Natural killer cell lymphoma in a pediatric patient with inflammatory bowel disease

Tumor necrosis factor α (TNF-α) antibody agents are an effective therapy for the treatment of inflammatory bowel disease (IBD); however, because of the potential for immune suppression with these drugs, TNF-α antibody agents can increase the risk of malignancy. We report here the case of an 11-year-old boy who presented with bowel obstruction. He also had a history of periodic fever, aphthous stomatitis, and cervical adenitis (PFAPA). Intestinal inflammation continued and impaired his quality of life; he was diagnosed with IBD of an undetermined type (IBD-U). Symptoms improved with infliximab, but he developed elevated transaminase levels with hepatosplenomegaly 1 year after scheduled infusions. Skin biopsy revealed an atypical lymphoid infiltrate consistent with an Epstein-Barr virus (EBV)-positive natural killer (NK)/T-cell lymphoma with associated hemophagocytic lymphohistiocytosis. Bone marrow biopsy revealed a similar EBV-positive lymphoid infiltrate consistent with an NK/T-cell lymphoma. EBV-positive tissue was present in gastrointestinal biopsies. Flow-cytometric analysis revealed an atypical, clonal NK-cell population, and biopsy specimens from several tissue sites tested positive for CD3, CD56, and CD30. The patient died soon after the diagnosis was made. This patient developed an EBV-driven malignancy while receiving infliximab. All patients with IBD who receive infliximab should be monitored for malignancy, especially young patients. This case underscores the need for future studies to better understand the biology of lymphoproliferative disorders.