We present a diagnostically complex case of primary CNS lymphoma (PCNSL) in a patient treated with ocrelizumab for tumefactive multiple sclerosis.

Differentiating between PCNSL and tumefactive MS presents a diagnostic challenge. They can mimic each other both clinically and radiologically, and they can both respond positively to steroid therapy. Also, PCNSL can be preceded by demyelinating lesions that histologically mimic multiple sclerosis, a phenomenon known as “sentinel demyelination.” Definitive diagnosis may require more than one biopsy in order to differentiate between tumefactive MS and a sentinel lesion of PCNSL.

A 55-year-old white female was diagnosed with tumefactive MS after biopsy of a large solitary lesion.  She was clinically and radiographically stable for three years on anti-CD20 monoclonal antibody ocrelizumab.  She presented with headache, left-sided weakness, and increased somnolence one month prior to her next Ocrelizumab infusion. MRI brain showed a stable left frontal lesion and a new mass-like lesion with surrounding edema in the right posterior frontal lobe.  She was treated with high-dose steroids for presumed relapse of tumefactive MS.  Symptoms returned and imaging worsened a few weeks later.  Subsequent treatment with high-dose steroids and plasma exchange completely resolved her symptoms.  Prior to completion of a prolonged oral prednisone taper, she returned with left hemiparesis, somnolence, and repeat imaging showing increased edema with uncal herniation. Decompressive craniectomy with open brain biopsy was performed. Pathology was consistent with diffuse large b-cell lymphoma (DLBCL). No systemic metastases were found.

This case highlights the importance of considering PCNSL in patients previously diagnosed with tumefactive MS. Development of new lesions while on high efficacy therapy and lack of sustained clinical or imaging response to acute immunotherapies warrant consideration of repeat biopsy.