Iatrogenic immunodeficiency-associated Epstein-Barr virus (EBV) -negative natural killer cell lymphoproliferative disorder in a patient undergoing rheumatoid arthritis therapy.

Here we present a patient with rheumatoid arthritis (RA), who was suspected to have developed malignant lymphoma during immunosuppressive therapy 5 years earlier. She temporarily achieved remission after discontinuing therapy; however, her disease worsened with remittent fever and splenomegaly. Splenic biopsy demonstrated infiltration by abnormal cells, which were positive for CD56 and T cell intracytoplasmic antigen, but negative for CD3 and Epstein-Barr virus (EBV) -encoded RNA. Cytogenetic analysis of bone marrow and lumbar spine tumor revealed common complex karyotype abnormalities. Thus, she was diagnosed with chronic natural killer cell lymphoproliferative disorder (NK-LPD) and finally died of disease progression. The most common type of LPD in methotrexate-related patients with RA is B-lymphoid LPD, whereas NK-LPD is extremely rare. Furthermore, almost all cases of NK-LPD have been reported to be positive for EBV. This is the first case report on a patient with EBV-negative NK-LPD developed during immunosuppressive therapy for RA.