Sclerosing Epithelioid Fibrosarcoma: A Distinct Sarcoma With Aggressive Features

Abstract

Since its original description in 1995, the concept of sclerosing epithelioid fibrosarcoma (SEF) as a distinctive tumor has evolved in the literature. Subsequent studies suggested that the presence of low grade fibromyxoid sarcoma (LGFMS)-like zones, occasional FUS gene rearrangements, and immunoreactivity for MUC4 all pointed to a close inter-relationship with LGFMS; however, more recent studies showed that SEF is genetically distinct from LGFMS with predominantly EWSR1-CREB3L1 fusion and complex secondary genomic alterations. To better understand the relationship between these tumors, we studied 51 cases of SEF, the largest reported series to date, and directly compared them to a previously published series of LGFMS from the same institution. The male-to-female ratio was 1.4:1 with a median age of 45 years. Tumors occurred primarily in the lower extremity (12), intra-abdominal area/visceral organs (9) and chest wall/paraspinal region (9) with a median size of 8.2 cm. The median follow-up was 49 months in 45 patients: 12 developed local recurrences and 36 developed metastases, mainly to lung and bone. Molecular studies showed EWSR1 gene rearrangement in 13 cases, 3' deletion of EWSR1 in 6, monosomy for EWSR1 in 2; FUS gene rearrangements in 3; EWSR1-CREB3L1 fusion in 7; EWSR1-CREB3L2 fusion in 1; and YAP1-KMT2A fusion in 2. Overall survival of SEF was significantly less compared with LGFMS (P≤0.0001). These results indicate that SEF is a distinct sarcoma that behaves more aggressively than LGFMS with a shorter survival, higher metastatic rate, and greater propensity to involve deep soft tissue and bone.