69-year-old woman with rheumatoid arthritis and remote breast cancer presented with an 18-month history of progressive fatigue, nausea and vomiting, cognitive impairment, gait instability with resulting recurrent falls, and lower extremity weakness.  Brain MRI showed multifocal white matter lesions thought initially to be acute disseminated encephalomyelitis (ADEM. CSF analysis showed elevated protein and myelin basic protein and no oligoclonal bands.  She then received rituximab, cyclophosphamide, and IVIG but her symptoms worsened, with expressive aphasia, dysphagia, and weakness. Serial MRIs revealed new, enhancing periventricular and deep white matter lesions. A brain biopsy showed inflammatory changes suggestive of demyelination. Further workup revealed CSF 14-3-3 and RT-QuIC positivity suspicious for Creutzfeldt-Jakob disease.  A second biopsy performed revealed diffuse large B-cell lymphoma with MYD88 L265P mutation, confirming primary CNS lymphoma. She received high-dose methotrexate, Rituximab, and Temozolomide with marked clinical and radiographic improvement.

Care report/ literature review

PCNSL is a rare CNS malignancy that presents with various neurological symptoms. Misdiagnosis common due to nonspecific symptoms and imaging findings that could overlap with other pathology. Immunosuppressive treatment may obscure histopathological findings of CNS lymphomas, further complicating the diagnosis. CSF biomarkers such as 14-3-3 and RT-QuIC, previously thought to be highly specific for prion disease, can be false positives in the setting of CNS inflammation or malignancies as demonstrated in our case. 

PCNSL should be in the differential diagnosis in rapidly progressive dementia. Biomarkers traditionally associated with CJD should be interpreted with caution. Immunosuppression might obscure biopsy results, so repeat biopsy might be needed in such cases.