Lymphomas specifically arising in HIV-induced immunosuppression. Stage of differentiation and the putative cell of origin. Lymphoma histotypes occurring specifically in HIV-infected patients exhibit a common normal cellular counterpart that might be defined as plasmablast. The figure defines the following main subgroups of lymphoma with plasmablastic differentiation: (1) HIV-associated lymphoma showing IB morphology with plasmacytoid differentiation; these lymphomas can be either systemic or primary central nervous system lymphomas; (2) tumors classified as PELs and their extracavitary variant exhibiting infection by both KSHV and EBV; (3) tumors classified as PBL of the oral cavity type, showing a monomorphic population of immunoblasts with no or minimal plasmacytic differentiation; most patients are HIV infected and tumor cells are EBV positive but KSHV negative; most cases present in the oral mucosa, whereas a significant number of cases present in other extranodal or nodal site; and (4) large B-cell lymphoma arising in KSHV-associated multicentric Castleman disease (MCD) consisting of KSHV-infected plasmablasts, which show evidence of light chain restriction and may represent a monotypic cell population, found in small clusters surrounding or replacing follicles, in MCD. Therefore, important features to subclassify these neoplasms include the stage of differentiation of the putative cell of origin and association with viruses. Lymphomas with plasmablastic differentiation are a heterogeneous group of neoplasms with different clinicopathological characteristics and different associations with specific viruses. DLBCL-IB indicates diffuse large B-cell lymphoma-immunoblastic; EBV, Epstein-Barr virus; KSHV, Kaposi sarcomaherpesvirus; MCD, multicentric Castleman disease; PBL, plasmablastic lymphoma; PC, plasma cell; and PEL, primary effusion lymphoma.