Pleomorphic xanthoastrocytoma with anaplasia and BEND5-NTRK2 fusion in a young adult with a history of cranial radiation for childhood rhabdomyosarcoma

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor, with an anaplastic variant (PXA3) exhibiting more aggressive behavior and worse prognosis. We report the case of a young adult who developed PXA3 with a novel BEND5-NTRK2 fusion 2 decades after receiving cranial radiation for childhood rhabdomyosarcoma. The tumor’s histopathology was challenging to classify, necessitating advanced molecular profiling, which confirmed the diagnosis. The identification of an NTRK2 fusion enabled targeted therapy with Larotrectinib, leading to sustained tumor control without further radiation. This case highlights the significance of comprehensive molecular testing in rare pediatric and young adult gliomas.