D0411 - Post-Transplant Lymphoproliferative Disorder Presenting as an Isolated Pre-Pouch Ileal Ulcer in a Liver Transplant Patient With Crohn’s Disease

Introduction: Post-transplant lymphoproliferative disorder (PTLD) can occur in solid organ and hematopoietic cell transplant recipients in the setting of chronic immunosuppression. It often results from Epstein-Barr virus (EBV) affected B-cell propagation. We present a case of PTLD in a liver transplant (LT) patient with Crohn’s disease (CD) on biologic therapy.

Case Description/Methods: A 67-year-old male with primary sclerosing cholangitis (PSC) cirrhosis status post living donor LT in 2001 on tacrolimus, multiple skin cancers, recurrent PSC after transplant and pan-ulcerative colitis on sulfasalazine underwent total proctocolectomy with ileo-anal anastomosis in 2013 to 2014 for colonic dysplasia. In 2019, he was diagnosed with moderate-to-severe CD of the J-pouch and pre-pouch ileum, up to 50cm from the entry site. Vedolizumab (VDZ), an α4β7 integrin monoclonal antibody, was initiated with steroid-free clinical response on every four week dosing. Repeat pouchoscopy on VDZ showed pre-pouch ileitis up to 30cm and a large, isolated ulcer in the pre-pouch ileum, 10cm proximal to the ileitis (Figure 1). Biopsies revealed B-cell lymphoma, consistent with PTLD. Negative EBV-encoded RNA (EBER) in-situ hybridization suggested that this diagnosis was unrelated to EBV exposure. Positron emission tomography (PET) scan did not identify distant disease activity, and bone marrow biopsy was unremarkable. VDZ was stopped due to loss of response, budesonide resumed and R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was subsequently initiated. Follow-up pouchoscopy showed lymphoma regression but persistent CD activity.

Discussion: PTLD typically presents as extra-nodal masses involving the central nervous system, lungs, gastrointestinal tract, liver, skin or allograft within one year of transplant. Immunosuppression reduction is the cornerstone of management; however, more aggressive cases, as in our patient, require systemic therapy. This case highlights a unique presentation of PTLD as an isolated ileal ulcer in a CD patient 19 years post-LT. Interestingly, the ulcer did not appear endoscopically distinct from CD-related ulceration. Furthermore, while malignancy is a potential risk of certain treatments for inflammatory bowel disease (IBD), our patient had never received thiopurines or anti-tumor necrosis factor (TNF) agents, and VDZ has not been associated with an increased risk of B-cell lymphoma. He is currently stable on low dose tacrolimus and budesonide.