TY - JOUR
T1 - Succinate dehydrogenase (SDH)-deficient renal carcinoma
T2 - a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients
AU - Gill, Anthony J.
AU - Hes, Ondrej
AU - Papathomas, Thomas
AU - Sedivcová, Monika
AU - Tan, Puay Hoon
AU - Agaimy, Abbas
AU - Andresen, Per Arne
AU - Kedziora, Andrew
AU - Clarkson, Adele
AU - Toon, Christopher W.
AU - Sioson, Loretta
AU - Watson, Nicole
AU - Chou, Angela
AU - Paik, Julie
AU - Clifton-Bligh, Roderick J
AU - Robinson, Bruce G
AU - Benn, Diana E.
AU - Hills, Kirsten
AU - Maclean, Fiona
AU - Niemeijer, Nicolasine D
AU - Vlatkovic, Ljiljana
AU - Hartmann, Arndt
AU - Corssmit, Eleonora P M
AU - van Leenders, Geert J L H
AU - Przybycin, Christopher
AU - McKenney, Jesse K
AU - Magi-Galluzzi, Cristina
AU - Yilmaz, Asli
AU - Yu, Darryl
AU - Nicoll, Katherine D
AU - Yong, Jim L
AU - Sibony, Mathilde
AU - Yakirevich, Evgeny
AU - Fleming, Stewart
AU - Chow, Chung W
AU - Miettinen, Markku
AU - Michal, Michal
AU - Trpkov, Kiril
PY - 2014/12
Y1 - 2014/12
N2 - 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.
AB - 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.
U2 - 10.1097/PAS.0000000000000292
DO - 10.1097/PAS.0000000000000292
M3 - Article
C2 - 25025441
SN - 0147-5185
VL - 38
SP - 1588
EP - 1602
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 12
ER -