Primary Intracranial Sarcoma, DICER1-Mutant, With Prominent Chondroid Differentiation: Case Report and Summary of Reported Patients in Literature

Primary intracranial sarcoma, DICER1-mutant, included as a new diagnostic entity in the 2021 WHO Classification of Central Nervous System Tumors, is a rare, but aggressive neoplasm generally identified in the supratentorial forebrain. The prognostic implications of these uncommon tumors and optimal treatment strategy remain unclear. A 19-year-old woman was found unresponsive after reporting a severe headache. CT demonstrated an intra-axial, mass-like hemorrhage in the left temporal lobe which was subsequently resected. A review of the electronic medical record, histologic characterization by hematoxylin and eosin-stained sections and a targeted panel of immunohistochemical stains, and molecular characterization was pursued. The tumor was pleomorphic and demonstrated varying cellularity. The tumor cells had hyperchromatic nuclei with a spindled to round appearance. Numerous mitoses, interspersed islands of mature hyaline cartilage, and scattered eosinophilic globules associated with cells with marked nuclear atypia were noted. The tumor cells were positive for desmin, myogenin, and SMSA (focal) and negative for other lineage markers, suggestive of a mesenchymal neoplasm with myogenic differentiation. Next-generation sequencing revealed DICER1 (E1705K and P1805fs) and KRAS (Q61H) variants; the composite methylation profile prompted a final diagnosis of primary intracranial sarcoma, DICER1-mutant. This lesion underscores the histologic and immunophenotypic variability of these rare tumors. Notable features include prominent cartilaginous islands, retained H3K27me3 expression, prominent expression of desmin, and the presence of the unique DICER1 P1805fs variant, which has not previously been reported in this tumor type. We compile the molecular and immunohistochemical findings of all primary intracranial sarcomas, DICER1-mutant to date.