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

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

The American Journal of Surgical Pathology: December 2014 - Volume 38 - Issue 12 - p 1588–1602
doi: 10.1097/PAS.0000000000000292
Original Articles

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.

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*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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Conflicts of Interest and Source of Funding: Supported in part by the Cancer Institute New South Wales and Czech Republic Government grant agency (IGA NT 12010-4). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Anthony J. Gill, MD, FRCPA, Department of Anatomical Pathology, Royal North Shore Hospital, Pacific Highway St Leonards, NSW 2065, Australia (e-mail:

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