Plasmablastic lymphoma: An update

Abstract

Plasmablastic lymphoma (PBL) is a highly aggressive B cell non-Hodgkin lymphoma frequently associated with immunosuppression, particularly human immunodeficiency virus (HIV) infection. Although PBL is rare globally, South Africa has a high burden of HIV infection leading to a higher incidence of PBL in the region. Laboratory features in PBL may overlap with plasmablastic myeloma and other large B cell lymphomas with plasmablastic or immunoblastic morphology leading to diagnostic dilemmas. There are, however, pertinent distinguishing laboratory features in PBL such as a plasma cell immunophenotype with MYC overexpression, expression of Epstein-Barr virus-encoded small RNAs and lack of anaplastic lymphoma kinase (ALK) expression. This review aims to provide a summary of current knowledge in PBL, focusing on the epidemiology, pathophysiology, laboratory diagnosis and clinical management.

Keywords: EBV; HIV; MYC; aggressive lymphoma; plasmablastic lymphoma; plasmablastic myeloma.

FIGURE 1

Morphological features of plasmablastic lymphoma diagnosed on bone marrow biopsy. The patient was HIV +ve, virally suppressed on antiretroviral therapy (HIV viral load of <100 copies/ml) and had an absolute CD4 count of 243 cells/μl. The bone marrow aspirate shows numerous plasmablasts of varying sizes (May‐Grünwald‐Giemsa, ×50) (A). The trephine biopsy demonstrates a heavy diffuse infiltrate of plasmablasts with round eccentric nuclei and coarse clock face chromatin. Multinucleated forms and numerous mitotic figures are also present (H&E, ×50) (B). Nuclear positivity for IRF4/MUM1 (×50) (C). High proliferation index (Ki67, ×50) (D). Weak Golgi positivity for CD138 in the tumour cells (×50) (E). Epstein–Barr virus encoded small RNA (EBER) positivity (×50) (F).

FIGURE 2

Pathogenesis of plasmablastic lymphoma. After undergoing clonal selection in the germinal centre light zone, normal B cells upregulate the expression of plasma cell markers including CD38, CD138 and IRF4/MUM1 with NF‐κB signalling. IRF4/MUM1 causes the upregulation of BLIMP1, which in turn suppresses PAX5 gene expression (bottom right of figure). BLIMP1 serves as a transcriptional repressor of MYC. Normal plasma cell differentiation is dependent on the expression and influence of IRF4/MUM1, BLIMP1 and XBP1. MYC overexpression, as seen in plasmablastic lymphoma, bypasses the inhibitory effect of BLIMP1 and prevents the differentiation of plasma cells from plasmablasts. EBV further inhibits pro‐apoptotic members of the BCL2 family of proteins and upregulates PD‐L1 expression on plasmablasts in some cases (bottom left of figure)., , EBV, Epstein–Barr virus; GC, germinal centre; IRF4, interferon regulatory factor 4; PD‐L1, programmed death‐ligand 1.