Characteristics of intracranial sclerosing epithelioid fibrosarcoma and review of related literature

Abstract To investigate the histological, immunohistochemical, and molecular characteristics of sclerosing epithelioid fibrosarcoma (SEF), a rare intracranial lesion, we analyzed the clinical, pathological, and molecular features of a group of cases involving both intracranial (case 1) and extracranial (cases 2, 3, and 4) soft tissue tumors. These tumors were located in the bilateral parietal sinuses (one of four cases; 25%), thoracic vertebrae (1 of 4 cases; 25%), mediastinum (1 of 4 cases; 25%), and parathyroid soft tissue (1 of 4 cases; 25%). Microscopically, tumor cells were observed in both sparse and dense areas, arranged in sheets, cords, and a fusiform braided pattern, all within a dense sclerotic matrix. All four patients exhibited strong and diffuse positivity for MUC4 . Cases 1 and 2 harbored an EWSR1–CREB3L1 fusion; case 3 had a CPSF6–ITPR2 fusion; and case 4 exhibited multiple fusion genes, including FUS–CREB3L2 , KDM5A–ERC1 , AKAP8L–BRD4 , and ATF2–CHN1 . Methylation analysis indicated that all cases clustered within the SEF spectrum. Copy number variation analysis revealed deletions in chromosomal arms 11p and 22q across all cases. The morphologies of intracranial and extracranial SEF were found to be similar. Although MUC4 serves as a reliable marker for diagnosing SEF, its molecular findings remain nonspecific. Methylation clustering and aneuploidy score assessment should be considered as additional tools to assist in diagnosis and prognostic monitoring.