title: Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism.
abstract: BACKGROUND
  Gonadectomy is avoided whenever possible in boys with 45,X/46,XY. However, no clinical markers are currently available to guide clinicians in predicting gonadal tumor risk or hormone production.
  
  
  OBJECTIVE
  The objective of the study was to test the hypothesis that gonadal histology and risk for development of a malignant germ cell tumor are reflected by the clinical presentation of a 45,X/46,XY individual.
  
  
  METHODS
  The design of the study was the correlation of clinical data [external masculinization score (EMS), pubertal outcome] with pathology data (gonadal phenotype, tumor risk).
  
  
  METHODS
  This was a multicenter study involving two multidisciplinary disorder of sex development teams.
  
  
  METHODS
  Patients included genetically proven 45,X/46,XY (and variants) cases, of whom at least one gonadal biopsy or gonadectomy specimen was available, together with clinical details.
  
  
  METHODS
  Patients (n = 48) were divided into three groups, based on the EMS. Gonadal histology and tumor risk were assessed on paraffin-embedded samples (n = 87) by morphology and immunohistochemistry on the basis of established criteria.
  
  
  METHODS
  Gonadal differentiation and tumor risk in the three clinical groups were measured. Clinical outcome in patients with at least one preserved gonad was also measured.
  
  
  RESULTS
  Tumor risk in the three groups was significantly related to the gonadal differentiation pattern (P < 0.001). In boys, hormone production was sufficient and was not predicted by the EMS.
  
  
  CONCLUSIONS
  The EMS reflects gonadal differentiation and tumor risk in patients with 45,X/46,XY. In boys, testosterone production is often sufficient, but strict follow-up is warranted because of malignancy risk, which appears inversely related to EMS. In girls, tumor risk is limited but gonads are not functional, making gonadectomy the most reasonable option.
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University Hospital Ghent and Ghent University, 9000 Ghent, Belgium. martine.cools@ugent.be
authors.forename: M
authors.initials: M
authors.lastname: Cools
authors.forename: J
authors.initials: J
authors.lastname: Pleskacova
authors.forename: H
authors.initials: H
authors.lastname: Stoop
authors.forename: P
authors.initials: P
authors.lastname: Hoebeke
authors.forename: E
authors.initials: E
authors.lastname: Van Laecke
authors.forename: S L S
authors.initials: SL
authors.lastname: Drop
authors.forename: J
authors.initials: J
authors.lastname: Lebl
authors.forename: J W
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: L H J
authors.initials: LH
authors.lastname: Looijenga
authors.forename: K P
authors.initials: KP
authors.lastname: Wolffenbuttel
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics* / Q000473:pathology; D006066:Gonads / Q000473:pathology*; D006801:Humans; D008297:Male; D009030:Mosaicism; D009369:Neoplasms / Q000235:genetics*; D010641:Phenotype; D012306:Risk; D012729:Sex Chromosome Aberrations; D014424:Turner Syndrome / Q000235:genetics* / Q000473:pathology