Primary intracranial sarcoma, DICER1-mutant: 5 cases highlighting variable clinical and molecular features

Primary intracranial sarcoma, DICER1-mutant, a novel, rare entity in the 2021 WHO classification of central nervous system tumors, is characterized by spindled to pleomorphic cells with eosinophilic cytoplasmic globules, immunophenotypic evidence of myogenic differentiation and DICER1 mutations. These tumors mainly occur in children and have a distinct methylation profile. We report 5 additional cases of primary intracranial sarcoma, DICER1-mutant (age range 6 to 40 years) identified by methylation profiling and/or sequencing, including 1 in an unusual infratentorial location, 1 in an adult patient and 1 in the setting of a germline DICER1 mutation. All tumors were surgically resected and demonstrated spindle cells with fascicular growth and variable pleomorphism; 3 showed variably prominent eosinophilic cytoplasmic globules and at least focal myogenic differentiation by immunohistochemistry. All cases had a hotspot DICER1 mutation; 2 had concurrent DICER1 loss; and 1 had a known germline truncating DICER1 mutation. Three cases also demonstrated a KRAS mutation, 1 of which had a TP53 mutation. Two patients were alive with no evidence of disease after 26.7 and 39.3 months; 1 patient died of disease after 20.1 months. We demonstrate the utility of methylation profiling in combination with next generation sequencing testing in the diagnosis of this rare entity.