History: This is a mass from the terminal ileum of a young adult. What is your diagnosis?
Answer: Clear cell sarcoma-like tumor of the ileum (also termed gastrointestinal neuroectodermal tumor).
Comment: These tumors express S100 protein but not "melanoma markers" (as opposed to classic clear cell sarcomas, which express "melanoma markers"). They often harbor EWSR1-CREB1 fusions as opposed to the usual EWSR1-ATF1 rearrangements of soft tissue clear cell sarcoma. They are very aggressive but some have responded to targeted therapy.
This case was provided Dr. Elizabeth Montgomery, Editor-In-Chief of the Pathology Survival Guides at Innovative Science Press, and Professor of Pathology and Vice Chair of Anatomic Pathology at the University of Miami. Her Survival Guides to Gastrointestinal and Soft Tissue Pathology will soon be out of stock! You can order them at: