Undifferentiated gonadal tissue, Y chromosome instability, and tumors in XY gonadal dysgenesis.

Patients with XY gonadal dysgenesis are at increased risk of developing gonadal tumors. The etiology of several cases of XY gonadal dysgenesis remains unknown, but X/XY gonadal mosaicism has been hypothesized to play a role. At the histologic level, the presence of persistent primitive sex cords containing immature germ cells in dysgenetic gonads (an entity called undifferentiated gonadal tissue, or UGT) was recently described, and these immature germ cells are thought to be at risk of neoplastic transformation. To further investigate both these aspects, we retrospectively studied the gonads from 30 patients with pure (22) and mixed (8) gonadal dysgenesis. Cytogenetic analyses performed on 35 gonads revealed that structurally abnormal Y chromosomes were lost in a majority of cells from the gonads, explaining the gonadal dysgenesis of patients bearing a rearranged Y chromosome. On the other hand, normal Y chromosomes were less often lost in gonads of patients with gonadal dysgenesis. At the histologic level, 43 of the 51 gonads presented areas characteristic of a streak; 13 of these streak gonads also presented areas of UGT. Structures resembling sex cords but without germ cells were found in many of the streaks not containing UGT, suggesting that UGT was initially present. Of the 13 gonads containing both UGT and a streak, 9 developed a tumor. The proximity of UGT with the tumors as well as the immunostaining patterns (PLAP+, OCT3/4+, and CD117/KIT+) suggests that germ cells found in UGT are a risk factor for gonadal tumors.