Malignant Gastrointestinal Neuroectodermal Tumor Mimicking Melanoma in the Small Bowel: A Diagnostic Challenge

Abstract

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare and aggressive mesenchymal neoplasm characterized by S100 and SOX10 expression and EWSR1 gene rearrangements. Diagnosis is challenging due to overlap with other gastrointestinal tumors, particularly malignant melanoma.

A 53-year-old woman presented with abdominal pain and melena. Physical examination revealed diffuse abdominal tenderness without peritoneal signs. Laboratory tests showed mild anemia (hemoglobin 11.5 g/dL) with no inflammatory markers. Upper endoscopy and colonoscopy were unremarkable. Contrast-enhanced computed tomography (CT) and CT enterography identified a 20 mm lesion in the jejunum. The patient underwent laparoscopic segmental enterectomy without complications. Initial histopathological evaluation suggested malignant melanoma. However, further analysis demonstrated diffuse S100 and SOX10 positivity with negative HMB-45, Melan-A, CD117, and CD34. Molecular testing confirmed an EWSR1 gene rearrangement, establishing the diagnosis of GNET. The patient was referred to a multidisciplinary oncology team, and surveillance was recommended. Follow-up positron emission tomography at three and six months showed no evidence of recurrence. GNET should be considered in the differential diagnosis of small bowel tumors with melanocytic features, particularly in the absence of conventional melanocytic markers. Although both GNET and melanoma express S100 and SOX10, only melanoma typically shows HMB-45 and Melan-A positivity and lacks EWSR1 rearrangements. Given the high risk of recurrence and the absence of standardized treatment protocols, accurate diagnosis is essential to guide management and avoid misclassification. This case highlights the importance of integrating histopathological, immunohistochemical, and molecular findings within a multidisciplinary approach.