Iatrogenic lymphoproliferative disorders in nontransplantation settings

Iatrogenic (IAT) immunosuppression-related lymphoproliferative disorders (LPDs) can occur outside the solid organ transplantation setting in patients who receive immunomodulatory therapy for a variety of underlying diseases. Most frequently, these patients suffer from rheumatologic diseases and are receiving one or more therapies during the time that LPDs develop. Specific therapies include methotrexate, azathiaprine, cyclosporine, prednisone, and others as well as combinations of therapies. In a significant subset of patients, these IAT LPDs spontaneously regress when therapy is discontinued, a finding that implicates immunomodulatory therapy, at least in part, in the development of these LPDs. The morphological spectrum of IAT LPDs includes atypical polymorphous LPDs, diffuse aggressive non-Hodgkin's lymphomas, Hodgkin's disease, and lymphoproliferations resembling Hodgkin's disease. The diagnosis requires a combined morphological and immunonphenotypic approach; in situ hybridization studies for Epstein-Barr virus (EBV) provide important information in the evaluation of these lesions. Withdrawal of immunosuppressive therapy and observation for a short period should be considered in the initial treatment of IAT LPDs, especially when they are EBV positive. This approach may obviate the need for unnecessary cytotoxic chemotherapy or radiation therapy in a significant subset of patients. However, some of these IAT LPDs behave in an aggressive manner; therefore, close clinical management is warranted.