CNS involvement by EBV-positive extranodal T-cell lymphoma harboring STAT3 Y640F mutation following allogeneic hematopoietic stem cell transplantation: A case report

Secondary central nervous system involvement by extranodal NK/T-cell lymphoma is rare and presents significant diagnostic challenges, particularly in immune compromised patients. We report a case of a 29-year-old man with chronic active Epstein–Barr virus infection and prior extranodal NK/T-cell lymphoma status post allogeneic hematopoietic stem cell transplantation who presented with a new-onset seizure and a ring-enhancing intracranial lesion. Initial imaging findings closely mimicked cerebral toxoplasmosis, leading to empiric antimicrobial therapy and delayed diagnosis. Despite treatment, the lesion demonstrated rapid progression, prompting stereotactic biopsy, which revealed Epstein–Barr virus-positive extranodal T-cell lymphoma with a pathogenic STAT3 p.Y640F activating mutation. This case highlights the substantial radiographic overlap between central nervous system lymphoma and infectious etiologies in immunosuppressed patients, where conventional imaging modalities may lack specificity. The presence of an aggressive molecular profile, including STAT3 activation, likely contributed to rapid disease progression and poor prognosis. This report underscores the importance of maintaining a high index of suspicion for lymphoma in patients with progressive intracranial lesions unresponsive to empiric therapy and emphasizes the critical role of early tissue diagnosis to guide appropriate management.