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Ameloblastic carcinoma of the jaws: Review of the literature

Article · January 2017

DOI: 10.4103/jdas.jdas_4_17

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 Volume 6 | Issue 2 | July-December 2017
Print ISSN 2277- 4696
E ISSN 2277- 6672
Journal of Dental and Allied Sciences · Volume 6 · Issue 2 · July-December 2017 · Pages 55-??

JDAS

Journal of
Dental &
Allied Sciences
Official Publication of Sinhgad Dental College & Hospital, Pune

www.jdas.in
 Review Article

Ameloblastic Carcinoma of the Jaws: Review of the Literature

Ramat Oyebunmi Braimah, Chibuzo Uguru1, Kizito Chioma Ndukwe2
Department of Dental and Maxillofacial Surgery, Usmanu Danfodiyo University Teaching Hospital, Sokoto, 1Department of Oral and Maxillofacial Surgery, University of
Nigeria, Enugu Campus, Enugu, 2Department of Oral and Maxillofacial Surgery and Oral Pathology, Obafemi Awolowo University Teaching Hospitals Complex,
Ile‑Ife, Osun State, Nigeria

Abstract
Ameloblastic carcinoma is a rare odontogenic malignancy that combines the histological features of ameloblastoma with cytological atypia,
even in the absence of metastases. The major prognostic factor is the clinical course of the disease which includes its aggressiveness, local
destruction, and distant metastatic spread preferentially through hematologic route if neglected. Histologically, ameloblastic carcinoma retains
the features of ameloblastic differentiation and exhibits cytological features of malignancy in a primary or recurrent tumor. Because it is a very
rare lesion, it poses a great difficulty in diagnosis. En bloc removal with 1–2 cm of normal bone margin has been regarded as the safest surgical
modality to ensure disease‑free survival. Literature search was carried out using the Boolean operator “And” between ameloblastoma and
carcinoma on PubMed. Retrieved articles were extensively reviewed for epidemiology, etiology, diagnosis, treatment options, and prognosis
of ameloblastic carcinoma.

Keywords: Ameloblastic carcinoma, cytological atypia, hematologic route, metastasis, odontogenic malignancy

Introduction carcinoma[3] with histologic features of malignancy found in

Ameloblastic carcinoma is a rare odontogenic tumor
accounting for 1.5%–2.0% of all odontogenic tumors.[1] Only
seventy cases have been reported in English literature from
1984 to 2011.[2] In 1982, the term “ameloblastic carcinoma”
was introduced by Elzay[3] to depict a malignant epithelial
odontogenic tumor that histologically retains the features of
ameloblastic differentiation and exhibits cytological features
of malignancy in a primary or recurrent tumor. In the last
WHO classification update published in 2005, it is defined “as
a rare odontogenic malignancy that combines the histological
features of ameloblastoma with cytological atypia, even in
the absence of metastases.”[2] It has characteristic histologic
features and clinical behavior that requires a more aggressive
surgery than that of ameloblastoma. Malignant ameloblastoma
differs from ameloblastoma due to the presence of metastases,
they both have the same benign histology.[4] Malignant
ameloblastoma and ameloblastic carcinoma have been used
interchangeably before in the past. However, it is now agreed
that malignant ameloblastoma has the ability to metastasizes
despite its benign histology in both the primary and the
metastatic lesion.[5] On the other hand, ameloblastic carcinoma
demonstrates histologic features of both ameloblastoma and
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both the primary and the metastases.[6]
Ordinarily, the tumor cells in ameloblastic carcinoma resemble
the cells seen in ameloblastoma, however they show cytologic
atypia. The tumor usually has direct extension, lymph node
involvement, and metastasis to distant sites especially
the lungs. Because it is a very rare lesion, it poses a great
difficulty in diagnosis. Literature search was carried out using
the Boolean operator “And” between ameloblastoma and
carcinoma on PubMed. Retrieved articles were extensively
reviewed for epidemiology, etiology, diagnosis, treatment
options, and prognosis of ameloblastic carcinoma.
Epidemiology
Ameloblastic carcinoma shows no age group predilection
appears more frequently in men (two‑third of cases) and
Address for correspondence: Dr. Ramat Oyebunmi Braimah,
Department of Dental and Maxillofacial Surgery,
Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria.
E‑mail: robdeji@yahoo.com
This is an open access article distributed under the terms of the Creative Commons
Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix,
tweak, and build upon the work non‑commercially, as long as the author is credited
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For reprints contact: reprints@medknow.com

DOI: How to cite this article: Braimah RO, Uguru C, Ndukwe KC. Ameloblastic
10.4103/jdas.jdas_4_17 carcinoma of the jaws: Review of the literature. J Dent Allied Sci
2017;6:70-3.

70 © 2017 Journal of Dental and Allied Sciences | Published by Wolters Kluwer - Medknow
 Braimah, et al.: Ameloblastic carcinoma of the jaws
involves more often the mandible (two‑third of cases).
According to Dhir et  al.,[7] age range of the patients varies
widely with a range of 51–84  years and a mean age of
53.5 years. No sex or race predilection has been noted;[8,9]
however, a male to female ratio ranging from 1.2:1 to
2.7:1[7,10,11] have been documented. Ramesh et al.[12] showed a
contrary sex ratio of female:male to be 3:2 showing a female
preponderance. It occurs primarily in the mandible in about
80% of cases reported.[7] Racial predilection of blacks over
whites have also been reported.[13]
Etiology
The etiology of ameloblastic carcinoma is largely unknown
and still controversial.[11] Most cases arise spontaneously
without a previous history of cancer (de novo) with few
cases arising following malignant transformation of
ameloblastoma.[14] Ndukwe et  al.,[10] in a multicenter study
of ameloblastic carcinoma in Nigerians reported that most
of the cases (85%) arise de novo with only 15% presenting
as carcinoma ex‑ameloblastoma. Researchers speculate that
genetic and immunologic abnormalities, environmental
factors (e.g., exposure to ultraviolet rays, certain chemicals,
ionizing radiation), diet, stress, and/or other factors may play
contributing roles in causing specific types of cancer.[15] In
individuals with cancer, malignancies may develop due to
abnormal changes in the structure and orientation of oncogenes
or tumor suppressor genes.[15] Oncogenes control cell growth
while tumor suppressor genes control cell division and ensure
that cells die at the proper time (apoptosis).[15] The specific
cause of changes to these genes is, however, unknown.
Conversely, current research suggests that abnormalities of
deoxyribonucleic acid, which is the carrier of the body’s
genetic code, are the underlying basis of cellular malignant
transformation.[15] These abnormal genetic changes may occur
spontaneously for unknown reasons or, more rarely, may be
inherited.[15] Hypermethylation of p16 gene have been reported
to be involved in the malignant transformation of initial benign
ameloblastoma to an ameloblastic carcinoma.[16] Ameloblastic
carcinoma may develop from the epithelial tissue that remains
after the development of the teeth and associated structures.[2]
In some cases, it results from malignant transformation of
an existing ameloblastoma or a benign odontogenic cyst.[14]
Benlyazid et al.[2] have reaffirmed this position of ameloblastic
carcinoma as arising de novo, or from odontogenic cyst, or
from ameloblastoma. The majority have been said to originate
de novo, and the remaining are malignant transformation of
an odontogenic cyst or ameloblastoma.[17]
Clinical Features
Unlike ameloblastoma, ameloblastic carcinomas are more
aggressive with perforation of the cortical plate, extension
into surrounding soft tissue,[18] lower lip paresthesia,[17] and
persistent pain.[18] Furthermore, numerous recurrent lesions
and metastasis, usually to cervical lymph nodes, bone, liver,
and brain have been reported.[5,19] In the series of ameloblastic
Journal of Dental and Allied Sciences  ¦  Volume 6  ¦  Issue 2  ¦  July-December 2017
carcinoma reported by Kruse et  al., [11] 34.6% revealed
metastasis while 23.1% demonstrated local recurrence. Out
of the 34.6% of metastasis, 26.9% was metastasis to the
lungs, while only one case involved neck lymph nodes.[11]
Dorner et al.[20] have also reported metastasis of ameloblastic
carcinoma to the lungs. This high percentage of pulmonary
metastasis emphasizes the importance of its detection using
either computed tomography or positron emission tomography
scans, as well as the need for long‑term follow‑up.[21]
Radiographic Features
Ameloblastic carcinoma and ameloblastoma can have a
comparable radiographical features; however, definite imaging
features may aid the diagnostic feature.[22] Both lesions can be
unilocular or multilocular radiolucencies with distinct borders
in ameloblastomas but ill‑defined borders in ameloblastic
carcinomas. The borders may show slight marginal sclerosis
without periosteal new bone formation.[22] There is loss of
lamina dura and resorption of tooth apex.[22] In ameloblastic
carcinoma, there is often the presence of focal radiopacity,
apparently reflecting dystrophic calcification.[2,23,24]
Diagnostic Criteria
The diagnostic criteria of an ameloblastic carcinoma that
distinguishes it from ameloblastoma are based largely on
cytologic atypia and increased mitotic figures.[25] When
ameloblastic carcinoma arise de novo, the microscopic
distinction from ameloblastoma is not very obvious and may
be subjective.[17] The presence of numerous mitotic figures are
unusual in ameloblastoma, cases where they are adequately
numerous most likely will justify the diagnosis of ameloblastic
carcinoma.[17] Existing literature suggests that the diagnosis
of ameloblastic carcinoma is based on several arbitrary
features, however four have been identified namely: (1) higher
proliferative mitotic index emphasized by higher mitotic
activity,[26] higher proliferating cell nuclear antigen expression
and higher Ki67; [27] (2) nuclear atypia such as nuclear
pleomorphism and basilar hyperplasia;[17] (3) hyperchromatic
nuclei of basaloid cells;[17] and (4) other features of malignancy
such as perineural or perivascular invasion.[17]
The main differential diagnosis of ameloblastic carcinoma
is the basaloid variant of squamous cell carcinoma.[28] The
distinguishing features of ameloblastic carcinoma from
squamous cell carcinoma include, the jigsaw puzzle‑type
nesting of the tumor cells, the presence of stellate reticulum,
and the distinctive cystic degeneration of the nests.[28] Another
possible differential diagnosis is craniopharyngioma because of
its similarities to odontogenic neoplasia and partially because
of its location in the cranial base.[6]
Treatment
Surgery is the mainstay of treatment,[12,29] including prophylactic
and therapeutic excision of involved lymph nodes.[30] En bloc
removal with 1–2 cm of normal bone margin has been regarded
71
 Braimah, et al.: Ameloblastic carcinoma of the jaws

as the safest surgical modality to ensure disease‑free survival.[22]

This method has resulted in local recurrence rates of <15%.[20]
Some other authors have advocated 2‑ or 3‑cm bony margins
by the means of an en bloc removal. [8,19] Ameloblastic
carcinomas have been reported to recur locally 0.5–11 years
after definitive therapy.[31] Some authors advocated the use
of adjuvant radiotherapy,[29] however others have questioned
its effectiveness.[11,32] Philip et al.[33] have suggested adjuvant
radiotherapy in patients with positive resection margins,
multiple positive lymph nodes, extracapsular spread,
perineural invasion, and those contraindicated for salvage
surgery. Similarly, Roy Chowdhury et  al.[17] have reported
that radiotherapy and chemotherapy seem to be of narrow
value; however, these methods need to be considered when
there is a locally advanced or metastatic disease not amenable
to surgical resection. Chemotherapy as primary treatment
for nonmetastatic disease has been poor.[34] However, when
there is metastatic disease, Ramadas et al.[35] found the use of
cisplatin, adriamycin, and cyclophosphamide to be valuable.
Methotrexate and leucovorin have been also used.[19]

Prognosis
The major prognostic factor is the clinical course of the disease
which include its aggressiveness, local destruction, and distant
metastatic spread preferentially through hematologic route if
neglected.[17] In addition, this relatively high risk of distant
metastasis differs with that of squamous cell carcinomas that
spread rather by the lymphatic way.[17] Distant metastasis is
usually fatal and may appear as early as 4 months or as late
as 12 years postoperatively.[31] However, once metastases
occurred, the median survival have been reported to be
2 years.[28] It is also important to note that distant metastasis
can occur in the absence of a local or regional recurrence.[13]
The location of ameloblastic carcinoma also contributes to
its prognosis as maxillary ameloblastic carcinoma have an
unfavorable prognosis as compared to that located in the
mandible.[12] In the Nigerian experience, recurrence ranged
from 6 to 96 months after the initial surgery. Six patients died
overall with three deaths within 3 years after the first surgery.[10]
One patient died about 8 years after the initial surgery.[10]
Summary of differences between ameloblastic carcinoma and
malignant ameloblastoma is given in Figure 1.
Conclusion
Ameloblastic carcinoma is an uncommon unit of odontogenic
tumors that exhibits malignant histologic features in the
primary or distant metastasis. This is in contrast to malignant
ameloblastoma where both primary and distant metastasis
exhibit benign histologic features. It is imperative to consider it
as a differential diagnosis in patients presenting with toothache
or mobile teeth in association with persistent jaw swelling,
pain, and rapid growth. Prognosis is good if early diagnosis is
made with prompt surgical intervention, however, in neglected
cases where there is distant metastasis, prognosis is guarded.
Figure 1: Differences between ameloblastic carcinoma and malignant
ameloblastoma
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Fonseca FP, de Almeida OP, Vargas PA, Gonçalves FJ, Corrêa Pontes FS,
Rebelo Pontes  HA. Ameloblastic carcinoma  (secondary type) with
extensive squamous differentiation areas and dedifferentiated regions.
Natl J Maxillofac Surg 2012;3:70‑4.
2. Benlyazid  A, Lacroix‑Triki  M, Aziza  R, Gomez‑Brouchet  A,
Guichard  M, Sarini  J. Ameloblastic carcinoma of the maxilla: Case
report and review of the literature. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2007;104:e17‑24.
3. Elzay RP. Primary intraosseous carcinoma of the jaws. Review and
update of odontogenic carcinomas. Oral Surg Oral Med Oral Pathol Oral
Radiol 1982;54:299‑303.
4. Ciment  LM, Ciment  AJ. Malignant ameloblastoma metastatic to
the lungs 29 years after primary resection: A case report. Chest
2002;121:1359‑61.
5. Corio  RL, Goldblatt  LI, Edwards  PA, Hartman  KS. Ameloblastic
carcinoma: A clinicopathologic study and assessment of eight cases.
Oral Surg Oral Med Oral Pathol Oral Radiol 1987;64:570‑6.
6. Ozlugedik S, Ozcan M, Basturk O, Deren O, Kaptanoglu E, Adanali G,
et al. Ameloblastic carcinoma arising from anterior skull base. Skull
Base 2005;15:269‑72.
7. Dhir K, Sciubba J, Tufano RP. Ameloblastic carcinoma of the maxilla.
Oral Oncol 2003;39:736‑41.
8. Avon SL, McComb J, Clokie C. Ameloblastic carcinoma: Case report
and literature review. J Can Dent Assoc 2003;69:573‑6.
9. Bedi RS, Chugh A, Pasricha N. Ameloblastic carcinoma of maxilla. Natl
J Maxillofac Surg 2012;3:70‑4.
10. Ndukwe  KC, Adebiyi  EK, Ugboko  VI, Adeyemo  WL, Ajayi  FO,
Ladeinde AL, et al. Ameloblastic carcinoma: A multicenter Nigerian
study. J Oral Maxillofac Surg 2010;68:2111‑4.

72 Journal of Dental and Allied Sciences  ¦  Volume 6  ¦  Issue 2  ¦  July-December 2017

 Braimah, et al.: Ameloblastic carcinoma of the jaws

11. Kruse  AL, Zwahlen  RA, Grätz KW. New classification of maxillary
ameloblastic carcinoma based on an evidence‑based literature review
over the last 60 years. Head Neck Oncol 2009;1:31.
12. Ramesh  M, Sekar  B, Murali  S, Mathew  S, Chacko  J, Paul  G.
Ameloblastic carcinoma: Review and histopathology of 5 cases. Oral
Maxillofac Pathol J 2011;2:154‑60.
13. Simko  EJ, Brannon  RB, Eibling  DE. Ameloblastic carcinoma of the
mandible. Head Neck 1998;20:654‑9.
14. Cox  DP, Muller  S, Carlson  GW, Murray  D. Ameloblastic carcinoma
ex ameloblastoma of the mandible with malignancy‑associated
hypercalcemia. Oral Surg Oral Med Oral Pathol Oral Radiol Oral Endod
2000;90:716‑22.
15. Cotran RS, Kumar V, Collins T. Robbins Pathologic Basis of Disease.
6th ed., Ch. 8. Philadelphia: WB Saunders; 1999. p. 260‑327.
16. Abiko  Y, Nagayasu  H, Takeshima  M, Yamazaki  M, Nishimura  M,
Kusano K, et al. Ameloblastic carcinoma ex ameloblastoma: Report of
a case‑possible involvement of CpG island hypermethylation of the p16
gene in malignant transformation. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2007;103:72‑6.
17. Roy Chowdhury  SK, Ramen  S, Chattopadhyay  PK, Moorchung  N,
Rajkumar K. Ameloblastic carcinoma of the mandible. J Maxillofac
Oral Surg 2010;9:198‑201.
18. Eversole LR. Malignant epithelial odontogenic tumors. Semin Diagn
Pathol 1999;16:317‑24.
19. Datta R, Winston JS, Diaz‑Reyes G, Loree TR, Myers L, Kuriakose MA,
et al. Ameloblastic carcinoma: Report of an aggressive case with
multiple bony metastases. Am J Otolaryngol 2003;24:64‑9.
20. Dorner L, Sear AJ, Smith GT. A case of ameloblastic carcinoma with
pulmonary metastases. Br J Oral Maxillofac Surg 1988;26:503‑10.
21. Fomete B, Adebayo ET, Ayuba GI, Okeke UA. Ameloblastic carcinoma
of the maxilla: A report of two cases and a review of the literature.
J Korean Assoc Oral Maxillofac Surg 2016;42:43‑6.
22. Kishore  M, Panat  SR, Aggarwal  A, Upadhyay  N, Agarwal  N.
Ameloblastic carcinoma: A case report. J Clin Diagn Res 2015;9:ZD27‑8.
23. Arotiba GT, Ladeinde AL, Arotiba JT, Ajike SO, Ugboko VI, Ajayi OF.
Ameloblastoma in Nigerian children and adolescents: A review of
79 cases. J Oral Maxillofac Surg 2005;63:747‑51.
24. Naik V, Kale AD. Ameloblastic carcinoma: A case report. Quintessence
Int 2007;38:873‑9.
25. Slater LJ. Odontogenic malignancies. Oral Maxillofac Surg Clin North
Am 2004;16:409‑24.
26. Gardner DG. Some current concepts on the pathology of ameloblastomas.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:660‑9.
27. Akrish  S, Buchner A, Shoshani  Y, Vered  M, Dayan  D. Ameloblastic
carcinoma: Report of a new case, literature review, and comparison to
ameloblastoma. J Oral Maxillofac Surg 2007;65:777‑83.
28. Ram H, Mohammad S, Husain N, Gupta PN. Ameloblastic carcinoma.
J Maxillofac Oral Surg 2010;9:415‑9.
29. Koul  R, Binahmed  A, Dubey  A, Nason  R, Cooke  AL. Maxillary
ameloblastic carcinoma. J Hong Kong Coll Radiol 2008;11:32‑4.
30. Marx RE, Stern D. Oral and Maxillofacial Pathology: A Rationale for
Diagnosis and Treatment. Chicago: Quintessence Publishing; 2003.
p. 657.
31. Ingram EA, Evans ML, Zitsch RP 3rd. Fine‑needle aspiration cytology of
ameloblastic carcinoma of the maxilla: A rare tumor. Diagn Cytopathol
1996;14:249‑52.
32. Angiero F, Borloni R, Macchi M, Stefani M. Ameloblastic carcinoma of
the maxillary sinus. Anticancer Res 2008;28:3847‑54.
33. Philip  M, Morris  CG, Werning  JW, Mendenhall  WM. Radiotherapy
in the treatment of ameloblastic carcinoma. J Hong Kong Coll Radiol
2005;8:157‑61.
34. Pandya NJ, Stuteville OH. Treatment of ameloblastoma. Plast Reconstr
Surg 1972;50:242‑8.
35. Ramadas  K, Jose  CC, Subhashini  J, Chandi  SM, Viswanathan  FR.
Pulmonary metastases from ameloblastoma of the mandible treated with
cisplatin, adriamycin, and cyclophosphamide. Cancer 1990;66:1475‑9.

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