ArticleEuropean archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery2026
Clinical, genetic and immunohistochemical characterization of sinonasal tumors with neuroectodermal differentiation.
Article in European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeSinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma (SNEC), and olfactory neuroblastoma (ONB) represent a heterogeneous group of high-grade sinonasal tumors with overlapping morphological and immunophenotypic features, making accurate classification challenging. Our aim was to apply genetic and immunohistochemical analyses to reclassify a cohort of cases and to compare their clinical features.
methodsWe analyzed 61 tumors originally diagnosed as ONB (n = 15), SNEC (n = 12), and SNUC (n = 34). Immunohistochemistry was performed for cytokeratin (CK), six neuroendocrine (NE) markers (synaptophysin, chromogranin A, CD56, INSM1, NeuroD1, ASCL1), p16, Ki67, SMARCB1, SMARCA4, and NUT. IDH2 R172 mutation status was assessed by Sanger sequencing and immunohistochemistry. Results were correlated with clinical and follow-up data.
resultsReclassification was required in 22/61 cases (36%) and concerned one SMARCA4-deficient carcinoma, one SMARCB1-deficient carcinomas, one NUT carcinoma, 14 IDH2-mutated carcinomas, and five cases consistent with olfactory carcinoma (OC). A NE-high profile was identified in all reclassified tumour subtypes except SMARCB1-, SMARCA4-, and NUT-rearranged carcinomas, occurring in 8/9 (89%) ONB, 4/5 (80%) OC, 3/9 (33%) SNEC, 6/21 (29%) SNUC, and 5/14 (36%) IDH2-mutated carcinomas. IDH2-mutated carcinomas were found across all 3 diagnostic categories and were associated with significantly better 5-year disease-free survival (83% versus 31%, p = 0.027). ONB patients showed the most favorable outcome with 5-year overall survival of 86% versus 46% for combined SNEC and SNUC (p = 0.133). A tendency toward longer overall survival was also observed for CK-negative tumors (81% versus 42%, p = 0.051) and for NE-high tumors (73% versus 40%, p = 0.086).. No associations were found between Ki67 index and outcome.
conclusionHigh-grade sinonasal tumors with neuroectodermal differentiation show substantial histological and immunophenotypic overlap, and over one-third required reclassification when applying extended immunohistochemical and genetic profiling. Our findings emphasize the clinical relevance of refining tumor classification, particularly regarding IDH2 mutation status and CK/NE expression patterns, to improve prognostication and therapeutic decision-making.
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