Figure 1.

Schematic representation of the various entities of testicular germ cell tumors (GCTs). The time line is indicated on the left side and the proposed animal models on the right. The GCTs include the non-GCNIS (germ cell neoplasia in situ) related GCTs (left panel) and GCNIS-related GCTs (right panel). The non-GCNIS related GCTs are subcategorized into the prepubertal teratomas (TE) and yolk sac tumors (YST) as well as the spermatocytic tumors. These are also referred to as Type I and III, respectively. The GCNIS-related GCTs are histologically (and clinically) subdivided into the seminomas (SE) and the various elements of nonseminomatous GCTs, being embryonal carcinoma (EC), YST, choriocarcinoma, and TE. Note the overlapping histology between the prepubertal TE/YST and the TE and YST elements in the GCNIS-related nonseminomas. However, they have a separate (and independent) pathogenesis (see text for further details). The presumed cells of origin are indicated in green, reflecting a (partially and fully erased) primordial germ cell (Type I and II), to partially paternal imprinted spermatogonium/spermatocyte (Type III). The precursors are indicated when known (preinvasive), while specifically the benign and malignant behavior of the pediatric TE and YST is highlighted. In addition, the most prominent and recurrent molecular genetic changes are indicated, of putative interest to be used for molecular pathological approaches. These include total genomic anomalies, like polyploid/aneuploid, specific chromosomal imbalances like losses (-) and gains (+), as well as recurrent mutations (italics). In addition, the methylation status is indicated as well as the possible use of miR-371a-3p as a liquid biopsy molecular biomarker (underlined). All malignant histological elements, independent of age, are identified by this biomarker (except TE). The WNT pathway is specifically involved in the YST components, independent of age and also of pathogenesis.