Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients

Anthony J. Gill (Lead / Corresponding author), Ondrej Hes, Thomas Papathomas, Monika Sedivcová, Puay Hoon Tan, Abbas Agaimy, Per Arne Andresen, Andrew Kedziora, Adele Clarkson, Christopher W. Toon, Loretta Sioson, Nicole Watson, Angela Chou, Julie Paik, Roderick J Clifton-Bligh, Bruce G Robinson, Diana E. Benn, Kirsten Hills, Fiona Maclean, Nicolasine D NiemeijerLjiljana Vlatkovic, Arndt Hartmann, Eleonora P M Corssmit, Geert J L H van Leenders, Christopher Przybycin, Jesse K McKenney, Cristina Magi-Galluzzi, Asli Yilmaz, Darryl Yu, Katherine D Nicoll, Jim L Yong, Mathilde Sibony, Evgeny Yakirevich, Stewart Fleming, Chung W Chow, Markku Miettinen, Michal Michal, Kiril Trpkov

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    Abstract

    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.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
    Original languageEnglish
    Pages (from-to)1588-1602
    Number of pages15
    JournalAmerican Journal of Surgical Pathology
    Volume38
    Issue number12
    DOIs
    Publication statusPublished - Dec 2014

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  • Cite this

    Gill, A. J., Hes, O., Papathomas, T., Sedivcová, M., Tan, P. H., Agaimy, A., Andresen, P. A., Kedziora, A., Clarkson, A., Toon, C. W., Sioson, L., Watson, N., Chou, A., Paik, J., Clifton-Bligh, R. J., Robinson, B. G., Benn, D. E., Hills, K., Maclean, F., ... Trpkov, K. (2014). Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients. American Journal of Surgical Pathology, 38(12), 1588-1602. https://doi.org/10.1097/PAS.0000000000000292