{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:21:46Z","timestamp":1784031706510,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["P3-0307 and P3-0054"],"award-info":[{"award-number":["P3-0307 and P3-0054"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995\u20132020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein\u2013Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4\/4 MD\/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11\/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs \u2265 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD\/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.<\/jats:p>","DOI":"10.3390\/cancers13194813","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T10:39:20Z","timestamp":1632739160000},"page":"4813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Neuroendocrine Carcinoma of the Larynx and Pharynx: A Clinical and Histopathological Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-112X","authenticated-orcid":false,"given":"Primo\u017e","family":"Strojan","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Institute of Oncology Ljubljana and Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"\u0160ifrer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana and Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-8002","authenticated-orcid":false,"given":"Alfio","family":"Ferlito","sequence":"additional","affiliation":[{"name":"Coordinator of the International Head and Neck Scientific Group, 35100 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5047-4034","authenticated-orcid":false,"given":"Cvetka","family":"Gra\u0161i\u010d-Kuhar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institute of Oncology Ljubljana and Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u0161tjan","family":"Lani\u0161nik","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, University Medical Center Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-8066","authenticated-orcid":false,"given":"Gaber","family":"Plavc","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Institute of Oncology Ljubljana and Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6866-3220","authenticated-orcid":false,"given":"Nina","family":"Zidar","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1634\/theoncologist.2018-0054","article-title":"Small cell and squamous cell carcinomas of the head and neck: Comparing incidence and survival trends based on Surveillance, Epidemiology, and End Results (SEER) data","volume":"24","author":"Bean","year":"2019","journal-title":"Oncologist"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1002\/lary.27785","article-title":"Nonsquamous cell laryngeal cancers: Incidence, demographics, care patterns, and effect of surgery","volume":"129","author":"Torabi","year":"2019","journal-title":"Laryngoscope"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12105-018-0894-6","article-title":"Neuroendocrine Carcinomas of the Larynx and Head and Neck: Challenges in Classification and Grading","volume":"12","year":"2018","journal-title":"Head Neck Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1093\/ajcp\/aqz106","article-title":"Update on Neuroendocrine Carcinomas of the Larynx","volume":"152","author":"Strosberg","year":"2019","journal-title":"Am. 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