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

Abstract

Secondary loss of INI1 immunohistochemical staining has been observed in various types of renal cell carcinoma (RCC), including TFE3-rearranged, fumarate hydratase-deficient RCC, and collecting duct carcinoma. We report the first tumor of secondary INI1 loss with SMARCB1 gene alteration in hereditary succinate dehydrogenase (SDH)-deficient RCC that presented in a 39-year-old woman with a germline SDHB 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 SDHB variant (p.C191Y, VAF 77%) and an SMARCB1 variant (p.P146Mfs33*, VAF 46%).

Keywords: SDHB gene; SMARCB1 gene; renal mass.