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

Abstract

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.

Fine-Needle Aspiration of Metastatic Central Type Primitive Neuroectodermal Tumors in Patients with a Germ Cell Tumor

“…In such scenarios, lesions at the metastatic sites can be misdiagnosed as an Ewing sarcoma or other small round blue cell tumor. Central-type PNET arising from germ cell tumors show a different immunostaining profile and lack the specific t(11: 22) translocation which is commonly present in Ewing sarcoma [3] . PNET arising from testicular germ cell tumors contain an isochromosome of the short arm of chromosome 12 [i(12p)], which is characteristic for all histological varieties of germ cell tumors of the testes [6] .…”

“…PNET arising from testicular germ cell tumors contain an isochromosome of the short arm of chromosome 12 [i(12p)], which is characteristic for all histological varieties of germ cell tumors of the testes [6] . A study of 14 cases of central type PNET arising in the testes or metastatic sites revealed that CD57, a neuroendocrine marker, was most frequently positive, followed by synaptophysin, NeuN, and neurofilament [3] . Cytokeratin AE1/3 was positive in neural tubules in a minority of the cases classified as medulloepithelioma.…”

“…Detection of a PNET component in metastatic germ cell tumors is not uncommon, although in some cases this is not appreciated in the primary tumor [2,3] . In such scenarios, lesions at the metastatic sites can be misdiagnosed as an Ewing sarcoma or other small round blue cell tumor.…”

“…It has been well documented that PNET arising from ovarian germ cell tumors or testicular germ cell tumors closely resemble CNS embryonal neoplasms or central type PNET morphologically [1][2][3] . Detection of a PNET component in metastatic germ cell tumors is not uncommon, although in some cases this is not appreciated in the primary tumor [2,3] .…”

“…Central type PNET are a family of central nervous system (CNS) neoplasms that occur mostly in children and are classified as medulloblastoma and CNS PNET including cerebral neuroblastoma, medulloepithelioma, ependymoblastoma, embryonal tumors with multilayered rosettes (also referred to as embryonal tumors with abundant neuropil and true rosettes), undifferentiated small cell embryonal tumors, and others [1][2][3][4] . However, in the new 2016 World Health Organization classification this group of tumors was further reclassified based on updated molecular studies in addition to their morphological features.…”