HPV-related Multiphenotypic Sinonasal Carcinoma

Justin A. Bishop, Simon Andreasen, Jen Fan Hang, Martin J. Bullock, Tiffany Y. Chen, Alessandro Franchi, Joaquin J. Garcia, Douglas R. Gnepp, Carmen Gomez-Fernandez, Stephan Ihrler, Ying Ju Kuo, James S. Lewis, Kelly R. Magliocca, Stefan Pambuccian, Ann Sandison, Emmanuelle Uro-Coste, Edward Stelow, Katalin Kiss, William H. Westra

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC), originally known as HPV-related carcinoma with adenoid cystic carcinoma-like features, is a peculiar neoplasm that is restricted to the sinonasal tract, exhibits features of both a surface-derived and salivary gland carcinoma (particularly adenoid cystic carcinoma), and is associated with high-risk HPV. Given the limited number of published cases, the full clinicopathologic spectrum of this neoplasm is unclear. Here, we present an updated experience of 49 cases. All cases of HMSC were obtained from the authors' files. Immunohistochemistry for p16, c-kit, and myoepithelial cell markers (S100, actin, calponin, p63, and/or p40) was performed along with RNA in situ hybridization for HPV (type 33-specific as well as a high-risk cocktail). Fluorescence in situ hybridization studies for fusions of MYB, NFIB, and MYBL1 was performed on a subset of cases. Clinical follow-up was obtained from medical records. A total of 49 cases of HMSC were collected. Twenty-eight (57%) were from women and 18 (43%) from men, ranging in age from 28 to 90 years (mean, 54 y). Of 40 cases with detailed staging information, 43% of HMSCs presented with a high T-stage (T3 or T4). Histologically, most grew predominantly as solid nests of basaloid cells exhibiting high mitotic rates and frequent necrosis, with histologic and immunohistochemical evidence of myoepithelial differentiation. Most cases also demonstrated foci of cribriform and/or tubular growth, along with an inconspicuous population of ducts. Thirty-four (69%) cases demonstrated an unusual pattern of surface involvement where markedly atypical squamous cells colonized tracts of the sinonasal mucosa. Less consistent histologic features included squamous differentiation within the invasive tumor (n=6), sarcomatoid transformation (n=5) including overt chondroid differentiation (n=3), and prominent epithelial-myoepithelial carcinoma-like growth (n=3). All cases were positive for p16 by immunostaining and HPV by RNA in situ hybridization. Thirty-three (67%) were positive for HPV 33. No cases tested for MYB, MYBL1, or NFIB gene fusions were positive. In the 38 cases with follow-up data, (mean follow-up, 42 mo) 14 recurred locally and 2 metastasized (lung, finger). There were no regional lymph node metastases, and no tumor-related deaths. HMSC is a distinct sinonasal neoplasm characterized by myoepithelial differentiation, frequent surface epithelial involvement, and the presence of high-risk HPV (especially type 33). Although it classically exhibits a cribriforming pattern that closely resembles adenoid cystic carcinoma, our expanded series highlights a histologic spectrum that is much broader than previously recognized, warranting a change in terminology. HMSC usually presents as a large and destructive sinonasal mass with high-grade histologic features, but it paradoxically behaves in a relatively indolent manner, underscoring the importance of distinguishing HMSC from true adenoid cystic carcinoma, squamous cell carcinoma, and other histologic mimickers.

Original languageEnglish (US)
Pages (from-to)1690-1701
Number of pages12
JournalAmerican Journal of Surgical Pathology
Volume41
Issue number12
DOIs
StatePublished - Jan 1 2017

Fingerprint

Carcinoma
Adenoid Cystic Carcinoma
Neoplasms
In Situ Hybridization
RNA
Gene Fusion
Growth
Salivary Glands
Fluorescence In Situ Hybridization
Terminology
Fingers
Medical Records
Actins
Squamous Cell Carcinoma
Mucous Membrane
Necrosis
Lymph Nodes
Immunohistochemistry
Neoplasm Metastasis
Lung

Keywords

  • adenoid cystic carcinoma
  • carcinoma with adenoid cystic-like features
  • human papillomavirus
  • multiphenotypic sinonasal carcinoma
  • MYB
  • MYBL1
  • squamous cell carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Bishop, J. A., Andreasen, S., Hang, J. F., Bullock, M. J., Chen, T. Y., Franchi, A., ... Westra, W. H. (2017). HPV-related Multiphenotypic Sinonasal Carcinoma. American Journal of Surgical Pathology, 41(12), 1690-1701. https://doi.org/10.1097/PAS.0000000000000944

HPV-related Multiphenotypic Sinonasal Carcinoma. / Bishop, Justin A.; Andreasen, Simon; Hang, Jen Fan; Bullock, Martin J.; Chen, Tiffany Y.; Franchi, Alessandro; Garcia, Joaquin J.; Gnepp, Douglas R.; Gomez-Fernandez, Carmen; Ihrler, Stephan; Kuo, Ying Ju; Lewis, James S.; Magliocca, Kelly R.; Pambuccian, Stefan; Sandison, Ann; Uro-Coste, Emmanuelle; Stelow, Edward; Kiss, Katalin; Westra, William H.

In: American Journal of Surgical Pathology, Vol. 41, No. 12, 01.01.2017, p. 1690-1701.

Research output: Contribution to journalArticle

Bishop, JA, Andreasen, S, Hang, JF, Bullock, MJ, Chen, TY, Franchi, A, Garcia, JJ, Gnepp, DR, Gomez-Fernandez, C, Ihrler, S, Kuo, YJ, Lewis, JS, Magliocca, KR, Pambuccian, S, Sandison, A, Uro-Coste, E, Stelow, E, Kiss, K & Westra, WH 2017, 'HPV-related Multiphenotypic Sinonasal Carcinoma', American Journal of Surgical Pathology, vol. 41, no. 12, pp. 1690-1701. https://doi.org/10.1097/PAS.0000000000000944
Bishop JA, Andreasen S, Hang JF, Bullock MJ, Chen TY, Franchi A et al. HPV-related Multiphenotypic Sinonasal Carcinoma. American Journal of Surgical Pathology. 2017 Jan 1;41(12):1690-1701. https://doi.org/10.1097/PAS.0000000000000944
Bishop, Justin A. ; Andreasen, Simon ; Hang, Jen Fan ; Bullock, Martin J. ; Chen, Tiffany Y. ; Franchi, Alessandro ; Garcia, Joaquin J. ; Gnepp, Douglas R. ; Gomez-Fernandez, Carmen ; Ihrler, Stephan ; Kuo, Ying Ju ; Lewis, James S. ; Magliocca, Kelly R. ; Pambuccian, Stefan ; Sandison, Ann ; Uro-Coste, Emmanuelle ; Stelow, Edward ; Kiss, Katalin ; Westra, William H. / HPV-related Multiphenotypic Sinonasal Carcinoma. In: American Journal of Surgical Pathology. 2017 ; Vol. 41, No. 12. pp. 1690-1701.
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T1 - HPV-related Multiphenotypic Sinonasal Carcinoma

AU - Bishop, Justin A.

AU - Andreasen, Simon

AU - Hang, Jen Fan

AU - Bullock, Martin J.

AU - Chen, Tiffany Y.

AU - Franchi, Alessandro

AU - Garcia, Joaquin J.

AU - Gnepp, Douglas R.

AU - Gomez-Fernandez, Carmen

AU - Ihrler, Stephan

AU - Kuo, Ying Ju

AU - Lewis, James S.

AU - Magliocca, Kelly R.

AU - Pambuccian, Stefan

AU - Sandison, Ann

AU - Uro-Coste, Emmanuelle

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AU - Westra, William H.

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