Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of renal neoplasm predominantly affecting younger individuals. It is characterized by germline mutations in SDHx genes, particularly type B. Histologically, SDH-deficient RCC features eosinophilic cytoplasmic cells forming solid nests or microcysts, sometimes entrapping normal tubules. We present three SDH-deficient RCC cases with overlapping morphological features with fumarate hydratase-deficient RCC and TFEB-rearranged RCC, an appearance that has not been previously described. All tumors lacked SDHB expression and harbored pathogenic SDHB mutations, with the germline nature confirmed in two cases. Metastasis developed in two patients. Our case set highlights the diagnostic challenges of molecularly defined renal tumors and expands the morphological spectrum of SDH-deficient RCC with unusual histological features. Clinically, these tumors appear to be aggressive.

Center for Urological Oncological Surgery National Institute of Oncology Budapest Hungary

Department of Medical Oncology and Clinical Pharmacology C National Institute of Oncology Budapest Hungary

Department of Molecular Genetics National Institute of Oncology Budapest Hungary

Department of Oncological Biobank National Institute of Oncology Comprehensive Cancer Center Budapest Hungary

Department of Oncotherapy Albert Szent Györgyi Medical School University of Szeged Szeged Hungary

Department of Pathology Albert Szent Györgyi Medical School University of Szeged Szeged Hungary

Department of Pathology and Experimental Cancer Research Semmelweis University Budapest Hungary

Department of Pathology and Laboratory Medicine Albany Medical Center Albany NY USA

Department of Pathology Faculty of Medicine in Pilsen Charles University and Teaching Hospital Pilsen Czech Republic

Department of Surgical and Molecular Pathology Tumor Pathology Center National Institute of Oncology Ráth György Utca 7 9 Budapest 1122 Hungary

National Tumor Biology Laboratory National Institute of Oncology Budapest Hungary

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