Skip to main content

Advertisement

SpringerLink
Log in

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

  • Review
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

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.”

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

Not Applicable.

Code Availability

Not Applicable.

References

  1. Kramer IRH, Pindborg JJ (1992) M: S. International histological classification of tumours: histological typing of odontogenic tumors, 2nd edn. Springer, Heidelberg

    Book  Google Scholar 

  2. Schuch LF, de Arruda JAA, Silva LVO, Abreu LG, Silva TA, Mesquita RA (2018) Odontogenic carcinosarcoma: a systematic review. Oral Oncol 85:52–59

    Article  PubMed  Google Scholar 

  3. Slater LJ (1999) Odontogenic sarcoma and carcinosarcoma. Semin Diagn Pathol 16(4):325–332

    CAS  PubMed  Google Scholar 

  4. Barnes L, Eveson JW, Rechart P, Sidransky D (2005) Pathology and Genetics Head and Neck Tumors, 3rd edn. IARC, Lyon

    Google Scholar 

  5. El-Mofty SK (2017) Odontogenic carcinosarcoma. WHO classification of Head and Neck Tumors, 4th edn. IARC, Lyon, p 213

    Google Scholar 

  6. Wright JW (2022) Odontogenic carcinosarcoma. In: Bishop JA, Chan JKC, Gale N, Helliwell T, Hyrcza MD, Lewis Jr (eds) et al., editors. WHO classification of Head and Neck tumors 9, 5th edn. JS, Lyon: IARC;. [Cited 3/19/2023].

    Google Scholar 

  7. Yoshida T, Shingaki S, Nakajima T, Suzuki M, Fukushima M (1989) Odontogenic carcinoma with sarcomatous proliferation. A case report. J Craniomaxillofac Surg 17(3):139–142

    Article  CAS  PubMed  Google Scholar 

  8. Tanaka T, Ohkubo T, Fujitsuka H, Tatematsu N, Oka N, Kojima T et al (1991) Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla. Arch Pathol Lab Med 115(1):84–87

    CAS  PubMed  Google Scholar 

  9. Shinoda T, Iwata H, Nakamura A, Ohkubo T, Yoshimi N, Sugie S et al (1992) Cytologic appearance of carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the maxilla. A case report. Acta Cytol 36(2):132–136

    CAS  PubMed  Google Scholar 

  10. Slama A, Yacoubi T, Khochtali H, Bakir A (2002) Mandibular odontogenic carcinosarcoma: a case report. Rev Stomatol Chir Maxillofac 103(2):124–127

    CAS  PubMed  Google Scholar 

  11. Kunkel M, Ghalibafian M, Radner H, Reichert TE, Fischer B, Wagner W (2004) Ameloblastic fibrosarcoma or odontogenic carcinosarcoma: a matter of classification? Oral Oncol 40(4):444–449

    Article  PubMed  Google Scholar 

  12. DeLair D, Bejarano PA, Peleg M, El-Mofty SK (2007) Ameloblastic carcinosarcoma of the mandible arising in ameloblastic fibroma: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(4):516–520

    Article  PubMed  Google Scholar 

  13. Chikosi R, Segall N, Augusto P, Freedman P (2011) Odontogenic carcinosarcoma: case report and literature review. J Oral Maxillofac Surg 69(5):1501–1507

    Article  PubMed  Google Scholar 

  14. Kim IK, Pae SP, Cho HY, Cho HW, Seo JH, Lee DH et al (2015) Odontogenic carcinosarcoma of the mandible: a case report and review. J Korean Assoc Oral Maxillofac Surg 41(3):139–144

    Article  PubMed  PubMed Central  Google Scholar 

  15. da Silva KD, Flores IL, Etges A, Vasconcelos ACU, Mesquita RA, Gomes APN et al (2017) Unusual osteolytic lesion of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 124(5):443–448

    Article  PubMed  Google Scholar 

  16. Dos Santos JN, Servato JPS, Cardoso SV, de Faria PR, Pires BC, Loyola AM (2018) Odontogenic carcinosarcoma: morphologic and immunohistochemical description of a case. Oral Surg Oral Med Oral Pathol Oral Radiol 126(5):e264–e70

    Article  PubMed  Google Scholar 

  17. Soares CD, Delgado-Azanero W, Morais TML, de Almeida OP, Ghersi Miranda H (2020) Odontogenic Carcinosarcoma: clinicopathologic features of 2 cases. Int J Surg Pathol 28(4):421–426

    Article  PubMed  Google Scholar 

  18. Niu X, Huang B, Yang J, Qiao X, Chen L, Liu J et al (2021) Odontogenic carcinosarcoma with dentinoid: a rare case report. J Int Med Res 49(9):3000605211045555

    Article  PubMed  Google Scholar 

  19. Majumdar S, Uppala D, Sreekanth K, Alekhya B (2022) Odontogenic carcinosarcoma—a rare case report with review of literature. J Oral Maxillofac Pathol 26(Suppl 1):S51–S8

    PubMed  PubMed Central  Google Scholar 

  20. Rahmat Abadi A, Daneste H, Ranjbar MA (2022) Odontogenic carcinosarcoma of the mandible, a case report. J Dent (Shiraz) 23(2 Suppl):419–423

    PubMed  Google Scholar 

  21. Tahsınoğlu M, Görgün B, Çöloğlu S (2013) Odontogenic carcinosarcoma of the mandible: a case report. J Istanbul Univ Fac Dent 15(3):267–273

    Google Scholar 

  22. Awang Hasyim N, Ismail S, Ling XF, Tilakaratne WM (2023) Odontogenic carcinosarcoma: an updated literature review and report of a case. Head Neck Pathol. https://doi.org/10.1007/s12105-023-01545-x

    Article  PubMed  Google Scholar 

  23. Bilodeau EA, Seethala RR (2019) Update on odontogenic tumors: proceedings of the North American head and neck pathology society. Head Neck Pathol 13(3):457–465

  24. Hosokawa Y, Minowa K, Abe S, Ohmori K, Yamasaki M, Shindoh M et al (1991) Invasion of the intracranial space by a malignant odontogenic mixed tumor: report of a case. Oral Radiol 7:1–6

    Article  Google Scholar 

  25. Matsuda K, Futenma C, Tesbina T, Itob T (1983) Yamamoto: H. Central pseudosarcomarous carcinoma of the mandible: report of a case. Japan J Oral Surg 29(11):2009–2015

    Google Scholar 

  26. Salem H, Ahmed Mohamed Mahmoud Badawy S, Amer H (2020) Case Report: odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved]. F1000Research. 9(603)

  27. Okada K, Hasegawa T, Yokoyama R, Beppu Y, Itoi E (2003) Osteosarcoma with cytokeratin expression: a clinicopathological study of six cases with an emphasis on differential diagnosis from metastatic cancer. J Clin Pathol 56(10):742–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Marin C, Dave M, Hunter KD (2021) Malignant odontogenic tumours: a systematic review of cases reported in literature. Front Oral Health 2:775707

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lee RJ, Tong EL, Patel R, Go LA, Christensen RE (2015) Epidemiology, prognostic factors, and management of malignant odontogenic tumors: an analysis of 295 cases. Oral Surg Oral Med Oral Pathol Oral Radiol 120(5):616–621

    Article  PubMed  Google Scholar 

  30. Lori A, Erickson VN (2022) Alfred King-yin Lam, Tetsuo Kondo, Simonetta Piana, Sylvia L. Asa, Justine Barletta. Anaplastic follicular cell derived thyroid carcinoma. In: Ronald A, Ghossein ZWB (eds) WHO Classification of Tumours Endocrine and Neuroendocrine Tumours, Vol. 8, 5th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  31. Sekine S, Sato S, Takata T, Fukuda Y, Ishida T, Kishino M et al (2003) Beta-catenin mutations are frequent in calcifying odontogenic cysts, but rare in ameloblastomas. Am J Pathol 163(5):1707–1712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yukimori A, Oikawa Y, Morita KI, Nguyen CTK, Harada H, Yamaguchi S et al (2017) Genetic basis of calcifying cystic odontogenic tumors. PLoS ONE 12(6):e0180224

    Article  PubMed  PubMed Central  Google Scholar 

  33. de Souza Vieira G, de Pinho Montovani P, Rozza-de-Menezes RE, Cunha KSG, Conde DC (2021) Comparative analysis between dentinogenic ghost cell tumor and ghost cell odontogenic carcinoma: a systematic review. Head Neck Pathol 15(4):1265–1283

    Article  PubMed  PubMed Central  Google Scholar 

  34. Seo J, Seong D, Lee SR, Oh DB, Song J (2020) Post-translational regulation of ARF: perspective in cancer. Biomolecules 10(8):1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhao R, Choi BY, Lee MH, Bode AM, Dong Z (2016) Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in Cancer. EBioMedicine 8:30–39

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tsihlias J, Kapusta L, Slingerland J (1999) The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer. Annu Rev Med 50:401–423

    Article  CAS  PubMed  Google Scholar 

  37. Karni-Schmidt O, Lokshin M, Prives C (2016) The roles of MDM2 and MDMX in Cancer. Annu Rev Pathol 11:617–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Patel RB, Li T, Liao Z, Jaldeepbhai JA, Perera H, Muthukuda SK et al (2017) Recent translational research into targeted therapy for liposarcoma. Stem Cell Investig 4:21

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sciot R (2021) MDM2 amplified Sarcomas: a Literature Review. Diagnostics (Basel). 11(3):496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Slootweg PJ, Odell EW, Baumhoer D, Carlos R, Hunter KD, Taylor AM et al (2019) Data set for the reporting of malignant odontogenic tumors: explanations and recommendations of the Guidelines from the International collaboration on Cancer Reporting. Arch Pathol Lab Med 143(5):587–592

    Article  PubMed  Google Scholar 

  41. ltoh K, Toeda D, Kaneda T (1962) An autopsy case of the malignant ameloblascoma with pulmonary metastasis. J Japan Stomat Soc 29:167

    Google Scholar 

  42. Sugimura M, Yamauchi T, Yashikawa K, Takeda N, Miyazaki MS (1969) Malignant ameloblastoma with metastasis to the lumbar vertebra; report of case. J Oral Surg 27:350

    CAS  PubMed  Google Scholar 

  43. Virchow R (1864) Die krankhaften geschwulste. Verlag von August Hirschwald, Berlin

    Google Scholar 

  44. Meyer R (1920) Bcitrag zur Verstandigung uber die Namengebung in der Geschwulstlehre. Zbl Allg Path 30:291

    Google Scholar 

  45. McCluggage WG (2002) Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas? J Clin Pathol 55(5):321–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Saphir O, Vass A, Carcinosarcoma (1938) Am J Cancer 33(3):331–361

    Google Scholar 

  47. Saltykow S (1914) Beitrage zur Kenntnis des Karzinosarkoms. Verhandl d deutsch path Gesellsch 17:351

    Google Scholar 

  48. Wick MR, Swanson PE (1993) Carcinosarcomas: current perspectives and an historical review of nosological concepts. Semin Diagn Pathol 10(2):118–127

    CAS  PubMed  Google Scholar 

  49. Zhuang Z, Lininger RA, Man YG, Albuquerque A, Merino MJ, Tavassoli FA (1997) Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity. Mod Pathol 10(4):354–362

    CAS  PubMed  Google Scholar 

  50. Teixeira MR, Qvist H, Bøhler PJ, Pandis N, Heim S (1998) Cytogenetic analysis shows that carcinosarcomas of the breast are of monoclonal origin. Genes Chromosomes Cancer 22(2):145–151

    Article  CAS  PubMed  Google Scholar 

  51. Dacic S, Finkelstein SD, Sasatomi E, Swalsky PA, Yousem SA (2002) Molecular pathogenesis of pulmonary carcinosarcoma as determined by microdissection-based allelotyping. Am J Surg Pathol 26(4):510–516

    Article  PubMed  Google Scholar 

  52. Zhang X, Bai Q, Xu Y, Wang W, Chen L, Han J et al (2019) Molecular profiling of the biphasic components of hepatic carcinosarcoma by the use of targeted next-generation sequencing. Histopathology 74(6):944–958

    Article  PubMed  Google Scholar 

  53. Ihrler S, Stiefel D, Jurmeister P, Sandison A, Chaston N, Laco J et al (2023) Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements. Histopathology 82(4):576–586

    Article  PubMed  Google Scholar 

  54. Ismail SB, Zain RB, Yaacob HB, Abraham MT (2009) Ameloblastic carcinoma (spindle cell variant). Pathology 41(3):292–295

    Article  CAS  PubMed  Google Scholar 

  55. Kamath VV, Satelur K, Yerlagudda K (2012) Spindle cell variant of ameloblastic carcinoma arising from an unicystic amelobastoma: report of a rare case. Dent Res J 9(3):328–333

    Google Scholar 

  56. Ansari HA, Ray PS, Khan N, Khan AH (2015) Spindle-cell ameloblastic carcinoma of the maxilla with adenoid cystic carcinoma-like areas: a new variant? Indian J Pathol Microbiol 58(4):513–515

    Article  PubMed  Google Scholar 

  57. McNaught MJ, Turella SJ, Fallah DM, Demsar WJ (2015) Spindle cell variant of ameloblastic carcinoma: a case report and review of literature. Mil Med 180(5):e614–e617

    Article  PubMed  Google Scholar 

  58. Matsushita Y, Fujita S, Yanamoto S, Yamada S, Rokutanda S, Yamashita K et al (2016) Spindle cell variant of ameloblastic carcinoma: a case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol 121(3):e54–61

    Article  PubMed  Google Scholar 

  59. McLean-Holden AC, Bishop JA, Kessler HP, Myers LL, Radwan AM, Wildey TC et al (2019) Spindle-cell variant of ameloblastic carcinoma: a report of 3 cases and demonstration of epithelial-mesenchymal transition in tumor progression. Oral Surg Oral Med Oral Pathol Oral Radiol 128(3):e113–e21

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Drs. Rayan Rammal, and Jacinthe Chênevert for their assistance with article translation. The authors would also like to thank the Departments of Pathology at Novant Health, Charlotte, NC, and Santa Clara Valley Medical Center, San Jose, CA, for providing additional slides and blocks for review.

Funding

None.

Author information

Author notes

  1. Elizabeth A. Bilodeau and Raja R. Seethala both authors share senior authorship.

Authors and Affiliations

  1. Department of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Grayson Cole & Elizabeth A. Bilodeau

  2. Woody L. Hunt School of Dental Medicine, Texas Tech University Health Science Center, El Paso, TX, USA

    Angela Chi

  3. Carolina Centers for Oral and Facial Surgery, Charlotte, NC, USA

    Daniel R. Cook

  4. Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Mark Kubik

  5. Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Raja R. Seethala

Authors
  1. Grayson Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angela Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel R. Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Kubik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elizabeth A. Bilodeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Raja R. Seethala
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: GC, AC, DRC, MK, EAB, RRS; Methodology: GC, EAB, RRS; Formal analysis and investigation: GC, RRS; Writing—original draft preparation: GC; Writing—review and editing: GC, AC, DRC, MK, EAB, RRS; Funding acquisition: N/A; Resources: EAB, RRS; Supervision: EAB, RRS.

Corresponding author

Correspondence to Raja R. Seethala.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to Participate

This study has obtained IRB approval from (University of Pittsburgh Human Research Protection Office) and the need for informed consent was waived.

Consent for Publication

For this type of study consent for publication is not required.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Part of this study was presented as a poster at the USCAP 2023 Annual Meeting in New Orleans (Abstracts from USCAP 2023: Head and Neck Pathology (1012) Lab Inv 2023; 103: S1027).

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cole, G., Chi, A., Cook, D.R. et al. Odontogenic Carcinosarcoma: Clinicopathologic and Molecular Features of Three Cases, a Literature Review and Nomenclature Proposal. Head and Neck Pathol 17, 751–767 (2023). https://doi.org/10.1007/s12105-023-01569-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-023-01569-3

Keywords

Search

Navigation