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

Abstract

Summary The clinical and histological presentations of angioimmunoblastic T‐cell lymphoma (AITL) often mimic an infectious process. Epstein–Barr virus (EBV) and human herpes virus (HHV6) are known to be associated with AITL, but whether these viral infections play a role in its pathogenesis is unclear. It also remains to be investigated whether there might be other viruses associated with AITL. We first screened 26 well‐characterised cases of AITL for herpesvirus by polymerase chain reaction (PCR) with universal primers and found evidence of only EBV and HHV6B infection. Subsequent PCR using virus‐specific primers demonstrated EBV and HHV6B infection in 40/49 biopsies (36/42 cases) and 21/49 biopsies (19/42 cases) of AITL respectively with both viral infections found in 17/49 specimens (15/42 cases). Importantly, simultaneous infection with both viruses was found only in specimens showing histological pattern II (n = 2) or III (n = 15). Interestingly, among specimens containing both viruses, there was a tendency towards an inverse correlation between the EBV and HHV6B viral load as shown by quantitative PCR. In specimens positive only for EBV, the viral load was significantly higher in specimens with histological pattern III than those with pattern II. High EBV load was also significantly associated with B‐cell monoclonality. Double EBV encoded small RNA (EBER) in situ hybridisation and immunohistochemistry indicated that EBV‐infected B cells had a late postgerminal centre immunophenotype. Our results demonstrate an association between EBV and HHV6B infection and the histological progression of AITL, suggesting that these viruses may play a role in the pathogenesis of this lymphoma.

Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA

“…As previously reported, 14 we found the EBV genome in the great majority of tumor samples. This observation has been proposed as a strong argument for a pathophysiological driving role of EBV in AITL.…”

“…Epstein-Barr virus (EBV)-infected B-blasts are detected in most AITL. 14 The biological significance and pathophysiological implications of this observation are still unclear. EBV infection/reactivation can occur as a consequence of an underlying "immune dysfunction", but no correlation between EBV and immune parameters has been documented in AITL.…”

Small Bowel Perforation Caused by Epstein-Barr Virus-Associated B Cell Lymphoma in a Patient with Angioimmunoblastic T-Cell Lymphoma

“…Moreover, a recent study has revealed that an increase in EBV load in lymph nodes is associated with histological progression of AITL. 23 However, because the occurrence of secondary EBV-associated B cell lymphoma is rare, it is considered that secondary lymphomas are induced not only by immunodeficiency of AITL, but also by additional factors such as treatment and patient's background. Recently, Weisel et al 15 reported a case where EBV-associated secondary B cell lymphoma developed after chemotherapy composed of alemtuzumab and fludarabine.…”

Angioimmunoblastic T Cell Lymphomas: Frequent Cutaneous Skin Lesions and Absence of Human Herpes Viruses

“…A recent study insisted that HHV-6 and EBV have a pathogenic role in AITL 12 . We speculate that viral pathogenesis of AITL may be related to common skin involvement or other systemic symptoms of AITL because the clinical presentation of AITL often mimics viral exanthem.…”