POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN LIVER ALLOGRAFT BIOPSIES - A COMPARISON OF 3 METHODS FOR THE DEMONSTRATION OF EPSTEIN-BARR-VIRUS

Posttransplant lymphoproliferative disorder (PTLD) is associated with Epstein-Barr virus (EBV), and may clinically resemble acute allograft rejection. Three methods to show EBV in tissue were evaluated in 15 li ver allograft biopsies from 12 patients including four with PTLD: (1) semiquantitative polymerase chain reaction (PCR) for EBV DNA; (2) in s itu hybridization for EBV RNA (EBER); and (3) immunoperoxidase for EBV latent membrane protein (LMP). Index cases had a PCR dot blot result of ''positive'' or ''weak positive.'' Findings were correlated with hi stology, clinical data, therapy, and outcome. All four PTLD patients h ad a clinical diagnosis of acute rejection. All four showed EBV: PCR 4 , LEER 4, LMP 3. Liver function tests were elevated in three, but EBV viral capsid antigen (VCA) IgM was not increased in three. Immunosuppr ession was withdrawn and all four patients underwent a second transpla ntation. One died 4 days posttransplant with disseminated PTLD, two di ed of sepsis at 1.5 and 14 months, and one is well at 3 years without PTLD. Eleven biopsies without PTLD showed: acute rejection 7, acute re jection and hepatitis 1, hepatitis B 1, and non-inflammatory changes 2 . In this group, EBV results included: PCR weak positive in 10 and 1in one, EBER negative in ten and rare positive cells in one, LMP negat ive in 11. Liver function tests were elevated in 10, whereas VCA IgM w as not increased in three and increased in one. Patients with acute re jection were treated with increased immunosuppression: none developed PTLD, with follow-up of at least 6 months in nine cases. Two patients died within 4 months of biopsy. One patient with PTLD in tonsils had a liver biopsy showing both acute rejection and EBV (PCR 1+, rare EBER + small cells). Histological studies combined with special EBV detecti on methods, can be useful to evaluate atypical lymphoid infiltrates in liver allograft biopsies and confirmation of a diagnosis of PTLD. All three methods are useful; EBER and PCR are the most sensitive. LEER a nd LMP fan use paraffin sections. Copyright (C) 1997 by W.B. Saunders Company.