Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma

Abstract

We studied 23 cases of angioimmunoblastic lymphadenopathy (AILD) and AILD-like lymphoma for evidence of Epstein-Barr virus (EBV) using the polymerase chain reaction (PCR) and in situ hybridization studies. EBV nucleic acid sequences were found by either PCR or in situ hybridization in 96% of the cases. There was a wide range in the number of EBV-positive cells among the different cases as detected by in situ hybridization. The EBV-positive cells most often possessed nuclei of intermediate to large size. Double-labeling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed the B-lineage antigen CD20 (as detected by L26), with a minority of the EBV-positive cells stained for the T-lineage associated antigen, CD43 (as detected by Leu 22). The abnormally high amounts of EBV found in AILD and AILD-like lymphoma may be a reflection of decreased immunocompetence in these patients. The presence of EBV- positive B cells may explain the presence of B-cell clones found by others as well as the paradoxical occurrence of B-cell lymphoma in a primary T-cell lymphoproliferative disorder.

Angioimmunoblastic T‐cell lymphoma: histological progression associates with EBV and HHV6B viral load

“…By PCR screening with universal primers targeting known herpesviruses, we found evidence of EBV and HHV6B, but not other herpesviruses, in AITL. Association of HHV6B and EBV with AITL has been previously reported (Weiss et al, 1992;Khan et al, 1993;Luppi et al, 1993;Vrsalovic et al, 2004;Attygalle et al, 2007b). We have now extended the previous observations, finding HHV6B in nearly half of a large series of AITL and EBV in almost all of our cases, and further showed that EBV was present in B cells that exhibit immunohistochemical features of postgerminal centre differentiation.…”

“…Among them, EBV, HHV6 and HHV8 appear to be most relevant as they are not only lymphotropic but also oncogenic. EBV is found in most cases of AITL as shown by EBV encoded small RNA (EBER) in situ hybridisation (ISH) (Weiss et al, 1992;Khan et al, 1993;Attygalle et al, 2007b), while HHV6 was reported in 22-58% cases of AITL by polymerase chain reaction (PCR) (Luppi et al, 1993;Vrsalovic et al, 2004). However, neither EBV nor HHV6 is found in the neoplastic T-cells themselves, suggesting a lack of a direct cell autonomous role in lymphomagenesis.…”

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).…”

“…). In addition, later in the 1980s, the identification of clonal cytogenetic abnormalities and of clonal T-cell receptor (TCR) gene rearrangements definitively established the neoplastic nature of the disease (Weiss et al, 1986;Feller et al, 1988;Kaneko et al, 1988;Tobinai et al, 1988).…”

The Germinal centre‐derived lymphomas seen through their cellular microenvironment

“…In AITL, virus presence can be detected in B lymphocytes as well as in B immunoblasts. It is possible that reactivation of EBV could be consequent to a decreased immune surveillance in the setting of a compromised immune system (Weiss et al, 1992), although EBVpositive B cells can be found very early during the course of the disease. In some cases, EBV infection of B cells progresses to such a state as to resemble to a B-cell lymphoproliferative disorder similar to a post-transplant polymorphic B-cell lymphoma.…”