title: p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: potential diagnostic pitfall with HPV-related carcinomas.
abstract: High-grade neuroendocrine carcinomas (HGNECs) of the head and neck have the morphological appearance of undifferentiated carcinomas and could be histologically similar to human papillomavirus (HPV)-associated non-keratinizing squamous cell carcinomas of the head and neck. The aim of the study is to characterize histologically, immunohistochemically, and virologically these unusual neoplasms. Nineteen HGNECs of the head and neck (1 oropharyngeal, 5 sinonasal, 7 of the larynx, and 6 of the parotid gland) were reviewed and analyzed with a immunohistochemical panel, with special emphasis on cell cycle proteins. The tumors were tested for HPV by in situ hybridization (GenPoint HPV, Dako) and PCR (SPF10-DEIA-LiPA25). Merkel cell polyomavirus was studied using the antibody CM2B4. Fifteen HGNEC were of small cell and 4 of large cell type. Most of the tumors (14/19, 73.7 %), including all the pure small cell carcinomas, showed a strong and diffuse positive staining for p16. Eleven of them (78.5 %) had Rb loss and a low or absent cyclin D1 expression. All cases were negative for HPV and polyomavirus. Most patients were smokers, diagnosed at advanced stages of the disease, and had a poor outcome, with a 5-year survival of 18 %. In conclusion, HGNECs of the head and neck are infrequently related to HPV infection, but usually show strong, diffuse positive p16 immunostaining due to Rb pathway dysregulation. Awareness of this immunohistochemical pattern of expression may avoid a potential diagnostic pitfall with HPV-associated non-keratinizing squamous cell carcinomas, which have a better prognosis.
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain. lalos@clinic.ub.es.
authors.forename: Llucia
authors.initials: L
authors.lastname: Alos
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
authors.forename: Sofia
authors.initials: S
authors.lastname: Hakim
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
authors.forename: Ana-Belen
authors.initials: AB
authors.lastname: Larque
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: de la Oliva
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Rodriguez-Carunchio
authors.affiliation: Department of Otolaryngology, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Caballero
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Nadal
authors.affiliation: Department of Maxillofacial Surgery, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Marti
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: Nuria
authors.initials: N
authors.lastname: Guimera
authors.affiliation: Department of Pathology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Fernandez-Figueras
authors.affiliation: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.affiliation: Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.|ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
keywords: HPV; Head and neck carcinoma; Neuroendocrine carcinoma; Rb; p16