Intracranial myxoid mesenchymal neoplasms with EWSR1 gene rearrangement: report of 2 midline cases with one demonstrating durable response to MET inhibitor monotherapy.

Abstract

Abstract EWSR1 fusions have been identified in multiple neoplasms involving bone and soft tissue. Recently, cases of intracranial myxoid mesenchymal neoplasms harboring EWSR1-CREB family gene fusions have been reported in young patients with histologic features reminiscent of the myxoid variant of angiomatoid fibrous histiocytoma. Here, we report two cases of adult males with midline intracranial EWSR1 myxoid neoplasms. Patient 1 (age 37) presented with headaches and magnetic resonance imaging (MRI) demonstrated an enhancing right thalamic mass extending into the quadrigeminal cistern. Near-total resection was achieved, and residual disease was treated with stereotactic radiosurgery (SRS). Five-year follow-up is negative for recurrence. Patient 2 (age 28) had a past medical history significant for high-grade B-cell lymphoma of his femur and kidney for which he received systemic and intrathecal treatment. He presented to our institution with headaches, visual changes, nausea and vomiting, and MRI demonstrated a homogenously enhancing intraventricular tumor. Gross total resection was achieved, yet despite post-operative radiation therapy, he progressed 11 months later. He was then treated with radiosurgery and crizotinib, leading to stable disease 23 months after start of targeted therapy. In both cases, EWSR1 gene rearrangement was identified by fluorescence in-situ hybridization (FISH). Reverse transcription polymerase chain reaction (rt-PCR) showed a CREB1 gene fusion partner in both cases. Our cases expand the clinicopathologic features of these newly recognized tumors and include an older age at presentation and a relatively elevated proliferation index. We also present a durable response to monotherapy with a MET inhibitor in response to this gene fusion.