Novel Germline SDHB Mutation in a 35-Year-Old Male with Malignant Bladder Paraganglioma

Abstract

ABSTRACT Objective Up to 25% of pheochromocytomas and paragangliomas (PGL) are associated with germline mutations in RET, VHL, NF1, and subunits A, B, C, or D of succinate dehydrogenase (SDH). SDHB mutations are associated with malignant extra-adrenal PGL. Codon specific genotype-phenotype relationships have not been identified. Herein is described a case of malignant bladder paraganglioma from a novel W200R SDHB mutation. The literature is reviewed and clinical management is discussed. Methods Literature review was performed to analyze the relationship between SDHB and PGL, yielding 45 unique articles, which were reviewed and cross-referenced. Results SDHB mutations have a 50% penetrance by age 35, 1/3 of paragangliomas are multifocal, 31 to 48% are malignant, and 50 to 70% of these malignant PGL develop metastases. Conclusion Based on the aggressive nature of the SDHB mutation, we recommend preoperative staging, an aggressive treatment regimen, and intensive screening for recurrence.