Background

The ameloblastoma is the most common neoplasm arising from the primary odontogenic, or tooth forming, tissue. In contrast to squamous cell carcinomas of the oral cavity, which are relatively, common, these tumors are rare. Pathologists who specialize in diagnosing these rare tumors of the oral cavity are called oral pathologists.

These tumors most commonly present with slow growing tumor and are usually asymptomatic until a large size is achieved. These tumors characteristically expand within the jaw and displace bone, teeth, and roots. Occasionally, infiltrating tumors may erode through the bone and extend into the soft tissue. A common scenario is a tumor arising in association with an impacted third molar.

The pathologist's role is to determine whether the tumor is infiltrative. If it is, more aggressive local excision should occur since these tumors may have a history or repeated recurrences.

OUTLINE

Epidemiology
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE	Most common odontogenic neoplasm
AGE RANGE-MEDIAN	Mean 33 years
SEX (M:F)	Equal
GEOGRAPHY	Caucasians favored African-Americans Asians (especially Chinese)

 

PATHOGENESIS	CHARACTERIZATION
CHROMOSOMAL ALTERATIONS
Allelic loss of tumor suppressor genes in ameloblastic tumors. Nodit L, Barnes L, Childers E, Finkelstein S, Swalsky P, Hunt J. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.	Mod Pathol. 2004 Sep;17(9):1062-7. Related Articles, Links Ameloblastoma is an odontogenic tumor with a variety of histologic appearances and an unpredictable biologic behavior. Little is known about allelic losses of tumor suppressor genes in ameloblastomas. This study surveyed DNA damage in ameloblastomas and correlated this with histologic sub-type and clinical outcome. There were 12 ameloblastomas (two peripheral, eight solid, and two unicystic) and three ameloblastic carcinoma studied for loss of heterozygosity of tumor suppressor genes on chromosomes 1p, 3p, 9p,10q, and 17p (L-myc, hOGG1, p16, pten, and p53). The frequency of allelic loss and the intratumoral heterogeneity were calculated. L-myc (71% frequency of allelic loss) and pten (62% frequency of allelic loss) had the most frequent allelic losses. Overall frequency of allelic loss and intratumoral heterogeneity were higher in mandibular and in unicystic tumors and lower in tumors that recurred/metastasized. The rate of allelic loss in the three carcinomas was similar to that seen in benign tumors. The frequency of allelic loss and intratumoral heterogeneity did not correlate with age, gender, histologic subtype, or prognosis. Since tumors that behaved aggressively did not harbor more allelic losses, it is likely that DNA damage in ameloblastomas and ameloblastic carcinomas is sporadic and cumulative. We conclude that other genetic or epigenetic mechanisms may be responsible for malignant behavior in ameloblastic carcinomas.
HUMAN PAPILLOMA VIRUS
Does HPV play a role in the etiopathogenesis of ameloblastoma? An immunohistochemical, in situ hybridization and polymerase chain reaction study of 18 cases using laser capture microdissection. Migaldi M, Pecorari M, Rossi G, Maiorana A, Bettelli S, Tamassia MG, De Gaetani C, Leocata P, Portolani M. 1Department of Pathologic Anatomy and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy.	Mod Pathol. 2005;18:283-289 Abstract quote   Ameloblastomas are epithelial tumors of odontogenic origin, biologically characterized by local recurrence. Among different etiologic factors, HPV infection has been recently postulated to be somehow involved in ameloblastoma etiopathogenesis. To address this issue, we studied 18 ameloblastomas by means of immunohistochemistry, in situ hybridization (conventional and amplified), polymerase chain reaction and nested-polymerase chain reaction analyses using laser capture microdissection in order to detect the occurrence of HPV in this setting. No evidence of HPV infection was detected by morphological examination, immunohistochemistry, in situ hybridization and conventional polymerase chain reaction, while nested-polymerase chain reaction showed a weak positive band in two cases. However, the subsequent restriction enzyme analysis carried out from the nested-polymerase chain reaction amplification products of these two samples excluded the presence of HPV subtypes 16, 18, 31, 33, 35, 52, and 58. The search for HPV 6 and 11 in the same specimens was also negative. In conclusion, our data do not support an etiopathogenetic evidence for HPV in ameloblastoma.

 

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Radiography	Multiloculated soap bubble appearance for infiltrating tumors
	Unicystic tumors show a demarcated unilocular radiolucency, usually associated with an impacted tooth

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
General	Unicystic cases occur about 1 decade earlier than multicystic cases Mandible:Maxilla tumors 4:1 Molar-ramus portion accounts for the majority of the tumors
Infiltrating	This comprises 80% of all cases Usually solid areas with white to gray color and little hemorrhage or necrosis
Desmoplastic	9-13% of cases Increased prevalence in Asians, especially Chinese and Malaysians Equal frequency in the maxilla and mandible Most common in the premolar and incisor area Ill-defined mixed radiolucent/radiopaque mass
Unicystic	Am J Surg Pathol 2000;24:1385-1392 Occur one decade or earlier than infiltrating tumors Usually simple cysts partially attached to the cervical line of the impacted tooth Although no recurrence of 29 patients <4 years, there was a 35% recurrence rate >4 years Average interval to recurrence 7 years Tumors invading the fibrous wall having a recurrence rate of 35.7% vs. other types of 6.7%
Peripheral	Least common variant Tumors are entirely extraosseous Older adults with mean age of 52.7 years Slight male predominance Mandible:maxilla 13:10 Elevated, sessile, pink to red masses resembling pyogenic granulomas or papillomas No radiographic evidence of communication with bone These tumors may be treated by excision with margin of normal tissue

 

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Most important feature is determine whether the tumor is infiltrating Follicular pattern resembles the enamel portion of the dental follicle Variably sized islands of epithelium with tall columnar peripheral cells with reverse nuclear polarity and subnuclear vacuoles Uniform nuclei Centers of the islands have loose-textured stellate epithelial cells with frequent microcyst formation Mitotic figures are rare and if present, is a worrisome feature
VARIANTS
ACANTHOMATOUS	Follicular tumor islands show squamous metaplasia and/or keratin production
BASALOID	Discrete small islands interconnected by narrow cords of cells No well-developed stellate-type centers Cuboidal cells lacking the reverse nuclear polarity or subnuclear vacuoles
DESMOPLASTIC	Has greater amounts of stroma and less epithelium Epithelium arranged in narrow, compressed cords occasionally rounding up into islands Center has compact spindled appearance Reverse polarity of columnar cells are uncommon
GRANULAR	Large cells with granular pink cytoplasm in the centers of the tumor islands, usually of the basic follicular type
PERIPHERAL	Follicular or plexiform pattern of infiltrating ameloblastomas >50% of cases show direct connection with overlying mucosal epithelium with no evidence of extension into underlying bone
PLEXIFORM	Broad anastomosing sheets of cells with centers of stellate epithelium and tall columnar peripheral cells with reverse nuclear polarity and subnuclear vacuoles
SPINDLE CELL
Malignant ameloblastoma, spindle cell variant. Zarbo RJ, Marunick MT, Johns R. Department of Pathology, Henry Ford Hospital, Detroit, MI 48202, USA.	Arch Pathol Lab Med 2003 Mar;127(3):352-5 Abstract quote In this report, we document the histologic and clinical features of a previously undefined spindle cell variant of ameloblastoma that eventually behaved in a malignant fashion during a protracted course. The predominant histologic pattern was a well-differentiated, cellular, spindled epithelial proliferation arising in the maxilla of a 14-year-old African American girl. Over 19 years, the patient experienced numerous local recurrences, metastases to distant bones after 15 years, and finally bulky local recurrence with intracranial extension resulting in death. This ameloblastic malignancy histologically simulates a low-grade true sarcoma or an ameloblastic sarcoma, but differs in that the extensive spindle cell proliferation is epithelial, characterized by strong cytokeratin immunoreactivity and negative vimentin staining.
UNICYSTIC	Am J Surg Pathol 2000;24:1385-1392 Cyst lined by ameloblatic epithelium with tall columnar basal layer, subnuclear vacuoles, reverse nuclear polarity, and thin layer of edematous, degenerate-appearing stellate cells May have superficial extension of ameloblastic epithelium into the connective tissue wall of the cyst-if there is a deep mural extension, the possibility of an infiltrating ameloblastoma must be communicated to the surgeon

 

SPECIAL STAINS/ IMMUNOPEROXIDASE	CHARACTERIZATION
Epithelium	Cytokeratin positive
Type IV collagen	Identified in desmoplastic tumors

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Determination of infiltrative border is most important as these tumors have marked recurrence rates
Unicystic Ameloblastoma A Clinicopathologic Study of 33 Chinese Patients Tie-Jun Li, D.D.S., Ph.D.; Yun-Tang Wu, M.D.; Shi-Feng Yu, M.D.; Guang-Yan Yu, D.D.S., Ph.D. From the Departments of Oral Pathology (T.-J.L., S.-F.Y.), Oral Radiology (Y.-T.W.), and Oral and Maxillofacial Surgery (G.-Y.Y.), School of Stomatology, Beijing Medical University, ROC.	Am J Surg Pathol 2000;24:1385-1392 Abstract quote The term unicystic ameloblastoma refers to those cystic lesions that show clinical, radiographic, or gross features of a jaw cyst, but on histologic examination show a typical ameloblastomatous epithelium lining part of the cyst cavity, with or without luminal and/or mural tumor growth. To ascertain the clinicomorphologic spectrum and biologic behavior of this tumor group, the clinicopathologic features of 33 unicystic ameloblastomas from Chinese patients were studied. This series represents approximately 19% of all cases of ameloblastoma accessioned in the authors' hospital during a 15-year period. Twenty-one patients were male and 12 were female, for a total of 33 patients. The age at diagnosis ranged from 8 to 60 years (mean, 25.3 yrs) and peaked at the second and third decades (70%). Thirty tumors (91%) occurred in the mandible and three in the maxilla. Of the 29 patients with a radiographic record, an expansive unilocular radiolucency was seen in 22 cases, and was multilocular in seven cases. Microscopically, all tumors demonstrated a generally monocystic growth pattern. Eight tumors were simple cystic, 10 comprised intraluminal tumor nodules, and the remaining 15 had a conspicuous component of infiltrative tumor islands in the cyst capsule. The cystic tumor linings invariably showed, at least in part, a typical ameloblastomatous pattern that was often accompanied by epithelial areas of various histologic appearance. Follow up of 29 patients revealed no recurrence in less than 4 years of follow up, but did reveal a 35% recurrence rate at more than 4 years of follow up. The average interval to recurrence was approximately 7 years. Recurrence also appeared to relate to histologic subtypes of unicystic ameloblastoma, with those invading the fibrous wall having a rate of 35.7%, but other types having a rate of 6.7%. Despite the fact that unicystic ameloblastoma may, in general, compare favorably with its solid or multicystic counterpart in terms of clinical behavior and response to treatment, the subsets of the maxillary lesions or tumors containing invading islands in the fibrous wall could have a high risk of recurrence. Furthermore, recurrence of unicystic ameloblastoma may be long delayed, and a long-term postoperative follow up is essential to the proper management of these patients.
Metastasis	Benign tumors
Infilrating tumors	No inherent metastatic potential but recurrences have occured for as long as 7-10 years after initial treatment
Non-infiltrating tumors	Recurrence in 10-25% of cases with conservative therapy
Treatment
Infiltrating tumors	Currettage alone leads to recurrence rates of 90% or more Must remove tumor with a border of radiographically normal bone, usually about 1 cm margins
Non-infiltrating tumors	Cystectomy with prolonged radiologic follow-up

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Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated February 4, 2005

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