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EBV-associated lymphoproliferative disorder of CNS associated with the use of mycophenolate mofetil

Departments of Neurology (B.P.O.) and Laboratory Medicine (A.D., C.G.), Mayo Clinic and Foundation and the Mayo Clinic Cancer Center, Rochester, MN 55905; and Department of Neurology (S.V.), University of Texas Southwestern Medical Center, Dallas, TX 75390; USA

Address correspondence to Brian Patrick O'Neill, Department of Neurology, 200 SW First Street, Rochester, MN 55905, USA.

Epstein-Barr virus (EBV)-associated lymphoid proliferations are a well-recognized complication of congenital or acquired systemic immunosuppression. The CNS is a frequent site for development of such lymphoid proliferations. We describe the clinical, imaging, and pathologic observations of a CNS disorder histologically similar to posttransplantation lymphoproliferative disorder that occurred in four patients with autoimmune disease treated with mycophenolate mofetil (MM). Two patients had polymorphous lymphoplasmacytic infiltration of brain parenchyma, and two had monomorphous infiltrations consistent with diffuse large B-cell lymphoma. In situ hybridization for EBV-encoded RNA was positive in all four patients. All patients improved after MM withdrawal and the use of rituximab. Because of a favorable toxicity profile, MM is now being used as steroid-sparing immunomodulatory therapy in autoimmune disorders. Based on our experience presented herein, we recommend caution in patient selection for MM and strict surveillance of those patients with autoimmune disorders who receive MM.

Key Words: CNS • EBV • lymphoproliferation • mycophenolate • primary CNS lymphoma

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