Molecular analysis of testicular germ cell tumor in a male patient with 45,X/46,XY mosaicism: case report with review of literature.

The 45,X/46,XY mosaicism is a rare condition with a wide range of phenotypes, including a nearly normal male or female phenotype and variable degrees of gonadal differentiation. Dysgenetic gonads containing Y chromosome material carry an increased risk of developing gonadal germ cell tumors. However, to date, molecular analyses of testicular germ cell tumors (TGCTs) in patients with 45,X/46,XY mosaicism have not been reported. We encountered a 17-year-old male patient with 45,X/46,XY mosaicism who presented with undervirilized external genitalia. Ultrasound examination revealed an abnormality in the right testis, and subsequent orchiectomy confirmed the presence of gonadoblastoma, germ cell neoplasia in situ, and seminoma. Molecular analysis of the tumor tissue revealed a heterozygous pathogenic KIT mutation (c.2446G>T, p.(Asp816Tyr)) and copy number gains across nearly all chromosomes, including 12p. This is the first report of genetic analysis of a TGCT in a patient with 45,X/46,XY mosaicism, revealing molecular abnormalities similar to those in male patients without differences of sex development. Furthermore, we reviewed five cases of seminoma in patients with 45,X/46,XY mosaicism, including the present case. These observations suggest that seminoma may develop after puberty regardless of the degree of masculinization, testicular position, or initial biopsy findings, highlighting the need for careful long-term surveillance in these patients.