{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:29:17Z","timestamp":1790285357921,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for &lt;1% of HN cancers (HNCs), with a 5-year overall survival (OS) &lt;20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min\u2013Max: 31\u201386)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II\/IVA\/B, all received (chemo)radiotherapy with\/without prior surgery or induction chemotherapy, with complete response in 7\/8 (87.5%). Among n = 6 recurrent\/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent\/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut\/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.<\/jats:p>","DOI":"10.3390\/cancers15092431","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T06:20:42Z","timestamp":1682317242000},"page":"2431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck"],"prefix":"10.3390","volume":"15","author":[{"given":"Santiago","family":"Cabezas-Camarero","sequence":"first","affiliation":[{"name":"Medical Oncology Department, Hospital Cl\u00ednico Universitario San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Garc\u00eda-Barber\u00e1n","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, Hospital Cl\u00ednico Universitario San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8827-2497","authenticated-orcid":false,"given":"Javier David","family":"Ben\u00edtez-Fuentes","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Cl\u00ednico Universitario San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel J.","family":"Sotelo","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Aliada Cancer Center, Lima 15036, Peru"},{"name":"Medical Oncology Department, Cl\u00ednica San Felipe, Lima 15072, Peru"},{"name":"Medical Oncology Department, Hospital Mar\u00eda Auxiliadora, Lima 15801, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Carlos","family":"Plaza","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Encinas-Bascones","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"De-la-Sen","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzin","family":"Falahat","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Gimeno-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Otolaryngology-Head and Neck Surgery Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-2278","authenticated-orcid":false,"given":"Manuel","family":"G\u00f3mez-Serrano","sequence":"additional","affiliation":[{"name":"Otolaryngology-Head and Neck Surgery Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Puebla-D\u00edaz","sequence":"additional","affiliation":[{"name":"Radiation Oncology Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"De-Pedro-Marina","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricruz","family":"Iglesias-Moreno","sequence":"additional","affiliation":[{"name":"Maxillofacial Surgery Department, Hospital Cl\u00ednico Universitario San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"P\u00e9rez-Segura","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Cl\u00ednico Universitario San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00428-016-1982-1","article-title":"p16 overexpression in high-grade neuroendocrine carcinomas of the head and neck: Potential diagnostic pitfall with HPV-related carcinomas","volume":"469","author":"Alos","year":"2016","journal-title":"Virchows Arch."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"780716","DOI":"10.3389\/fonc.2022.780716","article-title":"Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective","volume":"12","author":"Prisciandaro","year":"2022","journal-title":"Front. 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