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Spindle Cell Carcinomas of the Head and Neck Rarely Harbor Transcriptionally-Active Human Papillomavirus

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Abstract

Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma characterized by spindled or pleomorphic cells which appear to be a true sarcoma but are actually epithelial. Some head and neck squamous cell carcinoma variants can be human papillomavirus (HPV)-related and have improved outcomes. We sought to determine if spindle cell carcinomas are associated with transcriptionally-active HPV. Cases of spindle cell carcinoma were retrieved from department files. Transcriptionally-active HPV was determined by mRNA in situ hybridization for high risk HPV E6 and E7 transcripts and by a surrogate marker, p16 immunohistochemistry, with a 50 % staining cutoff. RT-PCR for high risk HPV mRNA was performed on the cases that were technical failures by in situ hybridization. Medical records and follow up information were retrieved for all patients. Of 31 cases, 5 were from the oropharynx, 12 from the oral cavity, and 14 from the larynx or hypopharynx. One purely spindled oral cavity spindle cell carcinoma was HPV positive. It was also diffusely positive for p16. Another laryngeal spindle cell carcinoma was HPV positive in both the squamous and spindle cell components, but was negative for p16. None of the five oropharyngeal spindle cell carcinomas were positive for p16 or HPV RNA. The HPV positive patients both presented at high stage (IV) and died with disease within 2 years of diagnosis. The majority of spindle cell carcinomas of the head and neck, including those arising in the oropharynx, are not related to transcriptionally active HPV. Although the number of cases is too small for any definitive conclusions, for the rare HPV positive spindle cell carcinoma cases, positive viral status does not appear to confer any prognostic benefit.

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References

  1. Ellis GL, Corio RL. Spindle cell carcinoma of the oral cavity. A clinicopathologic assessment of 59 cases. Oral Surg Oral Med Oral Pathol. 1980;50(6):523–33.

    Article  CAS  PubMed  Google Scholar 

  2. Olsen KD, Lewis JE, Suman VJ. Spindle cell carcinoma of the larynx and hypopharynx. Otolaryngol Head Neck Surg. 1997;116(1):47–52.

    Article  CAS  PubMed  Google Scholar 

  3. Leventon GS, Evans HL. Sarcomatoid squamous cell carcinoma of the mucous membranes of the head and neck: a clinicopathologic study of 20 cases. Cancer. 1981;48(4):994–1003.

    Article  CAS  PubMed  Google Scholar 

  4. Lewis JE, Olsen KD, Sebo TJ. Spindle cell carcinoma of the larynx: review of 26 cases including DNA content and immunohistochemistry. Hum Pathol. 1997;28(6):664–73.

    Article  CAS  PubMed  Google Scholar 

  5. Cardesa A, Zidar N. Spindle cell carcinoma. In: Barnes EL, Eveson JW, Reichart P, Sidranksy D, editors. World health organization pathology and genetics—head and neck tumours. Lyon: IARC Press; 2005. p. 127–8.

    Google Scholar 

  6. Lewis JS, Ritter JH, El-Mofty S. Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder-p63, MOC-31, and TTF-1. Mod Pathol. 2005;18(11):1471–81. doi:10.1038/modpathol.3800451.

    Article  CAS  PubMed  Google Scholar 

  7. Thompson LD, Wieneke JA, Miettinen M, Heffner DK. Spindle cell (sarcomatoid) carcinomas of the larynx: a clinicopathologic study of 187 cases. Am J Surg Pathol. 2002;26(2):153–70.

    Article  PubMed  Google Scholar 

  8. Viswanathan S, Rahman K, Pallavi S, Sachin J, Patil A, Chaturvedi P, et al. Sarcomatoid (spindle cell) carcinoma of the head and neck mucosal region: a clinicopathologic review of 103 cases from a tertiary referral cancer centre. Head Neck Pathol. 2010;4(4):265–75. doi:10.1007/s12105-010-0204-4.

    Article  PubMed  Google Scholar 

  9. Choi HR, Sturgis EM, Rosenthal DI, Luna MA, Batsakis JG, El-Naggar AK. Sarcomatoid carcinoma of the head and neck: molecular evidence for evolution and progression from conventional squamous cell carcinomas. Am J Surg Pathol. 2003;27(9):1216–20.

    Article  PubMed  Google Scholar 

  10. Takata T, Ito H, Ogawa I, Miyauchi M, Ijuhin N, Nikai H. Spindle cell squamous carcinoma of the oral region. An immunohistochemical and ultrastructural study on the histogenesis and differential diagnosis with a clinicopathological analysis of six cases. Virchows Arch A Pathol Anat Histopathol. 1991;419(3):177–82.

    Article  CAS  PubMed  Google Scholar 

  11. Thompson L, Chang B, Barsky SH. Monoclonal origins of malignant mixed tumors (carcinosarcomas). Evidence for a divergent histogenesis. Am J Surg Pathol. 1996;20(3):277–85.

    Article  CAS  PubMed  Google Scholar 

  12. Zarbo RJ, Crissman JD, Venkat H, Weiss MA. Spindle-cell carcinoma of the upper aerodigestive tract mucosa. An immunohistologic and ultrastructural study of 18 biphasic tumors and comparison with seven monophasic spindle-cell tumors. Am J Surg Pathol. 1986;10(11):741–53.

    Article  CAS  PubMed  Google Scholar 

  13. Rampias T, Sasaki C, Weinberger P, Psyrri A. E6 and e7 gene silencing and transformed phenotype of human papillomavirus 16-positive oropharyngeal cancer cells. J Natl Cancer Inst. 2009;101(6):412–23. doi:10.1093/jnci/djp017.

    Article  CAS  PubMed  Google Scholar 

  14. Ragin CC, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer. 2007;121(8):1813–20. doi:10.1002/ijc.22851.

    Article  CAS  PubMed  Google Scholar 

  15. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35. doi:10.1056/NEJMoa0912217.

    Article  CAS  PubMed  Google Scholar 

  16. Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–9. doi:10.1093/jnci/djn011.

    Article  CAS  PubMed  Google Scholar 

  17. Chung CH, Gillison ML. Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res. 2009;15(22):6758–62. doi:10.1158/1078-0432.CCR-09-0784.

    Article  CAS  PubMed  Google Scholar 

  18. Lewis JS Jr, Thorstad WL, Chernock RD, Haughey BH, Yip JH, Zhang Q, et al. p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010;34(8):1088–96. doi:10.1097/PAS.0b013e3181e84652.

    Article  PubMed  Google Scholar 

  19. Lewis JS Jr. p16 Immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Head Neck Pathol. 2012;6(Suppl 1):75–82. doi:10.1007/s12105-012-0369-0.

    Article  Google Scholar 

  20. Thomas J, Primeaux T. Is p16 immunohistochemistry a more cost-effective method for identification of human papilloma virus-associated head and neck squamous cell carcinoma? Ann Diagn Pathol. 2011;16(2):91–9. doi:10.1016/j.anndiagpath.2011.09.002.

    Article  PubMed  Google Scholar 

  21. El-Mofty SK. HPV-related squamous cell carcinoma variants in the head and neck. Head Neck Pathol. 2012;6(Suppl 1):55–62. doi:10.1007/s12105-012-0363-6.

    Article  Google Scholar 

  22. Chernock RD, Lewis JS Jr, Zhang Q, El-Mofty SK. Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol. 2010;41(7):1016–23. doi:10.1016/j.humpath.2009.11.015.

    Article  CAS  PubMed  Google Scholar 

  23. Bishop JA, Westra WH. Human papillomavirus-related small cell carcinoma of the oropharynx. Am J Surg Pathol. 2011;35(11):1679–84. doi:10.1097/PAS.0b013e3182299cde.

    Article  PubMed  Google Scholar 

  24. Kraft S, Faquin WC, Krane JF. HPV-associated neuroendocrine carcinoma of the oropharynx: a rare new entity with potentially aggressive clinical behavior. Am J Surg Pathol. 2012;36(3):321–30. doi:10.1097/PAS.0b013e31823f2f17.

    Article  PubMed  Google Scholar 

  25. Kryvenko ON, Habib F, Zarbo RJ, Torres F, Chitale DA. Role of high-risk human papilloma virus (HR-HPV) in carcinogenesis of spindle cell (sarcomatoid) squamous cell carcinoma of the head and neck. Mod Pathol. 2011;24(Supplement 1):279A.

    Google Scholar 

  26. Gao G, Chernock RD, Gay HA, Thorstad WL, Zhang TR, Wang H, et al. A novel RT-PCR method for quantification of human papillomavirus transcripts in archived tissues and its application in oropharyngeal cancer prognosis. Int J Cancer. 2012;. doi:10.1002/ijc.27739.

    Google Scholar 

  27. Lewis JS Jr. Spindle cell lesions–neoplastic or non-neoplastic?: spindle cell carcinoma and other atypical spindle cell lesions of the head and neck. Head Neck Pathol. 2008;2(2):103–10. doi:10.1007/s12105-008-0055-4.

    Article  PubMed  Google Scholar 

  28. Adelstein DJ, Ridge JA, Gillison ML, Chaturvedi AK, D’Souza G, Gravitt PE, et al. Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, DC. Head Neck. 2009;31(11):1393–422. doi:10.1002/hed.21269.

    Article  PubMed  Google Scholar 

  29. Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32(7):1044–50. doi:10.1097/PAS.0b013e31816380ec.

    Article  PubMed  Google Scholar 

  30. Jo VY, Mills SE, Stoler MH, Stelow EB. Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma. Am J Surg Pathol. 2009;33(11):1720–4. doi:10.1097/PAS.0b013e3181b6d8e6.

    Article  PubMed  Google Scholar 

  31. Masand RP, El-Mofty SK, Ma XJ, Luo Y, Flanagan JJ, Lewis JS Jr. Adenosquamous carcinoma of the head and neck: relationship to human papillomavirus and review of the literature. Head Neck Pathol. 2011;5(2):108–16. doi:10.1007/s12105-011-0245-3.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to acknowledge Jianping Li, BS and Neha Dahiya, MD, MBA of the Anatomic and Molecular Pathology Core Laboratory for their expert assistance with the p16 immunohistochemistry.

Conflict of interest

The RNA in situ hybridization assays used in this study were funded by and performed by the co-authors from Advanced Cell Diagnostics, Inc., Hayward, CA. These three co-authors (HW, YL, XM) all have stock in this company and stand to profit by any use of this testing through their company. The remaining co-authors have received nothing from the company and have no financial or other conflicts of interest to disclose.

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Authors and Affiliations

  1. Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, 660 S. Euclid Ave, St. Louis, MO, 63110, USA

    R. F. Watson, R. D. Chernock, S. K. El-Mofty & J. S. Lewis Jr.

  2. Otolaryngology—Head and Neck Surgery, Washington University School of Medicine, Campus Box 8118, 660 S. Euclid Ave, St. Louis, MO, 63110, USA

    R. D. Chernock & J. S. Lewis Jr.

  3. Radiation Oncology, Washington University School of Medicine, Campus Box 8118, 660 S. Euclid Ave, St. Louis, MO, USA

    X. Wang & W. Liu

  4. Advanced Cell Diagnostics, Inc., Hayward, CA, USA

    X. J. Ma, Y. Luo & H. Wang

Authors
  1. R. F. Watson
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  2. R. D. Chernock
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  3. X. Wang
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  4. W. Liu
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  5. X. J. Ma
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  6. Y. Luo
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  7. H. Wang
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  8. S. K. El-Mofty
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  9. J. S. Lewis Jr.
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Correspondence to J. S. Lewis Jr..

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Watson, R.F., Chernock, R.D., Wang, X. et al. Spindle Cell Carcinomas of the Head and Neck Rarely Harbor Transcriptionally-Active Human Papillomavirus. Head and Neck Pathol 7, 250–257 (2013). https://doi.org/10.1007/s12105-013-0438-z

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  • DOI: https://doi.org/10.1007/s12105-013-0438-z

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