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%; P ¼ .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.

Paraganglioma of the Bladder: a Case Report

“…The risk of metastases is higher in patients with paraganglioma of the bladder and the mutation. Consequently, an intensified follow-up and surveillance should be considered when such SDHB mutations are found [5,6].…”

“…Although rare, special attention should be paid when a SDBH mutation is found since the risk of metastases is higher in this group. The follow-up should be intensified [5,6]…”

Concurrent Urinary Bladder Paraganglioma and Adrenal Phaeochromocytoma With Succinate Dehydrogenase-B Mutation

“…PGL is associated with this syndrome caused by germline mutations in SDH [ 14 ]. Studies have demonstrated the association between PGLs in PHEO/PGLs syndrome and mutation in SDHB, SDHC, or SDHD genes [ 15 ]. PGLs in the thoracoabdominal region are associated with SDHB mutation whereas the head and neck PGLs are associated with SDHD.…”

Characteristics and genetic testing outcomes of patients with clinically suspected paraganglioma/pheochromocytoma (PGL/PCC) syndrome in Singapore

“…A study conducted in London on patients with bladder paraganglioma found pathogenic SDHB variants in 6/9 individuals, again mostly in male and younger individuals [ 25 ]. Although there have been several case series on urogenital paragangliomas in Asia, there is limited information on causative germline variants of these rare tumours [ 26 , 27 ]. In the few Asian genetic studies on urogenital paragangliomas, SDHB exon 7 deletion was reported in an Indian patient with bladder paraganglioma [ 28 ], while SDHB : c.112delC (p.Arg38fs) variant was reported in a Hong Kong Chinese patient with recurrent metastatic bladder paraganglioma [ 29 ].…”