Malignant Gastrointestinal Neuroectodermal Tumors: Challenging Tumors With Diverse Morphology and Different Considerations for Differential Diagnosis.

This article focuses on malignant gastrointestinal neuroectodermal tumor (MGNET), a rare and aggressive mesenchymal neoplasm primarily arising in the small intestine of young to middle-aged adults. MGNET is characterized by distinctive histopathological features, immunohistochemical profiles (notably S100 and SOX10 positivity without melanocytic marker expression), and frequent EWSR1 gene rearrangements, particularly EWSR1::ATF1 and EWSR1::CREB1 fusions, although these rearrangements are not universally present. Differential diagnosis is challenging due to overlap with other tumors such as malignant melanoma, gastrointestinal stromal tumors, and neuroendocrine neoplasms, necessitating comprehensive clinical, histological, immunohistochemical, and molecular analyses. Treatment primarily involves surgical resection, with limited and variable responses to chemotherapy and targeted therapies; prognosis remains poor due to high rates of metastasis and recurrence. The article underscores the need for further research into MGNET’s pathogenesis, molecular characteristics, and therapeutic strategies.