Sclerosing Epithelioid Fibrosarcoma: A Distinct Sarcoma With Aggressive Features

Area of Science:

• Oncology
• Surgical Pathology
• Molecular Diagnostics

Background:

• Sclerosing epithelioid fibrosarcoma (SEF) has an evolving classification, with prior links suggested to low-grade fibromyxoid sarcoma (LGFMS) based on morphology and gene fusions.
• Recent molecular data indicate SEF is genetically distinct from LGFMS, primarily characterized by EWSR1-CREB3L1 fusions and complex genomic alterations.

Purpose of the Study:

• To investigate the largest series of SEF cases to date (n=51) and directly compare their clinicopathological and molecular features with LGFMS.
• To clarify the distinct biological and clinical behavior of SEF relative to LGFMS.

Main Methods:

• Retrospective analysis of 51 SEF cases, including clinical data, histopathology, and molecular studies (gene rearrangements, fusions, and genomic alterations).
• Direct comparison of SEF cohort with a previously published institutional LGFMS cohort.

Main Results:

• SEF predominantly affects adults (median age 45) and occurs in deep soft tissues (lower extremity, abdomen, chest wall).
• High rates of local recurrence (12/45) and distant metastasis (36/45), primarily to lung and bone, were observed.
• Molecular findings in SEF included EWSR1 rearrangements (13), EWSR1-CREB3L1 fusion (7), and other fusions (YAP1-KMT2A, EWSR1-CREB3L2).
• SEF demonstrated significantly worse overall survival compared to LGFMS (P≤0.0001).

Conclusions:

• Sclerosing epithelioid fibrosarcoma is a distinct entity from LGFMS, characterized by unique genetic alterations.
• SEF exhibits a more aggressive clinical behavior than LGFMS, with higher metastatic potential, deeper tissue involvement, and inferior survival rates.