A Case Report of INI1 Loss and <i>SMARCB1</i> Mutation in Hereditary Succinate Dehydrogenase-Deficient Renal Cell Carcinoma

Secondary loss of INI1 immunohistochemical staining has been observed in various types of renal cell carcinoma (RCC), including <i>TFE3</i>-rearranged, fumarate hydratase-deficient RCC, and collecting duct carcinoma. We report the first tumor of secondary INI1 loss with <i>SMARCB1</i> gene alteration in hereditary succinate dehydrogenase (SDH)-deficient RCC that presented in a 39-year-old woman with a germline <i>SDHB</i> mutation. The tumor appeared as a tan-brown mass with focal hemorrhage, infiltrating the renal sinus and perinephric adipose tissue. Microscopically, it showed diverse architectural patterns, including solid, tubular, pseudopapillary, and sarcomatoid areas with focal necrosis. The stroma showed sclerotic and hyalinized changes with osseous metaplasia. Immunohistochemistry for SDHB was lost throughout, despite the tumor showing nonclassic cytomorphology for SDH-deficient RCC. INI1 retention was noted in low-grade areas, while it was lost in high-grade regions. Next-generation sequencing identified a pathogenic <i>SDHB</i> variant (p.C191Y, VAF 77%) and an <i>SMARCB1</i> variant (p.P146Mfs33*, VAF 46%).