Heterogeneous Epstein-Barr virus infection patterns in peripheral T- cell lymphoma of angioimmunoblastic lymphadenopathy type

Abstract

In this study, 32 cases of T-cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for their association with Epstein-Barr virus (EBV). For this purpose, three different approaches were applied: polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small nuclear RNAs (EBER), and immunohistology for EBV-encoded latent membrane protein (LMP). PCR and EBER-ISH produced almost identical results, showing that all but one case of AILD-TCL contained EBV genomes. Three distinctive patterns of EBV infection were observed after immunophenotypical characterization of EBER-positive cells: (1) in 26% of the cases, B and T cells were infected, the majority of which were B cells of immunoblastic morphology located in the remnants of lymphoid follicles; (2) in 42% of the cases, the vast majority of infected cells were neoplastic T cells diffusely distributed in the lymph nodes, but infected B cells were also present; and (3) in 32% of the cases, there were only a few infected small lymphoid cells. Detectable LMP was frequent in cases exhibiting patterns 1 and 2. These findings suggest that in AILD-TCL patients, B cells and especially T cells are highly susceptible to a persistent EBV infection, which often leads to a growth advantage of the infected cells. Thus EBV, in conjunction with genetic abnormalities and selective defects of the immune system, might be involved in the pathogenesis of AILD-TCL.

Distinguishing angioimmunoblastic T‐cell lymphoma from peripheral T‐cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics

“…This frequency is not as high as that documented in some studies that report EBV positivity in > 95% of cases of AITL. 24,25 The presence ⁄ absence of EBV-infected B cells in the present study correlates well with the outgrowth of dominant B-cell clones in 19% of AITL and its absence in PTLu. The lack of expansion of EBV-infected cells in PTLu and its presence in the majority of AITL is interesting, because although hitherto not used as a criterion to distinguish between AITL and PTLu, it may reflect true biological differences between the two entities.…”

An Autopsy Case of Angioimmunoblastic T‐cell Lymphoma with a High Content of Epithelioid Cells in the Lymph Node: Immunohistochemical and Genomic Analyses

“…In addition, several LMPI-positive large cells in the lymph node were observed in September of 1994. Those findings were compatible with the CD4+ phenotype seen in most cases of AILD-PTCL (18), and with the involvement ofEBV (15,(19)(20)(21)(22)(23)(24), especially LMPI ofEBV (24), in some cases of AILD-PTCL.…”

Peripheral blood sCD3−CD4+T cells: a useful diagnostic tool in angioimmunoblastic T cell lymphoma

“…In some cases of the disease, a misinterpretation of clinical and histopathological findings may occur. TCR rearrangement and Epstein-Barr virus or human herpesvirus 6 genomes can be detected as common genetic features in many but not all cases of AITL; however, these findings do not allow to exclude other mature T cell lymphomas [5][6][7][18][19][20].…”