To present an unusual case of primary diffuse large B-cell lymphoma of the CNS with stroke-like symptoms, imaging findings and anti-phospholipid antibodies.

Primary diffuse large B-cell lymphoma of the central nervous system is a rare primary tumor of the brain, that is challenging  to diagnose.

A 56-year-old man with hypertension, hyperlipidemia, and diabetes presented with acute onset L sided weakness with right midbrain, cerebral peduncle and thalamic increase DWI signal and antiphospholipid antibodies, initially suspected for possible stroke. Close follow up imaging with contrast study was planned due to atypical imaging findings. Patient was discharged to acute rehab on therapeutic Warfarin. Two weeks later, he returned with poor mental status, worsening left sided weakness, numbness, dysarthria and apathy. Repeat MRI brain showed increased DWI signal with increased mass effect.

Post contrast MRI brain revealed expansile infiltrative FLAIR and DWI hyperintensity in the right thalamocapsular region extending into the midbrain and anterior cerebellum with superimposed patchy enhancement in the right thalamocapsular area. Findings are suspicious of CNS lymphoma vs high-grade glioma vs inflammatory and infectious processes .Lumbar puncture was non-revealing.

A right thalamic biopsy confirmed neoplastic B-cells, positive for Bcl-2, subset Bcl-6 (50%) and MUM-1 (50%), negative for CD10, CD30, and Bcl-, compatible with primary diffuse large B-cell lymphoma of  CNS.

Immediate treatment with R-MPV regimen (rituximab, methotrexate, procarbazine, vincristine) was started, in addition to solumedrol and whole brain radiation therapy with rapid clinical improvements after steroids treatment before combination chemotherapy.

Primary CNS lymphoma is a rare and elusive disorder with variable symptoms, signs, clinical courses and images findings that can mimic stroke syndromes and requires vigilance and close follow up for accurate diagnosis and effective treatment. Hypercoagulable state or antiphospholipid antibodies can be associated with large B cell lymphoma.