Malignant lymphomas associated with immunodeficiency states.

Abstract

An increased incidence of malignant lymphomas is common to all types of immunodeficient patients whether they be of the natural or constitutionally occurring type, acquired as in acquired immunodeficiency syndrome (AIDS) or of iatrogenic origin as in organ transplantation. Although there is some degree of heterogeneity, the most characteristic feature of these immunodeficient states is alteration of T-cell cytotoxic function. The malignant lymphomas show a variety of relatively common features, notably: rapid onset following the appearance of the immunodeficient state, a high degree of clinical aggressiveness, and a tendency to present in extranodal sites, particularly the central nervous system (CNS) and gastrointestinal tract. The tumors are almost invariably of B-lymphocytic cell origin and while the histologic classifications reflect some diversity, the vast majority of tumors are described as Burkitt-like or diffuse large cell type. There appears to be a high degree of correlation with a preceding fulminant Epstein-Barr virus (EBV) infection resulting in marked B-cell lymphoproliferation in the absence of effective T-cell control. Initially, the B-cell proliferation is clearly polyclonal and reactive in nature, although as time evolves, there appears to be selection of oligoclonal and even monoclonal cell populations. Such cells are latently infected with EBV and may express EBV nuclear protein two and latent membrane protein, which are characteristically seen in proliferating B-lymphocytes in response to growth transformation by EBV. While desoxyribonucleic acid (DNA) probes may continue to demonstrate multiple lymphoid clonal populations, it is hypothesized that the hyperproliferative state favors genetic alterations which select out a single malignant clone. This transformed clone is evidenced by expression of a translocated, activated c-myc oncogene and decreased evidence of EBV nuclear protein two and latent membrane protein, that is, characteristics of Burkitt's lymphoma. Other large cell malignant lymphoma phenotypes may show similar findings. While most studies have continued to suggest that EBV plays a key role in the development of non-Hodgkin's lymphoma (NHL) of AIDS patients, some recent studies have suggested a less dominant role. Therefore, further exploration of the world of molecular biology will be needed to demonstrate whether other factors, namely additional viruses and/or oncogenes play a similar or significant role in the lymphomas of immunodeficient patients.