Diagnostic Uncertainty in Rapidly Progressive Brainstem Lesions: A Radiological Diagnosis of Probable CNS Relapse of Diffuse Large B-cell Lymphoma.

We present the case of a 78-year-old woman with a history of diffuse large B-cell lymphoma (DLBCL), previously treated as per the REMoDL-B (Randomised Evaluation of Molecular-Guided Therapy for Diffuse Large B-cell Lymphoma With Bortezomib) protocol with rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone, alongside intrathecal methotrexate for CNS prophylaxis, who presented 10 years after achieving systemic remission with a 15-day history of hyperactivity, choreiform movements, pressured speech, and incontinence. Initial differentials included mania, hyperactive delirium, and infective or autoimmune encephalitis. An extensive autoimmune, infective, and paraneoplastic screen, together with cerebrospinal fluid (CSF) cytology and flow cytometry, was unrevealing. Initial magnetic resonance (MR) imaging showed bilateral midbrain and pons hyperintensity on T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), with no evidence of restricted diffusion, a pattern that led the clinical team away from the diagnosis of central nervous system (CNS) lymphoma relapse and towards an inflammatory or infective process. Repeat MR imaging of the head was performed after the patient deteriorated clinically despite empirical treatment for infective encephalitis with intravenous ceftriaxone and aciclovir. This demonstrated marked radiological progression, with subsequent contrast-enhanced MRI revealing homogeneous enhancement extending to the bilateral thalami and basal ganglia, with newly developed diffusion restriction, a pattern substantially more typical of CNS lymphoma. Positron emission tomography-computed tomography (PET-CT) confirmed metabolically active disease at corresponding sites but identified no extracranial target for biopsy; the deep bilateral location of the lesion was deemed too high risk to allow stereotactic sampling. In the absence of histological confirmation, the case was discussed at the regional neuro-oncology multidisciplinary team (MDT) meeting, where isolated CNS relapse of DLBCL was adopted as the most probable diagnosis on radiological and clinical grounds alone. Given an Eastern Cooperative Oncology Group (ECOG) performance status of 4, the patient was not a candidate for treatment and was discharged on a palliative pathway. This case highlights three key learning points: CNS relapse of DLBCL should remain an active diagnostic consideration regardless of the duration of prior remission; the initial lack of diffusion restriction on early MR imaging is not sufficient to exclude CNS lymphoma; and, when tissue diagnosis is unattainable, early neuro-oncology MDT involvement is essential to reach a working diagnosis on radiological and clinical grounds before the window for potential treatment closes.