Human Immunodeficiency Virus-Associated Lymphoproliferative Disorders Amy J. Lilly, MD, Yuri Fedoriw, MD* ABSTRACT H IV infection is associated with an increased risk for developing B-cell lymphoprolifera- tive disorders. The spectrum of disease dif- fers in HIV-infected versus HIV-uninfected persons, with aggressive B-cell non-Hodgkin lym- phomas constituting a higher proportion of all lym- phoproliferative disorders in the HIV-positive population. Although antiretroviral therapy (ART) has significantly changed the landscape of lym- phomas arising in HIV-infected persons, popula- tion growth and aging are reflected in the steady increase in non–AIDS-defining cancers. In the ART era, outcomes for HIV-infected lymphoma patients are similar to those of HIV-negative pa- tients. This article reviews the diagnostic features and summarizes current biologic understanding of HIV-associated lymphomas. OVERVIEW HIV infection is associated with an increased risk for developing B-cell lymphoproliferative disorders, including bona fide malignant lym- phomas as well as polyclonal and virally driven expansions. Although the introduction of antiretro- viral therapy (ART) in the United States was asso- ciated with an early and marked decrease in the incidence of HIV lymphomas that plateaued in the late 1990s, improvements in overall survival, population growth, and aging resulted in an increased disease prevalence and steady rise in incidence of in non–AIDS-defining cancers, including Classic Hodgkin lymphoma (CHL). 1–3 The spectrum of lymphoproliferative disorders differs in HIV-infected versus HIV-uninfected persons, with aggressive B-cell non-Hodgkin lymphomas (NHLs) constituting a higher propor- tion of all lymphoproliferative disorders in the HIV-positive population. In terms of cellular ontogeny, the lymphomas arising in the setting of HIV infection, as a whole, tend to represent proliferations of more mature and near terminally differentiated B-cells. This is reflected in the immu- noblastic to plasmablastic morphology of many HIV-associated lymphomas. 4,5 Even CHL, which has shown a steadily increasing incidence since ART initiation, arises from germinal center (GC) Key Points  Infection with HIV continues to be associated with an increased risk of lymphoma development, and HIV has both direct and indirect roles in lymphomagenesis.  HIV-associated lymphomas tend to be high-grade, mature B-cell neoplasms and present at an earlier median age compared with those in the HIV-negative population.  Antiretroviral therapy has significantly changed the distribution of lymphomas arising in HIV-infected persons, with an associated steady increase in the incidence of Classic Hodgkin lymphoma. Disclosure Statement: The authors have nothing to disclose. Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, CB #7525, Chapel Hill, NC 27599-7525, USA * Corresponding author. E-mail address: yuri.fedoriw@unchealth.unc.edu KEYWORDS  HIV  HIV-associated Lymphoma  Epstein-Barr virus  B-cell lymphoma Surgical Pathology 12 (2019) 771–782 https://doi.org/10.1016/j.path.2019.03.005 1875-9181/19/Ó 2019 Elsevier Inc. All rights reserved. surgpath.theclinics.com