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

Arch Pathol Lab Med. 2017 May;141(5):671-677. doi: 10.5858/arpa.2016-0403-OA. Epub 2016 Nov 7.

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 = 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 = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation
  • Paraganglioma / enzymology*
  • Paraganglioma / genetics
  • Paraganglioma / pathology
  • Retrospective Studies
  • Succinate Dehydrogenase / genetics*
  • Succinate Dehydrogenase / metabolism
  • Urinary Bladder / enzymology
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / enzymology*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Young Adult

Substances

  • SDHD protein, human
  • Succinate Dehydrogenase