Epstein–Barr virus–associated lymphoproliferative diseases

Lore & Background

The Epstein–Barr virus, a Group I double-stranded DNA virus, spreads through oral or nasal secretions and initially infects epithelial cells in the oral cavity before invading naïve B cells in submucosal lymphoid tissue. The virus can establish lytic or latent phases, with latency III expressing multiple genes that immortalize and promote growth of infected B cells, while later latency phases (II, I, 0) limit gene expression to evade immune detection. The virus may also exit B cells to infect T cells, NK cells, or follicular dendritic cells, though infection of T cells and NK cells is not mediated by the CD21 receptor, as these cells generally do not express CD21.

Reader's Guide

EBV+ LPD are classified into five categories per the 2016 WHO revision: EBV-associated reactive lymphoid proliferations, B cell lymphoproliferative disorders, NK/T cell lymphoproliferative disorders, immunodeficiency-related lymphoproliferative disorders, and histiocytic-dendritic disorders. These include benign conditions like EBV-positive reactive lymphoid hyperplasia, which usually resolves spontaneously but rarely progresses to lymphoma, and infectious mononucleosis, a self-limiting illness common in adolescents and adults. The disorders disproportionately affect immunodeficient individuals, and the virus's ability to establish lifelong latency in memory B cells underlies its persistence and potential to drive malignant transformation.

Did You Know?

• About 50% of five-year-old children and 90% of adults show evidence of prior EBV infection.
• EBV-associated LPD include both non-malignant and malignant forms, with the virus sometimes being an 'innocent bystander'.
• The virus can force infected naïve B cells to arrest maturation at various stages, leading to excessive proliferation.
• Infectious mononucleosis is caused by EBV in about 90% of cases.