In a pathogenetic sense, epithelioid soft tissue tumors basically fall into three main genetic categories: (1) switch/sucrose non-fermenting (SWI/SNF) complex-deficient tumors (with epithelioid sarcoma as their prototype); (2) epithelioid neoplasms driven by specific rare gene fusions (such as sclerosing epithelioid fibrosarcoma with EWSR1 fusions and GLI1-related malignant epithelioid soft tissue neoplasms); and (3) a heterogeneous group encompassing epithelioid variants of diverse other entities.
Expression analysis of epithelioid sarcoma cell lines by transcriptome sequencing shows a unique profile that does not cluster with any particular tissue type or with other SWI/SNF-aberrant lines.