Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements.

Primitive neuroectodermal tumors (PNETs) are one of the most frequent types of 'non-germ cell' tumor in patients with testicular germ cell tumors and have a guarded prognosis when present in metastatic sites after cisplatin-based chemotherapy. Improved treatments, including targeted therapy, require understanding the biology of these neoplasms. We therefore analyzed the morphologic, immunohistochemical and molecular biologic features of 14 PNETs from 14 patients with concurrent or previous testicular germ cell tumors; 12 tumors were from metastatic sites and 2 were primary in the testis. Using standard light microscopic criteria for central nervous system and peripheral PNETs, we classified nine tumors as medulloepithelioma, three as medulloblastoma/supratentorial PNET, one as neuroblastic tumor with abundant neuropil and true rosettes and one as small cell embryonal tumor/PNET (Ewing sarcoma-like). Immunostains directed against INI1, CD57, S-100 protein, NeuN, WT1, neurofilament, CD99, GFAP, synaptophysin, chromogranin, AE1/AE3 cytokeratin, Fli-1 and collagen IV were performed for each case. INI1 was diffusely and strongly positive in all tumors whereas the other stains, except for cytoplasmic WT1 (which showed substantial reactivity in most tumors), were mostly focal to negative, including CD99 (eight negative, six focal) and Fli-1 (all negative). The most consistently reactive 'neuroendocrine' marker was CD57. Each case was also analyzed for chromosome 22 rearrangements using a FISH-based break-apart probe method. Only 1 tumor, classified as medulloepithelioma, was scored positive for chromosome 22 translocation (22% rearranged cells) and the remaining 13 were negative, including the one case that resembled peripheral PNET. We conclude that PNETs derived from testicular germ cell tumors mostly resemble central nervous system PNETs and generally lack the chromosome 22 translocation of peripheral PNETs. Future treatment strategies should take these findings into account.