Clinical implications of overt and cryptic Y mosaicism in individuals with dysgenetic gonads

The most common germ cell neoplasm in individuals with dysgenetic gonads who have Y-chromosomal material in their genome (45,X/46,XY;46,XY Swyer syndrome) is gonadoblastoma. Gonadoblastoma is considered to be an in situ germ cell neoplasm and recapitulates the embryonic development of the gonad. The clinical significance of gonadoblastoma is that it may progress to dysgerminoma and other highly malignant germ cell neoplasms. The current literature suggests that the overall incidence of germ cell neoplasms in individuals with mosaic 45,X/46,XY karyotypes varies from 10% to 30%. The purpose of this presentation is to review the available literature and the experience at the Medical College of Georgia to characterize and define the risks of germ cell tumors in 45,X individuals who carry a population of overt or cryptic 46,XY cells with or without a morphologically abnormal Y chromosome. The inappropriate and incomplete differentiation of the dysgenetic gonad sets the stage for an unstable situation that may lead to uncontrolled proliferation of primitive germ cells. The potential for these unpredictable transformations is what constitutes the true risk of the dysgenetic gonad and its precursor neoplasm-gonadoblastoma.