Potential role of tirabrutinib as part of an optimal treatment strategy for lymphomatosis cerebri: illustrative case

BACKGROUND: Lymphomatosis cerebri (LC) is a rare variant of primary CNS lymphoma characterized by diffuse fluid-attenuated inversion recovery (FLAIR) hyperintensity on MRI. OBSERVATIONS: A 71-year-old woman presented with a 1-month history of nausea. On admission, she showed no focal neurological deficits except dizziness. MRI revealed diffuse FLAIR hyperintensity from the cerebellar vermis to the midbrain involving the right temporal and parietal lobes, accompanied by partial diffusion-weighted imaging (DWI) hyperintensity and no gadolinium enhancement. 18F-fluorodeoxyglucose positron emission tomography demonstrated no abnormal uptake, and CSF analysis demonstrated elevated β2-microglobulin (MG) levels and an MYD88 mutation on cell-free DNA that leaked into the CSF. A targeted biopsy of the DWI-hyperintense region confirmed CD20-positive diffuse large B-cell lymphoma. She underwent therapy with rituximab, methotrexate, procarbazine, and vincristine followed by high-dose cytarabine, achieving temporary remission; however, relapse occurred 1 month after consolidation therapy. Tirabrutinib was initiated, resulting in complete radiological resolution for 5 months. LESSONS Diffuse white matter abnormalities without enhancement should raise suspicion of LC and prompt targeted biopsy, particularly from DWI-hyperintense regions. CSF β2-MG and MYD88 mutation analysis provide valuable diagnostic clues for distinguishing LC from malignant glioma. This case also suggests a potential therapeutic role for tirabrutinib in early-relapsing LC. https://thejns.org/doi/10.3171/CASE26337.