Diagnosis and treatment of Epstein-Barr virus-associated natural killer cell lymphoproliferative disease

Epstein-Barr virus (EBV) exhibits tropism for both lymphocytes and epithelial cells and can induce both replicative (productive/lytic) and latent (persistent) infections that result in a variety of human diseases. With regard to lymphocytes, latent EBV infection is linked to development of heterogeneous lymphoproliferative disease (LPD), such as B-cell LPD and T-cell/natural killer cell (T/NK cell) LPD. Unlike B-cell LPD, LPD derived from T-cells and NK cells sometimes has overlapping clinical symptoms, as well as histologic and immunophenotypic features, because both types of cells are derived from a common precursor. However, determination of cell lineage is important in classification of lymphoid neoplasms, and combined modern techniques allows us to distinguish NK cell LPD from T-cell LPD in most instances. Because NK cell LPD seems to be heterogeneous in terms of clinical features, prognosis, and diagnosis and has a monoclonal or polyclonal (or oligoclonal) nature, this review attempts to clarify recent research and clinical findings and to establish diagnostic and therapeutic strategies.