title: CHARACTERISTICS AND OUTCOMES OF METASTATIC SDHB AND SPORADIC PHEOCHROMOCYTOMA/PARAGANGLIOMA: AN NATIONAL INSTITUTES OF HEALTH STUDY.
abstract: OBJECTIVE
  Overall about 10 to 20% of pheochromocytomas/paragangliomas (PHEOs/PGLs) are metastatic, with higher metastatic potential observed in succinate dehydrogenase subunit B/fumarate hydratase (SDHB/FH)-related tumors. Due to the improved availability of biochemical and genetic testing and the frequent use of anatomical/functional imaging, there is currently a higher detection rate of metastatic PHEO/PGL.
  
  
  METHODS
  A retrospective analysis of 132 patients (27 children, 105 adults) with metastatic PHEO/PGL diagnosed and treated from 2000 to 2014 was conducted.
  
  
  RESULTS
  Seventy-seven (58%) males and 55 (42%) females were included; 39 (30%) have died, with no sex preference. Seventy-three (55%) patients had SDHB mutations; 59 (45%) patients had apparently sporadic tumors (AST). SDHB patients had an average age at primary tumor diagnosis of 31 ± 16 years compared to 40 ± 15 years in AST patients (P<.001). The average metastatic interval (MI) decreased with increasing age in both SDHB and AST patients (P = .013 for both). Only 16% of all primary tumors were smaller than 4.5 cm. Eleven percent of patients had biochemically silent disease, more with SDHB. Of SDHB patients, 23% had metastatic tumors at first diagnosis, compared to 15% of AST patients. Five- and 10-year survival rates were significantly better for metastatic AST than SDHB patients (P = .01). Overall survival was significantly different between children and adults (P = .037); this was mostly attributed to the SDHB patients, in whom children had statistically significantly longer survival than adults (P = .006). The deceased patients all died due to the PHEO/PGL and mainly had noradrenergic phenotypes.
  
  
  CONCLUSIONS
  In children, metastatic PHEOs/PGLs are mainly due to SDHB mutations; in adults they are equally distributed between in SDHB mutations and AST, with better 5- and 10-year survival rates for ASTs. In SDHB patients, children survive longer than adults. Primary metastatic tumors, most presenting as noradrenergic PGLs, are larger than 4.5 cm in >80% of patients. The frequency of metastatic tumors from primary AST increases with age, including a decreased MI compared to SDHB tumors. These results support several recommendations that are summarized in the Discussion.
authors.forename: Hana
authors.initials: H
authors.lastname: Turkova
authors.forename: Tamara
authors.initials: T
authors.lastname: Prodanov
authors.forename: Marek
authors.initials: M
authors.lastname: Maly
authors.forename: Victoria
authors.initials: V
authors.lastname: Martucci
authors.forename: Karen
authors.initials: K
authors.lastname: Adams
authors.forename: Jiri
authors.initials: J
authors.lastname: Widimsky
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
authors.forename: Alexander
authors.initials: A
authors.lastname: Ling
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D009362:Neoplasm Metastasis; D010235:Paraganglioma / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D010673:Pheochromocytoma / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: C491545:SDHD protein, human; D013385:Succinate Dehydrogenase