Nasal cavity, paranasal sinuses, nasopharynx
Sinonasal carcinoma
HPV related multiphenotypic sinonasal carcinoma

Editorial Board Member: Kelly Magliocca, D.D.S., M.P.H.
Editor-in-Chief: Debra Zynger, M.D.
Bin Xu, M.D., Ph.D.

Topic Completed: 20 June 2019

Revised: 26 June 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Human papillomavirus related sinonasal carcinoma


Bin Xu, M.D., Ph.D.
Page views in 2019 to date: 247
Cite this page: Xu B. HPV related multiphenotypic carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/HPVrelatedmultiphenotypiccarcinoma.html. Accessed July 18th, 2019.
Definition / general
  • Unique type of carcinoma characterized by its association with high risk human papillomavirus (HPV, in particular type 33), exclusive sinonasal location and mixed histologic phenotype (resembling both adenoid cystic carcinoma and squamous cell carcinoma)
Essential features
  • Located exclusively within the sinonasal tract
  • Positive for HPV, in particular type 33 and negative for MYB / MYBL1 / NFIB translocation
  • Exhibits various histologic features, including areas that resemble adenoid cystic carcinoma, squamous cell carcinoma, carcinoma with basaloid appearance
Terminology
  • HPV related sinonasal carcinoma with adenoid cystic carcinoma-like features
ICD coding
  • Newly described in 2013 and does not have its own ICD code (Am J Surg Pathol 2013;37:185)
  • Included in the current WHO classification as a provisional entity under sinonasal nonkeratinizing squamous cell carcinoma
    • ICD-0: 8072/3 - squamous cell carcinoma, large cell, nonkeratinizing, NOS
Epidemiology
Sites
Etiology
Clinical features
  • Usually present with nonspecific symptoms, e.g. nasal congestion, discharge, nasal obstruction, epistaxis and pain
Radiology description
Radiology images

Images hosted on other servers:

Aggressive mass in the inferior nasal cavity

Prognostic factors
Case reports
Treatment
  • Knowledge on the appropriate treatment for this rare tumor is limited; based on the reported cases (Am J Surg Pathol 2017;41:1690):
    • Surgical resection with appropriate margin is the main treatment approach
    • Approximately 40% of patients also receive adjuvant radiation therapy
    • Given the reported negligible risk of regional lymph node metastasis and low risk of distant metastasis, routine regional lymph node dissection or chemotherapy may not be indicated
    • Late local recurrence and distant metastasis may occur, therefore long term clinical follow up may be warranted
Microscopic (histologic) description
  • Typical microscopic features include:
    • Areas resemble adenoid cystic carcinoma of salivary gland origin, e.g. tubular, cribriform and solid architecture
    • Biphasic ductal and myoepithelial differentiation may be evident on H&E and on immunostain for myoepithelial markers (e.g. calponin, S100, SOX10 and smooth muscle actin)
    • Areas showing definite squamous differentiation may be seen in the forms of true keratinization, keratin pearls and intracellular bridges
    • Focally, the tumor may show basaloid features resembling cylindroma with peripheral palisading and high nuclear to cytoplasmic ratio, as well as tumor forming solid nests and lobules separated by hyalinized fibrous bands
    • Surface involvement with marked nuclear pleomorphism may be seen in about 70% of cases
    • At high power, typically shows randomly distributed tumor cells with marked nuclear pleomorphism and hyperchromasia
  • Other rare features that may be seen
    • Areas with pure sarcomatoid / spindle cell proliferation with or without dilated staghorn shaped vasculature
    • Heterologous mesenchymal component e.g. chondroid or osseous differentiation
Microscopic (histologic) images

Contributed by Bin Xu, M.D., Ph.D.

Surface involvement

Spindle cell area

Cribriform architecture

Tubular pattern


Basaloid area

Basaloid area with peripheral palisading

Resembling adenoid cystic carcinoma

Squamous differentiation


Calponin

SMA

p16

S100

p40

Positive stains
  • p16 consistently shows diffuse and strong nuclear and cytoplasmic staining
  • Myoepithelial differentiation by immunohistochemistry, i.e. it is typically positive for myoepithelial markers, e.g. calponin, S100 and smooth muscle actin
  • Also shows squamous differentiation by immunohistochemistry, i.e. it is typically positive for p40, p63 and high molecular weight cytokeratin (e.g. CK5 / 6 and 34βE12)
  • MYB immunohistochemistry can be positive (although negative for MYB fusion by FISH) (Head Neck Pathol 2019;13:220)
  • INI1 (retained)
Negative stains
Molecular / cytogenetics description
  • All reported cases are positive for high risk HPV using various detection methods, e.g. DNA in situ hybridization (ISH), RNA ISH and PCR based essays
  • EBV ISH (EBER)
  • Does not have any characteristic molecular or cytogenetic findings
  • Consistently negative for fusions characteristics for adenoid cystic carcinoma, e.g. MYB, MYBL1 and NFIB (Am J Surg Pathol 2017;41:1690)
Molecular / cytogenetics images

Contributed by Bin Xu, M.D., Ph.D.

RNA-ISH positive for HPV

Sample pathology report
  • Nasal cavity, left, resection:
    • HPV related multiphenotypic sinonasal carcinoma (see comment)
    • Comment: The tumor shows biphasic differentiation with ductal and myoepithelial cells arranged as tubular, cribriform and solid architecture. There are scattered tumor cells with marked nuclear pleomorphism. There is surface involvement. Immunohistochemistry studies show that the tumor is positive for S100, SMA, calponin and p16 (diffuse and strong nuclear and cytoplasmic). RNA in situ hybridization for high risk HPV is positive in this tumor. The overall histologic features and immunophenotype are consistent with the above diagnosis. In the current WHO classification (4th edition), HPV related multiphenotypic sinonasal carcinoma is considered as a provisional diagnosis in the category of sinonasal squamous cell carcinoma (Am J Surg Pathol 2017;41:1690).
Differential diagnosis
Board review question #1
A 45 year old man is present with a nasal cavity mass. A representative H&E of the mass is shown in the picture Which of the following statements is true?



  1. Differential diagnoses include adenoid cystic carcinoma of salivary gland origin and HPV related multiphenotypic sinonasal carcinoma
  2. Tumor is consistently negative for myoepithelial markers, e.g. SMA, calponin and S100
  3. Tumor may be positive for EBV
  4. 80% are positive for EWSR1 fusion
Board review answer #1
A. Differential diagnoses include adenoid cystic carcinoma of salivary gland origin and HPV related multiphenotypic sinonasal carcinoma

Reference: Nasal cavity - HPV related multiphenotypic sinonasal carcinoma

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Board review question #2
Which of the following statements is true for HPV related multiphenotypic sinonasal carcinoma?

  1. May contain areas resembling adenoid cystic carcinoma
  2. May show neuroendocrine differentiation
  3. Related with low risk HPV, e.g. type 6 and 11
  4. Typically negative for p40, p63 and high molecular weight cytokeratin
Board review answer #2
A. May contain areas resembling adenoid cystic carcinoma

Reference: Nasal cavity - HPV related multiphenotypic sinonasal carcinoma

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