Intracranial mesenchymal tumor with EWSR1-rearrangement (FET::CREB family): A case series with clinico-radiological and pathological correlation and review of literature.

Abstract

Intracranial mesenchymal tumors with female expressed transcript::cyclic AMP responsive element binding protein (FET::CREB) fusion, characterized by Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) rearrangements, represent a rare and complex category of neoplasms with varied morphologies and significant diagnostic challenges. These tumors commonly occur in young adults, presenting as dural-based masses with solid and cystic components on radiological imaging, often mimicking meningioma. Histopathologically, they exhibit a spectrum of features, including spindle, stellate, and epithelioid cells within myxoid or collagenous stroma, occasionally with hemangioma-like vasculature or chronic inflammatory infiltrates. Immunohistochemistry typically reveals strong positivity for cluster of differentiation 99 (CD99) and epithelial membrane antigen (EMA), with variable expression of Desmin, S100, and MUCIN 4 (MUC4). Molecular studies confirm EWSR1 rearrangements via fluorescence in situ hybridization (FISH), while RNA sequencing further elucidates specific fusion partners, such as cyclic AMP response element binding protein (CREB)1 or ATF1. Differential diagnosis includes solitary fibrous tumors, inflammatory myofibroblastic tumors, and chordoid meningiomas, necessitating thorough morphological and immunohistochemical analysis. Emerging genomic profiling divides these tumors into two epigenetic subgroups with distinct molecular and clinical profiles, influencing prognosis and progression-free survival. This case series highlights five instances of such tumors, underscoring the importance of recognizing their unique histopathological and molecular characteristics for accurate diagnosis. While the study employed FISH for cost-effective analysis, the absence of RNA sequencing limits identification of fusion partners. Overall, the study contributes valuable insights into these rare tumors, advancing understanding of their pathology and potential clinical implications.