Work

New Insights Into Succinate Dehydrogenase–Deficient Renal Cell Carcinoma: A Comprehensive Analysis of a Case Series With Novel Mutation Sites

Year: 2025

Type: article

Abstract: Context.—: Succinate dehydrogenase-deficient renal cell carcinoma (RCC) is a newly classified subtype of RCC in the World Health Organization classification of urinary and male genital tumours. However, systemic reports on this tumor are limited. Objective.—: To give new insights into the clinicopathologic and molecular features of succinate dehydrogenase complex iron sulfur subunit B (SDHB)-deficient RCC. Design.—: Data from 5 SDHB-deficient RCC patients diagnosed at our hospital between 2016 and 2022 were collected and studied through light microscopy, immunohistochemistry (IHC), ultrastructural analysis, and Sanger sequencing. Results.—: The median age of patients was 34 years; 2 were male and 3 were female. Grossly, the tumors were well defined, with an average diameter of 7 cm. Histologically, the cells were arranged in diverse patterns: solid, nested, glandular, or tubular with scattered cysts containing eosinophilic, wispy, or bubbly appearances. One patient's tumor exhibited an obvious papillary structure with focal aggregation of foam cells, and 3 tumors displayed focal micropapillary structures. Two patients presented with high-grade International Society of Urologic Pathology 3 nuclei. The tumor cells in all cases lacked SDHB expression by IHC stain. In addition, the average value of the combined positive score of programmed death ligand-1 (PD-L1, SP263) in all patients was 18. Electron microscopy revealed significant mitochondrial abnormalities. Genetic testing confirmed SDHB germline mutations in all tumors. One patient's tumor presented a novel, previously unreported mutation: c.697_700del in exon 7. Follow-up revealed metastasis in 1 patient, leading to mortality. Conclusions.—: Our findings broaden the morphologic spectrum and highlight a new point mutation in the SDHB gene, providing a genetic change spectrum for this tumor entity.

Source: Archives of Pathology & Laboratory Medicine

DOI: 10.5858/arpa.2025-0233-oa