Patients with disorders of sex development (DSD) at risk of gonadal tumour development: management based on laparoscopic biopsy and molecular diagnosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? In some individuals with disorders of sex development (DSD), gonadal tumour risk is increased. The individual risk is estimated based on the molecular diagnosis and the age and approaches 30% in the high‐risk group. In the past, early gonadectomy has been advised for all individuals with 46XY DSD. Gonadectomy clearly represents an overtreatment for many individuals with 46XY DSD. Thus, further clinical indicators of individual tumour risk are urgently needed. The present study provides a comprehensive description of gonadal morphology, as seen during laparoscopy. For the first time, laparoscopic features, molecular diagnosis and histopathological findings are presented in a comprehensive context. The present study adds a detailed morphological description of the variability found in different subgroups of 46XY DSD. As three of four detected tumours were microscopic, early diagnosis by inspection appears unfeasible. Biopsy, gonadopexy and precise localisation of the gonad will potentially allow for gonadal preservation in well‐defined clinical situations. OBJECTIVE To investigate the role of laparoscopy for the early detection of gonadal tumours, with emphasis on gonadal preservation, in patients with 46XY disorders of sex development (DSD). In patients with DSD, gonadectomy is frequently recommended and depending on the age and the molecular diagnosis, an increased gonadal tumour risk exists and undesired hormone effects may arise. However, gonadectomy is irreversible and impacts considerably on body image. It represents an overtreatment for some patients and should be considered after a comprehensive diagnostic evaluation. Laparoscopy is an important technique, because it is able to retrieve small gonads and allows guided biopsies. PATIENTS AND METHODS We performed laparoscopic assessment of the gonads in 40 patients with various 46XY DSD. In all, 77 gonads were evaluated, images were analysed and compared with histological findings. Laparoscopic procedures included gonadectomy, biopsy, laparoscopic orchidolysis or the Fowler–Stephens procedure as well as the removal or splitting of uterine remnants. RESULTS In all, 19 patients underwent gonadectomy and tumours were discovered in four. Three patients had only microscopic evidence of tumour, in one the tumour was diagnosed intraoperatively. In 21 patients, biopsies were taken and the gonads preserved. Laparoscopic biopsy and gonadopexy was performed in six patients with complete androgen insensitivity syndrome (CAIS). CONCLUSION Laparoscopy and biopsy detected three microscopic tumours, one tumour was macroscopically evident. In CAIS, gonadopexy improved the visibility of the gonads on postoperative ultrasonography. This procedure facilitated the examination of the gonad at follow‐up. In complete gonadal dysgenesis, a highly variable morphology of the gonads was found. Laparoscopy improved exposure of gonads and Müllerian structures, and facilitated biopsies and organ‐preserving procedures.