Mandible-Maxilla
Malignant tumors
Odontogenic carcinoma

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

Revised: 4 October 2016, last major update September 2016

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

PubMed search: Odontogenic carcinoma [title]

Cite this page: Odontogenic carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mandiblemaxillaodontogeniccarcinoma.html. Accessed December 5th, 2016.
Definition / General
Epidemiology
Metastasizing (malignant) ameloblastoma
  • Represent < 1 - 2% of all ameloblastomas
  • Usually occur a decade after treatment for primary ameloblastoma (range < 1 - 45 years)

Ameloblastic carcinoma
  • Rare, < 100 case reports in English literature
  • Represent < 1% of all odontogenic tumors

Primary intraosseous squamous cell carcinoma
  • Rare
  • ~ 1.5% of all oral squamous cell carcinomas

Clear cell odontogenic carcinoma
  • Rare, < 100 cases have been reported
  • Most common in 5th to 6th decades
  • More common in females

Ghost cell odontogenic carcinoma
  • Rare, < 40 cases reported in literature and more than half from Asia
  • More common in males
Sites
Metastasizing (malignant) ameloblastoma
  • Most common site of metastasis is the lungs (75 - 88%)

Ameloblastic carcinoma
  • More common in mandible (~ 80%)
  • Favors posterior mandible

Primary intraosseous squamous cell carcinoma
  • Mandible most commonly involved

Clear cell odontogenic carcinoma
  • Mandible most common site (75%)
  • Soft tissue involvement common as lesion often perforates through the bone

Ghost cell odontogenic carcinoma
  • Maxilla more common than mandible
Etiology
Metastasizing (malignant) ameloblastoma
  • Metastases develop from angiolymphatic spread from primary tumors
  • A few metastases are hypothesized to have occurred secondary to aspiration
    • Theory supported by tumor that grew within the bronchi and bronchioli
    • This assumption is further supported because such tumors are often located in the right lung

Ameloblastic carcinoma
  • Majority arise de novo
  • Less commonly arise from preexisting ameloblastoma, and are considered secondary or dedifferentiated lesions

Primary intraosseous squamous cell carcinoma
  • Can arise from odontogenic epithelial remnants
  • Can also arise secondarily from keratocystic odontogenic tumors or odontogenic cysts

Clear cell odontogenic carcinoma
  • Unknown, as with many translocation tumors, lesion tends to pursue a line of differentiation rather than originate from a particular line of derivation
  • However, the tumor cells resemble clear cell rests of primitive dental lamina that are frequently in the same locations

Ghost cell odontogenic carcinoma
  • Malignancy thought to arise from calcifying odontogenic cysts (COCs) with features of either calcifying cystic odontogenic tumor or dentinogenic ghost cell tumor
Clinical Features
Metastasizing (malignant) ameloblastoma
  • Clinically, symptoms of metastasis can be related to site or may be found incidentally with imaging after a local recurrence
  • For lung metastases, patients may exhibit cough, dyspnea and hemoptysis, rarely paraneoplastic syndrome (Ecancermedicalscience 2013;7:323)
  • Lymphadenopathy

Ameloblastic carcinoma
  • May be painful as they cause expansion of the jaw, grow rapidly and perforate the cortex
  • "Expansion" or "hard mass" is the most common chief complaint
  • Other complaints include toothache, ulceration, trismus and facial asymmetry

Primary intraosseous squamous cell carcinoma
  • Can be asymptomatic or have pain, swelling, numbness, and trismus

Clear cell odontogenic carcinoma
  • Often presents as jaw swelling with loosening of the teeth
  • Can be painful, asymptomatic or associated with paresthesias

Ghost cell odontogenic carcinoma
  • Can present as painful, hard swelling in the maxilla or mandible
Diagnosis
  • Diagnosis dependent on clinical, radiologic and pathologic correlation
Radiology Description
Metastasizing (malignant) ameloblastoma
  • Primary lesion will have classic appearance as ameloblastoma, namely well defined unilocular or multilocular radiolucent lesion, often with cortical expansion
  • Appearance of metastatic lesion will vary depending on site

Ameloblastic carcinoma
  • Well defined unilocular or multilocular radiolucent lesion
  • Often shows cortical expansion with perforation

Primary intraosseous squamous cell carcinoma
  • Varied, but can be radiolucent
  • Can show small or massive amounts of bone resorption, and more aggressive forms with irregular borders

Clear cell odontogenic carcinoma
  • Poorly defined radiolucency
  • May show cortical destruction of bone

Ghost cell odontogenic carcinoma
  • Most commonly seen as a mixed radiolucency and radiopacity with ill defined margins
Radiology Images

Images hosted on other servers:

Metastasizing (malignant) ameloblastoma

Cavitary lesion

Various imaging of pulmonary metastases



Ameloblastic carcinoma

Orthopantomogram

Lucent lesion

Axial non contrast CT

Axial MRI



Primary intraosseous squamous cell carcinoma

Various images



Clear cell odontogenic carcinoma

Bone destruction in symphysis region

Figure 1

Ill defined radiolucent lesion



Ghost cell odontogenic carcinoma

Clinical and MRI examination

Prognostic Factors
Metastasizing (malignant) ameloblastoma
  • Metastatic cases to lung tend to show indolent clinical behavior with long survival times
  • True long term followup is difficult to assess as many studies of malignant ameloblastomas also included ameloblastic carcinomas

Ameloblastic carcinoma
  • Malignant lesions have 30% recurrence rate, 22% metastasis rate
  • 5 year survival is 70% without metastases, 20% with metastases

Primary intraosseous squamous cell carcinoma
Clear cell odontogenic carcinoma
  • Recurrence rate of 30% of resected and 87% of curetted / enucleated lesions
  • Metastases to lymph nodes, lung and bone
  • Up to 25% die of disease

Ghost cell odontogenic carcinoma
  • Overall 5 year survival rate is 73% and recurrence is common
Case Reports
Metastasizing (malignant) ameloblastoma
Ameloblastic carcinoma
Primary intraosseous squamous cell carcinoma
Clear cell odontogenic carcinoma
Ghost cell odontogenic carcinoma
Treatment
Metastasizing (malignant) ameloblastoma
  • Surgical excision
  • Role of chemotherapy or radiation has yet to be defined; many case reports have seen clinical response with systemic therapy

Ameloblastic carcinoma
  • Composite surgical resection, with adjuvant radiation and chemotherapy as appropriate

Primary intraosseous squamous cell carcinoma
  • Composite surgical excision, usually followed by radiation

Clear cell odontogenic carcinoma
  • Must tailor surgical treatment to overall clinical and image findings, but often involves a composite / en bloc resection

Ghost cell odontogenic carcinoma
  • Composite surgical excision, may be followed by radiation
Micro Description
Metastasizing (malignant) ameloblastoma
  • Identical to ameloblastoma; odontogenic epithelial islands composed of:
    • Peripheral palisading columnar cells
    • Ameloblastic cells with reverse polarization
    • Stellate reticulum-like cells composed of loosely arranged angular cells
  • Many subtypes
    • 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

Ameloblastic carcinoma
  • Variable features of ameloblastoma: peripheral palisading, reverse polarization, stellate reticulum
  • Features of malignancy include cytological atypia, high N:C ratio, increased mitoses with atypical forms, necrosis

Clear cell odontogenic carcinoma - three histological patterns have been described
  • Biphasic
    • Nests of epithelial cells with clear or slightly eosinophilic cytoplasm admixed with more eosinophilic polygonal cells.
  • Monophasic
    • Nests and cords of only clear epithelial cells
    • Often separated by thin collagenous stroma
  • Ameloblastomatous
    • Nests of clear epithelial cells often with palisading of peripheral cells similar to ameloblastoma

Ghost cell odontogenic carcinoma
  • Ameloblastomatous areas (see above)
  • Ghost cells (polygonal epithelial cells with eosinophilic cytoplasm that have lost their nuclei but maintain a faint outline of cellular and nuclear membrane)
    • Ghost cells may be calcified
  • Atypia with changes such as increased cellularity, pleomorphism, mitosis, necrosis and infiltrative growth
Micro Images

Images hosted on other servers:

Metastasizing (malignant) ameloblastoma

Solid / multicystic type

Pulmonary metastasis

Acanthomatous

Various images



Ameloblastic carcinoma

Low power

Higher power

Cytological atypia

Necrosis



Primary intraosseous squamous cell carcinoma

Various images



Clear cell odontogenic carcinoma

Various images

Congo red stain

Tumor cells



Various H&E



Ghost cell odontogenic carcinoma

Various H&E

Molecular / Cytogenetics Description
Metastasizing (malignant) ameloblastoma - found molecular alterations
  • 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

Ameloblastic carcinoma
  • May harbor some of same mutations as ameloblastomas but currently not enough literature

Clear cell odontogenic carcinoma
Ghost cell odontogenic carcinoma
  • Not enough literature, but aberrations of Wnt signaling pathway with beta-catenin overexpression have been shown in calcifying cystic odontogenic tumors (APMIS 2008;116:206)
Differential Diagnosis
Metastasizing (malignant) ameloblastoma
  • Ameloblastoma: histologically identical but no metastases
  • Ameloblastic carcinoma
    • Variable features of ameloblastoma: peripheral palisading, reverse polarization, stellate reticulum-like cells
    • 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-like cells
    • Stroma is more primitive, delicate and lobular in appearance
    • Should not metastasize
  • Metastatic disease in lung
    • Primary squamous cell carcinoma of lung
    • Has cytologic features of malignancy
    • No other features of ameloblastoma; i.e. no peripheral palisading, no polarization, no stellate reticulum-like cells

Ameloblastic carcinoma
  • Ameloblastoma
    • Histologically, may share some of same features such as peripheral palisading, reverse polarization and stellate reticulum, but should not show features of malignancy (pleomorphism with hyperchromasia, atypical mitoses)
  • Clear cell odontogenic carcinoma
    • Malignant epithelial odontogenic tumor composed primarily of nests and islands of clear cells
    • May have focal peripheral palisading similar to ameloblastoma, but not as much cytologic atypia as ameloblastic carcinoma
    • More common in anterior mandible
    • EWSR mutation
  • Malignant ameloblastoma
    • Like amelobastoma histologically but termed "malignant" after discovery of metastases
    • Should not show any cytologic features of malignancy
  • Metastatic disease
  • Primary intraosseous squamous cell carcinoma
    • Carcinoma composed of moderately to poorly differentiated squamous epithelial cells with variable keratinization
    • Also derived from odontogenic epithelium

Primary intraosseous squamous cell carcinoma
  • Squamous odontogenic tumor
    • Benign tumor of odontogenic squamous epithelium
    • Very rare; thought to arise from rests of Malassez in periodontal ligament
    • Should not have cytologic atypia
  • Clear cell odontogenic carcinoma
    • Malignant epithelial odontogenic tumor composed primarily of nests and islands of clear cells
    • May have focal peripheral palisading similar to ameloblastoma
    • EWSR mutation
  • Calcifying epithelial odontogenic tumor (CEOT)
    • Benign epithelial odontogenic neoplasm
    • Occurs in posterior mandible, intraosseous location
    • Variably sized polyhedral eosinophilic epithelial cells with distinct cell borders are arranged in small clusters, trabeculae, islands or a sheet like pattern
    • Nuclear pleomorphism is expected, but without appreciable mitotic activity
    • Eosinophilic amyloid-like matrix material is haphazardly deposited in association with the tumor islands, and calcified concentric profiles (Liesegang rings) are often identified
  • Ameloblastic carcinoma
    • Variable features of ameloblastoma: peripheral palisading, reverse polarization, stellate reticulum-like cells
    • Features of malignancy include cytological atypia, high N:C ratio, increased mitoses with atypical forms, necrosis
  • Ameloblastoma
    • Variable features of ameloblastoma: peripheral palisading, reverse polarization, stellate reticulum-like cells
    • No features of malignancy
  • Keratocystic odontogenic tumor
    • Uniform epithelial lining 6 - 8 cells thick lacking rete ridges
    • Epithelium characterized by palisaded hyperchromatic basal cell layer comprised of cuboidal to columnar cells
    • Luminal surface has wavy (“corrugated”) parakeratotic epithelial cells
    • Should not have an invasive component

Clear cell odontogenic carcinoma
  • May vary based on biopsy sample size and whether histology is monophasic (predominantly clear cell), biphasic or ameloblastomatous

Monophasic (predominantly clear cell) or focal biphasic appearance:
  • Clear cell carcinoma of salivary gland
    • More common in minor salivary glands (~ 80%), particularly base of tongue, palate, floor of mouth, tongue and buccal mucosa in oral cavity / oropharynx
    • The nests or cords lack focal palisading of basal cells ("ameloblastic") seen in CCOC
    • Both lesions show EWSR1 rearrangements
    • May represent "salivary gland analogue"
  • Clear cell variant of calcifying epithelial odontogenic tumor (CEOT)
    • Benign epithelial odontogenic neoplasm, clear cell variant may be composed primarily of clear cells
    • Occurs in posterior mandible, intraosseous location
    • Variably sized polyhedral eosinophilic epithelial cells with distinct cell borders are arranged in small clusters, trabeculae, islands or a sheet like pattern
    • Nuclear pleomorphism is expected, but without appreciable mitotic activity
    • Eosinophilic amyloid-like matrix material is haphazardly deposited in association with the tumor islands, and calcified concentric profiles (Liesegang rings) are often identified
    • Ancillary studies show the epithelial cells of CEOT highlight with cytokeratin AE1 / 3, CK5 / 6 and p63, and amyloid-like material exhibits apple green birefringence when stained with Congo red and viewed with polarized light
  • Sclerosing odontogenic carcinoma
    • Rare and controversial entity, described in 2008
    • Low grade odontogenic carcinoma, locally aggressive
    • Infiltrating single file strands, cords and nests of cuboidal or polygonal epithelial cells with cytoplasmic clearing, similar to signet ring change
    • No prominent pleomorphism or mitotic figures; no necrosis
    • Skeletal muscle and perineural infiltration with stromal sclerosis are characteristic
  • Clear cell renal cell carcinoma (metastatic)
    • Usually a known history of renal cell carcinoma, which is PAX8+
  • Epithelial - myoepithelial carcinoma
    • Malignant biphasic tumor with an inner duct-like epithelial component and an outer S100+ myoepithelial component
    • Usually occurs in major salivary glands
    • CCOC has only a clear cell epithelial component, and is S100 negative
  • Mucoepidermoid carcinoma, clear cell variant
    • Malignant epithelial tumor with variable amounts of mucous, epidermoid and intermediate cells
    • Mucocytes are mucicarmine+
    • Can be associated with MAML2 rearrangement and NOT EWSR1
  • Sinonasal renal cell-like adenocarcinoma (SRCLA)
    • May be difficult to differentiate, but clear cell tumors involving the maxillary or palatal structures require consideration of a sinonasal neoplasm with secondary involvement of the oral region (Int J Clin Exp Med 2014;7:5469)
    • Rare tumor characterized by a clear cell glandular proliferation, most often involving the nasal cavity, associated with a favorable clinical course
    • Has round cells with clear cytoplasm and a prominent nucleolus arranged in a follicular pattern
    • A tubular arrangement and papillary architecture of the clear cell proliferation have also been described
    • No mucinous or myoepithelial differentiation, no necrosis, no hyalinization of stroma
    • SRCLA vs. hyalinizing clear cell carcinoma of salivary gland (HCCC): no stromal hyalinization, no stromal vascularity; often has larger clear cells than HCCC and CCOC; has robust CAIX immunostaining vs. focal positive in HCCC; negative for EWSR1 rearrangement

Ameloblastomatous appearance:
  • Desmoplastic ameloblastoma
    • Dense collagenous stroma with compressed, angular islands of basaloid odontogenic epithelium
  • Squamous odontogenic tumor
    • Benign tumor of odontogenic squamous epithelium
    • Very rare; thought to arise from rests of Malassez in periodontal ligament
    • No peripheral palisading or stellate reticulum
  • Odontogenic fibroma
    • Rare tumor, and poorly described in literature
    • Loose to dense collagenous stroma with small, rounded or elongated islands of bland odontogenic epithelial islands
    • Islands not elongated, interconnected or arborizing
    • Minimal clear cell change

Ghost cell odontogenic carcinoma
  • 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
    • Should not have cytologic atypia, increased mitotic activity, necrosis
  • Calcifying epithelial odontogenic tumor (CEOT)
    • Benign epithelial odontogenic neoplasm
    • Occurs in posterior mandible, intraosseous location
    • Variably sized polyhedral eosinophilic epithelial cells with distinct cell borders are arranged in small clusters, trabeculae, islands or a sheet like pattern
    • Nuclear pleomorphism is expected, but without appreciable mitotic activity
    • Eosinophilic amyloid-like matrix material is haphazardly deposited in association with the tumor islands, and calcified concentric profiles (Liesegang rings) are often identified
  • Ameloblastic carcinoma
    • Variable features of ameloblastoma: peripheral palisading, reverse polarization, stellate reticulum-like cells
    • Features of malignancy include cytological atypia, high N:C ratio, increased mitoses with atypical forms, necrosis
    • Can also metastasize
    • Will not have ghost cells