Ileocecal Epstein-Barr Virus-Associated Classical Hodgkin's Lymphoma arising in Crohn's Disease on Adalimumab

Summary: A 41-year-old man with a 15-year history of ileocecal Crohn's disease maintained on long-term immunosuppression with Adalimumab (40 mg/0.4 mL SC) presented with hematochezia and severe anemia (Hgb 6.4 g/dL). Colonoscopy revealed a large, ulcerated non-circumferential mass at the ileocecal valve. Mucosal biopsies showed changes consistent with severe active in ammatory bowel disease and scattered large mononuclear, bi-or polylobated cells with prominent eosinophilic inclusion-like nucleoli that were positive for CD15, CD30, PAX5, BCL6, MUM1, while negative for CD3, CD20, CD45 consistent with Hodgkin/Reed-Sternberg cells (HRS). HRS cells were positive for EBV-encoded RNA (EBER) in situ hybridization, and all cells were negative for CMV and HSV immunostains. A diagnosis of EBV (+) classical Hodgkin's lymphoma (EBV+CHL) arising in Crohn's disease was made. Despite the histologic diagnosis the patient underwent right hemicolectomy due to near complete obstruction and significant bleeding. The resection con rmed transmural Crohn's disease and EBV+CHL involving the intestine and mesenteric nodes. Diagnosis of CHL in the context of Crohn's disease is di cult given the presence of obscuring in ammation, reactive atypia in stromal cells and leukocytes, and potential presence of viral cytopathic changes. Most lymphomas occurring in the context of chronic in ammation or immunosuppression are non-Hodgkin type. The increased incidence is largely attributed to abnormal immune surveillance given the necessary use of steroids, immunomodulators and biologics. In our case, long-term treatment with a tumor necrosis factor alpha inhibitor and EBV positivity support an iatrogenic immunode ciency-associated, rather than a chronic in ammation-associated lymphoma.