Disorders of sex development (DSD) are those congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. The aim of this study was to characterize the histology of 46,XX DSD prepubertal gonads. We studied 25 gonads of fourteen 46,XX DSD patients. The age of biopsy/gonadectomy was 1.17 (0.084.17) years (median and range). Molecular studies confirmed the absence of SRY by PCR and/or MLPA in blood samples of all patients and in DNA from gonads from 8 patients. General gonadal histology was assessed on H&E stained sections from each sample by two double blinded specialists and the findings were classified as testicular, ovarian or ovotesticular parenchyma, undifferentiated gonadal tissue (UGT) and gonadoblastoma (GB). Immunohistochemical (IHC) analysis was used to identify Sertoli cells (SOX9), ovarian follicular cells (FOXL2), somatic cells (INHIBIN B), pluripotent germ cells (OCT3/4) and steroidogenic cells (HSD3B2 and CYP17A1). Twenty one gonads (corresponding to 12 patients) showed ovotesticular characteristics and 4 (2 patients) showed only testicular parenchyma. No histological alterations were found in the ovarian parenchyma. Testicular parenchyma showed signs of dysgenesis in all cases (seminiferous tubules inside the tunica albuginea) with significantly thick basal membrane (in some cases) and scarce germ cells. Regarding the patients with ovotestis, in 2/12 the first biopsy showed only testicular tissue and a second biopsy (performed 10 years later due to clinical characteristics of feminization) revealed ovarian tissue as well. Moreover, 3 cases presented UGT and in 2 other patients GB was found. IHC analysis of SOX9 and FOXL2 confirmed the presence of testicular or ovarian parenchyma, even in apparently undifferentiated structures. OCT3/4 was positive in 6 gonads (3 patients): 4 with UGT features (2 patients) and 2 with the presence of GB (1 patient). HSD3B2 and CYP17A1 revealed the presence of active steroidogenic cells. Expression of inhibin B, SOX9 and FOXL2 in UGT and GB was found. A careful histological analysis is crucial for the diagnosis. Nevertheless, the addition of several IHC markers is important to achieve a thorough characterization of the gonads. Interestingly, in all testicular parenchyma signs of dysgenesis were found. It is noteworthy that a second biopsy in 2 former testicular cases revealed the presence of ovarian parenchyma. Considering the histopathological findings in early childhood, a close clinical follow up of patients with a specialized DSD team is suggested.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology