Abstract
BACKGROUND: Ewing's sarcoma (ES) is an aggressive malignancy affecting bone and soft tissues, predominantly occurring in the skeletal system. The occurrence of Ewing's sarcoma (ES) or primitive neuroectodermal tumor (PNET) with in the female genital tract is rare. Even rarer is its occurrence in the vagina, with only 22 cases reported to date. Accurate diagnosis necessitates a multifaceted approach that includes morphology, immunohistochemistry, and molecular pathology; the gold standard for diagnosis is next-generation sequencing (NGS), which is characterized by chromosomal translocations resulting in FET-ETS gene fusions.Case description.We present an exceptionally rare case of Ewing's sarcoma in a 35-year-old woman of childbearing age. She exhibited a painless vaginal mass measuring approximately 2.5 × 2 × 0.9 cm, and according to the existing literature, our case represents the smallest tumor documented in primary vaginal Ewing's sarcoma. Immunohistochemistry (IHC) revealed membrane positivity for CD99, along with positive expression of NKX2.2, FLI-1, and VIM. Furthermore, next-generation sequencing (NGS) conducted at the Affiliated Cancer Hospital of Fudan University identified an EWSR1-FLI1 gene fusion, thereby confirming the diagnosis of vaginal Ewing's sarcoma. CONCLUSION: Vaginal Ewing's sarcoma is characterized by the absence of specific clinical manifestations and signs, along with a high rate of recurrence and metastasis. The management of these tumors primarily involves optimal local surgical intervention, followed by adjuvant therapies such as radiotherapy and/or chemotherapy.