SMARCA4-deficient carcinoma of the head and neck region: report of 8 new sinonasal and non-sinonasal cases and literature review

Neoplasms with inactivating mutations in SWI/SNF chromatin remodeling complex subunits gained attention in the head and neck (H&N) region due to their poor clinical outcomes. The sinonasal tract is a recognized "hot-spot" for SMARCA4-deficient cancers, including SMARCA4-deficient sinonasal carcinomas, and most sinonasal teratocarcinosarcomas. To date, only two H&N SMARCA4-deficient carcinomas have been reported outside the sinonasal region. We identified eight cases of SMARCA4-deficient H&N carcinomas from the authors' files and reviewed their clinicopathological features. All cases with available tissue blocks were investigated by molecular genetic methods using next-generation sequencing (NGS). The cohort included four sinonasal and four non-sinonasal tumors involving the tongue, oral floor, the upper jaw submucosa, and the hypopharynx. The extra-sinonasal cases affected three males and one female (ages 61-81). Histologically, two cases showed poorly differentiated small cell morphology, one case resembled salivary duct carcinoma, and one case had a dedifferentiated squamous cell carcinoma phenotype. Regional lymph node metastases were documented in two cases. Sinonasal tumors showed spindle cell morphology, olfactory neuroblastoma-like features with glandular or squamoid differentiation areas, and an undifferentiated small cell pattern. This study expands the known anatomical distribution and histological spectrum of SMARCA4-deficient H&N carcinomas. Their occurrence outside the sinonasal tract is rare and poses a diagnostic challenge. These tumors are highly aggressive and often present at advanced stages. In the sinonasal region, they can mimic olfactory neuroblastoma, while in other H&N sites, they can resemble neuroendocrine carcinoma.