Epstein-Barr virus-associated non-Hodgkin's lymphoma in patients infected with the human immunodeficiency virus.
Lymphoproliferations associated with Epstein-Barr virus (EBV) commonly arise in settings of immune dysfunction, including human immunodeficiency virus (HIV) infection. In this study, EBV was associated with 39 of 59 (66%) HIV-related systemic lymphomas. Unlike the lymphoproliferations that arise in the setting of transplantation, the HIV-related lymphomas were monoclonal, as evaluated by Ig heavy chain rearrangements and EBV termini analysis, and associated (40%) with c-MYC rearrangements. Furthermore, analysis of multiple lymphoma tissues from one autopsy showed evidence that a single lymphoma clone was responsible for dissemination. The latent EBV nuclear antigen (EBNA-1) transcripts detected in the HIV-related lymphomas were characteristic of the pattern found in Burkitt lymphoma (g1 EBNA1) and not in transplant-related lymphoproliferations. However, unlike Burkitt lymphoma, EBV latent membrane-associated protein (LMP) transcripts were also detected, thereby constituting an EBV expression pattern (g1 EBNA1+, LMP+) not previously observed in B-cell lymphomas. These findings demonstrate a high frequency of EBV-associated lymphomas in the setting of HIV infection that are distinct from the lymphoproliferations that arise during iatrogenic transplant-associated immuno-suppression or in the general population. However, it is also apparent that HIV-related lymphomas are biologically heterogeneous, which may reflect the multiple mechanisms or steps necessary for eventual malignant transformation.
Department of Pathology, Los Angeles County University of Southern California Medical Center 90033.
D
D
Shibata
L M
LM
Weiss
A M
AM
Hernandez
B N
BN
Nathwani
L
L
Bernstein
A M
AM
Levine
D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D015321:Gene Rearrangement; D016259:Genes, myc / Q000235:genetics; D015658:HIV Infections / Q000382:microbiology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics / Q000382:microbiology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D014763:Viral Matrix Proteins / Q000235:genetics
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins