Gastrointestinal Neuroectodermal Tumor (Clear cell Sarcoma-like Tumor of the Gastrointestinal Tract).

These aggressive neoplasms tend to arise in the muscularis propria of the ileum of young adults. Spread to the liver and other sites is common and there is poor response to current therapy. They can have a nested or pseudopapillary pattern. The pitfall is that they are easy to mistake for well-differentiated neuroendocrine tumors owing to their proclivity to express synaptophysin. Keratin expression, however, is absent and they are strongly reactive for S100 protein. Some examples, such as this one, feature macronucleoli, which makes their morphology similar to that of clear cell sarcoma of soft tissue. Most such gastrointestinal tumors harbor EWSR1-CREB1 gene fusions and lack expression of markers of melanocytic differentiation whereas soft tissue clear cell sarcomas usually have EWSR1-ATF1 rearrangements and stain with melanoma markers.


1: Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006 Sep 15;12(18):5356-62.

2: Stockman DL, Miettinen M, Suster S, Spagnolo D, Dominguez-Malagon H, Hornick JL, Adsay V, Chou PM, Amanuel B, Vantuinen P, Zambrano EV. Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract. Am J Surg Pathol. 2012 Jun;36(6):857-68.

3: Green C, Spagnolo DV, Robbins PD, Fermoyle S, Wong DD. Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review. Pathology. 2018 Aug;50(5):490-498.