Post-Transplant Lymphoproliferative Disorder: A Diagnostic Challenge Following Negative Needle Biopsy

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation, affecting around 1% of kidney transplant recipients. Epstein-Barr virus (EBV) infection and intense immunosuppression are major contributing risk factors. It usually affects extranodal sites and has a rapid course, especially following anti-rejection treatment. The diagnosis can be challenging due to limitations of needle biopsy and histologic variability. Case Description: We present a case of a 36-year-old male with end-stage kidney disease of hypertensive etiology who underwent a deceased donor kidney transplant in October 2023. The patient was maintained on tacrolimus, mycophenolate mofetil, and prednisone. He developed Banff 2B T-cell and antibody-mediated rejection in August 2024, managed with antithymocyte globulin, plasma exchange, and intravenous immunoglobulin. In November 2024, he presented with gastrointestinal symptoms and worsening renal function (Creatinine (Cr) 3.5 → 5.5 mg/dL). Imaging showed a new, rapidly growing allograft mass. CT revealed a large heterogeneous lesion at the renal hilum with ureteric involvement. Fine needle aspiration (FNA) showed necrotizing fibrohistiocytic inflammation with no evidence of malignancy. Renal function deteriorated (Cr peaked at 15.2 mg/dL), requiring dialysis. Pathology following nephrectomy (12/5/2024) revealed EBV-positive diffuse large B-cell lymphoma (DLBCL), consistent with monomorphic PTLD [figure 1]. The donor and recipient were both EBV-positive before transplantation. The patient was given four doses of rituximab; EBV DNA became undetectable. He remains dependent on dialysis. Discussion: PTLD may progress rapidly after anti-rejection treatment and can escape diagnosis on needle biopsy, mainly in necrotic lesions. High clinical suspicion for PTLD is warranted when transplant recipients develop new graft mass or dysfunction, even with a negative needle biopsy. Additionally, EBV-positive PTLD can occur in seropositive hosts, highlighting the importance of close EBV monitoring and timely management.Figure 1