metabolism reo
tio was 1:2.4. The male:female ratios in the suiting in osteolysis, isch emic marrow necro-
three studi es shown in Fig 39-3 were 1:1 sis, and failure of differentiation of osteogenic
(Hansen et al ' 6 ), 1:1.2 (Matsumura et al 17 ), cells. Although traum a has often been sug-
and 1:0.6 (Howe2 .3 ). gested as an initiating cause, a history oftrau-
ma is either infrequently or not convincingly
present.
3.4 Lo cation If one accepts the hypot hesis that men ex-
perience traumatic injury more frequentiy
The vast majority of SBCs occ ur in the man- tha n wom en and com bines this with a lack
dible. In a radiographic survey of 44 cases of gend er preditectlo n." th en the co ncept of
(Copete et al' "), 98% occ urred in the man- trauma being the sole causative factor is dis-
d ible, predominant ly in premo lar-molar ar- cred ited. It is likely that the reason the SBe
eas; 13% of the lesions crossed the midline. is so often an incidental finding is the fact that
In the report by Hansen et ai,16 two third s of it was detected on a posttrauma radiograph.
cases were located in the mandi ble. Rare It seems likely that the SBC does not have a
cases have been fou nd in the mand ibular single comm on cause but may be multitac-
cond yle 1S20 and zygomatic arch." Bilateral to rial in orig in.
and multiple lesions have been desc ribed in
4% to 10% of cases (see review by Shi- Melrose et al24 reported 34 cases of florid ce-
rnoyama et aI22 ). In MacDonald-Jankowski's mento-osseous dysplasias with co ncurrent
series,9 14 mand ibular lesions were fou nd in occurrence of an SBC in 17 cases. Fisher25
9 women, with no less than 5 SBCs diag- reported cysts in fibro-osseous lesions as
nosed in 1 patient. Th is author also meas- "bone cavity in fibra-osseous lesions" and
ured the size of the area of th e lesions dig i- that these cysts co uld be the result of cystic
tally on panoram ic radiograph s and found breakdown of the lesions. Hillerup and Hiert-
that the mean area differs significantly be- inq-Hansen-" repo rted a case of aneurysmal
tween the sexes (5.2 cm 2 1.4 for men ver- bon e cyst recurring after surgery on an SBe.
sus 2.5 cm 2 1.1 for women ). They suggested that aneurysmal bone cysts,
central g iant cell granulomas, and SBCs ali
arise fra m some vascular lesion or defect.
4. Pathogenesis
5. Path ol ogy
The path ogenesis of the SBC is still unclear.
Shear23 comprehensively surveyed the dif-
ferent theoriesthat have been advanced over 5 .1 Macrosc op y
the years. In short, the lesion is believed to
be of endosteal origin, primarily involving the When the bone cavity is ope ned at surgery,
medullary bon e with reactive second ary in- it is frequ ent ly found to be em pty; blood,
volvement of the co rtical bon e. The main th e- serous, or se rosangui neous fluid may be
ories of orgin are traumatically induced in- present. A lining usually is not seen. A thin
346
Pathology
membrane, gra nulation tissue, or blood c lot oft en shows osteo c lastic resorption. The
has also been de scribed. bo ne may exhibit fibrous or ce me nta-os-
seous dysplasia-like features.
5.2 Microscopy
5.2.2 Histopath olo gic find ings
5.2. 1 Histologic definitions
Donker and Punnia-Moorthy27 suggested a
Acco rding to the 1992 WHO classification," possible subc lassificatio n of sim ple bone
a solitary bone cyst is "an intraosseous cyst cavities based on content: em pty cavities
having a tenuous lining of connective tissue wo uld be called idiop athic; thos e with solid
with no epithelium." content wo uld be design ated according to
the histologic appearance of the bulk of the
The definition of an SBC used by the pres- solid (eg, fib rous or granu lation tissue); and
ent authors is as follows: cavities con taining fluid with a bioche mical
An intrabo ny cacity, the walls of which are profile sim ilar to that of serum would be
lined with a delicate mem brane co nsisting of called extravasation cysts.
loose fi brou s ti ssue of variable thic kness Another approach to the c lassification of
andj or granulation tissuewith hemoside rino- SBCs was proposed by Matsumura et al."
phages and scattered mu ltinuc leated osteo- who classified 53 cases of SBCs into types
clast-like cells (Fig 39-4). An epithelial lining A and B based on histology. In type A, the
is not present. If adjacent bone is inc luded cavity membrane consisted of a thin co n-
in th e surgical spec imen, the inner surface nective tissue lining and in type B, there was
a thick ened myxofibromatous wall and dys-
plastic bone form ation usually seen in benign
fibra-osseous lesions. The auth ors foun d
that bone expansion and radiopac ity were
closely related to histo patho logic fin dings.
They co nc luded that type A and type B bo ne
cysts may have different causes.
347
39: Simple Bone Cavity
6. Notes on treatm ent and cases of unicameral bon e cavities and is ap-
parently caused by erosion of the co rtical
rec urrence rate bone,whi ch permits th e intrabonyfluid to be-
com e clinically visible. Shimoyama et al,22
The low prevalence of SBCs in old age and based on a co mprehensive review of 111
the high prevalence in younger patients sug- published repo rts, suggeste d that SBCs
gests that self-healing can occur. Sapp and have at least two different patterns of clinical
Sta rk 29 foll owed two untrea ted c ases of behavior: (1) solitary, asymp tomatic, self-lim-
SBCs, one for 7.5 and the ot her for almost 3 itin g lesions with a te ndencyfor spontaneous
years. By the time bot h patients app roached healing , and (2) solitary or multiple progres-
age 22, their lesions had resolved, and th e sive lesions with a potential for recurrence. It
trabecu lar bone pattern had approa ched a is important th at SBCs be subjected to clini-
normal radiographic app earance. T he treat- cal fo llow-up, including radiologic examina-
ment used most often for SBCs is curettage. tion.
This is usually all that is necessary to institute
healing, whic h takes place within a year.
References
Som e surgeons advo cate provoki ng
bleedin g by scraping the cavity wall careful- 1. Jaff e H , Licht en stein L. So lita ry uni cameral bone
ly, w hic h sho uld enhance the healing cyst: With emphasis on the roentgen picture, the
process. However, this proced ure may dam- patho lo gic ap pearance and the path ogenesis.
age the inferior alveolar nerve or the tiny neu- Arch Surg 1942;44:1004-1025.
rovascular bu ndles to adjacent teeth. 2 . H owe GL. "Haemo rrha g ic cysts" of the ma nd ible.
I.Br J Oral Surg 1965:3:55-60.
There is too little expe rience with injection of 3 . Howe GL . "Ha emorrhag ic cysts" of t he mand ible.
autogeno us blood ,'o insertion of Gelfoam II. Br J Oral Surg 1965;3:77-9 1.
saturated with thro m bin and penic illin," 4 . Rusht o n M A. Solitary bo ne cys ts in the m andible.
bone alloqrafts.V or app lication of methyl- Br Dent J 1946;81 :37-49.
predn isolone acetate to the cavity to advo- 5. Virchow R. Uber d ie B ildu ng vo n K noch enzysten.
cate these treatment modalities,although the Sitzung d er A kad em ie de r Wissenschaften.
latter method has been reported to be suc- Berlin: Abt. F. Math. U. Nat urw issensc haften,
1875:76Q-769.
cessful in treating unicameral bone cavities
of long bon es.3 3 6. Lucas C D. Do all cys ts in the jaw s o rig inate from
the d ental syste m? J Am De nt A sso c 192 9;
16:647-661.
Currently there are no reliable predicto rs of
7 . K ram er IRH , Pind b org JJ, Shear M. Histological
the behavior of this lesion, although from the
Typ ing of O do ntogen ic Tu mo urs. 2n d ed. Benin:
few cases of recu rrence reported so far, the Sp ringer-Verlag, 199 2.
vast majority of rec urrences ap pear in
8 . Kaugars GE. Ca le AE. Tra um atic bo ne cyst. Oral
women.34-35 An association between multi- Surg Oral Med Oral PathoI 1987;63:318-324.
ple SBCs and a tendency toward recurrence
9 . MacDonald-J ankow ski OS. T raum atic bo ne cysts
finds agreement in some reports9 .30,36 but in th e jaws of a Ho ng Kong C hinese popu lation.
not in othersw.3 7-39 Kaugars and Cale8 re- Clin Radial 1995;50:787-791.
trieved literature cases of 10 (1 male and 9 10 . De To masi 0 , Harm J R. T raum atic bon e cyst Re-
female) patients with m ultip le lesio ns. A po rt of a case. J Am Dent Assoc 19 85;111:56-57.
bluish disco loration of the bo ne or mucosa 11. Co wa n eG . Traumatic bo ne cysts of the jaws and
was seen in 4 patients. A blue appearance their p rese ntat ion. Int J Oral Su rg 1980;9:287-
of the bone has also been noticed in some 291.
348
Referenc es
12. Harris SJ, Carroll KO, Gordy FM. Idiopathic bone 27 . Donkor P, Punnia-Moorthy A. Biochemic al analy-
cavity (traumatic bone cyst) with the radio qraph- sis of simp le bon e cyst flu id- report of a case. lnt
ic app earance of a fibro-osseous lesion. Oral Surg J Oral Maxillo!ac Surg 1994;23 :296-297.
Oral Med Oral PathoI 1992 ;74;118-123.
28. Schwenzer N, Ehrenfeld M, Roos R. Uber die so-
13. Copete MA, Kawamata A, Lang lais RP. Solitary genannte sol.tare Knoch enzyste. Dtsch Zahnarztl
bone cyst of the jaws. Radiographic review of 44 Z 1985 ;40:573-575.
cases. Oral Surg Oral Med Oral Pathoi Oral Rad i-
29 . Sapp JP, Stark ML. Self-healing traumatic bone
al Endo d 1998;85:22 1-225.
cysts. Oral Surg Oral Med Oral Pathol 1990 ;69:
14. Waldron CA. Solitary (he morrhagic) cyst of the 597-602.
mand ible. Oral Surg Oral Med Oral Patho11954;
30 . Precio us OS, McFadden LA. Treatment of trau-
7:88-95.
matic bone cyst of mandible by injection of auto-
15. Robinson RA. Trauma tic hemorrhagic cyst of the geneic bloo d. Oral Surg Oral Med Oral Pathal
mandible in an infant. J Am Dent Assoc 1945; 1984;58:13 7-140.
32:774-775.
3 1. Thoma KH. The treatment of extravasation cysts
16. Hansen LS,Sapone J, Sproat RC.Traumatic bone with the use of Gelfoam. Oral Burg Oral Mad Oral
cysts of the jaws. Report of sixty-six cases. Oral Pathol 1955:8: 950 -954 .
Surg Oral Med Oral PathoI 1974 ;3 7:89 9-9 1O.
32 . Lin dsay JS, Mart in WR, Green HG, Traumatic
17. Matsumura S, Murakami S, Kakimoto N, et al. bone cyst treated with homogen eous bone graft.
Histopathologic and radiographic findings of t he Report of a case. Oral Surg Oral Med Oral Patho l
simp le bo ne cyst. Oral Surg Oral Med Oral Pathol 1966;21:536-54 2.
Oral Rad ial Endod 1998;85:619-62 5.
33 . Capa nna R, Dal Monte A, Gitelis S, Campanacci
18. Gilman RH, Dingm an RO. A solitary bone cyst of M. The natu ral history of unicameral bone cyst af-
th e mand ibular co ndyle. Plast Reco nst r Surg te r steroid injection . Olin Orthop 198 2;166:204-
1982;70:6 10-6 14 . 21 1.
19. Persson G. An atypical solitary bone cyst. J Oral 34. Horner K, Forman GH. Atyp ical simp le bone cyst
Maxillofac Surg 1985;43 :905-907. of the jaws. II. A possible association with benign
fibro-osseous (cemental) lesions of the jaws. Clin
20. Telfer MR, Jones GM , Pell GM, Eveson JW. Pri-
Radia l 1988:39:59-63.
mary bone cyst of the mandibular condyle. Br J
Oral Maxillofac Surg 199 0;28:340-343. 35. Feinberg SE, Finkelstein MW, Langley Page H,
Dernbo JB. Recurrent "traumatic" bone cysts of
21. Bradley JC. Solitary bo ne cyst of the zygomatic
th e mand ible. Oral Surg Oral Med Oral Pathol
bone. Br Dent J 1982;152:203-204.
1984;57:4 184 22.
22. Shimoyama T, Horie N, Nasu 0 , et al. So-called
36. Gardn er AF, Stoller SM, Steig JM. A study of the
simple bo ne cyst of the jaw: A family of pseudo-
traumatic bone cyst of the jaws. Can Dent Assoc
cysts of diverse nature and etiology. J Oral Sci
J 1962:28:15 1-166.
1999;4 1:93-98.
37 . Morris CR, Steed DL, Jacoby JJ . Traumatic bone
23. Shear M. Cysts of the Oral Regions. 3d ed . Ox-
cysts. J Oral Surg 1970;28:188-195.
ford: Wright, 1992:17 1-176.
38. Kuroi M. Simp le bon e cyst of the jaw: Review of
24. Melrose RJ, Abrams AM, Mills BG. Florid osseous
the lite rature and rep ort of case. J Oral Surg
dysplasia. A clinical-pathologic study of th irty-four
1980;38:456-459.
cases. Oral Surg Oral Med Oral Pathal 1976;4 1:
62-82. 39. Raibly SO, Beck ett P, Nowa kowski A. Multiple
traum atic bone cysts of the mandible. J Oral Surg
25. Fisher AD. Bone cavities in fibro-osseous lesions.
1979 ;3 7:335-337.
Br J Oral Surg 1976;14:120-127.
26. Hillerup S, Hiertinq-Hansen E. Aneu rysmal bone
cyst-simp le bone cyst, two aspects of the same
pathologic entity? Int J Oral Surg 197 8;7:16-22,
349
Chapter 40
35 1
C linical and radiologic profile
With its enh anced def inition of adjac ent soft radiographs than do the LMBDs and is lo-
tissue, CT may reveal submandibular salivary calized posterior to the mandibu lar lingual
gland tissue extending into the lingual bon e foramen, just below and infe rior to the neck
d epressions (Figs 40-4 and 40-5). of the co ndyle (Fig 40-7).
The ALM BD may be superimposed on the
roots of inc isors, can ines, an d premolars
(mimicking a per iapical lesion) or may occur
in an interrad icular location (Fig 40-6). T he
rare MRBD often appears mo re c ircu lar on
353
40: Lingual Mandibular Bone Depression
A B
:j
/
c
Fig 40-5 Schematic drawing of the development of a PLMBO Fig 40 -6 Int raoral radi ograph
(modified from Ariji et aI7 ). The depression develops from a showing an ALMBD situated in-
shallow eros ion (A) to a deep cavity (B and C) caused by terradicularly between the mane-
pressu re resorption from a lobe of the submandibular salivary ibular right lateral incisor and ca-
gland (0 ). nine.
(\
......./ \)
""
""v,
0 0\,. ----'~--\1\ ;"
. &:50
' -: ' ~~- - );/ ,:_! \~
0 ?,,:-~coo_'._) ( y o" Fig 40-7 Schematic illustration ofl he location and
'--' -' shape of the PLMBO and ALMBO. Note the de-
pression interrupting the dorsal border of the ra-
mus (MRBO, arrow).
354
Epidemiological data
Age in years
30-39 ::=::::J 6
6
355
40: Lingual Mandibular Bone Depression
predominance. The corresponding ratio for in origin when he and Tolman 15 reported two
ALMBD cases (n=4 0 ) was 3:1. Presently, cases in which the radiolucencies developed
there are only 13 reported cases (all of them after middle age.
in men) of the MRBD; 6 were clinical cases Fordyce 16 was the first author to describe
as mentioned earlier, and 7 were reported in the presence of salivary gland tissue in the
archaeological material (dried mandibles)." radiolucencies of PLM BDs after doing biop-
sies on two cases; he suggested that the
cause is inclusion of salivary gland tissue
3.4 Locati on within the mand ible dur ing ossification. He
further suggested the use of sialography in
The PLMBD occ urs between the ang le of the investigating such lesions. Kay,17 in review-
mand ible and the first molar, below the infe- ing dry skull spec imens, proposed that the
rior alveolar canal. A detailed analysis of the depression was caused by abnormal vascu-
relationship of PLMBDs to both the inferior lar pressure in the facial artery as it pursues
alveolar canal and the lower border of the its course over the inferior borde r of the man-
mandible can be found in a report by Chen di ble, the reby prod ucing necrosis and re-
and Ohba.13 The ALMB D has appeared in sorption of bone similar to that of an aortic
every lingual mandibu lar location approxi- aneurysm causing resorption of the ribs. Lel-
mated by the sublingual salivary gland, from 10 and Makek 18 argued that the defect was
the central incisor to the seco nd premolar, a result of ischemia due to the combined ef-
above the mylohyoid muscle. The ALMBD fect of unfavorable hemodynamics of the fa-
has well-defined sclerotic borders on plain cial artery and the dege nerative arterial
radiographs less often than do PLMBDs and change in midd le age. These ideas have not
thus is more difficult to diagnose. The loca- yet been substantiated.
tion of the MRBD is shown in Fig 40-7. Surgical exploration and biopsy results
from various authors have yielded equivocal
results. The majority of reports desc ribed
salivary gland tissue with a few yielding lym-
phatic tissue, muscle, and blood vessels;
4. Pathogenesis some were devoid of contents. Simpson19
repo rted on a PLMBD containing a pleo-
mo rphic adenoma, but the only documenta-
Since the LMBD was first described 60 years tion presented-an out-of-focus phot omicro-
ago, there has been a lot of spec ulation con- g raph- is not convincing. The diverse results
ceming its etiology/pathogen esis. Stafne1 of surgery and biopsy may be explained by
proposed that the radiolucencies represent the fact that surgeons have simply displaced
areas of Meckel's cartilage that failed to os- the contents of the defect and have taken
sify. Peterson." the first to explore such a biopsies from tissues adjacent to the bone
depression surgically, found that the area depressio n.
was devoid of content, supporting Stafne's
concept of a conge nital origin. However, the The present theory is that the LMBD in its
congenital theory is unlikely since no such various subtypes is caused by a hyper-
occ urrence has been docu mented in chil- plastic (or hypertrophic) lob e or an aber-
dren under the age of 11 years. Infact, Stafne rant lobe of the sublingual (ALMBD ), sub-
abandoned the cong enital hypoth esis and mandibu lar (PLMBD), or parotid salivary
proposed that the lesion was developmental glands (MRBD), leading to focal atrophy or
356
Pathology
resorption in response to pressure. As point- material (in the majority of cases from dry
ed out by Sandy and Williams ,2o "whe n the mandible material) is cleariy visible around
mob ilrty of the floor of the mouth is consid- the age of 35 to 40 years. Obviously, it takes
ered, it is perhaps surprising that the gland another 10 years before the reduction in min-
remains in close proximity to the mandible eralized bone volume reaches a stage where
for sufficiently long periods to cause resorp- th e d epr ession s becom e evident radi-
tion." It is, however, well known that with in- ographically-that is, wh en they are quite ad-
creasing age, the major salivary glands are vanced . (For a more detailed account of the
the sites of nonspe cific (lymphocyt ic) inflam- etiology/patho genesis of LMBOs, see the re-
mato ry infiltrations with resulti ng fibrosis, hy- view by Philipsen et a1. 3 )
pertrophy , and hyperplasia of varying inten-
sity. These proce sses gradually change the
co nsistency of the glands from a soft to a fi-
b rous, and sometimes quite hard, tissu e
mass. In youth and middl e age, pressure ex- 5. Pathology
erted by a fibro us gland on the mandibular
bone may be suffic iently intense overtime to
produ ce foca l bone resorption. However, it 5.1 Macroscopy
should be added that there is a lack of sub-
stantiation evide nce for this phenomenon. The LM BO varies in size from a few millime-
ters ac ross to 35 x 20 mm or (occas ionally)
Support of an explanation involving local re- more.
sorption of an earlier intact inner cortical plate
was supplied by Harvey and Noble.2 1 These
auth ors made a histologic examination of 5.2 Microscopy
PLMBOs diagnosed in dry mand ibles and
5.2. 1 Histologic definition
found that the surface of th e de pression s
showed an osteoc lastic resorption in all six The LM BO and MRBO are not included in
cases examined. They also presented evi- any of the Wor ld Health Organ ization (WHO)
dence in two cases for active resorption of classifications. The present authors define
bone wit h nearby regions of bone deposition, th ese defects as follows:
the typical response of bone to an expand- Bone depressions with various locations in
ing lesion. These obse rvations strongly fa- the mandible; as suc h, they are not charac-
vor the conclusion that th e depressions de- terized by histologic features apart from th e
velop after initial ossification of th e mand ible. fact that the surface of th e dep ressions show
osteoc lastic activity. If meticulous surgical in-
Individ uals with LMBOs who have been fol- terventions and biopsy procedures can be
lowed with periodical radiographic examina- performed ,the depressions are seen to "co n-
tion for some years have shown no change tain" normal, hyperplastic, or hypertroph ic
in the size or shape of th e mandibular de- salivarygland tissuefrom the sublingual,sub-
pressions. However, Oikarinen and Julku ,22 mandibular, or parotid glands, respectively.
who studied 10 cases of PLMBOs,fou nd that
th e largest depressions were seen in the old-
est of the series. It seems the foca l bone re-
so rption that eventu ally produced the de-
pressions diagnosed radiologically in clinical
357
40 : Ling ual Mand ibular Bo ne Depression
6. Notes on treatment and 8. Slasky BS, Sar-Ziv J. Lingual mandibular bone de-
fects: CT in the buccolingual plane. J Comput As-
rec urrence rate sist Tornoq r 1996;20:439 - 443.
9. Graham RM, Dunc an KA, Needham G. The ap-
pearance of Statue's idiopathic bone cavity on
Sinc e LM BDs have bee n shown to be
magn etic resonance imaging. Dento rnaxillofac
anatomic ratherthan pathologic in origin,the Radio I 1997;26:74- 75.
present authors supportth e conservative use
10. Samson J, Carlino P, di Felice R, Fiore-Denno G
of know ledge-based rad iolog ic di agnosis lnclusloni intramandibo lari di tessuto ghiandolare
with appropriate clinicalfollow-up ratherthan safivare. Minerva Stom atoI 1990 ;39:573- 585.
surgical biopsy. Withthe aid of CT, CT sialog- 11. Bende r lB. Factors influencing radiographic ap-
raphy,and MRI,surgery can be avoided. The pearance of bony lesions. J Endod 1982:8:16 1-
clinical significance of these bony de pres- 170.
sions is that they must be d ifferentiated from 12. Left GS, Schw artz SF, del Rio CEoXeroradio-
other lesions that may require treatment. grap hic interpretation of experimental lesions. J
It seems irrelevant to discuss recurrence Endod 1984;10 :188- 198.
rate when dealing with LMBDs. 13. Chen CY, Ohba 1. An analysis of radiological find-
ings of Staf ne's idiopathic bo ne cavity. Den-
tornaxillofac Radial 1981 ;10 :18-23.
358
Ch apte r 41
359
4 1: Focal Marrow-con taining Jaw Cavity
3. Epidemiological dat a
3.2 Age
360
Pathogenesis
No. of cases
70
60
61 60 OJ Women
50
OJ Men
n:::::2 77
40 38
29
30
20
10
o L-~=-JJL-.JL.LJJLJL~.L.J.!..LJ.LJL.L-'LJLL-.J.L.J.LIJL-JL_
3.3 Gender
3
3.4 Location
361
4 1: Focal Marrow-conta ining Jaw Cavity
~~
'W'~'!,!{:...,p, J;'!W ,&,~y,
,",.",?" ~,, __e\ '~~';
,.
f.{~
, ~;~.;r~...ot:~.Y" - ...,,~~ '-" ,: "
~ ..... . - ~~, -- 4r l~ ~' '~ -l\I:1 . ..
~th1'?"'I.{~'Wt't.'i"-l.~~t~~~,);~\..
t. "'.
~~""'~~
~f ''Th,~
"'\~ ji{?'i'~~i
f":'-~ i~:"i" I'~ih"'~~~"'
':<J~.t''Hi 'Y'~~
'; 4if4t1..-
,~J/ );. 6. Notes on treatment and
~;.\"".:r~i,,- f.<,-<',>'i,\ ,;t~~~ . A , 2~~
r,x'/ v
'l-"__ J ", . ,,; ~ ,V' q"d;' ~f,'''''r.'\.. "'...,......o{~ '1,;Jif~-~> .l\. J~~. recurrence rate
r <~"" L ." "'~}',:~"' '''?'';-:.,<:~ :...~ ~ ~w~';(.: . "
~,~':!::.~,
1;Y~fi':~l';~
"~""~~::;;:''fir*,'"
., ~ 4ilYc.~
'1ft~J;l~$~;~H.~$
I"'?'j.. ~+ . <'if,'2t~,""~
"+i a-~~ ' ' ~~t'l'
-,
.1 . ,
362
References
363
Chapte r 42
The melanotic neuroectodermal tumor of in- The MNTI usually presents as a rapidly en-
fancy (MNTI) is a fairly rare , ben ig n, pig- largi ng exophyt ic mass most often localized
mented lesion that commonly occurs In the in the anterior alveolar ridge of the maxilla
anterior maxillaof infants youngerthan 1 year of an infant. Lesions are occa sionally de-
and mainly in the first 6 months of life. The scribed in th e mandible (Fig 42-1) and in ex-
tumor was first described by Krompecher in tragn athic sites such as brain, epid idymis,
19 18' as a congenital melanocarcinoma. uterus, ovary, and mediastinum . The MNTI
The multip licity ofterms that have been used usually presents as a single lesion, but mul-
throu ghout the years mirrors t he confusing tiple lesions have been reported 4 .5 The le-
and co nflicting pathogenet ic th eories that sion often appears to have irregu lar pig-
have been advocated for this lesio n: melan- mentation, although th is pigmentation is not
otic epithelial odontome, melanotic pro - alwa ys clinically evident. Th e nontender
gonoma, pigmented adamantinoma, melan- growt h is of a rubbery co nsistency, may con-
otic ameloblastoma, congenital pigmented
epulis, retinal anlage tumor, melanocytoma,
and pigmented neuroectodermal tumor ofin-
fancy. A complete list of syno nyms can be
found in a report by Nozicka and Spacek."
The current consensus favors the use olthe
term melanotic neuroectodermal tumor of in-
fancy, a desig nation accepted by and used
in the 199 2 Wor ld Health Organization
(WHO) classification of odo ntogen ic tu-
rnors." As the end of 2000, an estimated 250
cases of MNTls have been publ ished in the
literature.
Fig 42-1 Intraoral ap pearance of an MNTI in a 5-
month-old girl. The presence of the tumor has re-
sulted in premature eruption of the mand ibular
left second deciduous molar. Note the brownish-
blue pigmentation of the tumorsutface.(Courtesy
of Prof A. Eckardt, Hannover, Germany.)
367
42: Melanotic Neuroectodermal Tumor of Infancy
No. of cases
10
9 8 DJwomen
81 7
7 DJ Men
6
6 5 n=35
5
4
3
6i,L'~J~I~J~~I~~'1J
2
0 -8
I I +1~1J~~llJ;1tl~1~I~J
9 - 16 17 -24 25 -60
1 IJ
--;-;-;-_
11 Y
rno mo mo mo Fig 42-2 Age and gender
Age in months and years distribut ion of 35 cases of
MNTI.
tain prematurely erupted or displaced pri- thus greatly assist in surgical planning .
mary teeth and may have an ulcerated sur- These rad iographic methods subject very
face. Most tumors measure from 1 to 4 cm young patients to significant radiation expo-
at their greatest diameter. The case of a gi- sure, but they can provide important infor-
gantifo rm MNTI occurring in a 7-month-old mation and are diagnostically superiorto oth-
girl and measuring 18 cm in greatest diam- er routine imaging methods.
eter was recently publ ished by Bouckaert
and Haubenhelrner.v
The typical radiogra phic appearance of
the MNTI is that of an intrabony radiol ucent
lesion with poorly demarcated borders , pre- 3. Epidemiological data
sumably caused by rapid growth and a ten-
dency to locally invade bone . The area of
bone destruction may be traversed by bone 3 .1 Prevalence, incidence, and
septa. Teeth involved in the lesion may ap- relat ive frequency
pear to be floating with in the radiolucent area
ofthetumor because they are displaced from No data are available.
the ir normal development sites. This radi-
ographic appearance can unde rstandably
mislead a clinician into making a provisional 3.2 Age
diagnosis of malignancy . Another potential-
ly m islead ing feature is a common os- Figure 42-2 shows the age distribution of 35
teogenic reaction that exhibits a "sunray" ra- MNTI cases. The data are retrieved from a
diographic pattern which may be mistaken review of cases publ ished between 1980
for an osteosarcoma. Computed tomogra- and 1992.8 The lesion was usually not pres-
phy and magnet ic resonance imagery7,8 are ent at birth, and 85 .7% ofthe cases occurred
able to define the extent of the lesion pre- before the age of 24 weeks (6 months).
cisely, localize possible mu ltiple sites, and
368
Pathology
369
4 2 : Me la notic Neuroectod ermal Tu mo r of Infancy
Fig 42-4 Higher magnification of thesametumor Fig 42-5 A cluster of neuroblast-like cells show-
showing the pigmented cells and scattered ing strong positivity for neuron-specific enolase
smaller neuroblast- or lym phocyte-like cells (NSE, x400). (Courtesy of Prof A. Eckardt, Han-
(H&E. x250). (Courtesy of Prof A. Eckardt. Han- nove r, Germany.)
nover, Germany.)
loose groups of large and epithe lium-like vimentin was focally expressed in the pig-
ce lls usual ly exhibitin g abu nda nt b rown mented cells. De Souza et al 14 stud ied the
pig mentthat is positive for melanin. The sec- immunoh istochemical expression of several
ond cell type consists of clusters of poorly co- cell cycle proteins (p53, MDM-2, cyclin D1 ,
hesive nests of smaller, no n-melanin-con- cyclin A, and proliferating cell nuclear anti-
taining ovoid cells wit h minimal cytoplasm gen [pe NA]) in three cases of MNTI. A dif-
and a hyperchrom atic nucleus, resembling fuse immunoreactivity of the me lanin-con-
neuroblast- or lymphocyte-like cells are pres- tainin g cells for MDM-2 and a complete
ent in the alveolar spaces or as isolated nests absence of p53 exp ression were found.
in the stroma (Fig 42-4). Nuclear atypia and These find ings suggest that the large ep-
mitotic figu res are noticeably absent. Inva- ithelium-like cells are t he pro liferative ele-
sion of tumor cells into possib ly existing tooth ment of the tumor and that MDM-2 protein
germs may occ ur. may be important for MNTI developm ent.
Khod dami et al 15 perform ed an immuno-
histochemical, molecular genetic, and fluo-
5.2.2 HistochemicaVimmunohistochemi-
rescence in situ hybridization (FISH) study
cal findings
with the pur pose of elucidating a possible re-
Immunohistoche mically, the large melanin- lationship between MNTls and other pedi-
containing epithelium-like cells react with a atric small cell tumors with neuroectodermal
monoclonal antibody directed against anti- features (suc h as neuroblastom as, Ewing
human melanoma HMB-45 9 The same au- sarcomas/pe ripheral pr imitive neuroecto-
thors also found that the small lymph ocyte- dermal tu mors. and desm oplastic small
like cells were positive for neuron-specific round cell tum ors). The melanin-eontaining
enolase (NSE) (Fig 42-5). Antibodies direct- large cells showed strong reactivity for low-
ed against S-1 00 protein did not label the tu- molecular keratin, epithelial memb rane anti-
mor cells. Bouckaert and Raubenheimer" ge n, and HMB-45 and weak positivity for
confirmed these findings and also found that NSE. The smaller neurob lastic cells were
370
Notes on treatme nt and recurrence rate
strong ly positive for NSE. Neither cell type tie nts w ith MNTls, VMA is believed to be
manifested S-100 protein react ivity. Ac- st rongly circumstantial evidence of a neuro-
cordi ng to the authors, the molecular genet- ectodermal origin. However, most patients
ics and FISH tests showed that there is no with MNTls show normal levels of V M A, 8.24-
basis to link MNTls with any of the other small 27 The fact that Dehner at al23 reported ele-
cell tumors with neuroectode rmal features. vated VMA levels in a malignant transformed
MNTI, whereas other malignant cases were
not associated with its elevation,>4.26 seems
5.2.3 Ultrastructural findings
to indicate that VMA levels have no relation
Several reports give details about the ultra- to biologic behavior.
structure of the benign melanotic neuroec-
tod erma l tumor of infancy, as well as the
malignant variant 22,23 All except Palacios ' "
desc ribe three basic cellu lar constituents: a
pigmented cell,a small immature neuroblast- 6. Notes on treatment and
like cell, and fibroblasts. Cutler et al ' 6 de-
tailed the intercellula r junct io ns between recurrence rate
t umor cells, t he occu rrence of cilia and
melanocyte filaments, and patte rns of Although the MNTI d isplays a disturbingly
melanin granule formation-all findings that rapid growt h and invasive rad iographic ap-
are compatible with cells of neural crest ori- pearance, it has a benign course in most cas-
gin. es. There is a 15% propens ity for local re-
currence and a malig nancy rate of about
7%.21 The few available studies using flow
5.2.4 Tissue culture findings
cytometry analysis21.28 suggest that tumors
The predominance of melanin-contai ning with aneuploid cells may recur more often
dendritic cells in culture from MNTls was re- than those without. The need for agg ressive
ported by Claman et al,' 8who found that this surgery is usually not advocated for MNTls.
was the only celltype present after prolonged The recommended treatment involves con-
passage in vitro. In their study on a case of servative excisio n, enucleation, and curet-
malignant MNTI, Dehner et al23 placed sam- tage. Conservative local excision of recur-
ples of the onginal maxillary tumor in tissue rent tu mo rs is alrnost invariably curat ive.
culture, but a fib roblast growt h was the on ly However, sorne recurrent cases, particularly
result. In co ntrast, tissue explants from the multifocal MNTls, rnay require a wide r exci-
two recurrences yielded three cell types in sion. The apparent success of a conservative
vitro after 14 days' g rowth: pigment-produc- approach to surgical removal does not re-
ing cells, small round cells with processes duce the need for regu lar follow-up exami-
consistent with neuritis, and bipolar fibro- nations, because the potential for recurrence
blasts. still rernalns.s?
37 1
42: Melanotic Neuroectodermal Tumor of Infancy
Refer ences 14. de Souza PEA, Merly F, Maia oM F, et al. Cell cy-
cle-asso ciated proteins in melanotic neuroecto-
1, Krompecher E. Zur Histoqenese and Morpholo- der mal tu mo r of infancy. Oral Surg Oral Med Oral
gie de r Ad ama ntinome und son stig er Kiefer- Pathol Oral Radiol Endod 1999 ;88:466-468.
gesc hwu]ste . Beit r Pathol An at 191 8;64 :165- 15. Khoddam i M, Squire J, Ziele nska M, Thorner P.
197. Melanotic neuroectodermal tum or of infancy: A
2. Nozicka Z, Spac ek J. Melanotic neuroectodermal molecular gen etic study.Ped iatrDev Patho11998:
tumor of infancy with hig hly differentiated neural 1:295- 299.
compo nent: Light and electron m ic rosc opi c 16. Cutler LB, Chaud hry AP, Topazia n R. Melanotic
stud y. Ac ta Neuropat hol (Berl) 19 78 ;44 ;229- neuroectoderm al tumor of infancy: An ultrastruc-
233. tural study, literature review , and reevaluation.
3. Kramer IRH, Pindborg JJ, Shear M. Histological Canc er 198 1;48:257- 270.
Typing of Odontogenic Tu mo urs. 2d ed. Berlin: 17. Nika i H, ljuhin N, Yamasaki A, et at. Ultrastructur-
Springer-Verlag, 1992. al evide nce for neural crest origin of the melanot-
4. Ste inberg B, Shule r C, Wilson S. Melanotic neu- ic neuroect odermal tum or of infancy.J Oral Pathol
roec toder mal tumor of infancy: Eviden ce for mul- 1977; 6 :22 1- 232.
tice ntricity. Oral Burg Oral Med Oral Pathol 1988; 18. C1aman LJ,Stetso n D, Steinberg B, Shuler CF, Ul-
66 :666-669 . trastructural ch aracteristics of a cell line derived
5. Pontius EC, Dziabis MD, Foster JA. Multicentric from a melanotic neuroectodermal tumor of in-
melanoam elob lastom a of the m axilla. Can c er fancy. J Oral Pathol 199 1;20 :245- 249.
1965; 18:38 1- 387 . 19. Nelson ZL, Newm an L, Loukota OM. Melanotic
6. Bouckaert MMR, Raubenheimer EJ. Gigantiform neuroectod ermal tumou r of infan cy: An immuno-
melanotic neuroectodermal tu mor of infancy. Oral histoc hemical and ultrastructural study. Sr J Oral
Surg Oral Med Oral Pathol Oral Radiol Endod Max illofac Su -q 1995 ;33:375-380.
1998 ;86:569 - 572 . 20. Sousa Sa M, Araun o NS, Sesso A, Araujo YC. Im-
7. At kinson GO, Davis PC, Patrick LE, et al. Melan- mu nohistoch em ica l, ultrastru ctural, and histo-
otic neuroectodermal tumor of infancy. MR find- ge nic co nsiderations in a patient with melanotic
ings and a review of the literature. Ped iatr Radiol neuro ect odermal tum or of infancy. J Oral Max-
1989;20 ;20- 22. il1ofacSur9 1992;50: 186-189.
8. Mosby EL, Lowe MW, Cobb eM , Ennis RL, Melan- 2 1. Pettinato G, Maniv el JC, d 'A more ES, et al. Melan-
otic neuroectodermal tum or of infancy: Review of otic neuroect ode rm al tumour of infancy: A re-
the literatu re and report of a case. J Oral Maxillo- examination of a histogenetic probl em based on
fac Surg 1992 ;50:88 6- 894. im munoh istoch emical, flow cytornetric, and ultra-
str uctural study of 10 cases. Am J Surg Pathol
9. Hosh ina Y, Hamam oto Y, Suzuki I, et al. Melanot- 1991 ;15:233-24 5.
ic neuroectoderm al tum or of infancy in the man-
dible. Repo rt of a case. Oral Surg Oral Med Oral 22. Palaci os JJN. Malignant mela notic neuroecto-
Pathol Oral Rad iol Endod 2000;89:594-599. dermal tumor . Light and elect ron mic roscopic
stud y. Cancer 1980 ;46:529- 536.
10. Kerr DA, Pullen PA. A study of the pigm ented tu-
mou rs of jaws of infants. Oral Surg 1964 ;18 : 23 . Dehner LP, Sibley RK, Sauk JJ, et al. Malignant
759- 772. melanotic neur oect od ermal tumor of infancy. A
clinica l, pat hologic, ultrastructural and tissue cul-
11. Stownes D. A pigmented tumor of infancy: The tur e stu dy. Canc er 1979 ;43:1389-1 410.
melanotic progonoma. J Pathol Bacteriol 1957;
73:43 - 5 1. 24. Ogata A, Fujio ka Y, Nagash ima K. et al, Malignant
melan otic neuroect odermal tum or of infancy aris-
12. Halpert B, Patzer R. Maxillary tum or of retinal an- ing from the pineal bod y. Acta Neuropatho! (Bert)
lage. Surgery 1947;22:837-841 . 1989;77 :654- 658.
13. Bo rello ED, Gor lin RJ. Melanotic neuroecto der- 25. Hupp JR, Topazian RG, Krutchko ff OJ. The mel-
mal tumor of infancy--e neop lasm of neu ral crest anotic neuroectoderm al tum or of infancy. Report
origin. Report of a case assoc iated wit h high uri- of tw o cases and review of the literature. lnt J Oral
nary exc retion of van ilmandelic ac id . Canc er Surg 1981 ;10 :432-436.
1966; 19:196 - 206.
372
Refere nces
26. Johnson RE, Scheihauer BW, Dahlin DC. Melan- 28 . Kapad ia S, Frisman D, Hitchcock C, et al. Melan-
otic neuroectodermal tumor of infancy. A review otic neuroectoderrmal tu mor of infancy (MNTI),
of seven cases. Cance r 1983;52:6 61 -666. immunohistochem ical and flow cytometric study.
27. Nagase M, Usda K, Fukushima M, Nakajima T. Mod Pathol 1992:5:71A. Abstract.
Rec urrent neuroectod ermal tum or of in fancy : 29. Demas PN, Braun TW. Nazif MM. Melanotic neu-
Case report and survey of 16 cases. J Maxiflofac roectodermal tumo r of infancy: A report of two
Sur9 1983: 11:131-136. cases. J Oral Maxillofac Surg 199 2;50:894 - 898.
373
Index
375
Index
376
Index
377
Index
B pathogenesis of, 97
Bandeirea simplic ifolia agglutinin I, 84 patho logy of, 98 - 102
Basal cell intraosseous ameloblastoma, 51 prevalence of, 95
Benign ceme ntob lastom a (BC), 21, 180, radiograph ic profile of, 93
199- 203 recurrence rate of, 102-1 03
age and, 200 termin ology of, 93
clinical profile of, 199- 200 treatment of, 102-1 03
frequency of, 200 unerupted permanent teeth and, 96-97
genderand, 200 Calcifying ghost ce ll odo ntogenic cysts/tumors
histochemical/i mmu nohistoch emical (CGCOT), 2 1, 155- 168
findings in, 203 age and, 163
histologic definition of, 202 classification of, 156- 161
histopathologic findings in, 202 -203 clinical profile of, 16 1- 162
inciden ce of, 200 freq uency of, 163
location and, 20 1 gende r and, 163 -1 64
macroscopy, 202 histochemical/immunohistochemical
microscopy, 202-203 findings in, 16 7
pathogenesis of, 20 1 histologic definition of, 164-1 65
pathology of, 202 histopath ologi c find ings in, 165-1 67
prevalence of, 200 inc idence of, 163
radiologic profile of, 199-200 loc ation and, 164
recurrence rate of, 203 macroscopy, 163
terminology of, 199 microsco py, 163 -1 68
treatment of, 203 pathoge nesis of, 164
ultrastructural findings in, 203 pathology of, 163-1 68
BMP. See Bone mo rphogenetic protein prevalence of, 163
Bone morphogenetic protein (BMP), 152- 153 rad iologic profile of, 161 -1 62
Bromodeoxyuridin e (BrdU), 13 7 recurrence rate of, 16 8
terminology of,1 55-1 6 1
C treatment of, 168
Calcifying epithe lial odo ntogen ic tumo r (CEOT), ultrastructural findings in, 167-1 68
2 1, 93- 103 Cemento blasto ma, benign. See Benign
ade nomato id odo ntogenic tu mor a nd , 101, cementob lasto ma (BC)
112,113 Central giant cell lesion (CGCl), 22, 185,
age and, 95-96 3 19-330
amyloid-like mate rial in, 9 9 age and, 32 1-3 22
cementu m-like com ponents of, 99- 100 agg ressive, 326 -3 27
clear cell, 100 - 101 clin ica l profile of, 320
clinical profile of, 93 frequency of, 320
frequency of, 95 gend eran d, 322
gender and , 96 histochemical/i mmunohistochemical
histologic definition of, 98-99 finding s in, 3 25
histopatholog ic findings in, 99- 102 histologi c definition of, 323-324
incidence of, 9 5 histopatholoq ic find ings In, 324-325
Lange rhans ce ll occu rrence in, 10 1 hyperparathyroidism and, 32 5- 326
location and, 96 incide nce of, 32 0
macroscopy of, 98 location and , 322
microscopy of, 98- 102 mac roscop y, 323
myoepithelial cells and, 101-1 02 of maxillofacial skeleton, 329-330
378
Index
379
Index
380
Index
38 1
Index
38 2
Index
383
Index
384
Index
385
Index
386
Index
T V
Teeth Vanillyl mandelic acid (VMA), 3 71
development of, 25
unerupted, solidjmulticystic ameloblastoma
and, 47
387