Intracranial mesenchymal tumours with FET::CREB fusions: Two case reports and literature review

Intracranial mesenchymal tumours with in-frame gene fusions of the FET family of RNA-binding proteins to the cyclic AMP response element-binding protein family of transcription factors are exceptionally rare primary central nervous system neoplasms, with morphological similarities to angiomatoid fibrous histiocytoma. Despite their recent inclusion in the 2021 World Health Organisation classification of tumours of the central nervous system, only a limited number of cases have been reported. We describe two cases of intracranial mesenchymal tumours harbouring fusion of the Ewing sarcoma breakpoint region 1 gene with the activating transcription factor 1 gene, both arising from the falx cerebri. Clinical, radiological, pathological, molecular, and therapeutic findings are detailed. A literature review was performed to contextualize our observations. Case 1 involved a 32-year-old man with a parafalcine lesion initially mimicking meningioma, treated with subtotal resection followed by adjuvant radiotherapy. Case 2 concerned a 69-year-old woman with a similar lesion, managed with gross total resection and radiotherapy. Histopathology in both cases revealed epithelioid morphology within myxoid or fibrous stroma, with desmin, epithelial membrane antigen, and CD99 positivity. Molecular analyses confirmed fusion of the Ewing sarcoma breakpoint region 1 gene with the activating transcription factor 1 gene. After 38 and 30 months of follow-up, respectively, both patients remained recurrence-free. These cases reinforce the recognition of intracranial mesenchymal tumours with gene fusions of the FET family of RNA-binding proteins to the cyclic AMP response element-binding protein family of transcription factors as a distinct entity. Accurate diagnosis requires combined histopathological and molecular evaluation. While gross total resection remains the preferred approach, adjuvant radiotherapy may improve disease control. Larger multicentre studies are needed to refine prognostic factors and therapeutic recommendations.