Primary Gliosarcoma With Mesenchymal Differentiation Resembling Follicular Dendritic Cell Sarcoma

Gliosarcoma of the central nervous system (CNS) is a rare and aggressive neoplasm exhibiting biphasic differentiation into glial and mesenchymal components. We report a primary gliosarcoma with mesenchymal differentiation resembling follicular dendritic cell sarcoma (FDCS). A 72-year-old man presented with a rim-enhancing lesion in the left frontotemporal parenchyma. Histologically, the tumor was biphasic, comprising a glioblastoma (GBM) component of diffusely infiltrative GFAP- and Olig2-positive oligodendroglial-like cells with microvascular proliferation, and an FDCS component composed of cohesive sheets, nests, and fascicles of CD21-, CD23-, and CD35-positive plump spindle cells. NGS analysis performed on the microdissected components revealed shared PTEN p.N48S mutations with high variant allele frequencies and MGMT promoter methylation, suggesting a monoclonal origin. Furthermore, the two components exhibited divergent genetic profiles: the glial component was characterized by an FGFR1 mutation, PDGFRA fusion, KIT/KDR amplification, and a whole-arm 1p/19q codeletion, whereas the sarcomatous component harbored an ERBB4 p.S853F mutation. These alterations predominantly converged on the RAS-MAPK and PI3K-AKT-mTOR signaling pathways. No IDH1/2 mutations, EGFR gene amplification, or TERT promoter mutations were detected in either component. This case represents the first documented instance of primary gliosarcoma with FDCS differentiation, thereby expanding its known differentiation spectrum. Furthermore, it demonstrates the necessity of separately analyzing each histological component in the diagnosis of challenging cases.