Odontogenic Carcinosarcoma: Clinicopathologic and Molecular Features of Three Cases, a Literature Review and Nomenclature Proposal

Abstract

Background: Odontogenic carcinosarcoma (OCS) is a rare odontogenic malignancy with limited characterization and unexplored molecular features. We report clinicopathologic and molecular findings in 3 additional OCS and review the literature.

Methods: 3 OCS (5.1%) were identified among 59 malignant odontogenic tumors (in our archives from 1992 to 2022). Clinical, radiologic, histopathologic, immunophenotypic, and molecular findings were reviewed. Data from prior case reports and systematic or non-systematic reviews were extracted for analysis.

Results: Three mandibular OCS (age range: 66 to 72 years; 1 male, 2 females) were identified. Case 1 had novel clear-cell morphology, multiple recurrences, and a lethal outcome 28 months after resection. EWSR1 rearrangements were negative, but the tumor showed focal nuclear β-catenin and strong LEF-1 immunoreactivity. Case 2 demonstrated ameloblastic and sclerosing features and encased the inferior alveolar nerve; the patient was disease-free 22 months after resection with adjuvant chemoradiation therapy. LEF-1 was again strongly positive, and next-generation sequencing demonstrated 9p region-(CDKN2A, CDKN2B) copy number loss, and 12q region-(MDM2, CDK4) copy number gain. Case 3 showed clear-cell and markedly sclerosing features; no follow-up information was available. Literature review along with the current cases yielded 20 cases. OCS showed a male predilection (1.5:1), mandibular predominance (80%, typically posterior), and a bimodal age distribution (modes: 27.7 years, 62.7 years). OCS presented as masses (100%), often with pain (55%), and paresthesia (45%). Tumors were typically radiolucent (88.9%), with bone destruction (61.1%), and/or tooth effacement (27.8%). Preoperative biopsy was sensitive for malignancy (85.7%). At least 45% show evidence for a precursor lesion. 3-year DSS and DFS were 58% and 35%, respectively. Regional and distant (usually lung) metastatic rates were 25% and 31.3%, respectively. Increased mitotic rates and presence of tumor necrosis trended toward worse DSS and DFS.

Conclusion: OCS is a rare but aggressive malignancy, often arising from precursor tumors and may represent a terminal phenotype rather than a distinct entity. We describe novel clear-cell and sclerosing morphologies. Wnt pathway alterations appear important. Mitotic rates and necrosis may be adverse prognosticators. In keeping with nomenclature trends in other sites, OCS may be more appropriately designated as "biphasic sarcomatoid odontogenic carcinomas."

Keywords: Ameloblastic Carcinosarcoma; Malignant Odontogenic Tumors; Molecular; Odontogenic Carcinosarcoma.

Fig. 1

Distribution of malignant odontogenic and central tumors at UPMC by category. Abbreviation: NOS not otherwise specified

Fig. 2

Case 1 biopsy. A Surface and deep components on biopsy. B A superficial clear cell carcinoma-like component that C transitions to a more atypical squamoid/acanthomatous component. D Other areas are biphasic with a polygonal spindled component and necrosis. E The tumor shows nuclear β-catenin in spindled and scattered epithelial cells. F LEF-1 shows strong positivity in the spindled component with some epithelial cell staining

Fig. 3

Case 1 resection and recurrences/metastases. A Resection showing obliteration of bone and extension into submucosa. Inset: Biphasic morphology with a CCOC-like epithelial component. B Neck recurrence demonstrating biphasic morphology and obliteration of a lymph node. C Parotid recurrence is showing spindle cell predominance

Fig. 4

Case 2 radiologic and gross appearance. A CT demonstrates a ground glass mixed radiolucent-radioopaque expansile left posterior mandibular mass with cortical disruption. B PET-CT shows strong avidity. C Sagittal section through hemimandibulectomy specimen showing a firm ill-defined white lesion extending into soft tissue. Inset: Tumor effaces medullary cavity and encases the inferior alveolar nerve (arrow)

Fig. 5

Case 2 morphologic features. A Invasive biphasic tumor invading bone imparting a fibrous dysplasia like appearance and invading the inferior alveolar nerve (right) B Ameloblastic nodule juxtaposed to myxoid spindled component. C Bone invasion and more haphazard pattern and sclerosis with ropey collagen. D AE1/3 and E. P40 show stronger staining in epithelial components. F LEF-1 strong positivity throughout

Fig. 6

Case 3 morphologic features. A A biphasic tumor with myxoid and sclerosing components invading extending into skeletal muscle. B The epithelial component shows a reticular clear cell anastomosing/plexiform growth. C The spindled component is embedded in a collagenous stroma with a paucicellular appearance and storiform pattern. D Primitive osteoid-like matrix is noted (right). E Epithelial elements focally demonstrate a pseudovascular pattern highlighted by F CAM 5.2, and G p63. Only rare spindled elements are positive for these markers

Fig. 7

Outcomes for OCS reported to date. A Disease course by individual patient. Abbreviations: XRT Radiotherapy; NED no evidence of disease. DOD died of disease. B Disease-specific survival (DSS) and C Disease-free survival (DFS) for OCS. Shading represents 95% confidence intervals and dotted intercept represents 3-year survival. D DSS and E DFS stratified by mitotic counts. Abbreviations: HiMit Numerous Mitoses; LowMit Moderate and Occasional Mitoses. F DSS and G DFS stratified by necrosis