Molecular histogenesis of plasmablastic lymphoma of the oral cavity

Abstract

Summary. 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 ¼ 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.

Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles

“…7 Previous reports have shown that plasmablastic lymphoma has a terminally differentiated B-cell or plasma cell immunophenotype, characterized by weak or absent expression of conventional B-cell markers, and strong expression of the post germinal center B-cell-and plasma cell-associated markers MUM1/IRF4 and CD138/syndecan-1. [1][2][3]8,9 This immunophenotype is similar to that reported for plasmablastic plasma cell myeloma. 1,8,10,11 In practice, the distinction between plasmablastic lymphoma and plasmablastic plasma cell myeloma frequently depends on clinical correlation.…”

“…In agreement with previous studies, all of the plasmablastic lymphoma cases in this study had a post-germinal center B-cell/plasma cell phenotype, expressing MUM1/IRF4 and CD138/syndecan-1, but negative for CD20. 3,[20][21][22] Furthermore, we observed that several markers that may be aberrantly expressed in plasma cell neoplasms, CD56, CD10 and CD4, were also expressed in most cases of plasmablastic lymphoma. CD56 and CD10, markers frequently expressed in plasma cell myeloma, [23][24][25] were positive in 5/9 and in 6/9 of the plasmablastic lymphoma cases in our series, respectively.…”

“…Immunoblastic diffuse large B-cell lymphoma can be excluded on the basis of the characteristic immunophenotypic pattern of plasmablastic lymphoma, with CD20 negativity in combination with markers of postgerminal center B cells and plasma cells, such as CD138/syndecan-1. 3,4 Diffuse large B-cell lymphoma with expression of ALK and extramedullary myeloid tumor can be excluded by immunohistochemical studies for ALK and myeloid markers, respectively. 5,6 However, in many cases of plasmablastic lymphoma, the most difficult issue in the differential diagnosis is excluding plasmablastic plasma cell myeloma with extramedullary involvement.…”

Plasmablastic Lymphoma in a Previously Undiagnosed Aids Patient: A Case Report

“…PBL is strongly associated to EBV [1,4,6,10,20,29,30] and is not necessarily confined to head and neck area as once believed [1,10,16,[30][31][32][33][34].…”

Plasmablastic Lymphoma of Head and Neck: Report of Two New Cases and Correlation with c-myc and IgVH Gene Mutation Status

“…Gaidano et al investigated 12 cases of PBL of the oral cavity for somatic IgV H hypermutations and found 4 of 10 cases to be positive for this mutation while six cases displayed germline IgV H genes. Whereas all of their cases, regardless the IgV H mutational state were BCL-6 negative, indicating a lack of transit through the germinal center, all of the cases consistently revealed strong expression of CD138 and MUM-1, markers of preterminal plasma-cell differentiation [17]. From these studies the authors concluded that the IgV H hypermutated subset carried the molecular clues of germinal center transit and conceivably originated from a post-germinal center B-cell, while the IgV H unmutated group appeared to originate from a naïve B-cell that had undergone post-germinal differentiation independent of germinal center transit.…”