Hepatitis C virus (HCV) infection and lymphoproliferative disorders

Several infectious agents have been associated with development of lymphoproliferative disorders. Among these is hepatitis C virus (HCV), which infects more than 200 million people worldwide. HCV infection has been linked to progression of type II mixed cryoglobulinemia (MC) syndrome and has also been suggested to contribute to development of B-cell non-Hodgkin's lymphoma (NHL). Mechanisms responsible for development of lymphoproliferative disorders among HCV-positive patients remain unclear. Accumulating evidence supports a model in which chronic stimulation of B-cells by antigens associated with HCV infection causes nonmalignant B-cell expansion that may evolve into B-cell NHL. The course of disease among HCV-positive B-cell NHL patients may be complicated by coinfection with other infectious agents. This possibility has been explored by studies that have investigated potential interactions between HCV and human immunodeficiency virus (HIV) as well as between HCV and Epstein-Barr virus (EBV). Further characterization of the mechanisms by which HCV promotes development of lymphoproliferative disorders may improve diagnosis, classification, and treatment of these conditions.

Second primary lymphoma or recurrence: a dilemma solved by VDJ rearrangement analysis.

A lymphoma patient in remission that develops a second lymphoma is frequently assumed to have had a relapse of the original lymphoma. However, the second lymphoma may instead be a new lymphoma with a different clonal origin. Comparison of histological characteristics alone is insufficient in many cases to distinguish new lymphomas from recurrent lymphomas. In contrast, clonal origins of B-cell lymphomas can be reliably compared by VDJ rearrangement analysis of B-cell IgH genes. Simultaneous lymphomas have similarly been analyzed by this technique to determine whether or not both tumors share a common clonal origin. Application of VDJ rearrangement analysis in clinical research has been important for characterizing mechanisms of lymphoma development. Furthermore, this technique has the potential to improve treatment of lymphoma patients because management of recurrent lymphomas differs from that of new lymphomas.