Frequency of gonadal tumours in complete androgen insensitivity syndrome (CAIS): A retrospective case-series analysis

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. Objective and hypotheses To establish the frequency of histological abnormalities in CAIS in relation to the age at gonadectomy. Method 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. Discussion 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. Conclusion Summary tableAbnormal histology. Benign tumour n = 6 Sertoli cell adenoma (SCA)n = 8 testicular hamartoma (TH)n = 2 mixed SCA + TH Germ cell neoplasia in situ (GCNIS) (age at gonadectomy) n = 6 (2 years 9 months, 16 years, 17 years,*17 years, 20 years,*53 years)*Associated with benign changes Malignant tumour (age at gonadectomy) n = 1 malignant sex cord stromal tumour (68 years)n = 1 seminoma (30 years) Open table in a new tab