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Embryonic-type neuroectodermal tumor (ENT; previously referred to as primitive neuroectodermal tumor, PNET) of the testis and gynecologic tract share morphologic features with small round blue cell tumors, including Ewing sarcoma (ES), yet are biologically, therapeutically, and prognostically distinct. The diagnosis of ENT can be challenging, and it is unclear if there are reliable biomarkers that can be used to confirm this diagnosis. This study characterized 50 ENTs arising from the testis (n=38) and gynecologic tract (n=12; 7 ovary/5 uterus) with 27 biomarkers (AE1/AE3, ATRX, CD99, chromogranin-A, Cyclin D1, Fli-1, GFAP, GLUT-1, IDH1/2, INSM1, MTAP, NANOG, Nestin, neurofilament, NKX2.

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Ewing sarcoma (EwS) is characterized by a balanced chromosomal translocation in which a member of the FET gene family is fused with an E26 transformation specific (ETS) transcription factor: the most common fusion being EWSR1-FLI1. Traditionally, EwS includes Ewing-like tumors, Askin tumors, and peripheral primitive neuroectodermal tumors (PNET), indicative of a neuroectodermal relationship. Previously, in the absence of genetic diagnostics, extraosseous EwS could be mistaken for neuroblastoma (NB), which has become particularly clear in the history of the CHP100 cell line.

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Large circumferential tumors encasing the heart are exceedingly rare, and the differential diagnosis include primary pericardial sarcomas, non-Hodgkin lymphoma, pericardial primitive neuroectodermal tumor, primary pericardial mesothelioma, and exceptionally mature benign lipoma. Lipomas are rare primary heart tumors. Most are epicardial in origin, although they may arise in the myocardium.

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Ewing's sarcoma, though rare, primarily affects children and young adults, commonly manifesting in long bones. Cranial involvement, particularly in the frontal bone, is exceptionally uncommon, posing diagnostic and therapeutic challenges. Meticulous pathological assessment is crucial for recognizing and managing such atypical presentations.

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