Advances in the Pathogenesis of EBV-Associated Diffuse Large B Cell Lymphoma

SIMPLE SUMMARY: The last World Health Organization classification of Tumours of Haematopoietic and Lymphoid Tissues defines a new category, EBV + DLBCL, NOS, which incidence varies among different populations. Given the oncogenic characteristics of both latent and lytic viral proteins, EBV could replace some of the cellular pathways and/or mutations observed in non EBV-associated cases. In addition, the virus may turn the tumor microenvironment in a tolerogenic, in order to promote tumorigenesis, and may have also influence on survival in specific populations. The analysis of EBV pathogenesis in DLBCL may exhibit new potential targets for DLBCL treatment. ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma (NHL) in adults. Epstein–Barr virus (EBV) positive DLBCL of the elderly was defined by the World Health Organization (WHO) in 2008, it was restricted only to patients older than 50 years old, and it was attributed to immunesenescence associated with physiological aging. After the description of EBV-associated DLBCL in children and young adults, the WHO redefined the definition, leading to the substitution of the modifier “elderly” with “not otherwise specified” (EBV + DLBCL, NOS) in the updated classification, and it is no more considered provisional. The incidence of EBV + DLBCL, NOS varies around the world, in particular influenced by the percentage of EBV+ cells used as cut-off to define a case as EBV-associated. EBV has effect on the genetic composition of tumor cells, on survival, and at the recruitment of immune cells at the microenvironment. In this review, the role of EBV in the pathogenesis of DLBCL is discussed.