[New insights from basic research on testicular germ cell tumors and updated tumorigenesis]

Type II testicular germ cell tumors (GCT) are the most common malignant disease in young men, with a steadily increasing incidence. They originate from germ cell neoplasia in situ and are classified into seminomas (SE) and nonseminomas (NS). The NS subtype embryonal carcinoma (EC) exhibits stem cell-like characteristics and, thus, has the potential to differentiate into teratomas (TE) or extraembryonic tissues, such as yolk-sac tumors (YST) and choriocarcinomas (CC). Despite the success of cisplatin-based therapy, 10-15% of GCT patients do not (or no longer) respond to this treatment. Possible reasons include the development of cisplatin-induced resistance mechanisms as well as the plasticity of GCT, which can lead to the emergence of rare, therapy-resistant subtypes and, therefore, complicate treatment. In this review article, we present an updated perspective on the current model of GCT development and summarize new molecular insights regarding the emergence of occult/resistant YST populations within SE, the growing teratoma syndrome (GTS), and somatic-type malignancies (STM). These tumor subtypes are characterized by particularly aggressive and treatment-resistant behavior. However, little is currently known about these special GCT forms. Consequently, the heterogeneity and plasticity of these GCT components complicate treatment strategies. Therefore, we also describe promising biomarkers specific for the identification of YST, GTS, and STM to enhance current diagnostic approaches and, in particular, introduce new, alternative, and targeted therapeutic options for resistant YST components.