Spontaneous Regression of Colonic Lymphoma Following Infliximab and Azathioprine Withdrawal in Patients with Crohnʼs Disease: Presidential Poster

Abstract

Purpose: We describe two cases of spontaneous regression of Epstein-Barr virus (EBV)-positive colonic lymphoma following immunosuppressive withdrawal in patients receiving combination therapy for Crohn's disease. Case 1: A 36-year-old male with a 5 year history of Crohn's disease underwent colonoscopy following therapy escalation. He had failed azathioprine and lost response to adalimumab. He was treated with infliximab 10 mg/kg every 4 weeks, azathioprine 2.5 mg/kg, oral and topical mesalamine for 9 months prior to colonoscopy. At colonoscopy, inflamed, nodular, ulcerated mucosa was noted from the descending colon to the rectum, interspersed with areas of near-healing. An ulcerated stenosis was seen in the left colon and biopsies revealed diffuse large B-cell lymphoma. Stains were positive for CD20 and BCL-2, negative for BCL-6, CD10, CD21, and Cyclin D1. Ki-67 proliferative index was 60%. In situ hybridization for EBV was positive. Infliximab and azathioprine were discontinued. Laparoscopic total proctocolectomy with end ileostomy was performed 6 weeks after colonoscopy. Operative pathology revealed no evidence of lymphoma. Stains were positive for CD20, BCL-2, and MUM1and negative for CD5, CD10, Cyclin D1, and BCL-6. Ki-67 proliferative index was 10%. EBV was equivocal. The patient received three cycles of Rituximab, Cyclophosphamide, Adriamycin, Vincristine, and Prednisone. Lymphoma is in clinical remission 6 months after his diagnosis. Case 2: A 52-year-old male with a 25 year history of Crohn's disease was found to have an ulcerated stricture at the sigmoid colon during surveillance colonoscopy. He had failed azathioprine. He received azathioprine 2.5 mg/kg and infliximab 5 mg/kg every 6 weeks for 2 years prior to colonoscopy. At colonoscopy, severe disease activity was noted throughout the sigmoid colon with an ulcerated stenosis. Biopsies from the stenotic region revealed diffuse lymphoplasmacytic proliferation composed of Reed-Sternberg cells. Stains were positive for CD30, CD15, and PAX-5, consistent with Hodgkin's lymphoma. In situ hybridization for EBV was positive. Immunosuppressive therapy was discontinued. Laparoscopic total proctocolectomy with end ileostomy was performed 10 weeks after colonoscopy. Surgical pathology revealed no evidence of lymphoma. Whole body PET/CT scans completed 9 and 14 months following diagnosis confirmed no evidence of malignancy. Conclusion: Some cases of lymphoma may regress spontaneously in patients with Crohn's disease after withdrawal of immunosuppressive therapy. The long-term outcome in these patients is unknown and warrants further study. The role of EBV is unclear, but may serve as a positive prognostic factor. Disclosure: Dr. Chiorean - Speakers Bureau and advisor for Abbott, Janssen, and UCB.