Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Clinical features | Classification | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosisCite this page: Magliocca K, Martinez A. Ameloblastoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/mandiblemaxillaameloblastoma.html. Accessed March 3rd, 2021.
Definition / general
- Benign, locally aggressive tumor (25 - 35% recur) of odontogenic epithelium
- Previously called adamantinoma, but this term is inaccurate as it implies the presence of hard tissues, which do not occur in ameloblastoma
- 1% of jaw tumors and cysts
Terminology
- Multicystic ameloblastoma is also referred to as conventional or infiltrating ameloblastoma
Epidemiology
- Second most common odontogenic tumor after odontoma
- Equal gender distribution; men and women of all ages, mean age 39 years
- Multicystic / conventional ameloblastoma occurs in the 4 - 5th decades, represents ~ 85% of all ameloblastomas
- Unicystic ameloblastoma occurs ~ 2 decades earlier than multicystic tumors
- Occasionally associated with basal cell nevus syndrome and rarely with Gardner syndrome (see case reports)
- Peripheral ameloblastoma represents ~ 1% of ameloblastomas
- Tend to present on gingiva
Sites
- Mandible is most common site for most types (~ 80%)
- ~ 2 / 3 occur along posterior mandible
- Desmoplastic ameloblastoma tends to occur in anterior mandible
- ~ 20% occur in maxilla
Etiology
- Unknown and somewhat controversial, but leading hypotheses include remnants of dental lamina, basal layer of oral mucosa and, less commonly, arising within pre-existing dentigerous cyst
Clinical features
- Usually asymptomatic and can be found incidentally on routine dental examinations
- Can also present as a painless swelling or expansion of jaw
- Pain and paresthesia are uncommon
- Slow growing, rarely metastasizes to lungs or CNS
- Metastases associated with tumor of long duration, multiple surgical procedures, radiation therapy
- Associated with nevoid basal cell carcinoma (Gorlin) syndrome (Fam Cancer 2012;11:411)
- Peripheral soft tissue variant:
- Men and women ages 40 - 60 years
- Soft tissue of posterior gingiva and ascending ramus
- True peripheral variants may be less aggressive than intraosseous tumors
- Arise from dental lamina remnants in gingiva (rests of Serres) or from surface epithelium with potential to differentiate along odontogenic lines
- Cross sectional imaging, rather than plain film imaging, is imperative to exclude an intraosseous ameloblastoma with a prominent extraosseous component; gingival lesions with radiographic ‘cupping’ of the bone may not be peripheral ameloblastoma, but a very peripherally placed intraosseous ameloblastoma that has perforated (Head Neck Pathol 2010;4:192)
- Same histology as intraosseous tumors (palisading basaloid cells with stellate reticulum) but benign behavior
- Occurs in soft tissue of posterior gingiva and ascending ramus, may occur in buccal mucosa
Classification
- WHO classifies ameloblastoma into four variants:
- Solid / multicystic
- Extraosseous or peripheral
- Desmoplastic
- Unicystic
- Note: 2005 WHO classification designates ameloblastoma as benign, not malignant
Diagnosis
- Based on clinical, radiologic and pathologic correlation
Radiology description
- Conventional ameloblastoma:
- Expansile lesion with multilocular lytic lesion, or soap bubble
- May or may not be associated with impacted tooth
- Resorption of tooth roots and bone formation may occur
- Desmoplastic ameloblastoma
- Mottled, mixed radiolucency / radio-opacity strongly resembles fibro-osseous lesion
Radiology images
Prognostic factors
- Multicystic tumors have recurrence rate of 25 - 55%, may be dependent on treatment
- Unicystic tumors have recurrence rate of 5 - 10%
Case reports
- 14 year old with Gardner's Syndrome has unusual case of a unicystic ameloblastoma mimicking a dentigerous cyst (Br Dent J 2005;198:747)
- 50 year old man with right lung tumor (Case of the Week #318)
- Ameloblastoma associated with the nevoid basal cell carcinoma (Gorlin) syndrome (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:e10)
- Unicystic ameloblastoma presenting in Gardner's syndrome (Head Neck Pathol 2014;8:239)
Treatment
- Individualized surgery
- In general, multicystic or conventional require en bloc or segmental resection with wide margins
- Although BRAF inhibitors have been used (Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122:e5), no advantage over traditional surgical treatment for a primary, intraosseous benign ameloblastoma has been documented
Gross description
- Solid and cystic
- May be multicystic and intraosseous or extraosseous
- Rarely is unicystic
Microscopic (histologic) description
- Odontogenic epithelial islands composed of:
- Peripheral palisading columnar cells at basal layer, hyperchromatic
- Cells show reverse polarization away from basement membrane (Vickers-Gorlin change)
- Stellate reticulum-like cells, suprabasal cells composed of loosely arranged angular cells
- No dentin or enamel formation
- Many subtypes known and are most commonly described in the context of conventional ameloblastoma (likely have no prognostic significance)
- Follicular: most common subtype; islands of odontogenic epithelium in fibrous connective tissue; may be cystic
- Acanthomatous: squamous metaplasia and variable keratinization of stellate reticulum-like cells
- Plexiform: cords and sheets of anastomosing odontogenic epithelial cells
- Granular cell: granular eosinophilic cytoplasm often located within stellate reticulum-like cells
- Basaloid: least common variant; nest or islands of hyperchromatic basal cells without stellate reticulum-like
- Macrocystic degeneration of the tumor islands may occur. When a portion of this phenomenon is sampled for biopsy, the appearance may suggest a cyst, a unicystic ameloblastoma or cystic CCOT
- Used to be called “cystic ameloblastoma” but use of this terminology is discouraged as may be confused with variants of unicystic ameloblastoma
- Desmoplastic variant: dense collagenous stroma with compressed, angular islands of odontogenic epithelium
- Diagnosis may be difficult on small biopsies (see differential diagnosis)
- Rarely, involvement of the inferior alveolar nerve has been reported in benign ameloblastoma (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:557, Br J Oral Maxillofac Surg 2013;51:757)
Microscopic (histologic) images
Contributed by Kelly Magliocca, D.D.S., M.P.H.
Images hosted on PathOut servers:
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Positive stains
Electron microscopy description
- Epithelial differentiation (tonofilaments, complex desmosomes)
Molecular / cytogenetics description
- Somatic mutations in the Hedgehog and MAPK pathways have been identified
- One study showed about 40% have SMO mutations and about 45% have BRAF mutations (Nat Genet 2014; 46: 722)
- Most plexiform variants had SMO mutations
- Most follicular and desmoplastic variants carried either SMO or BRAF mutations
- KRAS and FGFR2 mutations were also found
- Mutations may vary by anatomic site:
- SMO most common in maxillary ameloblastoma
- BRAF most common in mandibular ameloblastoma
- Another study showed BRAF, RAS and FGFR2 mutations in 44 of 50 (88%) of ameloblastomas (Clin Cancer Res 2014;20:5517)
- BRAF V600E was the most common mutation (62%)
- 100% concordance for BRAF mutational status was observed between molecular and IHC results
- Other mutations include KRAS and FGFR2
- One study showed about 40% have SMO mutations and about 45% have BRAF mutations (Nat Genet 2014; 46: 722)
Differential diagnosis
Differential diagnosis of conventional multicystic ameloblastoma
Differential diagnosis of desmoplastic ameloblastoma
- Malignant ameloblastoma
- Also called metastasizing ameloblastoma
- Identical histology but with metastasis
- Ameloblastic carcinoma
- Variable features of amelobastoma: peripheral palisading, reverse polarization, stellate reticulum
- Features of malignancy include cytological atypia, high N:C ratio, increased mitoses with atypical forms, necrosis
- Can also metastasize
- Ameloblastic fibroma
- Histologically, may share same features within the odontogenic epithelial component strands, cords and islands that may exhibit peripheral palisading, reverse polarization and stellate reticulum
- Stroma is essential to the diagnosis and appears more primitive, delicate and lobular in appearance
- Adenomatoid odontogenic tumor
- Benign tumor of odontogenic epithelium with basaloid duct-like nest or cords lined by cuboidal or columnar cells
- Can have focal reverse polarity, like ameloblastoma
- Duct-like spaces contain eosinophilic secretions and amyloid-like material may be present
- 2/3 are female, usually occurs in 2nd decade in anterior maxilla
- Squamous odontogenic tumor
- Benign tumor of odontogenic squamous epithelium
- Very rare; thought to arise from rests of Malassez in periodontal ligament
- Should not have peripheral palisading or stellate reticulum
- Calcifying cystic odontogenic tumor (CCOT)
- Benign cystic tumor of odontogenic origin aka “Gorlin cyst” or “Calcifying odontogenic cyst”
- Can have “ameloblastic” features: columnar or cuboidal basal cells with lumen lined by tissue resembling stellate reticulum
- Will have ghost cells or anucleate epithelial cells
- In cases exhibiting predominantly cystic architecture, differential includes
- Dentigerous cyst
- Variants of unicystic ameloblastoma
- Cystic CCOT
- A sampling of the macrocystic degeneration of a conventional ameloblastoma
Differential diagnosis of desmoplastic ameloblastoma
- Ameloblastic fibroma
- Histologically, may share same features within the odontogenic epithelial component strands, cords and islands that may exhibit peripheral palisading, reverse polarization and stellate reticulum
- Stroma is essential to the diagnosis and appears more primitive, delicate and lobular in appearance
- Squamous odontogenic tumor
- Benign tumor of odontogenic squamous epithelium
- Very rare; thought to arise from rests of Malassez in periodontal ligament
- Should not have peripheral palisading or stellate reticulum
- Odontogenic fibroma
- Sclerosing odontogenic carcinoma