Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma: 42 novel tumors in 38 patients

Background: Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of renal cell carcinoma representing approximately 0.05-0.2% of all renal carcinomas (Am J Surg Pathol 2014; 38: 1588-602). As this is a relatively recently described tumor type, we sought to document additional cases seen across multiple institutions internationally. Design: Collaborators with a special interest in urogenital pathology were invited to contribute RCCs with compatible morphology including intracytoplasmic inclusions, flocculent eosinophilic cytoplasm, cystic change and entrapped benign tubules. Following centralized review and SDHB IHC, only cases with loss of expression of SDHB were included. Putative prognostic factors including ISUP nucleolar grade, presence of coagulative necrosis and mitoses per 10 high power fields (hpfs) were recorded. Results: The age range was 19 to 72 years, with a mean of 43.1 years, and a slight male predominance (male-to-female ratio 1.2:1). A relevant family history was identified in two patients only. Multifocal or bilateral tumors were identified in 4 patients. Tumors ranged in size from 10 to 200 mm in diameter (mean 81.2 mm). The morphologic growth patterns were in keeping with those previously described. Most tumors were of low ISUP nucleolar grade (Grade 1-2, 55%, Grade 3, 20%, and Grade, 4 25% [with focal pleomorphism only]), and had eosinophilic cytoplasm with the inclusion of at least focal cytoplasmic vacuoles or watery-appearing flocculent inclusions. Necrosis, which was often focal, was present in 26%. Loss of SDHA expression (implying SDHA mutation) was uncommon, being present in only 1 case. CK7 staining was only present focally in 1 case. Stage was pT1 in 36%, pT2 in 32% and pT3 or higher in 32%. One patient died of disease at 26 months after diagnosis. One patient was alive with lung metastases and another with retroperitoneal lymph nodes. Conclusions: We document the clinicopathological spectrum of a novel series of 42 SDH-deficient RCCs occurring in 38 patients, which is the largest cohort assembled to date. We confirm that the recognition of these tumors rests on the morphology and the immunohistochemistry for SDHA and SDHB. Identification of such tumors necessitates long-term patient follow-up and surveillance, as well as potential genetic counseling and investigation of family members.