Pathogenesis of Testicular Germ Cell Tumors from a Developmental Point of View

Current classification systems of human germ cell tumors (GCTs) are based on histological composition. In the group of nonseminomas, different variants of teratoma (somatic differentiation), yolk sac tumor and choriocarcinoma (extra-embryonic differentiation), are recognized, as well as their stem cell component embryonal carcinoma. In addition, the seminomatous tumors are distinguished, subdivided into classic - and spermatocytic variants. The morphologically similar classic seminomas of the ovary are called dysgerminomas, and those of the brain germinomas. Tumors containing both a (classic) seminoma and a nonseminoma component are referred to as combined tumor according to the British classification , and as nonseminoma in the World Health Organisation (WHO) Classification. This traditional histological description obscures the biological diversity of this type of cancer, which hampers identification of pathogenetic mechanisms and proper comparison of the neoplastic cells to their normal counterparts. Therefore, an alternative classification was proposed, recognizing five categories (I-V) of GCTs (see Table 1), based on site of presentation, age of the patient at diagnosis, histological composition, as well as pattern of genomic imprinting, and chromosomal constitution. This thesis will deal only with the type II GCTs, predominantly of the testis, and therefore the other types will not be discussed here. The testicular type II GCTs will be referred as TGCTs.