Background: Gonadectomy is generally postponed until early adulthood in complete androgen insensitivity syndrome (CAIS) and close surveillance of gonads in situ proposed in males with partial AIS (PAIS). Delaying gonadectomy further is controversial given the lack of data regarding germ cell cancer (GCC) development in adulthood and the absence of biomarkers for noninvasive GCC screening.
Aims and objectives: To study the prevalence of invasive GCC, carcinoma in situ (CIS), or signs of pre-malignancy (combined aberrant OCT3/4 and KITLG expression) in genetically confirmed AIS cases at a (post)pubertal age and study the correlation with a genetic predisposition for GCC based on allele sequencing of 13 GCC-associated SNPs.
Methods: Immunohistochemical study of 96 samples (CAIS: 72 gonadectomy, seven biopsy; PAIS: ten gonadectomy, seven biopsy). All surgical procedures were performed at or after the age of 14 years (median 17, range 1454). Allele sequencing of 13 GCC-associated SNPs.
Results: No invasive GCC were encountered. Changes suggestive for premalignancy were found in 8/79 (10.1%) CAIS samples from five women (5/41; 12.2%) at a mean age of 16.6 (1421) years; three women had bilateral changes. CIS was detected in one girl with PAIS (1/10; 10%) gonadectomised at 15 years. Preliminary analysis in 47 samples reveals a significant association between the occurrence of (pre)malignancy and a high genetic relative risk for GCC (P=0.003).
Conclusions: The prevalence of premalignant lesions in CAIS women in this cohort was 12%. Lesions are already present during adolescence and often bilateral. No prospective data exist regarding progression of such lesions to GCC. A comparable prevalence was seen in PAIS, with possibly a higher risk of malignant progression given the residual AR activity. Preliminary data suggest a significantly higher risk of (pre)malignancy in individuals with a genetic predisposition for GCC.
Funding: This work was supported by a Senior clinical investigatorship grant from the Research Foundation Flanders.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology