Succinate Dehydrogenase (SDH)-deficient Renal Carcinoma: A Morphologically Distinct Entity A Clinicopathologic Series of 36 Tumors From 27 Patients

AJ Gill, O Hes, Thomas Papathomas, M Sedivcova, PH Tan, A Agaimy, PA Andresen, A Kedziora, A Clarkson, CW Toon, L Sioson, N Watson, A Chou, J Paik, RJ Clifton-Bligh, BG Robinson, DE Benn, K Hills, F Maclean, Nienke NiemeijerL Vlatkovic, A Hartmann, EPM Corssmit, Arno van Leenders, C Przybycin, JK McKenney, C Magi-Galluzzi, A Yilmaz, D Yu, KD Nicoll, JL Yong, M Sibony, E Yakirevich, S Fleming, CW Chow, M Miettinen, M Michal, K Trpkov

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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.
Original languageUndefined/Unknown
Pages (from-to)1588-1602
Number of pages15
JournalAmerican Journal of Surgical Pathology
Issue number12
Publication statusPublished - 2014

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