Acute cellular rejection and Epstein–Barr virus‐related post‐transplant lymphoproliferative disorder in a pediatric lung transplant with low viral load

F. Calabrese, M. Loy, F. Lunardi, D. Marino, S.M.L. Aversa, F. Rea. Acute cellular rejection and Epstein–Barr virus‐related post‐transplant lymphoproliferative disorder in a pediatric lung transplant with low viral load.
Transpl Infect Dis 2010: 12: 342–346. All rights reserved. Abstract: We report the case of an 18‐year‐old male who underwent bilateral lung transplantation for end‐stage cystic fibrosis. No Epstein–Barr virus (EBV) or cytomegalovirus serology mismatch was detected on pre‐transplant evaluation (donor and recipient were both positive). Two months after lung transplantation a computed tomography scan showed multiple nodules throughout both lungs. At that time a low EBV DNA blood level was detected (<300 copies/100,000 lymphomonocytes). Scheduled follow‐up transbronchial biopsy (TBB) revealed a prevalent finding characterized by perivascular lymphoid infiltrates with endothelitis. Extensive tissue coagulative necrosis with peripheral areas of dense aggregates of larger lymphoid cells were detected in the trans‐thoracic fine needle core biopsy (FNCB) performed on the largest nodule. The immunophenotypic profile characterized the perivascular lymphoid cells in TBB as mainly composed of T lymphocytes (CD3 positive) while the larger number of lymphocytes in FNCB as B cells (CD20 positive). In situ hybridization for EBV (EBER mRNA) was negative in TBB while it was positive in many lymphocytes of the FNCB. Real‐time polymerase chain reaction (PCR) for EBV was performed on paraffin‐embedded FNCB and detected a high quantity of EBV genomes (1260 copies/cell). IgH gene rearrangement using a fragment size PCR technique revealed a monoclonal B‐cell population in FNCB. Morphological and molecular findings suggest a final diagnosis of acute cellular rejection and a post‐transplant lymphoproliferative disorder (PTLD) EBV‐related in a lung transplant recipient with a low EBV DNA blood level. A possible coexistence of PTLD and acute rejection should be considered both for diagnosis and treatment. EBV PCR in the peripheral blood is a useful screening tool in transplant recipients; however, rare cases with PTLD may not have detectable levels of EBV DNA. This aspect should be taken into consideration to avoid false negatives.