Heterogeneity of gonadoblastoma germ cells: similarities with immature germ cells, spermatogonia and testicular carcinoma in situ cells.

Gonadoblastoma is defined as a neoplasm containing nests of germ cells and cells resembling Sertoli cells or granulosa cells. Gonadoblastomas arise almost exclusively in dysgenetic gonads. They are associated with an increased risk of developing germ cell tumours. Testicular germ cell tumours in adults are preceded by carcinoma in situ cells, which are characterized by their morphology, by their immunohistochemical expression of placental-like alkaline phosphatase, the proto oncogene c-kit and/or epitopes for the monoclonal antibodies M2A, 43-9F and TRA-1-60, and by their aneuploid DNA content. In order to elucidate if gonadoblastomas are in situ neoplasms from the beginning, showing similarities with carcinoma in situ cells in otherwise normal testes, we investigated the germ cells in gonadoblastomas for their expression of the immunohistochemical markers of carcinoma in situ cells from six patients aged 8 1/2 months to 20 years and 4 months. In addition, the DNA content of the germ cells from five of the six patients was also determined by densitometric measurement on Feulgen stained specimens. The germ cell populations were heterogeneous both within the same patient and between the patients. Expression of the testicular carcinoma in situ markers was detected in specimens from all the patients and germ cells with an aneuploid DNA distribution pattern in accordance with testicular carcinoma in situ cells were detected. However, apparently normal immature germ cells were also present in four of the patients of whom two also had germ cells with a morphology similar to normal spermatogonia. Thus, gonadoblastoma is most likely an in situ germ cell neoplasia from the beginning. It seems probable that the germ cell tumours associated with gonadoblastomas originate from the carcinoma in situ cells inside the gonadoblastoma. Our findings of carcinoma in situ cells in gonadoblastomas from children support the theory that the cells arose prenatally.