Advances in the diagnosis and treatment of EBV-associated lymphoproliferative diseases in immunocompromised hosts.

The clinical, immunopathologic, and virologic features of the lymphoproliferative diseases occurring after renal transplantation have been characterized. Clinically, patients may present with an infectious mononucleosis-like illness or with localized solid tumor masses. These lymphoproliferative diseases have unique histologic features that can be classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic B-cell lymphoma (PBL). Immunologic cell-typing studies have shown that the majority are polyclonal B-cell proliferations, but monoclonal B-cell tumors have also been documented. These B-cell proliferations may, however, evolve from a benign polyclonal B-cell hyperplasia to a monoclonal malignant lymphoma. The Epstein-Barr virus (EBV) has been implicated as the cause of these disorders. Serologic studies frequently demonstrate evidence of a primary or reactivation infection, touch imprints from involved tissue may stain for the presence of EBNA (Epstein-Barr nuclear antigen), and EBV DNA hybridization studies demonstrate the presence of EBV-specific DNA sequences within tumor cells. Since EBV induces a polyclonal B-cell proliferation in vitro and in vivo, the polyclonality of these diseases also implicates EBV. Acyclovir, a new synthetic antiviral agent that inhibits EBV DNA replication may be effective in some patients during the polyclonal growth phase but is ineffective once the tumor evolves into a monoclonal lymphoma. We have identified several factors that may be useful in predicting responsiveness to acyclovir therapy.