The Sanctuary Within: Development of CD20+ CNS Lymphoma Despite Peripheral B‐Cell Depletion by Rituximab in a Multiple Sclerosis Patient

Introduction Patients with multiple sclerosis (MS) are not immune to developing comorbid conditions, including malignant disorders. A new neurologic worsening in a known MS patient, despite being on immunosuppressive or even antineoplastic therapy, could be a malignant condition, other than MS relapse. Case Presentation We report a middle‐aged woman with a known history of MS and under treatment with rituximab from a few years ago, who subsequently developed clinical and imaging features that were not typical for MS relapse, which was pathologically confirmed to be a diffuse large B‐cell lymphoma (DLBCL). Conclusion It is important to consider the possibility of superimposed comorbid disorders, especially malignant conditions, in the setting of immunosuppressive therapy in MS patients. Considering red flags is an important task before the diagnosis of MS relapse as an explanation for new neurologic worsening.