Intracranial Mesenchymal Tumors with FET::CREB Fusion: Case Report and Systematic Review of the Literature

Intracranial mesenchymal tumors (IMTs) with FET::CREB fusion are rare mesenchymal neoplasms that rely on the confirmation of the molecular hallmark FET::CREB gene fusion for diagnosis. We report a case of a 53-year-old female presenting with neurocognitive decline and seizures. Neuroimaging demonstrated a heterogeneously enhancing solid-cystic lesion in the left frontal lobe. Gross total resection (GTR) of the tumor was achieved and the patient recovered to premorbid status. Definitive diagnosis was achieved via next-generation sequencing that identified an EWSR1 (exon 7)::CREM (exon 7) fusion transcript. A systematic literature review of 72 IMTs with FET::CREB-positive cases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Publications reporting confirmed FET::CREB fusion-positive IMTs, without restriction on year of publication, were included to analyze clinicopathological correlations and prognostic determinants. Mean age at diagnosis was 27.8 (±18.3). Patients who underwent GTR demonstrated a significantly lower rate of recurrence compared to those who underwent subtotal resection (STR) (p < 0.001), suggesting that extent of resection may be an important prognostic factor; however, causal inference is precluded by the observational nature of the data. Patients who received adjuvant therapy had a higher rate of recurrence (p = 0.043); however, this association is likely attributable to confounding by indication, as adjuvant treatment was predominantly administered to patients with subtotal resection or more aggressive disease. No causal inference regarding adjuvant therapy efficacy can be drawn from these data. Our study results corroborate that accurate diagnosis relies on molecular interrogation and the extent of resection appears to be an important prognostic factor for IMTs with FET::CREB fusion.