Diffuse large B-cell lymphoma of the central nervous system in mycophenolate mofetil-treated patients with systemic lupus erythematosus

Abstract

We report the third case of primary lymphoma of the central nervous system (PCNSL) in a patient with systemic lupus erythematosus (SLE) given long-term mycophenolate mofetil (MMF). Our 43-year-old patient has a history of lupus nephritis and has been treated with MMF 500 mg/day in addition to azathioprine (AZA) for 8 years. She presented with subacute left-sided weakness. Magnetic resonance imaging revealed a gadoliniumenhancing mass in the right parietal region which was isointense on T2-weighted imaging. Brain biopsy revealed diffuse sheets of large lymphoid cells which demonstrated strong membranous expression of CD20 by immunohistochemistry and positive signal for Epstein Bar virus (EBV)–encoded RNA by in-situ hybridization study. Complete remission of PCNSL was achieved after discontinuation of MMF and administration of rituximab and whole brain radiotherapy. Patients with SLE are predisposed to development of lymphoma regardless of immunosuppressive use. One meta-analysis found that non-Hodgkin’s lymphoma was more common in SLE patients with a standardized incidence rate ranging from 5.2 to 44.4. However, the development of PCNSL secondary to immunosuppressive use is being increasingly recognised especially in MMF-treated renal transplant recipients with onset of PCNSL after a median of 14 months. It has also been described in some MMF-treated autoimmune conditions such as myasthenia gravis, dermatomyositis and relapsing polychondritis. Although AZA in combination with corticosteroids has been shown to predispose post-renal transplant patients to lymphoproliferative disease with a relative risk of 12.7, the association of AZA and EBV-related lymphoma is rare. The approach to management of this condition includes withdrawal of MMF and judicious use of future immunosuppressive agents.