Ameloblastic carcinoma: case report and literature review.

Abstract

Ameloblastic carcinoma is a rare malignant lesion with characteristic histologic features and behaviour that dictates a more aggressive surgical approach than that of a simple ameloblastoma. However, reliable evidence of its biologic activity is currently unavailable due to the scarcity of well-documented cases. It occurs primarily in the mandible in a wide range of age groups; no sex or race predilection has been noted. It may present as a cystic lesion with benign clinical features or as a large tissue mass with ulceration, significant bone resorption and tooth mobility. Because the lesion is usually found unexpectedly after an incisional biopsy or the removal of a cyst, a guide to differential diagnosis is not usually useful. The identifying features of ameloblastic carcinoma must be known and recognized by dental practitioners. Our understanding of the histologic features of ameloblastic carcinoma is somewhat vague. The tumour cells resemble the cells seen in ameloblastoma, but they show cytologic atypia. Moreover, they lack the characteristic arrangement seen in ameloblastoma. The clinical course of ameloblastic carcinoma is typically aggressive, with extensive local destruction. Direct extension of the tumour, lymph node involvement and metastasis to various sites (frequently the lung) have been reported. Wide local excision is the treatment of choice. Regional lymph node dissection should be considered and performed selectively. Radiotherapy and chemotherapy seem to be of limited value for the treatment of ameloblastic carcinomas. At the moment, there are too few reported cases to make a definite recommendation regarding treatment. Close periodic reassessment of the patient is mandatory.

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C L I N I C A L
P R A C T I C E
T
genic cyst; dental lamina or enamel organ; stratified
squamous epithelium of the oral cavity; or displaced
epithelial remnants. The lesion comprises about 1% of all
cysts and tumours occurring in the jaws, making it the
most common, clinically significant odontogenic tumour.
This neoplasm is generally recognized as a locally invasive
tumour that demonstrates considerable tendency to recur,
but rarely behaves aggressively or shows metastatic
dissemination.1
The question of malignancy in ameloblastoma has been
the subject of considerable discussion and controversy for
many years. There can be little argument that an ameloblas-
toma that metastasizes is malignant, even if the tumour
he ameloblastoma is an odontogenic tumour of the
jaws, arising from dental embryonic remnants
possibly from the epithelial lining of an odonto-
shows benign histologic features. In other instances,
ameloblastomas have been considered to be malignant on
the basis of an aggressive clinical course in the absence of
metastasis. These lesions often show unusual or atypical
histologic features.2Carcinomas derived from ameloblas-
tomas have been designated by a variety of terms, including
malignant ameloblastoma,3–5ameloblastic carcinoma,6
metastatic ameloblastoma7and primary intra-alveolar
epidermoid carcinoma.8
In 1971, the World Health Organization (WHO)9
published its classification of odontogenic carcinomas
recognizing the following subtypes:
• malignant ameloblastoma
• primary intraosseous carcinoma
• other carcinomas arising from odontogenic epithelium,
including those arising from odontogenic cysts.
Ameloblastic Carcinoma:
Case Report and Literature Review
• Sylvie Louise Avon, DMD, MSc •
• John McComb, DDS, MSc, FRCD(C) •
• Cameron Clokie, DDS, PhD, FRCD(C) •
A b s t r a c t
Ameloblastic carcinoma is a rare malignant lesion with characteristic histologic features and behaviour that dictates
a more aggressive surgical approach than that of a simple ameloblastoma. However, reliable evidence of its
biologic activity is currently unavailable due to the scarcity of well-documented cases. It occurs primarily in the
mandible in a wide range of age groups; no sex or race predilection has been noted. It may present as a cystic lesion
with benign clinical features or as a large tissue mass with ulceration, significant bone resorption and tooth
mobility. Because the lesion is usually found unexpectedly after an incisional biopsy or the removal of a cyst, a
guide to differential diagnosis is not usually useful. The identifying features of ameloblastic carcinoma must be
known and recognized by dental practitioners. Our understanding of the histologic features of ameloblastic
carcinoma is somewhat vague. The tumour cells resemble the cells seen in ameloblastoma, but they show cytologic
atypia. Moreover, they lack the characteristic arrangement seen in ameloblastoma. The clinical course of ameloblas-
tic carcinoma is typically aggressive, with extensive local destruction. Direct extension of the tumour, lymph node
involvement and metastasis to various sites (frequently the lung) have been reported. Wide local excision is the
treatment of choice. Regional lymph node dissection should be considered and performed selectively. Radiotherapy
and chemotherapy seem to be of limited value for the treatment of ameloblastic carcinomas. At the moment, there
are too few reported cases to make a definite recommendation regarding treatment. Close periodic reassessment of
the patient is mandatory.
MeSH Key Words: ameloblastoma/pathology; carcinoma/pathology; case report
© J Can Dent Assoc 2003; 69(9):573–6
This article has been peer reviewed.

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Avon, McComb, Clokie
In this classification, “malignant ameloblastoma” refers
to a neoplasm in which typical histologic features of
ameloblastoma are seen in the primary tumour located in
the jaw as well as in any associated metastatic deposits.
“Primary intraosseous carcinoma” (PIOC) refers to a
primary carcinoma of the jaw not having features of
ameloblastoma and not arising from an odontogenic cyst.
The “other carcinomas” category refers to carcinomas aris-
ing from odontogenic epithelium, including those arising
from odontogenic cysts.9
In 1982, Elzay10argued that the WHO classification
does not make provision for separating tumours that are
histologically identical to classic ameloblastoma and
metastasize from ameloblastoma-like lesions that are histo-
logically malignant before metastasizing. He proposed a
modification of the classification in which all primary
intraosseous carcinomas that do not involve the salivary
glands would be classified as PIOCs, which would then be
subclassified as follows:
• Type 1: arising from an odontogenic cyst
• Type 2: arising from an ameloblastoma
a. well differentiated (malignant ameloblastoma)
b. poorly differentiated (ameloblastic carcinoma)
• Type 3: arising de novo
a. nonkeratinizing
b. keratinizing.
In 1984, Slootweg and Müller7further emphasized that
ameloblastomas may exhibit malignant features other than
metastasis and suggested a modified classification system
for malignant tumours with features of ameloblastoma,
based on characteristics of malignancy:
• Type 1: PIOC ex odontogenic cyst
• Type 2:
a. malignant ameloblastoma
b. ameloblastic carcinoma, arising de novo, ex
ameloblastoma or ex odontogenic cyst
• Type 3: PIOC arising de novo
a. nonkeratinizing
b. keratinizing.
Elzay,10Slootweg and Müller7use the term ameloblastic
carcinoma to convey the presence of cytologic features of
malignancy. The degree of differentiation in epithelial
neoplasms is usually considered to be significant in predict-
ing biologic behaviour of metastasis. The main difference
between Elzay’s and Slootweg and Müller’s schemes relates
to the minor point of histogenesis.2According to these
authors, the term ameloblastic carcinoma should be used to
designate lesions that exhibit histologic features of both
ameloblastoma and carcinoma.7,10,11The tumour may
metastasize and histologic features of malignancy may be
found in either the primary tumour, the metastases or
both.7,11,12The term malignant ameloblastoma should be
confined to those ameloblastomas that metastasize despite
an apparently typical benign histology in both the primary
and the metastatic lesions.3–5,7,11,13The incidence of
ameloblastic carcinoma is greater than that of malignant
ameloblastoma by a 2:1 ratio.2
Case Report
A 68-year-old man presented to the Oral and
Maxillofacial Surgery Clinic at Toronto General Hospital
complaining of a persistent hole in his left posterior maxilla
following the extraction of the left maxillary third molar.
Clinical examination revealed a persistent oro-antral
communication that appeared to be trapping food and,
as a result, was secondarily infected. Plain radiographic
imaging and axial computed tomography (CT) scans were
carried out, revealing an oval corticated lucency occupying
a large portion of the left maxillary sinus (Fig. 1). The radi-
ographic report suggested that the sinus was filled with soft
tissue, probably representing inflamed sinus membrane
or mucus. There was also indication of hypertrophy of
the nasal mucosa of the left nasal fossa and deviation to the
right side of the maxilla. The alveolar crest in the area of the
left maxillary tuberosity was destroyed, and there was some
evidence of lateral expansion. Air in the soft tissue sinus was
also noted.
Based on these findings, the diagnosis was a cystic lesion
involving the maxillary sinus. The area was surgically
excised under local anesthesia. The cavity in the sinus
appeared to be well demarcated and was thoroughly curet-
ted at the time of surgery. On gross examination, the tissue
within the sinus appeared to be a mucoid material within a
central cavity.
Microscopic examination showed an epithelial tumour
consisting of a delicately trabecular and plexiform arrange-
ment intermixed with solid epithelial sheets and islands.
The stroma contained very pale-staining fibrous connective
tissue. In areas, the epithelium had a columnar basal cell
configuration bounding a stellate reticulum-like interior
that is characteristic of ameloblastoma (Fig. 2). Closer
examination of the solid areas revealed cellular variation
and variability of nuclear staining from dark to lighter and
vesicular, some nuclei with prominent nucleoli. There was
some pleomorphism. Numerous apoptotic cells were seen.
Although not plentiful, mitoses were found with relative
ease at high power (Fig. 3). The specimen also incorporated
fragments of vital bone and was in contact with oral surface
epithelium. Some of the architecture was that of an
ameloblastoma, but the cytology of other areas warranted
the designation of ameloblastic carcinoma.
The area was re-examined using both axial and coronal
CT scans. This approach revealed a well-circumscribed,
predominantly cystic mass in the floor of the left maxillary

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sinus. A small focus of air was apparent in the centre of the
lesion. The patient was scheduled for more definitive
surgery that included a left posterior maxillectomy and
reconstruction with a vascularized free forearm flap. The
patient was followed every 3 months. After 2 years follow-
up, there was no clinical or radiologic sign of recurrence.
Discussion
In 1983, Shafer6introduced the term ameloblastic
carcinoma to describe ameloblastomas in which there had
been histologic malignant transformation. Ameloblastic
carcinoma occurs in a wide range of age groups, but the
mean age of 30.1 years is in agreement with that reported
for ameloblastomas.11 There is no apparent sex predilec-
tion.11The most commonly involved area is the posterior
portion of the mandible.11Involvement of the maxilla by
ameloblastic carcinoma seems to be less frequent than that
of the mandible.7,11,14–17The most common sign described
has been swelling, although others include associated pain,
rapid growth, trismus and dysphonia.11
In our case study, the radiographic appearance of the
lesion was consistent with that of an ameloblastoma except
for the presence of some focal radiopacities, apparently
reflecting dystrophic calcifications. These histologic and
radiologic features are not generally seen in conventional
ameloblastomas. Clinically, these carcinomas are more
aggressive than most typical ameloblastomas. Perforation of
the cortical plate, extension into surrounding soft tissue,
numerous recurrent lesions and metastasis, usually to
cervical lymph nodes, can be associated with ameloblastic
carcinomas.11
The characterization of carcinoma arising centrally
within the mandible and the maxilla is an uncommon but
complex problem. The first step in the staging process must
be the exclusion of metastasis or invasion of bone by
tumour from adjacent soft tissue or paranasal sinus. The
neoplasm may be derived from a number of different
sources, such as those of odontogenic origin, including
ameloblastoma, odontogenic cysts or epithelial odonto-
genic rests, as well as entrapped salivary gland epithelium or
epithelium entrapped along embryonic fusion sites.11
Carcinomas in the jaws metastasizing from primary loca-
tions such as the lung, the breast and the gastrointestinal
tract may mimic ameloblastic carcinoma and must always
be ruled out clinically before that diagnosis is made.11,18
Primary intra-alveolar epidermoid carcinoma must be
considered in the differential diagnosis of ameloblastic
carcinoma. This tumour, developing within bone, probably
originates from odontogenic epithelial remnants.11
According to Shear,8these lesions occur over a wide age
range, but most occur in the sixth to seventh decade of life.
Ninety percent occur in the mandible, and they are seen
twice as often in male patients as in female patients.
Although the primary intra-alveolar carcinoma and the
ameloblastic carcinoma exhibit some clinical differences,
their histologic features are similar enough to suggest a
histogenetic relation. It is possible, then, that the primary
intra-alveolar carcinoma may represent simply a less-
differentiated, usually nonkeratinizing form of amelo-
blastic carcinoma, both lesions being derived from odonto-
genic remnants.11
Two types of typical ameloblastoma must also be consid-
ered in the differential diagnosis of ameloblastic carcinoma.
The acanthomatous ameloblastoma exhibits varying
degrees of squamous metaplasia and even keratinization of
the stellate reticulum portion of the tumour islands;
however, peripheral palisading is maintained and no cyto-
logic features of malignancy are found.11,18The so-called
kerato-ameloblastoma is a rare variant of ameloblastoma
that contains prominent keratinizing cysts that may cause
some alarm and distract the pathologist from the otherwise
ameloblastomatous feature.11
Figure 1: Computed tomography revealed
the presence of a large, oval, partly
corticated soft tissue mass occupying a large
portion of the left maxillary sinus.
Figure 2: Microscopic examination shows
the epithelial tumour consisting of strands
of epithelial cells in a fibrous connective
tissue stroma. The epithelium has a peripheral
columnar basal cell configuration bounding a
stellate reticulum-like epithelium that is
characteristic of ameloblastoma (hematoxylin
and eosin stain; magnification ×40).
Figure 3: Cellular pleomorphism, apoptotic
cells and mitotic figures were found with
relative ease at high power (hematoxylin
and eosin stain; magnification ×100).

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An additional consideration in the differential diagnosis
is the squamous cell carcinoma arising in the lining of an
odontogenic cyst.18,19Histologically, this lesion tends to
more closely resemble oral squamous cell carcinoma than
what we have described for ameloblastic carcinoma.
However, it is of interest that ameloblastic carcinoma can
apparently arise from a cystic lining.11
The squamous odontogenic tumour may also be
mistaken for ameloblastic carcinoma.20It is composed of
islands of squamous epithelium that lack stellate reticulum-
like zones and peripheral palisading. In addition, microcys-
tic changes and dystrophic calcifications are occasionally
seen in this lesion. However, the epithelium of the squa-
mous odontogenic tumour lacks any cytologic evidence of
malignant disease.11
Thus, the term ameloblastic carcinoma can be applied to
our case, which showed focal histologic evidence of malig-
nant disease including cytologic atypia and mitoses with
indisputable features of classic ameloblastoma.
Whether ameloblastoma may transform biologically and
histologically from a classic ameloblastoma to a malignant
lesion is controversial. Although various authors have
shown that metastasizing ameloblastomas are histologically
indistinguishable from classic ameloblastomas, others have
identified unequivocal malignant features in the recurrent
or metastatic tumour, usually many years after repeated
surgical excisions.4,17It has been suggested that the high
rate of recurrence is due to its mode of growth and surgical
mismanagement rather that any inherent malignant prop-
erties and metastases are “exceedingly rare.”11
The lesion that we have described as ameloblastic carci-
noma falls into a completely different category. This lesion
exhibits histologic evidence of malignancy, regardless of
whether it has metastasized. We have had no report of
metastasis in the case presented in this publication,
although we must bear in mind the possibility that this may
yet occur. Unfortunately, it is not possible to differentiate
clearly between ameloblastic carcinoma and malignant
ameloblastomas reported in the literature on a retrospective
basis. Nevertheless, it is important that, in the future, these
lesions be accurately identified, differentiated from malig-
nant ameloblastoma and followed so that their natural
history and prognosis can be further defined.11
Conclusion
It is reasonable to assume that this case illustrates the
malignant portion in the spectrum of ameloblastomas. It is
possible that ameloblastoma shows a variety of histologic
and biologic behaviours ranging from benignity to frank
malignancy. Cases of ameloblastoma should thus be studied
carefully, correlating their histologic pattern with biologic
behaviour to detect subtle changes in histology that may
predict aggressive behaviour.
What therapeutic assessments should be considered in
cases like these? When the diagnosis of an ameloblastic
carcinoma is made, an assessment of nodal metastasis and
evidence of distant metastasis is required. A staged work-up
consisting of a neck examination, a CT scan of the area and
a chest radiograph becomes necessary. The treatment of
ameloblastic carcinoma is controversial, but the recom-
mended surgical treatment usually requires jaw resection
with 2- to 3-cm bony margins and consideration of
contiguous neck dissection, both prophylactic and thera-
peutic.21Documented case reports with meaningful
follow-up are rare. Meticulous follow-up is essential
because recurrence and metastasis in the lung and regional
lymph nodes have been reported.7,11,17,22Presurgical radia-
tion therapy has been suggested to decrease tumour size,16
but chemotherapy is as yet unproven.22Reconstruction of
the post-resection defect may proceed as one would
normally expect following any head or neck carcinoma
resection. Sufficient time should be allotted before
reconstruction because of potential tumour recurrence. C
Dr. Avon is a specialist in oral pathology and oral medicine, faculty of
dentistry, Laval University, Ste-Foy, Quebec.
Dr. McComb is head, oral pathology and oral medicine, faculty of
dentistry, University of Toronto, Toronto, Ontario.
Dr. Clokie is head, oral and maxillofacial surgery, faculty of dentistry,
University of Toronto, Toronto, Ontario.
Correspondence to: Dr. Sylvie Louise Avon, Faculty of Dentistry,
Laval University, Cité universitaire, Ste-Foy, QC G1K 7P4.
E-mail: sylvie-louise.avon@fmd.ulaval.ca.
The authors have no declared financial interests.
References
1. Neville BW, Damm DD, Allen CM, Bouquot JE, editors. Oral and
maxillofacial pathology. 2nd ed. Philadelphia: WB Saunders Co.; 2002.
p. 611–9.
2. Regezi JA, Kerr DA, Courtney RM. Odontogenic tumors: analysis of
706 cases. J Oral Surg 1978; 36(10):771–8.
3. Carr RF, Halperin V. Malignant ameloblastomas from 1953 to 1966.
Review of the literature and report of a case. Oral Surg Oral Med Oral
Pathol 1968; 26(4):514–22.
4. Sugimura M, Yamauchi T, Yashikawa K, Takeda N, Sakita M, Miyazaki
T. Malignant ameloblastoma with metastasis to the lumbar vertebra:
report of case. J Oral Surg 1969; 27(5):350–7.
5. Herceg SJ, Harding RL. Malignant ameloblastoma with pulmonary
metastases. Report of a case and review of the literature. Plast Reconstr
Surg 1972; 49(4):456–60.
6. Shafer WG, Hine MK, Levy BM, editors. A textbook of oral pathol-
ogy. 4th ed. Philadelphia: WB Saunders Co.; 1983. p. 280–1.
7. Slootweg PJ, Müller H. Malignant ameloblastoma or ameloblastic
carcinoma. Oral Surg Oral Med Oral Pathol 1984; 57(2):168–76.
8. Shear M. Primary intra-alveolar epidermoid carcinoma of the jaw.
J Pathol 1969; 97(4):645–51.
9. Pindborg JJ, Kramer IR, Torloni H, editors. Histological typing of
odontogenic tumours, jaw cysts, and allied lesions. International
Histological Classification of Tumours. World Health Organization
(book 5). Geneva; 1971. p. 24–28.
10. Elzay RP. Primary intraosseous carcinoma of the jaws. Review and
update of odontogenic carcinomas. Oral Surg Oral Med Oral Pathol 1982;
54(3):299–303.

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October 2003, Vol. 69, No. 9
576a
Journal of the Canadian Dental Association
Ameloblastic Carcinoma: Case Report and Literature Review
11. Corio LR, Goldblatt LI, Edwards PA, Hartman KS. Ameloblastic
carcinoma: a clinicopathologic study and assessment of eight cases.
Oral Surg Oral Med Oral Pathol 1987; 64(5):570–6.
12. Lau SK, Tideman H, Wu PC. Ameloblastic carcinoma of the jaws.
A report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1998; 85(1):78–81.
13. Nagai N, Takeshita N, Nagatsuka H, Inoue M, Nishijima K, Nojima
T, and others. Ameloblastic carcinoma: case report and review. J Oral
Pathol Med 1991; 20(9):460–3.
14. Lee L, Maxymiw WG, Wood RE. Ameloblastic carcinoma of the
maxilla metastatic to the mandible. Case report. J Craniomaxillofac Surg
1990; 18(6):247–50.
15. McClatchey KD, Sullivan MJ, Paugh DR. Peripheral ameloblastic
carcinoma: a case report of a rare neoplasm. J Otolaryngol 1989;
18(3):109–11.
16. Andersen E, Bang G. Ameloblastic carcinoma of the maxilla. A case
report. J Maxillofac Surg 1986; 14(6):338–40.
17. Daramola JO, Abioye AA, Ajagbe HA, Aghadiuno PU. Maxillary
malignant ameloblastoma with intraorbital extension: report of case.
J Oral Surg 1980; 38(3):203–6.
18. Gandy SR, Keller EE, Unni KK. Ameloblastic carcinoma: report of
two cases. J Oral Maxillofac Surg 1992; 50(10):1097–102.
19. Gardner AF. The odontogenic cyst as a potential carcinoma: a
clinicopathology appraisal. J Am Dent Assoc 1969; 78(4):746–55.
20. Pullon PA, Shafer WG, Elzay RP, Kerr DA, Corio RL. Squamous
odontogenic tumor. Report of six cases of a previously undescribed lesion.
Oral Surg Oral Med Oral Pathol 1975; 40(5):616–30.
21. Marx RE, Stern D, editors. Oral and maxillofacial pathology.
A rationale for diagnosis and treatment. Illinois: Quintessence Publishing
Co, Inc.; 2003. p. 657.
22. Bruce RA, Jackson IT. Ameloblastic carcinoma. Report of an aggres-
sive case and review of the literature. J Craniomaxillofac Surg 1991;
19(6):267–71.