title: Human papillomavirus-related carcinoma with adenoid cystic-like features of the sinonasal tract: clinical and morphological characterization of six new cases.
abstract: OBJECTIVE
  Human papillomavirus (HPV) is known as causative for squamous cell carcinoma (SCC) of the oropharynx, but is also found not infrequently in carcinomas of the sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour HPV33 and have a significant morphological overlap with adenoid cystic carcinoma (ACC), a rare and aggressive carcinoma originating in the minor salivary glands. Termed 'HPV-related carcinoma with ACC-like features', only nine cases have been reported. To clarify the occurrence of these tumours we screened a large material for the presence of HPV-related ACC-like carcinoma. The identified tumours were characterized immunohistochemically and with fluorescence in-situ hybridization, and clinicopathological information for all cases is presented.
  
  
  RESULTS
  Forty-seven candidate cases were screened for presence of HPV. Six cases were identified and genotyped as HPV types 33, 35, and 56. All six cases had areas of dysplastic mucosal lining and showed remarkable heterogeneous morphologies. MYB, MYBL1, and NFIB genes were intact and, interestingly, staining for MYB protein was largely negative in contrast to what was found in ACC. One patient experienced a local recurrence 11 years after initial treatment and the remaining five patients were alive without evidence of disease.
  
  
  CONCLUSIONS
  We report six new cases of HPV-related ACC-like carcinoma and found that, although in a small material, the prognosis for these patients seems more favourable than for ACC. For the distinction between ACC and HPV-related ACC-like carcinoma, p16, MYB immunohistochemistry or investigation of MYB, MYBL1 and NFIB gene status are valuable.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Otorhinolaryngology and Maxillofacial Surgery, Zealand University Hospital, Køge, Denmark.
authors.forename: Simon
authors.identifier: http://orcid.org/0000-0002-1528-4988
authors.initials: S
authors.lastname: Andreasen
authors.affiliation: Departments of Pathology, Otolaryngology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Thomas van Overeem
authors.initials: TV
authors.lastname: Hansen
authors.affiliation: Departments of Pathology, Otolaryngology and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Bilde
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000473:pathology* / Q000821:virology*; D003528:Carcinoma, Adenoid Cystic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications; D010255:Paranasal Sinus Neoplasms / Q000473:pathology* / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
keywords: HPV; MYB; MYBL1; NFIB; adenoid cystic carcinoma; human papillomavirus; human papillomavirus type 33; sinonasal