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.