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Mandible & maxilla

Malignant odontogenic tumors

Ameloblastic carcinoma

Author: Kelly Magliocca, D.D.S., M.P.H.

Editorial Board Members: Elizabeth Ann Bilodeau, D.M.D., M.D., M.S.Ed., Molly Housley Smith, D.M.D.

Last author update: 23 June 2025

Last staff update: 23 June 2025

Copyright: 2004-2025, PathologyOutlines.com, Inc.

PubMed Search: Ameloblastic carcinoma

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Table of Contents

Cite this page: Magliocca K. Ameloblastic carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/mandiblemaxillaameloblasticcarcinoma.html. Accessed September 23rd, 2025.

Definition / general

Ameloblastic carcinoma is a rare primary odontogenic carcinoma of the jaw that exhibits ameloblastic differentiation, cytologic atypia, an increased number of mitotic figures, expansion of the basal layer and often punctate tumor necrosis
Most commonly arises within the bone of maxilla and mandible

Essential features

Rare; represents ≤ 2% of all odontogenic tumors (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:191, Int J Oral Maxillofac Surg 2007;36:20, Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:151)
Essential criteria: exhibits a histological resemblance to ameloblastoma with increased cytologic atypia
Desirable criteria: intraosseous jaw tumor, tumor necrosis, associated ameloblastoma precursor, BRAF mutations in a subset
May show a combination of spindle cell, stellate, squamous, epithelioid or (limited) clear cell morphologies
Evidence of squamous differentiation is most reliably demonstrated by immunostaining for p40, p63 and CK5

Terminology

Not recommended by WHO: malignant ameloblastoma, dedifferentiated ameloblastoma

ICD coding

ICD-O: 9270/3 - ameloblastic carcinoma
ICD-11: 2B5J & XH4M89 - malignant miscellaneous tumors of bone or articular cartilage of other or unspecified sites & odontogenic tumor, malignant

Epidemiology

Accounts for ≤ 2% of all odontogenic tumors (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:191, Int J Oral Maxillofac Surg 2007;36:20, Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:151)
Mean age: 46.1 years (median: 45 years; range: 2 - 93 years) (J Oral Pathol Med 2024;53:174)
Sex predilection appears to vary between studies
- Slight female predominance (J Oral Pathol Med 2024;53:174)
- Male predominance (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:799, Oncol Lett 2014;8:914, Eur Arch Otorhinolaryngol 2017;274:3803)

Sites

More common in mandible than maxilla (Eur Arch Otorhinolaryngol 2017;274:3803, Oral Surg Oral Med Oral Pathol Oral Radiol 2016;121:e154, Head Neck 2019;41:4191)

Pathophysiology

BRAF p.V600E or TP53 mutations have been reported in up to 40% of cases (Tumour Biol 2015;36:5649, Oral Oncol 2015;51:e77, J Oral Pathol Med 2019;48:413, Orphanet J Rare Dis 2020;15:316)

Etiology

Etiology is largely unknown
Majority of cases arise de novo
Some develop in longstanding untreated ameloblastoma or in locally recurrent ameloblastoma after treatment (Oral Surg Oral Med Oral Pathol 1984;57:168, Oral Surg Oral Med Oral Pathol Oral Radiol 2014;118:e146, Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:716)

Clinical features

Many cases present with rapidly progressive jaw swelling at the involved site, which may extend into the overlying mucosa (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:904, Oral Surg Oral Med Oral Pathol Oral Radiol 2016;121:e154)
Symptoms such as nasal congestion, exophthalmos, toothache, paresthesia, toothache or tooth mobility are related to localized mass effect of the tumor in maxilla or mandible (Eur Arch Otorhinolaryngol 2017;274:3803, Head Neck 2019;41:4191)

Diagnosis

WHO blue book histological criteria for diagnosis of ameloblastic carcinoma
- Essential: exhibits a histological resemblance to ameloblastoma with increased cytologic atypia
- Desirable: an intraosseous jaw tumor, tumor necrosis, associated ameloblastoma precursor, BRAF mutations in a subset

Laboratory

Occasionally associated with hypercalcemia of malignancy (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:716)
In hypercalcemia of malignancy, laboratory abnormalities may include
- Elevated total and ionized calcium
- Suppressed parathyroid hormone (PTH) levels
- Normal or low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels
- Increased alkaline phosphatase levels

Radiology description

Contrast enhanced computed tomography (CT) shows an expansile, largely hypodense lytic intraosseous jaw lesion with poorly defined margins as well as medullary and cortical bone destruction (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:904)
Commonly exhibits extension into soft tissues; magnetic resonance imaging (MRI) may help delineate (J Clin Imaging Sci 2022;12:58)
Moderate fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) CT helps detect metastasis (Dentomaxillofac Radiol 2010;39:449)

Radiology images

Contributed by Kelly Magliocca, D.D.S., M.P.H.

Maxillary tumor on CT

Mandibular tumor on CT

Mandibular tumor axial CT

Images hosted on other servers:

Orthopantomogram

Lucent lesion

Axial noncontrast CT

Axial MRI

Prognostic factors

Ameloblastic carcinoma is rare and the paucity of cases not only precludes an accepted pathologic staging paradigm but also undermines assessment of most prognostic factors; some investigators have attempted to understand the importance of some factors below (see associated references)
Points to consider in assessment of prognosis
- Stage: no accepted staging paradigm for odontogenic malignancies
- Age: disease spans a broad age range
- Primary anatomic location: mandible versus maxilla
- Tumor size
- Extension beyond bone into soft tissues
- Histological variables
  - Presence / absence of benign precursor ameloblastoma (Oral Surg Oral Med Oral Pathol 1984;57:168, J Oral Maxillofac Surg 2007;65:777)
  - Histopathological patterns (Oral Oncol 2018;77:118)
  - Tumor necrosis
  - Mitotic rate
  - Perineural or lymphovascular invasion
  - Margin status (note: without an R0 initial resection, there is no disease free interval)
- Presence of specific gene alterations
- Variability in treatment
  - Use of surgery alone
  - Surgery in combination with adjuvant radiation therapy or proton therapy
  - Use of standard chemotherapy versus targeted therapy
Local recurrence: up to 40% of cases (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:904, Oncol Lett 2015;9:459)
Regional metastases to cervical nodes occur in up to 13% of patients (Eur Arch Otorhinolaryngol 2017;274:3803, Pol J Pathol 2018;69:243, Orphanet J Rare Dis 2020;15:316)
Distant metastasis develops in 33% of cases, most commonly in the lung, followed by the brain, liver and bone (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:e17, Eur Arch Otorhinolaryngol 2017;274:3803)
5 year overall survival rate is 70% (Orphanet J Rare Dis 2020;15:316, Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:904)

Case reports

31 year old man with headache and vision loss (J Clin Imaging Sci 2022;12:58)
61 year old woman with neck pain and right arm weakness (Neurosurgery 2021;88:E537)
68 year old man with a maxillary mass (Int J Surg Pathol 2023;31:442)
72 year old woman with mandibular pain (Maxillofac Plast Reconstr Surg 2023;45:17)

Treatment

Primary treatment is heterogeneous, ranging from surgery alone to a combination of adjuvant therapies, including radiation therapy, traditional chemotherapy or targeted therapy (Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:e56, Eur Arch Otorhinolaryngol 2016;273:3293)
- Surgery: radical surgical resection is treatment of choice
- Radiation therapy: no established protocol
- Targeted therapy: BRAF or ALK inhibitor, depending on molecular findings (Eur Arch Otorhinolaryngol 2016;273:3293)

Clinical images

Images hosted on other servers:

Erythematous growth

Proliferative growth

Extraoral swelling

Pus discharge

Intraoral swelling

Gross description

Cut surfaces reveal a solid mass with irregular borders and limited cystic change (Dentomaxillofac Radiol 2010;39:449, Oral Surg Oral Med Oral Pathol Oral Radiol 2016;121:e54)

Gross images

Contributed by Kelly Magliocca, D.D.S., M.P.H.

Largely solid, tan-white tumor

Images hosted on other servers:

Resected specimen

Microscopic (histologic) description

Malignant tumor with varied morphology
Most commonly, tumor architecture is follicular, plexiform or solid nests of ameloblastoma-like epithelium
Peripheral palisading, nuclear reverse polarity and stellate reticulum must be evident at least focally
Tumor may comprise areas of squamous, spindle cell morphology or clear cell change (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:799, Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:904, Oral Surg Oral Med Oral Pathol Oral Radiol 2014;118:e146, Histopathology 2016;69:687, Oral Surg Oral Med Oral Pathol Oral Radiol 2019;128:e113)
Tumor grows in undulating bulky cords, nests or sheets with pushing borders or angulated infiltrative nests at the advancing front
Tumor cells at the periphery of islands are often large with prominent nucleoli
Pleomorphism can be marked
Increased mitotic activity
Necrosis is often present (central tumor islands or single cell)
Extension into the mucosa does not distinguish benign ameloblastoma from carcinoma
Dispersed invasion and perineural infiltration are uncommon findings (Arch Pathol Lab Med 2019;143:587, Orphanet J Rare Dis 2020;15:316)

Microscopic (histologic) images

Contributed by Kelly Magliocca, D.D.S., M.P.H.

Tumor necrosis

Mass merging with oral mucosa

Cyst-like spaces

Squamous / squamoid nests

High grade cytologic features

Squamous cell carcinoma mimic

Elevated mitotic count

BRAF V600E IHC

Cytology description

Fine needle aspiration (FNA) biopsy may detect possible metastasis in known cases (Dentomaxillofac Radiol 2010;39:449)

Cytology images

Images hosted on other servers:

Skull lesion, mandible primary

Positive stains

CK19, CK5, p63 (Med Oral Patol Oral Cir Bucal 2017;22:e324)
SOX2 can be positive but is variable and of limited utility in confirming a diagnosis of ameloblastic carcinoma (F1000Res 2024;13:557, Head Neck Pathol 2024;18:92)
p53 overexpression in some but not all cases (Histopathology 2016;69:687, F1000Res 2024;13:557, J Microsc Ultrastruct 2022;12:165)
Ki67 often elevated (F1000Res 2024;13:557, Head Neck Pathol 2024;18:92)
BRAF V600E immunostain positive in a subset of cases (J Oral Pathol Med 2021;50:85)

Negative stains

SOX10, S100 (Case Rep Dent 2023;2023:8755637)

Molecular / cytogenetics description

BRAF is the most frequently mutated gene; the most frequent mutation is BRAF V600E (Tumour Biol 2015;36:5649, Orphanet J Rare Dis 2020;15:316)
Molecular abnormalities involving ALK or TP53 may also occur but are less common (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;118:e146, Oral Oncol 2022;132:105946)
TERT promoter mutations are uncommonly identified (J Oral Pathol Med 2023;52:271)

Sample pathology report

Bone, left mandible and level 1 neck contents, radical resection:
- Ameloblastic carcinoma (8.2 cm) (see comment)
- Tumor necrosis: present
- Mitotic rate: 15 per 2 mm²
- Soft tissue invasion: present
- Perineural invasion: not identified
- Lymphovascular invasion: not identified
- Specimen surgical margin status
  - All surgical margins negative for carcinoma
  - Carcinoma, 2 mm from nearest margin; posterior soft tissue
- Level I neck contents
  - 6 lymph nodes, negative for carcinoma (0/6)
  - Submandibular salivary gland with reactive changes
- Comment: At present, there is no universally accepted pathologic staging protocol for ameloblastic carcinoma, reflecting the rarity of this malignancy. In view of this limitation, a detailed summary of histopathologic features with potential relevance to clinical management is provided above.

Differential diagnosis

Ameloblastoma:
- May share some of the same histological features (peripheral palisading, reverse polarization, stellate reticulum) but should not show features of malignancy (pleomorphism with hyperchromasia, atypical mitoses)
- Maxillary ameloblastoma can show high cellularity but is less commonly BRAF mutated
Oral squamous cell carcinoma:
- Ideally exhibits surface dysplasia; mucosal precursor lesion
- May invade underlying bone but uncommonly is centered within the bone of the jaw
- Displays prominent intercellular bridges, a hallmark of squamous differentiation
- BRAF V600E negative
Clear cell odontogenic carcinoma (Am J Surg Pathol 2013;37:1001):
- Malignant epithelial odontogenic tumor composed primarily of nests and islands of clear cells
- May have focal peripheral palisading similar to ameloblastoma but typically lacks the cytologic atypia seen in ameloblastic carcinoma
- EWSR mutation

Additional references

WHO Classification of Tumours Editorial Board: Head and Neck Tumours, 5th Edition, 2024

Practice question #1

When confronted with an intraosseous mandibular epithelial tumor, which collection of microscopic features is most suggestive of ameloblastic carcinoma?

Acantholysis, dyskeratosis, extensive ghost cell type keratinization
Cellular atypia, increased mitotic activity, tumor necrosis
Fibrous stroma, psammoma bodies, multinucleated giant cell reaction
Perineural invasion, clear cytoplasm, EWSR1 mutation

Practice answer #1

B. Cellular atypia, increased mitotic activity, tumor necrosis would be most suggestive for ameloblastic carcinoma of the available choices. Answer A is incorrect because extensive ghost cell type keratinization is more commonly seen in odontogenic ghost cell tumors and not typically in ameloblastic carcinoma. Answer C is incorrect because fibrous stroma, psammoma bodies and multinucleated giant cell reaction are often described in papillary thyroid carcinoma and are unrelated to ameloblastic carcinoma. Answer D is incorrect because perineural invasion, clear cytoplasm and EWSR1 mutation are features of clear cell odontogenic carcinoma, not ameloblastic carcinoma.

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