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

Abstract

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.

Fig. 1

Distinctive MRI of patient 2. The initial scan after the onset of new symptoms showed contrast-enhancing lesions in each middle cerebellar peduncle. The prebiopsy scan demonstrates new contrast-enhancing lesions in the right and left temporal lobes, the left parietal, and the left occipital lobes. The figure displays the left occipital lobe lesion on fluid-attenuated inversion recovery (FLAIR) (A) and postgadolinium (B) images; and the left temporal lobe lesion on FLAIR (C) and postgadolinium (D) images.Note homogeneous and dense contrast enhancement. A scan 11 months after diagnosis and treatment with rituximab and cyclophosphamide showed only scattered T2 hyperintensities without contrast enhancement.

Fig. 2

Characteristic features of Epstein-Barr virus (EBV)–associated polymorphous B-cell lymphoproliferative disorder observed in patient 2. There is evidence of a polymorphous infiltrate involving both leptomeninges (A, D) and parenchyma (B), with perivascular distribution. The infiltrate is composed predominantly of lymphocytes and plasma cells, as confirmed by the plasma cell marker CD138 (E). The kappa/lambda light chain stains displayed an excess of lambda light-chain–expressing plasma cells (F). The EBV in situ hybridization showed the presence of EBV-positive populations of lymphocytes and plasma cells both in parenchyma (C) and leptomeninges (H).