Atlas of Genetics and Cytogenetics

in Oncology and Haematology

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Solid Tumour Section

Review

Head and Neck: Odontogenic tumor:

Ameloblastoma
Punnya V Angadi
Department of Oral and Maxillofacial Pathology, KLE VK Institute of Dental Sciences and Hospital,
Nehrunagar, Belguam-590010, Karnataka state, India (PVA)

Published in Atlas Database: May 2010

Online updated version : http://AtlasGeneticsOncology.org/Tumors/AmeloblastomID5945.html
DOI: 10.4267/2042/44972
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
2011 Atlas of Genetics and Cytogenetics in Oncology and Haematology

Identity
Alias: Adamantinoma
Note
It is considered to be the most common odontogenic
tumor. It is a tumor of the enamel organ without
formation of enamel. Robinson has defined it as:
Unicentric, nonfunctional, intermittent in growth,
anatomically benign and clinically persistent. The
importance of this tumor lies in its common
occurrence, locally invasive behavior which causes
marked deformity and serious debilitation. They also
demonstrate increased recurrence rate after surgery.

Clinics and pathology

Note
History: Gorlin identifies Cusack as the first person to
identify ameloblastoma in 1827. Falkson gave a
detailed description in 1879. The first histopathologic
description was given by Wedl (1853) who called the
tumor cystosarcoma or cystosarcoma adenoids and
thought that it could have arisen from tooth bud/dental
lamina. Wagstaffe (1871) gave the first histological
drawing. Malassez (1885) introduced the term
"adamantine epithelioma" while Derjinsky (1890)
introduced the term "adamantinoma". However, this
term has become obsolete and has to be avoided. Ivy Figure 1. Mandibular ameloblastoma presenting as swelling
and Churchill in 1930 encouraged the use of the term causing facial asymmetry.
"Ameloblastoma" which is the preferred terminology Embryonic origin
till date.
Ameloblastoma arise from remnants of odontogenic

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Head and Neck: Odontogenic tumor: Ameloblastoma Angadi PV

epithelium i.e. from rests of dental lamina. If these rests rarely the ameloblastoma can ulcerate through the
are situated outside the bone in the soft tissues of mucosa.
gingiva or alveolar mucosa may give rise to peripheral Peripheral ameloblastoma usually presents as normal
ameloblastoma. Other possible sources of origin colored, smooth surfaced nodules or enlargements but
include gingival surface epithelium and lining of occasional tumors may present with erythematous or
odontogenic cysts. papillary surface. They are slow growing and cause
little or no bone erosion. Any saucerisation of the
Epidemiology
underlying bone is due to pressure rather than invasion.
Ameloblastoma although rare, is the most common Radiology: Ameloblastoma usually present as a well
odontogenic tumor accounting for 1% of all tumors in defined, multilocular radiolucency with scalloped
head and neck region and around 11% of all border typically described as 'honeycomb' or soap
odontogenic tumors. They usually occur in middle age bubble appearance. However, unicystic ameloblastoma
group i.e. 20-40 years with highest incidence noted in typically presents as a unilocular radiolucency
33 years. They are rare in children (8.7% - 15%). containing an impacted tooth. They typically infiltrate
Maxillary ameloblastoma and extraosseous through the medullary bone, therefore the radiographic
ameloblastoma occur in a slightly older age group margins are not accurate indicators of the extent of
while unicystic ameloblastoma (Avg 10.8 years) and involvement. Expansion of buccal and lingual cortical
granular cell ameloblastoma occur in a younger age plates, displacement and root resorption may also be
group. It shows equal sex predilection with no specific seen.
racial predominance. There is conflicting evidence on Desmoplastic ameloblastoma present with a ill-defined
the incidence rates in different races. Although some radiolucent radiopaque lesion reminiscent of a fibro-
reports claim an increased incidence of ameloblastoma osseous lesion.
in black individuals, a large study identifies Asians as
the population with greatest number of affected
patients.
Ameloblastoma occurs in all areas of jaws, but the
mandible is the most commonly affected area i.e. more
than 80% of cases are seen here. Within the mandible,
the molar angle ramus area is involved three times
more commonly than are premolar and anterior regions
combined. In the maxilla, most usually occur in the
molar area, but may be seen occasionally in the anterior
region, maxillary sinus and nasal cavity. Based on the
clinical, radiographic, histopathologic and behavioral
aspects, four subtypes of ameloblastoma are currently
identified namely:
- Classic/solid/multicystic ameloblastoma
- Unicystic ameloblastoma
- Peripheral ameloblastoma
- Desmoplastic ameloblastoma
Clinics
Ameloblastoma grow slowly and usually are
asymptomatic until a swelling is noticed. Most patients
thus typically present with a complaint of swelling and
facial asymmetry. Occasionally, small tumors may be
identified on routine radiography. As the tumor
enlarges, it forms a hard swelling and later may cause
thinning of the cortical bone resulting in an egg shell
crackling which can be elicited. The slow growth also
allows for reactive bone formation leading to gross
enlargement and distortion of the jaw. If the tumor is
neglected, it may perforate the bone and spread into the
soft tissues making excision extremely difficult. Pain Figure 2. A: Ameloblastoma presenting as a multilocular
radiolucency involving the left mandibular angle and ramus
has been reported as an occasional finding which could region. B: Unicystic ameloblastoma presenting as an unilocular
be attributed to secondary infection. Other effects radiolucency associated with an impacted mandibular third
include tooth mobility, displacement of teeth, molar. C: Desmoplastic ameloblastoma depicting a ill-defined
resorption of roots, paraesthesia if the inferior alveolar radiolucency with specks of radiopacities in mandibular anterior
region.
canal is involved, failure of eruption of teeth and very

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Head and Neck: Odontogenic tumor: Ameloblastoma
Cytology
Ameloblatoma cytologically usually presents with
basaloid cells arranged in cells and clusters. These
basaloid cells have scanty cytoplasm and dense oval
nucleus. Palisading of these basaloid cells in cell
clusters is a noticable feature. Additionally, squamous
cells with abundant cytoplasm and central nucleus can
also be seen if there is evidence of squamous
metaplasia. The background is usually eosinophilic and
shows scattered spindle cells and inflammatory cells.
Pathology
There are six histopathologic subtypes which have been
identified for ameloblastoma i.e. follicular, plexiform,
acanthomatous, basal cell, unicystic and desmoplastic
ameloblastoma. Mixtures of different patterns are
commonly observed and the lesions are usually
classified based on the predominant pattern present.
Follicular ameloblastoma: These are most readily
recognizable and common type of ameloblastoma
histologically. The follicular pattern consist of islands
of epithelial cells with a central mass of polyhedral
cells or loosely arranged angular cells resembling
stellate reticulum, surrounded by well organized single
layer of cuboidal or tall columnar cells with nuclei
placed at the opposite pole of basement membrane
resembling pre-ameloblasts. This peripheral cell layer
tends to show cytoplasmic vacuolization. Cystic
formation is often seen in the center of the epithelial
islands due to degeneration of stellate reticulum like
cells.
Plexiform ameloblastoma: The tumor epithelium is
arranged in form of network/tabeculae which is bound
by a layer of cuboidal or columnar cells and stellate
reticulum like areas are usually minimal. Cyst
formation occurs but is usually due to stromal
degeneration rather than cystic change in the
epithelium. The stroma consists of loose, vascular
sparsely cellular connective tissue.
Acanthomatous ameloblastoma: It resembles a
typical follicular ameloblastoma except it shows
extensive squamous metaplasia sometimes with keratin
formation within the epithelial islands.
Granular cell ameloblastoma: When the central
stellate reticulum cells show extensive granular cell
transformation i.e. in the form of sheets of large
eosinophilic granular cells, the tumors are referred to as
granular cell ameloblastoma. Sometimes this change,
may be so extensive that the peripheral columnar cells
may also be replaced making the diagnosis difficult
especially in a small biopsy. Ultrastructurally, it is seen
that the granules consist of pleomorphic, osmiophilic,
lysosome like organelles.
Basal cell ameloblastoma: This variant shows
predominant basaloid pattern consisting of darkly
stained cells with minimal cytoplasm and little
evidence of palisading at the periphery resembling
those seen in basal cell carcinoma.
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Angadi PV
Desmoplastic ameloblastoma: This variant was first
described in detail by Eversole et al. in 1984 and is
characterized by extensive stromal collage-
nization or desmoplasia surrounding compressed
small/irregular islands of odontogenic epithelium
making it a distinct entity. Cyst formation is common
and ameloblast like areas are present only in small foci.
Calcification in the fibrous stroma and occasional bone
formation can also be seen. Histochemical evaluation
of the collagen suggests that the dense stroma is not
scar tissue but represents active denovo synthesis of
extracellular matrix proteins. It typically presents
radiographically as a mixed radiolucency and
radiopacity mimicking a fibrosseous lesion. In contrast
to typical ameloblastoma, this variant frequents the
maxilla and the anterior region of the jaws.
Unicystic ameloblastoma: This is considered as an in-
situ or superficially invasive form of ameloblastoma
and consists of a single cyst lined by ameloblastic
epithelium. It presents clinically similar to a
dentigerous cyst and is usually associated with an
impacted tooth (usually 3rd molars). They are usually
seen in younger patients with an average age of
diagnosis being 22 years and generally involve the
mandible.
This variant histologically presents as a single cyst
lined by ameloblastomatous epithelium and is divided
into several subgroups based on pattern and extent of
ameloblastomatous proliferation in relation to cyst
wall.
Reichart et al. classification modified from Ackermann
et al.:
-1. Luminal UA: Cystic lesion lined by epithelium
which exhibits columnar differentiation and reverse
polarization of the basal cell layer. The connective
tissue adjacent to the epithelium often exhibits a
uniform, thin band like area of hyalinization.
-1.2. Luminal and intraluminal UA: Is the simple type
but exhibits one or more nodules projecting into the
lumen. No extension is seen into the surrounding
connective tissue wall. Occasionally, this form of UA
can produce an intraluminal plexiform pattern of
odontogenic epithelium that lacks typical
ameloblastomatous differentiation and is called as
unicystic plexiform ameloblastoma.
-1.2.3. Luminal, intraluminal and intramural UA: Here
there is occurrence of intramural proliferation of
ameloblastoma along with subgroup 1.2 features.
-1.3. Luminal and intramural UA: exhibits a cyst with a
luminal lining in combination with intramural nodules
of SMA tissues. The intramural ameloblastoma tissue
may be seen as an infiltration from the cyst lining or as
free islands of follicular ameloblastoma.
Peripheral ameloblastoma: They present
histologically with follicular or plexiform pattern as
well as acanthomatous pattern. In most cases, the tumor
is well separated from the overlying epithelium but
many are confluent with the overlying mucosa.
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Head and Neck: Odontogenic tumor: Ameloblastoma Angadi PV

Figure 3. Figure 3A: Photomicrograph depicting a typical follicular ameloblastoma with islands demonstrating peripheral columnar cells
exhibiting reversal of polarity and central stellate-reticulum lie cells demonstrating cytic degeneration. Figure 3B and C:
Photomicrographs depicting acanthomatous variant of ameloblastoma depicting follicles exhibiting extensive squamous metaplasia and
keratin formation. Figure 3D: Plexiform ameloblastoma with odontogenic epithelium arranged in the form of interlacing trabeculae and
evidence of stromal degeneration.
Figure 4. Figure 4A and B: Granular cell ameloblastoma: the central stellate reticulum cells show presence of eosinophilic cells with
granular cytoplasm. B: demonstrates aplexiform pattern where the peripheral cells have also been replaced by the granular cells. Figure
4C: Photomicrographs depicting basaloid areas in an ameloblastoma. Figure 4D: Desmoplastic ameloblastoma: Photomicrographs
depicting compressed epithelial islands surrounded by dense fibrous stroma with evidence of bone formation.

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Head and Neck: Odontogenic tumor: Ameloblastoma
Figure 5. Figure 5A and B: Unicystic ameloblastoma: A: Luminal type and B: Plexiform unicystic ameloblastoma. Figure 5C and D:
Photomicrographs depicting mucous cells in ameloblastoma.
Other rare variants: Clear cell variant which may
contain clear PAS positive cells are localized in the
stellate reticulum like areas.
Papilliferous keratoameloblastoma show occurrence of
areas of ameloblastoma with keratinisation, tumor
islands with papilliferrous appearance along with cystic
areas resembling odontogenic keratocysts.
Mucous cells can also be demonstrated rarely in
ameloblastoma.
Treatment
The diagnosis has to be confirmed by a biopsy, but
occasionally in cystic variants it may be made only
after excision.
Ameloblastomas, although benign are relentlessly
infiltrative. Conventional ameloblastoma infiltrates into
surrounding bone and extends beyond the apparent
radiographic boundaries seen in plain radiographs. The
rate of recurrence reported varies from 20-90%.
Treatment planning should take into consideration
tumor size, location, histopathology, and
clinical/radiographic presentation.
Treatment with curettage is clearly inadequate and may
leave small islands of tumor within the bone. Marginal
or en bloc resection is the most widely used form of
therapy with many surgeons advocating margins of
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Angadi PV
excision to include 1.5 cm of clinically normal bone.
Maxillary ameloblastoma are particularly dangerous
due to bony architecture and they grow upwards to
involve the sinonasal passages, pterygomandibular
fossa, orbit, cranium, and brain. Maxillary
ameloblastomas thus warrant radical surgery as close
proximity to vital structures makes recurrence
potentially dangerous in this area.
Reichart et al. reveal that the overall recurrence rate is
around 22% and half of them appear 5 years after the
initial surgical management. Lifelong follow up is
strongly recommended. Rare malignant transformation
has also been documented.
For the luminal and intraluminal variants of unicystic
ameloblastoma, the tumor is usually confined by the
fibrous connective tissue wall of the cyst and isusually
treated with complete enucleation. However, in the
intramural variants which show invasion into the cyst
wall is thought represent a typical ameloblastoma and
warrants a more aggressive treatment. Long term
follow up however remains mandatory.
Peripheral ameloblastomas are not aggressive clinically
and can be managed by local excision. A recurrence
rate of 8% has been reported and a further and wider
local excision can be curative.
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Genetics
Note
Ameloblastoma usually occur sporadically without any
apparent genetic predisposition. However, only few
cases have been reported associated with known
genetic syndrome i.e. Gorlin Goltz syndrome.
Cytogenetics
Note
There are no specific genetic alteration reported that
indicate an increase risk in development of
ameloblastoma.
The various genetic events reported include:
Loss of tumor suppressor genes L-MYC and PTEN;
Expression of nrob1-the earliest gene in zebrafish tooth
development;
Increased methylation of p16 and p21;
Aberrant CTNNB1 (beta-catenin gene) and APC
(adenomatosis polyposis coli gene);
Increased expression of amelogenin gene.
Mutations of PTCH1 gene, ameloblastin (ABMN) gene
and K-RAS gene have been reported.
References
SMALL IA, WALDRON CA. Ameloblastomas of the jaws. Oral
Surg Oral Med Oral Pathol. 1955 Mar;8(3):281-97
Eversole LR, Tomich CE, Cherrick HM. Histogenesis of
odontogenic tumors. Oral Surg Oral Med Oral Pathol. 1971
Oct;32(4):569-81
Mller H, Slootweg PJ. The ameloblastoma, the controversial
approach to therapy. J Maxillofac Surg. 1985 Apr;13(2):79-84
Waldron CA, el-Mofty SK. A histopathologic study of 116
ameloblastomas with special reference to the desmoplastic
variant. Oral Surg Oral Med Oral Pathol. 1987 Apr;63(4):441-
51
Kahn MA. Ameloblastoma in young persons:
clinicopathologic analysis and etiologic investigation. Oral Surg
Oral Med Oral Pathol. 1989 Jun;67(6):706-15
Gold L.. Biologic behaviour of ameloblastoma. Oral Maxillofac
Surg Clin North Am. 1991;3:21-30.
Kramer IRH, Pindborg JJ, Shear M.. Histological typing of
odontogenic tumors. Berlin: Springer-Verlag. 1992:11-14.
Snead ML, Luo W, Hsu DD, Melrose RJ, Lau EC, Stenman G.
Human ameloblastoma tumors express the amelogenin gene.
Oral Surg Oral Med Oral Pathol. 1992 Jul;74(1):64-72
Radhika S, Nijhawan R, Das A, Dey P. Ameloblastoma of the
mandible: diagnosis by fine-needle aspiration cytology. Diagn
Cytopathol. 1993;9(3):310-3
Regezi JA, Sciubba J.. Odontogenic tumors. Oral Pathology:
Clinical pathological correlations (2nd ed); Philadelphia:
Saunders Elsevier. 1993:363-71.
Pinsolle J, Michelet V, Coustal B, Siberchicot F, Michelet FX.
Treatment of ameloblastoma of the jaws. Arch Otolaryngol
Head Neck Surg. 1995 Sep;121(9):994-6
Raubenheimer EJ, van Heerden WF, Noffke CE. Infrequent
clinicopathological findings in 108 ameloblastomas. J Oral
Pathol Med. 1995 May;24(5):227-32
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(2)
Angadi PV
Reichart PA, Philipsen HP, Sonner S. Ameloblastoma:
biological profile of 3677 cases. Eur J Cancer B Oral Oncol.
1995 Mar;31B(2):86-99
Cawson RA, Binnie WH, Spieght PM, Barrett AW, Wright JM..
Ameloblastoma. Lucas's Pathology of tumors of the oral
tissues (5th ed); London: Churchill Livingstone. 1998:25-44.
Philipsen HP, Reichart PA. Unicystic ameloblastoma. A review
of 193 cases from the literature. Oral Oncol. 1998
Sep;34(5):317-25
Curran AE.. Peripheral Odontogenic tumours. In: White DK,
Editor. Odontogenic Tumors. Oral and Maxillofacial surgery
clinics of North America. 2001;16:309-322.
Kessler HP.. Intraosseous ameloblastoma. In: White DK,
Editor. Odontogenic Tumors. Oral and Maxillofacial surgery
clinics of North America. 2001;16:309-322.
Neville BW, Damm DD, Allen CM.. Odontogenic cysts and
tumors. In: Gnepp DR, Editor. Diagnostic Surgical Pathology of
the head and neck (Ist ed). Philadelphia: W. B. Saunders
company. 2001:622-633.
Ord RA, Blanchaert RH Jr, Nikitakis NG, Sauk JJ.
Ameloblastoma in children. J Oral Maxillofac Surg. 2002
Jul;60(7):762-70; discussion, 770-1
Regezi JA. Odontogenic cysts, odontogenic tumors,
fibroosseous, and giant cell lesions of the jaws. Mod Pathol.
2002 Mar;15(3):331-41
Tsamis I, Giatromanolaki A, Tamiolakis D, Georgiou L,
Manavis J, Alexiadis G, Thomaidis V, Sivridis E. Fine needle
aspiration cytology in ameloblastoma of the mandible.
Cytopathology. 2002 Dec;13(6):375-8
Kumamoto H, Takahashi N, Ooya K.. K-Ras gene status and
expression of Ras/mitogen-activated protein kinase (MAPK)
signaling molecules in ameloblastomas. J Oral Pathol Med.
2004 Jul;33(6):360-7.
Nodit L, Barnes L, Childers E, Finkelstein S, Swalsky P, Hunt
J. Allelic loss of tumor suppressor genes in ameloblastic
tumors. Mod Pathol. 2004 Sep;17(9):1062-7
Perdigo PF, Gomez RS, Pimenta FJ, De Marco L.
Ameloblastin gene (AMBN) mutations associated with
epithelial odontogenic tumors. Oral Oncol. 2004
Sep;40(8):841-6
a
Reichart PA, Philipsen HP.. Odontogenic tumours and allied
lesions. Quintessence Publishing Co UK. 2004:41-77.
Gardner DG, Heikinheimo K, Shear M, Philipsen H P, Coleman
H. Ameloblastomas. In: L Barnes, JW Eveson , P Reichart and
D Sidransky, Editors. World health organization classification
of tumors. Pathology and genetics of head and neck tumors,
IARC Press, Lyon. 2005:296-300.
Kawabata T, Takahashi K, Sugai M, Murashima-Suginami A,
Ando S, Shimizu A, Kosugi S, Sato T, Nishida M, Murakami K,
Iizuka T. Polymorphisms in PTCH1 affect the risk of
ameloblastoma. J Dent Res. 2005 Sep;84(9):812-6
Dalati T, Zhou H. Gorlin syndrome with ameloblastoma: a case
report and review of literature. Cancer Invest. 2008
Dec;26(10):975-6
Punnya AV, Rekha K. "Ameloblastoma with mucous cells":
review of literature and presentation of 2 cases. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 2008 Dec;106(6):e20-6
Moreira PR, Guimares MM, Gomes CC, Diniz MG, Brito JA,
de Castro WH, Gomez RS. Methylation frequencies of cell-
cycle associated genes in epithelial odontogenic tumours. Arch
Oral Biol. 2009 Oct;54(10):893-7
228
Head and Neck: Odontogenic tumor: Ameloblastoma Angadi PV

Powers J, Zhao Y, Lin S, McCabe ER. The expression of This article should be referenced as such:
nr0b1, the earliest gene in zebrafish tooth development, is a
marker for human tooth and ameloblastoma formation. Dev Angadi PV. Head and Neck: Odontogenic tumor:
Genes Evol. 2009 Aug;219(8):419-25 Ameloblastoma. Atlas Genet Cytogenet Oncol Haematol.
2011; 15(2):223-229.
Siriwardena BS, Kudo Y, Ogawa I, Tilakaratne WM, Takata T.
Aberrant beta-catenin expression and adenomatous polyposis
coli gene mutation in ameloblastoma and odontogenic
carcinoma. Oral Oncol. 2009 Feb;45(2):103-8

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