title: Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma.
abstract: OBJECTIVE
  Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology.
  
  
  METHODS
  We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease.
  
  
  RESULTS
  The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p < 0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm.
  
  
  CONCLUSIONS
  von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.
authors.affiliation: Department of Medicine, Albert-Ludwigs-Universität, Freiburg, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Neumann
authors.forename: B U
authors.initials: BU
authors.lastname: Bender
authors.forename: D P
authors.initials: DP
authors.lastname: Berger
authors.forename: J
authors.initials: J
authors.lastname: Laubenberger
authors.forename: W
authors.initials: W
authors.lastname: Schultze-Seemann
authors.forename: U
authors.initials: U
authors.lastname: Wetterauer
authors.forename: F J
authors.initials: FJ
authors.lastname: Ferstl
authors.forename: E W
authors.initials: EW
authors.lastname: Herbst
authors.forename: G
authors.initials: G
authors.lastname: Schwarzkopf
authors.forename: F J
authors.initials: FJ
authors.lastname: Hes
authors.forename: C J
authors.initials: CJ
authors.lastname: Lips
authors.forename: J M
authors.initials: JM
authors.lastname: Lamiell
authors.forename: O
authors.initials: O
authors.lastname: Masek
authors.forename: P
authors.initials: P
authors.lastname: Riegler
authors.forename: B
authors.initials: B
authors.lastname: Mueller
authors.forename: D
authors.initials: D
authors.lastname: Glavac
authors.forename: H
authors.initials: H
authors.lastname: Brauch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*