Primary Clear Cell Sarcoma of the Ileum: A Case Report With Next-Generation Sequencing Analysis

Abstract

As the concept of clear cell sarcoma–like tumor or malignant gastrointestinal neuroectodermal tumor (CCS-LT/MGNET) has been widely accepted, primary CCS of the gastrointestinal tract (CCS-GI) is becoming a rare entity. In this article, we describe a case of primary CCS-GI that occurred in the ileum of a 65-year-old male to further illustrate its rare occurrence. Similar to CCS of soft tissue (CCS-ST), the tumor was composed of spindled to epithelioid cells displaying fascicular, nested, or pseudopapillary arrangement. The tumor cells had large round to ovoid nuclei with vesicular chromatin and prominent nucleoli, containing eosinophilic to pale cytoplasm. In contrast to CCS-LT/MGNET, immunohistochemical study also showed variable positivity of HMB45, melan A, and MiTF besides the strong and diffuse staining of S100 protein and SOX10. Fluorescence in situ hybridization (FISH) using fusion probes identified EWSR1 and ATF1 genes rearrangement. Next-generation sequencing (NGS) analysis further revealed EWSR1 exons9/8- ATF1 exon4 and ATF1 exon3- EWSR1 exon11 fusion genes. CCS-GI and CCS-LT/MGNET possibly represent 2 related entities of the same spectrum, which differentiate along 2 different pathways.

Multiple metastases of clear cell sarcoma at diagnosis presented in bone marrow aspirate: A case report

“…3,7 Recently, next-generation sequencing was performed to identify gene fusions with advantage of revealing chimerical types and fusion sites. 8 Even functional landscape of CCS genome has been rendered by copy number observations in human tumors and genetic experiments in mice in a study. 7 Slight and focal positivity of S100 was observed in immunohistochemistry in this case, which was slightly different from the literature in which S100 reacted as strong positivity.…”

“…Another chromosomal translocation [ t (2;22) (q34; q12)] resulting in chimeric EWSR1/CREB1 gene fusion also drives sarcoma‐genesis in CCS 3,7 . Recently, next‐generation sequencing was performed to identify gene fusions with advantage of revealing chimerical types and fusion sites 8 . Even functional landscape of CCS genome has been rendered by copy number observations in human tumors and genetic experiments in mice in a study 7 .…”