Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study

Abstract

Context.—Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied. Objective.—To define the clinicopathologic and molecular characteristics of PBPGs. Design.—A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed. Results.—The clinicopathologic features were analyzed for 52 cases (M:F ¼ 27:25), with a mean age of 56 years (range, 22–79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1–161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P , .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P ¼ .002), and frequent lymphovascular tumor invasion (33% versus 7%; P ¼ .02) and metastases (22% versus 2%; P¼.02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only. Conclusions.—Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma. (Arch Pathol Lab Med. 2017;141:671–677; doi: 10.5858/arpa.2016-0403-OA)