Molecular histogenesis of plasmablastic lymphoma of the oral cavity

Plasmablastic lymphoma (PBL) of the oral cavity is an aggressive B-cell lymphoma associated with human immunodeficiency virus infection. Although the lymphoma phenotype is consistent with late B-cell maturation, the molecular histogenesis of PBL is unknown. We investigated PBL of the oral cavity (n 1/4 12) for mutations of immunoglobulin variable heavy chain (IgV_H) and BCL-6 genes, which are acquired by B cells at the time of germinal centre (GC) transit, and for expression of BCL-6, MUM-1 and CD138, which distinguish GC B cells from post-GC B cells. Somatic IgV_H hypermutation occurred in 4/10 PBL whereas 6/10 PBL displayed germline IgV_H genes. Among PBL carrying hypermutated IgV_H genes, the pattern of IgV_H mutations was consistent with antigen stimulation in two cases. Mutations of the BCL-6 gene were restricted to 1/12 patients with PBL of the oral cavity. All cases of PBL of the oral cavity displayed the BCL-6^-/MUM-1⁺/CD138⁺ phenotype that is consistent with late stage of B-cell differentiation. Overall, these data indicate that, despite a common phenotype and an apparently similar degree of differentiation, PBL of the oral cavity are characterized by histogenetic heterogeneity. A subset of PBL of the oral cavity carried the molecular clues of GC transit and conceivably originated from a B-cell subset corresponding to post-GC B cells. Conversely, another fraction of these lymphomas were devoid of somatic IgV_H mutations and appeared to originate from naive B cells that have undergone preterminal differentiation independent of GC transit.