New Insights Into Succinate Dehydrogenase–Deficient Renal Cell CarcinomaA Comprehensive Analysis of a Case Series With Novel Mutation Sites
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 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.
Contributor Notes
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The authors have no relevant financial interest in the products or companies described in this article.
This research was supported by the National Natural Science Foundation of China (grant number 82072654) and the Key Research and Development Program of Shaanxi Province (grant number 2025SF-YBXM-322).
Junfeng Wu, Yilin Wang and Linni Fan contributed equally to this work