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

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.

• Authors: Anthony J Gill, Ondrej Hes, Thomas Papathomas, Monika Šedivcová, 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 Niemeijer, Ljiljana 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
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 38 Issue 12 Pg. 1588-602 (Dec 2014) ISSN: 1532-0979 [Electronic] United States
• PMID: 25025441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Succinate Dehydrogenase

Topics

• Adolescent
• Adult
• Aged
• Carcinoma, Renal Cell (enzymology, genetics, pathology)
• DNA Mutational Analysis
• Female
• Humans
• Immunohistochemistry
• Kidney Neoplasms (enzymology, genetics, pathology)
• Male
• Middle Aged
• Polymerase Chain Reaction
• Succinate Dehydrogenase (biosynthesis, genetics)
• Tissue Array Analysis
• Young Adult