Carcinoma in situ of the testis in children with 45,X/46,XY gonadal dysgenesis.

The frequency of gonadal tumors in intersex patients with a karyotype including a Y chromosome is very high. In other at-risk groups, testicular germ cell tumors have been shown to be preceded by carcinoma in situ (CIS) changes. We investigated gonadal tissue from four children, aged 1 month to 18 years, with 45,X/46,XY gonadal dysgenesis, and with male or ambiguous genitalia, for the presence of CIS germ cells. Twelve gonadal biopsies and gonadectomy specimens were analyzed by means of conventional histology and densitometric DNA measurements. CIS changes were detected in specimens from all four patients, and aneuploid DNA distributions of the CIS germ cells confirmed the malignant potential of these cells. In one case, electron microscopic analysis revealed the same ultrastructural features of the CIS germ cells as previously described in seminoma cells. These observations indicate that in all patients with 45,X/46XY gonadal dysgenesis and a male phenotype, gonadal biopsies should be considered as soon as the syndrome is diagnosed. We believe that the finding of CIS warrants gonadectomy.