SMARCB1 (INI1)-deficient sinonasal carcinoma: a series of 13 cases with assessment of histologic patterns

A significant proportion of sinonasal malignancies comprise poorly differentiated/undifferentiated carcinomas that defy accurate histologic classification and behave aggressively. Recent years have seen a refinement of this spectrum by inclusion of novel entities harboring specific genetic alterations, including SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC), characterized by inactivating alterations in SMARCB1 gene, as demonstrated by loss of INI1 immunoexpression. Cyclin D1 is a cell-cycle regulatory protein downstream of INI1. Loss of INI1 leads to derepression of cyclin D1 transcription, suggesting its role as a putative therapeutic target. However, cyclin D1 expression has not been assessed in SDSCs. We retrieved all sinonasal carcinomas, including sinonasal undifferentiated carcinoma, undifferentiated carcinoma, poorly differentiated squamous cell carcinoma, and adenocarcinoma. Histopathologic features were reviewed. INI1 immunohistochemistry was performed. Cyclin D1 was performed in cases showing INI1 loss. Loss of INI1 staining was seen in 13 cases (5.8%), including 11 males and 2 females (age range, 11-65 years). Original diagnoses included SDSC (3/13), sinonasal undifferentiated carcinoma (3/13), adenocarcinoma (3/13), poorly differentiated squamous cell carcinoma (2/13), and poorly differentiated carcinoma (2/13). Tumors were predominantly basaloid in 6 cases and plasmacytoid/rhabdoid in 5 cases. We identified 2 cases having oncocytoid cells arranged in a gland-like pattern. Significant cyclin D1 immunoexpression was absent. SDSC is a rare, emerging entity that resembles a poorly differentiated carcinoma. Histomorphologic spectrum of these tumors is evolving. In addition to basaloid and plasmacytoid/rhabdoid cells, oncocytoid/adenocarcinoma-like pattern can also be seen in SDSC and predicts INI1 loss. These histologic patterns can further be subjected to INI1 immunohistochemistry for correct diagnosis.