Tumor risk and clinical follow-up in patients with disorders of sex development

A subset of patients with disorders of sex development (DSD) is at risk for malignant germ cell tumors (GCTs). The degree of gonadal differentiation (or "testicularization" in the presence of a specific part of the Y chromosome), in combination with expression of embryonic germ cell markers, and (a) Y specific gene(s) related to cell-cycle control and proliferation, determines this risk. Incompletely matured Sertoli/granulosa cells are insufficiently capable of directing the normal mitotic block/meiotic induction germ cell program, and as a result, embryonic germ cells are delayed or blocked in their normal maturation process. Thereby, they remain pluripotent and gain increased mitotic and survival characteristics, being the first step in the pathogenesis of GCTs. The patient's underlying genetic defect and phenotype might be informative in assessing the degree of gonadal "testicularization" on a clinical basis. Current knowledge allows development of an informative cancer risk assessment of DSD patients.