Olfactory carcinoma: a distinct high-grade neuroepithelial carcinoma of the sinonasal tract

BACKGROUND: Olfactory carcinoma (OC) is an emerging high-grade malignancy of the sinonasal tract with combined neuroepithelial and epithelial differentiation. Historically, tumors with these features were variably classified as olfactory neuroblastoma (ONB) with epithelial differentiation, mixed ONB-carcinoma, or high-grade neuroepithelial carcinoma. Increasing evidence suggests that OC represents a distinct biological entity. This systematic review aims to consolidate the current literature and clarify the diagnostic, molecular, and clinical characteristics of OC.METHODS: A systematic literature search was conducted according to PRISMA guidelines using PubMed, Embase, and Scopus databases. Studies published between 2015 and 2025 were screened using predefined eligibility criteria. Eligible studies included case reports, case series, cohort studies, and molecular profiling analyses describing sinonasal tumors with combined neuroepithelial and epithelial differentiation consistent with OC.RESULTS: Nine studies met the inclusion criteria (approximately 65 cases). OC typically arises in the superior nasal cavity and frequently presents at advanced stages. Histologically, tumors demonstrate high-grade neuroepithelial morphology combined with glandular or epithelial differentiation and diffuse cytokeratin expression. In contrast to ONB, sustentacular S100 staining is absent. Molecular analyses reveal recurrent alterations involving the Wnt signaling pathway, particularly CTNNB1 mutations, and genes of the SWI/SNF chromatin-remodeling complex. Evidence from synchronous tumors suggests that OC may arise either de novo or through clonal progression from ONB.CONCLUSIONS: Olfactory carcinoma represents a distinct high-grade neuroepithelial carcinoma of the sinonasal tract with characteristic morphologic, immunophenotypic, and molecular features. Recognition of this entity is essential for accurate diagnosis, improved classification, and future development of standardized therapeutic strategies.