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.

Cutaneous presentation of post‐renal transplant lymphoproliferative disorder: a series of four cases

“…Some argue that EBV infection is causative while others maintain that it is merely an epiphenomenon. 62,74,75 EBV is only detected in a portion of tumor cells, corroborating epiphenomenon hypothesis, secondary infection, or down regulation of viral genes after malignant transformation. Evidence to suggest that EBV is causative in PTLD is the observation that it is transcriptionally active in the infected neoplastic cells and that LMP causes lymphomagenesis.…”

“…Evidence to suggest that EBV is causative in PTLD is the observation that it is transcriptionally active in the infected neoplastic cells and that LMP causes lymphomagenesis. 61,74 EBV may also have an indirect effect in neoplastic transformation by acting as a co-factor that increases the likelihood that a second oncogenic event may occur. 76 EBV is thought to initiate polyclonal B-cell proliferation and subsequently, somatic mutations such as specific chromosomal translocations may occur promoting the development of oligoclonal and monoclonal neoplasms.…”

Advances in the understanding and management of angioimmunoblastic T‐cell lymphoma

“…Varying numbers of small B cells and polytypical plasma cells are distributed randomly in single cells or as small clusters in association with FDC aggregates. In addition, a population of large B-blasts, which may sometimes mimic Reed-Sternberg cells, usually infected by Epstein-Barr virus (EBV), is almost invariably present (Anagnostopoulos et al, 1992;Weiss et al, 1992).…”

Comprehensive Epstein-Barr Virus Transcriptome by RNA-Sequencing in Angioimmunoblastic T Cell Lymphoma (AITL) and Other Lymphomas

“…Increased numbers of follicular dendritic cells are observed near abundant arborescent endothelial venules. EBV is detected in 85-95% of AITL, being most often present in large B blasts, but sometimes described in neoplastic T cells [23][24][25][26][27]. It has been proposed that AITL generates an immunodeficiency at the origin of EBV reactivation promoting the expansion of Tfh and B cells, thus playing a role in the development of the tumor microenvironment.…”