Ameloblastoma, conventional

 

Odontogenic epithelial neoplasm characterized by slow, expansile growth of ameloblast-like cells and stellate reticulum. Is caused by dysregulated MAPK and Hedgehog signaling pathways, BRAF p.V600E mutation is the most common activating mutation in the MAPK pathway, followed by mutually exclusive mutations in RAS genes (KRAS, NRAS, HRAS) and FGFR2.


Hyperchromatic palisaded tumor cells (blue arrows), stellate reticulum-like arrangement (black arrows), expected location of subnuclear vacuoles (red arrows), 200x.

 

Classified as a benign neoplasm; ameloblastoma behaves in a locally aggressive manner with a tendency to recur, most commonly occurs in mandible, there are multiple microscopic variants:

·         Follicular

·         Plexiform

·         Acanthomatous

·         Granular cell

·         Basal cell

·         Desmoplastic

 

Localization

Up to 87% of AM arise in the mandible, predominantly in the posterior molar area, ~20% cases occur in maxilla, especially Desmoplastic ameloblastoma in anterior jaws, especially in anterior maxilla.

 

Clinical Features

Painless, slow-growing mass that, if untreated, reaches a large size, displaces and loosens teeth, expands and perforates the cortices, may cause paresthesia and ultimately causes disfigurement and risks adjacent vital structures.

Bone formation in desmoplastic AMs may producing a fine honeycomb mixed radiolucent appearance resembling a fibro-osseous  lesion.




Large ameloblastoma of the mandible causing facial deformity.

Panoramic radiograph of an ameloblastoma forming a typical radiolucent, multilocular, soap-bubble pattern lesion with cortical expansion, tooth displacement and root resorption.

3D CT reconstruction highlights expansion and multilocularity of the tumor.

 

Macroscopic Features

Solid and yellowish-white to multicystic tumors with little intervening solid tissue.


Solid and cystic (star annotation) tumor appearance. Location of inferior alveolar nerve (blue arrow).

 

Microscopic Features

Follicular subtype, there are islands of epithelium resembling the epithelial component of the enamel organ in a fibrous stroma.  Peripheral cells are columnar-to-cuboidal (ameloblast-like), with hyperchromatic nuclei arranged in a palisading pattern with reverse polarity, and often subnuclear vacuolation. The central epithelium is reminiscent of stellate reticulum, with loosely arranged angular cells and often undergoes cystic change.


Mandibular ameloblastoma with follicular growth (arrow outline), cystic change (star annotation) and plexiform pattern growth (solid black arrow), 40x.

Plexiform, composed of anastomosing strands of ameloblastomatous epithelium with an inconspicuous stellate reticulum, less prominent ameloblast-like cells and cyst-like degeneration in the stroma rather than the epithelium. Mitoses are usually scattered but posterior maxillary ameloblastoma may have high cellularity and frequent mitoses.


Higher magnification ameloblastoma with plexiform growth, 200x.

 

Acanthomatous subtype has squamous differentiation centrally in islands but maintains the reverse polarization of the nuclei in peripheral columnar cells. In the granular cell subtype the central epithelium develops abundant eosinophilic granular cytoplasm.


Basal cell subtype comprises islands and strands of basaloid cells with scanty cytoplasm and peripheral palisading, reminiscent of basal cell carcinoma.


 

 

 

 

 

The desmoplastic subtype has more widely dispersed islands with a spiky outline, cuboidal to flat peripheral cells and central spindle shaped cells in a densely collagenous stroma, sometimes with osteoplasia.


 

Prognosis and prediction 

AM recurs if inadequately removed.  The standard of care is complete excision with negative margins at least 10mm beyond the radiographic margin to ensure removal of AM permeating medullary bone, usually a segmental resection, mandibulectomy or maxillectomy, depending on size (1)

References

1. Petrovic ID, Migliacci J, Ganly I, Patel S, Xu B, Ghossein R, et al. Ameloblastomas of the mandible and maxilla. Ear Nose Throat J. 2018 Jul;97(7):E26–32.

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