Benign tumors / tumor-like conditions: ameloblastoma

Mandible & maxilla
Benign tumors / tumor-like conditions
Ameloblastoma

Authors: Kelly Magliocca, D.D.S., M.P.H., Anthony Martinez, M.D.

Topic Completed: 1 June 2016

Minor changes: 28 May 2020

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: Ameloblastoma mandible maxilla

See also: Unicystic variant

Page views in 2019: 26,669

Page views in 2020 to date: 11,219

Table of Contents

Cite this page: Magliocca K, Martinez A. Benign tumors / tumor-like conditions: ameloblastoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/mandiblemaxillaameloblastoma.html. Accessed May 29th, 2020.

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

Images hosted on other servers:

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

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

Clinical images

Images hosted on other servers:

Various images

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

Images hosted on PathOut servers:

Case of the Week #318

CK-AE1 / AE3

p63

Images hosted on other servers:

Follicular pattern low power

Columnar cells surrounding stellate reticulum

Desmoplastic ameloblastoma

Follicular ameloblastoma (figure 1)

Plexiform pattern low power

CK19

IHC in ameloblastoma

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

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
- 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