Integrated histopathology, immunoprofile, and molecular findings are necessary to diagnose rare uterine cPNETRare Uterine Tumor Analysis Highlights Complex Diagnostic Challenges

Primitive neuroectodermal tumors (PNETs) arising in the uterus, particularly those classified as the central-type (cPNET), are exceedingly rare. To date, approximately 30 cases of uterine cPNET have been reported, and their clinicopathological features remain poorly characterized. These tumors typically present as highly aggressive small round cell neoplasms with variable neuroectodermal differentiation, often posing significant diagnostic challenges owing to their overlap with other uterine malignancies, including neuroendocrine carcinoma, endometrial stromal sarcoma, and undifferentiated carcinoma. Here, we report a rare case of uterine cPNET characterized by a diffuse small round cell morphology and prominent neuroendocrine differentiation. Immunohistochemical analysis demonstrated positivity for synaptophysin, INSM1, and CD56, whereas markers associated with Ewing’s sarcoma (CD99, FLI1 and NKX2.2) were negative. Next-generation sequencing revealed no Ewing sarcoma breakpoint region 1 rearrangements, supporting the exclusion of peripheral PNET. This case highlights the diagnostic complexity of uterine tumors with neuroectodermal differentiation and expands the current morphological and immunophenotypic spectra of this entity. Accurate recognition requires the integration of histopathology, immunoprofile, and molecular findings, with particular attention paid to the differential diagnosis of other high-grade uterine malignancies.