Cabezas Camarero, SantiagoGarcía Barberán, VanesaBenítez Fuentes, Javier DavidSotelo, Miguel J.Plaza Hernández, José CarlosEncinas Bascones, AlejandroDe la Sen, OscarFalahat Noushzady, FarzinGimeno Hernández, JesúsGómez Serrano, ManuelPuebla Díaz, FernandoDe Pedro Marina, ManuelIglesias Moreno, María CruzPérez Segura, Pedro2026-02-042026-02-042023-04-24Cabezas-Camarero S, García-Barberán V, Benítez-Fuentes JD, Piñero-Alfaro V, et al. Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck. Cancers (Basel). 2023 Apr 24;15(9):2431. doi:10.3390/cancers150924312072-669410.3390/cancers15092431https://hdl.handle.net/20.500.14352/131475Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <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–Max: 31–86)): 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 diseaseengAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.3390/cancers15092431https://www.mdpi.com/2072-6694/15/9/2431open access616.99head and neck cancerneuroendocrineT-cell repertoiretumor mutational burdenimmunotherapyCiencias Biomédicas32 Ciencias Médicas