SMARCB1-deficient Sinonasal Carcinoma: Expanding the Pathologic Spectrum With a Series of 32 Cases.

SMARCB1-deficient sinonasal carcinoma (SDSC) is a recently recognized rare malignancy. Despite growing awareness, SDSC remains susceptible to misdiagnosis owing to its rarity and overlapping features with diverse mimics. A retrospective review of the clinical and pathologic features of 32 SDSC including 4 SMARCB-1 deficient adenocarcinoma (SDAC) cases was performed. The patients were aged 19 to 76 years with a male predominance. Most tumors arose in the naso-ethmoid (75%), and advanced stage (93.6%), with frequent multi-sinus (90.5%) involvement. Histologically, tumors exhibited diverse morphologies, including basaloid (50%), rhabdoid (25%), and undifferentiated (12.5%) types. SDAC cases showed glandular differentiation with intraluminal and stromal mucin. Empty vacuoles (62.5%), pagetoid spread (31.3%), eosinophilic-granular bodies (18.8%), hyaline globules (15.2%), and florid glomeruloid neovascularization (15.6%) were additional findings. Yolk sac-like areas were encountered in 18.6%. Immunohistochemically, tumors were defined by a complete loss of SMARCB1 (100%); a variable reactivity for p40 (65.6%), synaptophysin (13.6%), glypican3 (6.1%), and CD34 (6.1%) was present. Notably, >90% of our patients had different initial diagnoses before referral. Lymph node metastasis, locoregional recurrence, and distant metastasis were seen in 23.3%, 24.1%, and 27.6% patients, respectively; 37.9% died of disease. In conclusion, SDSCs are rare and aggressive sinonasal malignancies that display a wide histologic spectrum including glandular differentiation. This study expands on the morphologic spectrum of SDSC by analyzing a large cohort of 32 cases, adding comprehensive clinical, histopathologic, and immunohistochemical data, and highlighting features to improve diagnostic accuracy. The emergence of targeted therapies, such as EZH2 inhibitors, further underscores the importance of accurate diagnosis.