POLYCLONAL AND MONOCLONAL POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASES (LPD)

The Epstein-Barr virus (EBV) causes a spectrum of B-cell lymphoproliferative diseases that are reviewed. There are three groups classified by their clinical presentation, morphologic characteristics, and clonality as determined by staining for heavy- and light-chain surface and cytoplasmic immunoglobulin, cytogenetic analysis, and immunoglobulin gene rearrangement studies. There are benign polyclonal hyperplasias without cytogenetic abnormalities and immunoglobulin gene rearrangements that resemble infectious mononucleosis and respond to acyclovir, oftentimes not requiring decrease in immunosuppression. There are malignant monoclonal lymphomas with clonal cytogenetic abnormalities and with clonal immunoglobulin gene rearrangements in a majority of cells. These patients present with solid tumors that are not dependent on EBV replication for growth and are therefore acyclovir-resistant, respond poorly to chemotherapy and radiation therapy, and have a high mortality. There are immediate lesions that are morphologically malignant and contain clonal cytogenic abnormalities and immunoglobulin gene rearrangements in a subpopulation of cells, but are predominantly made up of a polyclonal B-cell proliferation. These patients present with a clinical syndrome resembling infectious mononucleosis as in the first group, respond to acyclovir, but should also have their immunosuppression decreased because of the documented risk of progression from a polyclonal to monoclonal lymphoproliferation. These findings have important implications for the pathogenesis of EBV-related lymphoproliferative diseases, which are discussed.