Mandible-Maxilla
Benign tumors
Ameloblastoma

Authors: Kelly Magliocca, D.D.S., M.P.H. and Anthony Martinez, M.D. (see Authors page)

Revised: 23 June 2016, last major update June 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Ameloblastoma mandible maxilla

See also: Peripheral soft tissue variant, Unicystic variant
Cite this page: Ameloblastoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mandiblemaxillaameloblastoma.html. Accessed December 4th, 2016.
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)
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

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CT scan showing lesion containing bone-like tissues

Multilocular, mixed radiolucent-radio-opaque lesion

Panoramic radiograph

Diffuse unilocular radiolucency

CT scans showing buccal cortical plate expansion

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
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
Clinical Images

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Various images

Gross Description
  • Solid and cystic
  • May be multicystic and intraosseous or extraosseous
  • Rarely is unicystic
Micro 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)
Micro Images

Images hosted on PathOut servers:

Case of the Week #318

CK-AE1 / AE3

p63



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Palisading basal cells and stellate reticulum

Follicular pattern low power

Columnar cells surrounding stellate reticulum



Desmoplastic ameloblastoma

Follicular ameloblastoma (figure 1)

Plexiform pattern low power

Positive Stains
  • CK5, CK6, CK13, CK14, CK19, calretinin, CD56
    • CK13 and CD56 are preferentially expressed in the stellate reticulum-like cells, CK14 and CD56 in the peripheral cells and CK19 in all cells


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CK19

IHC in ameloblastoma

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
Differential Diagnosis
Differential diagnosis of conventional multicystic 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

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