title: Frequency of gonadal tumours in complete androgen insensitivity syndrome (CAIS): A retrospective case-series analysis.
abstract: BACKGROUND
  Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder of sex development (DSD) where affected individuals are phenotypically female, but have an XY karyotype and testes. The risk of gonadal tumour development in CAIS may increase with age; incidence rates have been reported to be 0.8-22% in patients who have retained their gonads into adulthood. Consequently, gonadectomy has been recommended either during childhood or after puberty is complete, although there is no consensus on the optimal timing for this procedure.
  To establish the frequency of histological abnormalities in CAIS in relation to the age at gonadectomy.
  
  
  METHODS
  Data were collected from the Cambridge DSD database on patients with CAIS (n = 225; age range 3-88 years) who had undergone gonadectomy, and their age of gonadectomy, gonadal histology and immunohistochemistry.
  
  
  RESULTS
  Evaluable data were obtained from 133 patients. Median age at gonadectomy was 14.0 years (range: 18 days-68 years). Pubertal status was: prepuberty, n = 62; postpuberty, n = 68. Thirteen cases were aged >20 years at gonadectomy. The pattern of histology is summarised in the Summary table.
  
  
  CONCLUSIONS
  In this large case series of CAIS patients who had undergone gonadectomy, while the combined malignant and premalignant gonadal histology prevalence was 6.0%, the findings confirm the low occurrence of gonadal malignancy in CAIS, with a frequency of 1.5%. The two cases of malignancy were postpubertal. Germ cell neoplasia in situ (GCNIS) was observed in six cases, of which one occurred prepuberty and five postpuberty. The study highlighted difficulties in diagnosis of GCNIS and the need for histological analysis in expert centres.
  
  
  CONCLUSIONS
  The results support the current recommendation that gonads in CAIS can be retained until early adulthood. The small number of individuals with gonadectomy after age 20 years do not allow firm conclusion regarding later adulthood. Therefore, it is recommended that the option of gonadectomy be discussed in adulthood. Some form of regular surveillance of the gonads is then recommended, although none of the available options are ideal.
authors.affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Chaudhry
authors.affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. Electronic address: rt268@medschl.cam.ac.uk.
authors.forename: R
authors.initials: R
authors.lastname: Tadokoro-Cuccaro
authors.affiliation: Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands; Sophia Children's Hospital, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: S E
authors.initials: SE
authors.lastname: Hannema
authors.affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Acerini
authors.affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: I A
authors.initials: IA
authors.lastname: Hughes
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D013734:Androgen-Insensitivity Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000601:surgery*; D001707:Biopsy, Needle; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006066:Gonads / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology* / Q000473:pathology / Q000601:surgery*; D010053:Ovary / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D018570:Risk Assessment; D046468:Sexual Development / Q000502:physiology; D013737:Testis / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D055815:Young Adult
keywords: Androgen insensitivity syndrome; Carcinoma in situ (CIS); Germ cell neoplasia in situ (GCNIS); Gonadal tumour; Gonadectomy