Heterogeneity of Epstein-Barr virus infection in angioimmunoblastic lymphadenopathy type T-cell lymphoma

Abstract

To investigate the relationship of Epstein-Barr virus (EBV) and angioimmunoblastic lymphadenopathy with dysproteinemia, we performed DNA analysis using the polymerase chain reaction (PCR), Southern blot, in situ hybridization, and immunohistochemical analysis of lymph nodes in five patients who were followed up and biopsied more than once. In the course of the disease, nodal architecture diminished, cellular atypia worsened, and clear cells increased in number. In the DNA analysis of the receptor genes, the clonal population increased in number. EBV nucleic acid sequences were found by either PCR or in situ hybridization in all examined nodes. The number of EBV-positive cells varied widely among the cases and throughout the course of the disease in the same patients. The analysis of EBV terminal repeats or lymphocyte-determined membrane antigen genes showed polyclonal populations of EB-infected cells. EBV-positive cells possessed intermediate- to large-sized nuclei, and the cells with large nuclei, especially, expressed latent membrane protein of EBV. These large cells varied among the cases. Double-labelling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed B-cell antigen (CD20). The presence of EBV seems to be associated with the selective defects of the immune system, rather than with the direct pathogenesis of angioimmunoblastic lymphadenopathy.

Epstein-Barr Virus–Negative Hodgkin's Lymphoma After Mycosis Fungoides: Molecular Evidence for Distinct Clonal Origin

“…A distinct phenomenon is the appearance of RSlike cells expressing B-cell markers in some periph- eral T-cell lymphomas (11,12,27). In incipient adult T-cell leukemia/lymphoma with Hodgkin-like features, Oshima et al (29) demonstrated the presence of unrelated immunoglobulin gene rearrangements in isolated RS-like cells.…”

Angio-immunoblastic T cell lymphoma (AILD-TL) rich in large B cells and associated with Epstein–Barr virus infection. A different subtype of AILD-TL?

“…12 EBV presence in AILD was first reported by Bornkamm et al 13 in 1976. It was subsequently identified in this disorder [14][15][16][17] affecting both T and/or B cells, 18 but its pathogenic role in lymphoma development is not clear.…”

AILD-Like Dysplasia Transformed in AILD-Type T Cell Lymphoma in an HTLV-1 Carrier: Usefulness of Interferon-α

“…Details of the methods are given in our previous report [19]. The T cell receptor genes Cp and Jr, the immunoglobulin heavy chain (Jh) gene, HTLV-1 (full length: gag, pol, env, pX, LTR) and EBV genes (BamHl W region; Enzo, Hudson, N.Y., USA) were used as probes [17,20).…”

“…Hematoxylin-eosin staining was done on paraffin sections of the biopsy specimens. Immunohistochemical staining was applied to frozen sections of the biopsy specimens, using an avidin-biotin complex alkaline phosphatase immunohistochemi cal method and monoclonal antibodies for T cells (CD2, CD3, CD4 and CD8), B cells (CD20 and CD22), activated cells and others (CD25, CD30, Ki67 and la) [17).…”

“…HTLV-1 virus is recognized as the etiologic agent of ATLL [8][9][10], In HTLV-1 carriers, AILD may be the result of immunological disturbances as in HTLV-1-associated myelopathy [11], HTLV-1-associ ated bronchopneumopathy [12,13], HTLV-1-associated arthropathy [ 14] and HTLV-1 uveitis [15], To understand better the pathogenesis and clinical course of AILD pa tients, molecular biological studies in combination with chromosome analysis and immunohistobiology were done. Epstein-Barr virus (EBV) and HTLV-1 have been investigated with respect to the etiology [16,17], Interfer on (IFN)-a therapy was prescribed in place of intensive chemotherapy and was found to be an effective treatment of AILD. The relationship between IFN-a effects and clinicopathological findings during the clinical course of this patient was examined.…”