title: Association of urinary bladder paragangliomas with germline mutations in the SDHB and VHL genes.
abstract: OBJECTIVE
  Our primary goal was to examine the clinical characteristics of a series of patients with urinary bladder paragangliomas (UBPGLs), focusing particularly on their genetic backgrounds.
  
  
  METHODS
  We analyzed the medical records of patients who presented to the National Institutes of Health with UBPGL from 2000 to 2013 to determine their clinical characteristics and outcomes, biochemical phenotype, tumor size, and genetic background.
  
  
  RESULTS
  Of the 27 patients with UBPGLs who were identified, 17 (63%) had underlying genetic mutations. Overall, 14 (51.9%) patients had a germline mutation in the succinate dehydrogenase subunit B gene (SDHB), and 3 (11.1%) had mutations in the von Hippel-Lindau gene (VHL). Of the 21 patients who had biochemical data available before their first operation, 19 (90.5%) presented with a noradrenergic biochemical phenotype; 7 (33.3%) patients had tumors that also secreted dopamine. In addition, 1 patient (4.8%) had elevated metanephrine levels, and 2 (9.5%) had normal biochemical data. In total, 13 (48.1%) patients in the series were diagnosed with metastatic disease, at either first presentation or follow-up; 6 of these patients (46.1%) had SDHB mutations.
  
  
  CONCLUSIONS
  UBPGLs typically present with a noradrenergic phenotype and are frequently associated with underlying germline mutations. Patients presenting with these rare neuroendocrine tumors should be screened for these mutations. In addition, patients with UBPGLs should be followed up closely for metastatic development regardless of genetic background, as almost half of the patients in this series presented with metastatic disease and less than half of them had SDHB mutations.
authors: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors: Victoria L
authors: VL
authors: Martucci
authors: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; Section of Endocrinology and Metabolism, Department of Medicine, University of Santo Tomas Hospital, Manila, Philippines.
authors: Zarina G
authors: ZG
authors: Lorenzo
authors: Urologic Oncology Branch, National Cancer Institute, Bethesda, MD.
authors: Michael
authors: M
authors: Weintraub
authors: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors: Jaydira
authors: J
authors: del Rivero
authors: Radiology and Imaging Sciences Department, Warren Magnuson Clinical Center, National Institutes of Health, Bethesda, MD.
authors: Alexander
authors: A
authors: Ling
authors: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Maria
authors: M
authors: Merino
authors: Urologic Oncology Branch, National Cancer Institute, Bethesda, MD.
authors: Minhaj
authors: M
authors: Siddiqui
authors: Urologic Oncology Branch, National Cancer Institute, Bethesda, MD.
authors: Brian
authors: B
authors: Shuch
authors: Urologic Oncology Branch, National Cancer Institute, Bethesda, MD.
authors: Srinivas
authors: S
authors: Vourganti
authors: Urologic Oncology Branch, National Cancer Institute, Bethesda, MD.
authors: W Marston
authors: WM
authors: Linehan
authors: Urologic Oncology Branch, National Cancer Institute, Bethesda, MD. Electronic address: piyush.agarwal@nih.gov.
authors: Piyush K
authors: PK
authors: Agarwal
authors: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Electronic address: karel@mail.nih.gov.
authors: Karel
authors: K
authors: Pacak
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: Paraganglioma; SDHB; Succinate dehydrogenase; Urinary bladder; von Hippel-Lindau