Lymphoma transformation of tumor infiltrating lymphocytes observed in testicular patient­derived xenograft models.

Testicular germ cell tumors (TGCTs) are highly sensitive to cisplatin­based chemotherapy. Nevertheless, there are metastatic tumors that do not completely respond to front­line chemotherapy. For these tumors, surgical resection of residual masses is necessary to achieve long­term disease control. Resected tissues represent valuable clinical material, which may be used for the engraftment into immunocompromised mice to produce patient­derived xenografts (PDXs). They typically maintain similarities to the parental tumors and therefore serve as more realistic preclinical models. Moreover, a correlation between PDX treatment outcomes and clinical response to chemotherapy has been previously described. The aim of the present study was to establish and characterize TGCT patient­derived xenografts. These originated from retroperitoneal lymph node metastases infiltrated with TGCTs following previous cisplatin­based chemotherapy, in order to analyze novel treatment options for cisplatin­resistant testicular tumors. We generated two testicular patient­derived xenograft models in SCID beige male mice. Immunohistochemical analyses demonstrated that histological characteristics of the primary tumor were not retained, and transformation into lymphoma, and eventually plasmocytoma, was observed. A potential explanation for the lymphoma transformation observed in PDXs may include tumor­infiltrating lymphocytes (TILs) in xenografted samples of patients, which are transformed following engraftment into immunodeficient recipient mice. Based on these data, we indicated that lymphomagenesis prevention and terminal differentiation represent new challenges in the establishment of PDX models derived from patients with germ cell tumors.