ETMR-02. First Reported Saudi Cases of Intracranial Myxoid Mesenchymal Tumors with EWSR1-CREB Fusions: Diagnostic and Therapeutic Dilemmas.

Intracranial Myxoid Mesenchymal Tumors (IMMTs) are rare tumors with distinct histological and genetic features. Recently identified as a new distinct entity in the WHO 2021 CNS tumor classification, they pose diagnostic and therapeutic challenges due to their rarity and overlap with other CNS tumors. Herein, we present the first two known cases in Saudi Arabia diagnosed with this entity in both pediatric and adult populations. The aim of our study is to analyze the clinical, radiological, and histological features, including molecular hallmarks, and to review the literature of all reported cases since its introduction in the CNS WHO classification. Our two cases were diagnosed at King Fahad Specialist Hospital, Dammam, Saudi Arabia. We collected diagnostic reports, including clinical presentation, imaging studies, histopathological findings, and treatment outcomes. Molecular analysis was performed using next-generation sequencing (NGS) to confirm the presence of EWSR1-CREB fusions. We concluded that there are two variants of this disease with specific clinical, histopathological, and molecular characteristics. Case 1 involves a 4-year-old pediatric patient with a lesion arising from the left supratentorial region. It demonstrated high-grade histology with extensive necrosis and perivascular pseudorosettes, mimicking ependymoma or high-grade glioma. Case 2 involves a 25-year-old individual with an intraventricular mass and a low-cellularity, myxoid-rich lesion. Both cases exhibited different EWSR1-CREB fusion subtypes: EWSR1-CREM and EWSR1-CREB1 fusions, respectively. However, they developed multiple recurrences and were managed differently. Both patients are still alive with stable disease. The variety of clinical and histological presentations further complicates their management. These cases strongly highlight the complexities involved in diagnosing IMMTs, treatment strategies, disease control, and therapeutic options. We believe that this report makes a valuable contribution to the scientific literature on Intracranial Myxoid Mesenchymal Tumors (IMMTs), particularly in the context of the Middle East. This will further refine our diagnostic skills and aid in developing therapeutic strategies.