Oncology: Study of tumors

Tumor means swelling

Today the word “tumor” is applied to only neoplastic masses

Neoplasia – Definition
Literally means “new growth”
Willis Definition: An abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with that of the normal tissues and
persists in the same excessive manner after the cessation of the
stimuli.

Neoplasia is an abnormality of
1. Cellular Differentiation
2. Maturation
3. Control of growth
Fundamental to the origin of all neoplasms is loss of
responsiveness to normal growth controls.

Neoplastic cells are said to transformed, i.e. they continue

to replicate oblivious to the regulatory influences that
control normal cell growth and division

Neoplastic cells behave as parasites and compete with

normal cells and tissues for their metabolic needs.

Neoplastic cells enjoy certain degree of autonomy and they

steadily increase in size regardless of their local
environment and the nutritional status of the host
 Tumors
• Non odontogenic
• Odontogenic
 Non odontogenic
• Epithelial
• Benign • Fibrous Connective tissue
•
• Malignant •
Adipose
Cartilage
• Hamartoma •
•
Bone
Vascular
• Choristoma •
•
Neural
Muscle
• Lymphoid
• Neural crest cell – melanoma
• Teratoma
• Giant cell lesions
• Myeloma
• Salivary gland tumors
Hamartomas and Choristomas:
1. These are tumor-like growths that are thought to be
developmental anomalies.
2. They are not true neoplasms, i.e. they do not show continuous
growth

Hamartoma: These tumor-like lesions are composed of tissues that

are normally present with in an organ in which the tumor arises
e.g.. Odontoma comprises of tooth material and tooth forming
tissues.

Choristoma: These are tumor like lesions that contains tissues that
are not normally present in its site of origin e.g.. Tooth in the
ovary or disorderly mass of smooth muscle and pancreatic acini
in the stomach wall.
Classification of Odontogenic Tumors: WHO – Krammer et al
Benign Tumors
1. Odontogenic epithelium with mature, fibrous stroma without odontogenic
ectomesenchyme \

Ameloblastoma, solid/multicystic type

Ameloblastoma, extraosseous/peripheral type
Ameloblastoma, desmoplastic type
Ameloblastoma, unicystic type
Squamous odontogenic tumour
Calcifying epithelial odontogenic tumour
Adenomatoid odontogenic tumour
Keratocystic odontogenic tumour
2. Odontogenic epithelium with odontogenic ectomesenchyme,
with or without hard tissue formation
Ameloblastic fibroma
Ameloblastic fibrodentinoma
Ameloblastic fibro-odontoma
Odontoma
Odontoma, complex type
Odontoma, compound type
Odontoameloblastoma
Calcifying cystic odontogenic tumour
Dentinogenic ghost cell tumour
3. Mesenchyme and/or odontogenic ectomesenchyme with
or without odontogenic epithelium

Odontogenic fibroma
Odontogenic myxoma/myxofibroma
Cementoblastoma
Classification of Odontogenic Tumors: WHO 2005– Philipsen
and Reichart - IARC

Malignant Tumors

1. Odontogenic Carcinomas:
-Malignant Ameloblastoma
- Primary Intraosseus Carcinoma
- Malignant variants of other odontogenic epithelial tumors
- Malignant changes in odontogenic cysts

2. Odontogenic Sarcomas :
- Ameloblastic fibrosarcoma (Ameloblastic sarcoma)
- Ameloblastic fibrodentinsarcoma and ameloblastic fibro-odontosarcoma
- Odontogenic carcinosarcoma
Ameloblastoma : Definition

A true neoplasm of enamel organ type tissue which does not

undergo differentiation to the point of enamel formation.

Robinson defines it as : Tumor that is “usually unicentric, non-

functional, intermittent in growth, anatomically benign, and
clinically persistent
The first time………
Malassez first called it Admantinoma in 1885 but was
replaced by amelobalstoma as it did not produce any hard
tissue
Term Ameloblastoma first applied to this tumor was
suggested by Churchill in 1934
An unconfirmed first report by Guzack in 1826
The first neoplasm reported by Broca in 1868
First thorough description by Falkson in 1879
Frequency:

Second most common odontogenic neoplasm; only outnumbered

by Odontoma

Excluding odontoma, the incidence of amelobalsotma is at least

equal to the incidence of all other odontogenic neoplasms
combined

Its incidence combined with its clinical behavior makes

ameloblastoma the most significant odontogenic neoplasm of
concern to oral and maxillofacial surgeons
Pathogenesis: Ameloblastoma is of varied origin and stimulus initiating it is
unknown. Possible sources:
1. Cell rests of the enamel organ, either remnants of the dental lamina or
remnants of Hertwig’s sheath namely Rests of Malassez
2. Epithelium of odontogenic cysts particularly dentigerous cyst and
odontomas
3. Disturbances in the developing enamel organ
4. Basal cells of the surface of the jaws
5. Heterotrophic epithelium in other parts of the body, especially pituitary
gland
6. Presently it is thought that it is likely the result of alterations or mutations
in the genetic material of cells that embryologically preprogrammed for
tooth development. Environmental factors and individual patient variables
(eg. General health status, nutritional status) also likely to have a
modulating role- demonstrated by higher incidence in industrialized
nations – 10 to 15 %
At present, it is known that the potential sources to develop
an odontogenic tumor are varied, and these include:
1. The pre-functional dental lamina (odontogenic epithelium
with ability to produce a tooth), which is more
abundant for obvious reasons distally to the lower third
molars.
2. The post functional dental lamina, a concept that covers
those epithelial remnants such as Serre´s epithelial rests,
located within the fibrous gingival tissue; the epithelial
cell rests of Malassez in the periodontal ligament and the
reduced enamel organ epithelium, which covers the enamel
surface until tooth eruption.
3. The basal cell layer of the gingival epithelium, which
originally gave rise to the dental lamina.
4. The dental papilla, origin of the dental pulp, which has
the potential to be induced to produce odontoblasts and
synthesize dentin and/or dentinoid material.
5. The dental follicle.
6. The periodontal ligament, which has the potential to
induce the production of fibrous and cemento-osseous
mineralized material.
Ameloblastoma types:
1. Intraosseous
A. Admantinoma of long bones
B. Ameloblastoma of Jaws – two main histologic types
I-The conventional solid/multicystic
a. Follicular:
acanthomatous,
granular cell,
desmoplastic,
basal cell
b. Plexiform
II- Unicystic
2. Extraosseous: Soft tissue
Another interesting classification:

1.Ameloblastoma in situ

a)Mural Ameloblastoma: Limited within the lining, curable by

enucleation

b) Intraluminal Ameloblastoma: Arising from the epi lining –

proliferating into the lumen, cyst enucleation
II. Microinvasive Ameloblastoma

a) Intramural Microinvasive Ameloblastoma: Arising from

the Epi lining and proliferating into the connective tissue
layer of the cyst wall. More aggressive pathology and
requires resection approaches for cure

b) Transmural Microinvasive Ameloblastoma: Arising from

the Epi lining and proliferating through the complete
thickness of the connective tissue layer of the cyst wall.
More aggressive and invasive pathology and requires
resection approaches for cure
III. Invasive Ameloblastoma

a)Invasive Ameloblastoma arising from the lining of a cyst:

Arising from the Epi lining and proliferating through the
complete thickness of the connective tissue layer of the cyst
wall and into the adjacent bone. More aggressive and invasive
pathology and requires resection approaches for cure

b) Invasive Ameloblastoma : A solid or multicystic

Ameloblastoma unassociated with a cyst. More aggressive and
invasive pathology and requires resection approaches for cure
Clinical features:
AGE: Lesion of Adults, 4 –5th decades of life. Age range is
broad , extending from childhood to adulthood (mean age,
approx 40 years).

GENDER: There appears to be no gender predilection.

Race: No racial predilection, though some studies indicate a
higher frequency in blacks

Site: Mandibular molar-ramus area is the most favored site. In

maxilla, it is usually molar and anterior area
Clinical features: contd.
Lesions are usually asymptomatic and are discovered either during routine
radiographic examination or because of asymptomatic jaw expansion. Occasionally,
tooth movement or malocclusion may be the initial presenting sign.

Radiography: Ameloblastomas are osteolytic, typically found in the tooth bearing

areas of the jaws. The most typical radiographic presentation is that of a multilocular
radiolucent lesion. The lesion is often described as having a “SOAP BUBBLE
APPEARANCE” when the radiolucent loculations are large and “HONEY
COMBED” when the loculations are small. Buccal and lingual cortical expansions are
frequently present. Resorption of roots of teeth adjacent to the tumor is common. Solid
ameloblastomas may appear unilocular and these usually have irregular scalloping.
These features are not diagnostic of ameloblastomas as other lesions may show similar
picture. Desmoplastic ameloblastomas appear differently as they are seen in anterior
mandible and shows mixed radiolucent radiopaque like fibro osseous lesions due to
osseus metaplasia within dense fibrous septa, the tumor does not produce mineralized
prodcut.
Pathogenetic mechanism: Mechanisms by which ameloblastomas gain growth
and invasion advantage include overexpression of antiapoptotic proteins (Bcl-2, Bcl-
xL) and inerface proteins (FGF, MMPs). Ameloblastomas have a low proliferation rate
as shown by staining for cell-cycle related protein, Ki-67.

AMELOBLASTOMA: BIOLOGIC SUBTYPES:

Solid ameloblastoma
Cystic ameloblastoma
Peripheral ameloblastoma
Malignant ameloblastoma
Ameloblastic carcinoma
Cystic Ameloblastoma: formerly called unicystic ameloblastoma
Change in name as these lesions are often multilocular,
Considered a separate entity based on clinical, radiographic, and pathologic features and
its response to treatment.
10 to 15 % of all intra osseous ameloblastomas.
Whether it arises de novo or arises from cyst epithelium cannot be obtained, but noth
processes may be possible
Usually asymptomatic, large lesions may cause painless swellings
Site: 90% in mandible, posterior region
Cortical perforation in 25% of the cases
Recurrence: as high as 40% as treated by curettage as late as 9 yrs post op
Age: Seen in younger age groups-mean age –23yrs, 35 yrs. Second decade of life
Radiographically: may appears as a circumscribed radiolucency that surrounds the crown
of an unerupted mandibular third molar and clinically resembling a dentigerous cyst and
diagnosis of ameloblastoma is only made by microscopic study of specimen
Histopathologic features: Three variants:
1. Luminal unicystic ameloblastoma: confined to luminal surface of the cyst. The
lesion consists of fibrous cyst wall with a lining that consists of totally or partially
of ameloblastic epithelium. The epithelium demonstrates a basal layer of columnar
to cuboidal cells with hyperchromatic nuclei that shows reverse polarity and basilar
cytoplasmic vacuolization. The overlying epithelial cells are loosely cohesive and
resemble stellate reticulum and is not related to inflammatory edema
2. Intraluminal unicystic ameloblastoma: one or more nodules of ameloblastoma
project from cystic lining into the lumen of the cyst. Nodule may be small or large
to fill the lumen. Sometimes nodule demonstrates edematous, plexiform pattern
and hence called plexiform unicystic ameloblastoma. Intraluminal cellular
proliferation does not always meet the strict histopathologic criteria for
amelobalstoma and may be secondary to inflammationthat nearly always
accompanies this pattern.
3. Mural unicystic ameloblastoma: Here the fibrous wall of the cyst is infiltrated by
typical follicular or plexiform ameloblastoma. The extent and depth of
ameloblastic infiltration may vary considerably. Multiple sections through many
levels of specimen are necessary to rule out the possibility of mural invasion of
tumors.
Malignant Ameloblastoma and Ameloblastic carcinoma:
Rarely exhibits frank malignant behavior, less than 1 %
Malignant Ameloblastoma includes lesions where the primary and secondary metastatic
tumor shows histopathologic features of ameloblastoma. Metastases from ameloblastoma
are most often found in the lungs. These are sometimes are regarded as aspiration or
implant metastases. However, the peripheral location of some of these suggest that they
must have occurred through blood or lymphatic routes rather than aspiration. Cervical
nodes are the second most common site for metastasis of an ameloblastoma. Spread to
vertebrae, other bones, and viscera has been confirmed. Prognosis is poor
Ameloblastic carcinoma includes ameloblastoma that has cytologic features of
malignancy in the primary tumor, in a recurrence or in any metastatic deposit. These
include an increased nuclear to cytoplasmic ratio, nuclear hyperchromatism and the
presence of mitoses. Necroses in tumor islands and dystrophic calcification may also be
present These lesions may follow a markedly aggressive local course, but metastases do
not necessarily occur.
PERIPHERAL AMELOBLASTOMA:
Uncommon, only 1% of al ameloblastomas
Arises from the rests of dental lamina beneath the oral
mucosa or from the basal epithelial cells of the surface
epithelium
Histopathologically same features as the intraosseus form of
the tumor.
Clinically: Painless, non-ulcerated sessile or pedunculated
gingival or alveolar mucosal lesion. Usually misdiagnosed as
pyogenic granuloma or Fibroma as features are non specific
Lesions are less than 1.5 cm, average age abt 52 yrs.
Site: Posterior gingival/alveolar mucosa , mandible greater
than maxilla
Peripheral Ameloblastoma: Histologic features

Islands of ameloblastic epithelium that occupy the lamina propria

underneath the surface epithelium. The proliferating epithelium may
show any of the features of the intraosseus ameloblastoma namely the
follicular and Plexiform
Connection the basal cell layer of the surface eptiehlium is seen in
50% of the lesions, whether represent origin of tumor or merging has
not been ascertained.
Basal cell carcinomas of the oral mucosa but may represent
peripheral ameloblastoma.
May be even confused with peripheral odontogenic fibroma,
differentiated by the presence of dentin or cementum like material in
the tumor.