• Epstein-Barr virus (EBV) genotypes among human immunodeficiency virus (HIV)-related B-cell lymphomas and B-cell post-transplant lymphoproliferative disorders (B-PTLD)--late-onset lymphomas, especially in the HIV setting, are associated with type-B-EBV.

      Ibrahim, H; Menasce, Lia P; Pomplun, S; Burke, M; Bower, M; Naresh, K; Departments of Histopathology, Hammersmith Hospital and Imperial College, London, London, UK. (2010-09)
      We investigated 26 B-cell post-transplant lymphoproliferative disorders (B-PTLD) and 15 human immunodeficiency virus-related aggressive B-cell lymphomas (HIV-BCL) from England that were associated with Epstein-Barr virus (EBV) for the polymorphic sequences of the EBV-encoded nuclear antigen 3C (EBNA3C) gene to distinguish the two different EBV strains. Type-A-EBV was identified in 92% of B-PTLDS and in 53% of HIV-BCL (P = 0.003). Among HIV-BCL, patients associated with type-B-EBV had been HIV positive for significantly longer when compared to those associated with type-A (P = 0.037) although there were no correlations with ethnicity, CD4 cell counts or plasma HIV viral load.
    • Presence of monoclonal T-cell populations in B-cell post-transplant lymphoproliferative disorders.

      Ibrahim, H; Menasce, Lia P; Pomplun, S; Burke, M; Bower, M; Naresh, K; Department of Histopathology, Hammersmith Hospital, Imperial College, London, UK. (2011-02)
      As has been previously shown, the lack of immune surveillance plays a major role in the unchecked proliferation of Epstein-Barr virus (EBV)-infected B cells in the pathogenesis of B-cell post-transplant lymphoproliferative disorders. We hypothesised that the lack of immune surveillance should possibly also affect T cells, and this should lead to subsequent emergence of T-cell clones. The presence of both B- and T-cell clones in post-transplant lymphoproliferative disorders samples has rarely been demonstrated in the past. We systematically evaluated 26 B-cell post-transplant lymphoproliferative disorder, 23 human immune deficiency virus-associated B-cell lymphoma and 10 immune-competent diffuse large B-cell lymphoma samples for B- and T-cell clonality (polymerase chain reaction and heteroduplex analysis using BIOMED-2 protocol), T-cell subsets (immunohistochemistry) and EBV association (in situ hybridisation using EBER). One-half of B-cell post-transplant lymphoproliferative disorders showed evidence of monoclonal T-cell expansion, and among the T cells present in the tissue samples, CD8-positive cells predominated. Although 9/13 (69%) B-cell post-transplant lymphoproliferative disorders with the presence of monoclonal T-cell population had a CD4:CD8 ratio of ≤0.4, 0/13 of the cases without monoclonal T-cell expansion had a ratio ≤0.4 (P = 0.002). Only 2/26 (8%) demonstrated significant cytological atypia in the CD3/CD8-positive cells. There was no association between EBV and presence of T-cell clones. T-cell clones were not identified in lymphomas other than B-cell post-transplant lymphoproliferative disorders. Among 53.8% cases of EBV-positive B-cell post-transplant lymphoproliferative disorders with associated clonal expansion of T-cells tested, none had EBV-positive T cells. We conclude that half of B-cell post-transplant lymphoproliferative disorders are associated with clonal expansion of CD8-positive T cells, most of which do not amount to the coexistence of a T-cell post-transplant lymphoproliferative disorders.