Epstein-Barr virus-negative post-transplant lymphoproliferative disorders - A distinct entity?

Post-transplant lymphoproliferative disorders (PTLDs) are usually but not i nvariably associated with Epstein-Ban virus (EBV). The reported incidence, however, of EBV-negative PTLDs varies widely, and it is uncertain whether t hey should be considered analogous to EBV-positive PTLDs and whether they h ave any distinctive features. Therefore, the EBV status of 133 PTLDs from 8 0 patients was determined using EBV-encoded small ribonucleic acid (EBER) i n situ hybridization stains with or without Southern blot EBV terminal repe at analysis. The morphologic, immunophenotypic, genotypic, and clinical fea tures of the EBV-negative PTLDs were reviewed, and selected features were c ompared with EBV-positive cases. Twenty-one percent of patients had at leas t one EBV-negative PTLD (14% of biopsies). The initial EBV-negative PTLDs o ccurred a median of 50 months post-transplantation compared with 10 months for EBV-positive cases. Although only 2% of PTLDs from before 1991 were EBV negative, 23% of subsequent PTLDs were EBV negative (p <0.001). Of the EBV -negative PTLDs, 67% were of monomorphic type (M-PTLD) compared with 42% of EBV-positive cases (p <0.05). The other EBV-negative PTLDs were of infecti ous mononucleosis-like, plasma cell-rich (n = 2), small B-cell lymphoid neo plasm, large granular lymphocyte disorder (n = 4) and polymorphic (P) types . B-cell clonality was established in 14 specimens and T-cell clonality was established in three (two patients). None of the remaining specimens were studied with Southern blot analysis and some had no ancillary studies. Rear rangement of c-MYC was identified in two M-PTLDs with small noncleaved-like features, arid rearrangement of BCL-2 was found in one large noncleaved-li ke M-PTLD. Ten patients were alive at 3 to 63 months (only three patients r eceived chemotherapy). Seven patients, all with M-PTLDs, are dead at 0.3 to 6 months. Therefore, EBV-negative PTLDs have distinct features, but some d o respond to decreased immunosuppression, similar to EBV-positive cases, su ggesting that EBV positivity should not be an absolute criterion for the di agnosis of a PTLD.