Malignant Germ Cell Tumors and Disorders of Sex Development

Abstract

The thesis focuses on selected disorders of sex development (DSD) with an increased risk of gonadal germ cell cancer (GCC) and aims to contribute to the refinement of management of the DSD at risk. The introductory parts review our current knowledge on development of GCC, its prevalence and diagnostics with an emphasis on the relation to DSD. Two of the included studies correlate phenotypic features with risk of GCC development (based on histological assessment) in patients with complete androgen insensitivity syndrome (CAIS) and with 45,X/46,XY mosaicism, respectively. We did not confirm any significant difference in tumor risk between CAIS patients with different gonadal position (abdominal vs. inguinal) or different level of androgen receptor activity. Based on the findings, we suspect that not all precursor germ cell lesions evolve into invasive cancer in this disorder. Level of masculinization of external genitalia reflects gonadal phenotype and risk of GCC development in patients with mosaicism. Results allow us to propose management guidelines for this disorder. Another part of the thesis describes in detail case of 45,X/46,X,psu dic (Y) gonadal dysgenesis and emphasize the need of complex approach to this disorder. Last study analyses and confirms the association between KITLG detection pattern and number of germ cell abnormalities. This is in line GCC pathogenic model proposed by van der Zwan et al. General discussion summarizes results of the studies, underlines their clinical output and presents future prospects of the research in this field