title: Acute cellular rejection and Epstein-Barr virus-related post-transplant lymphoproliferative disorder in a pediatric lung transplant with low viral load.
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.
authors.affiliation: Department of Diagnostic Medical Sciences and Special Therapies, University of Padua, Padua, Italy. fiorella.calabrese@unipd.it
authors.forename: F
authors.initials: F
authors.lastname: Calabrese
authors.forename: M
authors.initials: M
authors.lastname: Loy
authors.forename: F
authors.initials: F
authors.lastname: Lunardi
authors.forename: D
authors.initials: D
authors.lastname: Marino
authors.forename: S M L
authors.initials: SM
authors.lastname: Aversa
authors.forename: F
authors.initials: F
authors.lastname: Rea
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D006084:Graft Rejection / Q000150:complications / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D008214:Lymphocytes / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D019562:Viral Load / Q000502:physiology*
chemical_list: D004279:DNA, Viral