Succinate dehydrogenase (SDH)-deficient renal carcinoma has been accepted as a provisional entity in the 2013 International Society of Urological Pathology Vancouver Classification. To further define its morphologic and clinical features, we studied a multi-institutional cohort of 36 SDH-deficient renal carcinomas from 27 patients, including 21 previously unreported cases. We estimate that 0.05% to 0.2% of all renal carcinomas are SDH deficient. Mean patient age at presentation was 37 years (range, 14 to 76 y), with a slight male predominance (M:F=1.7:1). Bilateral tumors were observed in 26% of patients. Thirty-four (94%) tumors demonstrated the previously reported morphology at least focally, which included: solid or focally cystic growth, uniform cytology with eosinophilic flocculent cytoplasm, intracytoplasmic vacuolations and inclusions, and round to oval low-grade nuclei. All 17 patients who underwent genetic testing for mutation in the SDH subunits demonstrated germline mutations (16 in SDHB and 1 in SDHC). Nine of 27 (33%) patients developed metastatic disease, 2 of them after prolonged follow-up (5.5 and 30 y). Seven of 10 patients (70%) with high-grade nuclei metastasized as did all 4 patients with coagulative necrosis. Two of 17 (12%) patients with low-grade nuclei metastasized, and both had unbiopsied contralateral tumors, which may have been the origin of the metastatic disease. In conclusion, SDH-deficient renal carcinoma is a rare and unique type of renal carcinoma, exhibiting stereotypical morphologic features in the great majority of cases and showing a strong relationship with SDH germline mutation. Although this tumor may undergo dedifferentiation and metastasize, sometimes after a prolonged delay, metastatic disease is rare in the absence of high-grade nuclear atypia or coagulative necrosis.

*Department of Anatomical Pathology †Cancer Diagnosis and Pathology Research Group §§Cancer Genetics Kolling Institute of Medical Research Royal North Shore Hospital ‡University of Sydney Sydney ††Histopath Pathology ¶¶Douglass Hanly Moir Pathology North Ryde ‡‡Department of Anatomical Pathology St Vincents Hospital Darlinghurst §§§Department of Anatomical Pathology South Western Area Pathology Service Liverpool NSW ∥∥Pathology Queensland Gold Coast University Hospital Qld ****Department of Anatomical Pathology Royal Children's Hospital Parkville Vic Australia §Department of Pathology Medical Faculty and Charles University Pilsen Czech Republic ∥Department of Pathology Josephine Nefkens Institute Erasmus Medical Centre Rotterdam Department of Endocrinology Leiden University Medical Center Leiden The Netherlands ¶Department of Pathology Singapore General Hospital Singapore Singapore Institute of Pathology Friedrich Alexander University Erlangen Germany **Department of Pathology Oslo University Hospital ***Department of Pathology The Norwegian Radium Hospital Oslo University Hospital Oslo Norway †††Robert J Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic Cleveland OH ¶¶¶Department of Pathology Alpert Medical School of Brown University Rhode Island Hospital Providence RI ††††Laboratory of Surgical Pathology National Cancer Institute Bethesda MD ‡‡‡Department of Pathology and Laboratory Medicine Calgary Laboratory Services and University of Calgary Calgary AB Canada ∥∥∥Department of Pathology Hopital Cochin Université Paris Descartes Paris France Department of Molecular Pathology University of Dundee Ninewells Hospital Dundee UK

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