Epstein Barr virus-associated primary CNS lymphomas in elderly patients on immunosuppressive medications.
Unlike primary central nervous system lymphomas (PCNSLs) in patients with AIDS or organ transplants, PCNSLs in the elderly are usually not considered to be mediated by Epstein Barr virus (EBV); hence, diagnostic studies for EBV are not routinely performed. We encountered 4 patients, 65 years or older, who developed EBV-associated PCNSLs and who had been treated with a variety of immunosuppressive drugs for different autoimmune/collagen vascular disorders, including autoimmune polyneuropathy (mycophenolate mofetil for 5 years), polymyositis (prednisone for 16 years with intermittent methotrexate, azathioprine, and cyclophosphamide), myasthenia gravis (azathioprine >10 years), and rheumatoid arthritis (methotrexate >10 years). All patients had multifocal, necrotic brain lesions typical of EBV-positive PCNSLs on neuroimaging. Withdrawing immunosuppressives lead to PCNSL regression in some patients. The patient who had received mycophenolate mofetil was treated successfully for his EBV-associated PCNSL with rituximab and methotrexate, but later developed fatal systemic malignant melanoma, which was likely immunosuppression related. The striking feature of these cases is the variety of underlying diseases-and hence accompanying medications-that can be associated with EBV-associated PCNSLs. They serve as a diagnostic alert for neuropathologists and suggest that increased testing of PCNSLs for EBV by immunohistochemistry or in situ hybridization may be warranted in any patient on any immunosuppressive medication, but particularly the elderly.
Kleinschmidt-DeMasters
B K
BK
Department of Pathology , University of Colorado Health Sciences Center, Aurora, Colorado 80045, USA. bk.demasters@uchsc.edu
Damek
Denise M
DM
Lillehei
Kevin O
KO
Dogan
Ahmed
A
Giannini
Caterina
C
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D000069283:Rituximab; D015898:Tomography Scanners, X-Ray Computed
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D017252:CD3 Complex; D007143:Immunoglobulin Heavy Chains; D007166:Immunosuppressive Agents; D000069283:Rituximab; D008727:Methotrexate