Studies also find that 60-75% of individuals diagnosed with PBL have Epstein–Barr virus-infected plasmablasts. EBV infects ~95% of the worlds population to cause no symptoms, minor non-specific symptoms, or infectious mononucleosis. The virus then enters a latency phase in which infected individuals become lifetime asymptomatic carriers of the virus in a set of their B-cells. Some weeks, months, years, or decades thereafter, a very small fraction of these carriers, particularly those with an immunodeficiency, develop any one of various EBV-associated benign or malignant diseases, including, in extremely rare cases, Epstein–Barr virus-positive plasmablastic lymphoma. The virus in infected plasmablastic cells appears to be in its latency I phase; consequently, these infected cells express EBV products such as EBER nuclear RNAs and BART microRNAs. These RNAs promote infected cells to proliferate, avoid attack by the hosts immune systems cytotoxic T-cells, and, possibly, block the infected cells apoptosis (i.e. programmed cell death) response to injuryThe predisposing conditions described in the previous paragraph can serve to enhance the ability of the plasmablasts in PBL to: avoid the hosts immune surveillance; survive for prolonged periods, grow excessively, and acquire pro-malignant gene abnormalities.
Some of the gene abnormalities found in PBL include: 1) increased expression  of the MYC proto-oncogene due to its rearrangement with an antibody gene by genetic recombination or, less commonly, other causes (Myc protein, the product of this gene, enhances cell proliferation, inhibits apoptosis, and promotes malignancy); 2) loss in the expression of the PRDM1 gene whose product, PRDM1/BLMP1 protein, represses the expression of Myc protein;) 3) frequent duplications in certain areas of chromosomes 1, 7, 11, and 22 (these duplications are similar to those often seen in diffuse large cell lymphoma); 4) reduced expression of at least 13 genes that are involved in B-cell responses to signaling agents. 5) increased expression of genes which promote the maturation of B-cells toward plasma cells (e.g. CD38, CD138, IR4/MUM1, XBP1, IL21R, and, as just indicated, PRDM1); and 6) reduced expression of genes characteristic of B-cells (e.g. CD20 and PAX5). Diagnosis
Microscopic examination of involved PBD masses and infiltrates generally reveals diffuse proliferations of immunoblast-like cells with prominent features of plasma cells, i.e. plasmablastic cells. Immunostaining of these cells indicate that they lack B-cell marker proteins (e.g. CD20 and PAX5 [in ~10% of cases CD20 may be expressed at very low levels]) but rather express plasma cell marker proteins (e.g. CD38, CD138, IR4/MUM1, XBP1, IL21R, and/or PRDM1). The abnormalities in gene structures and expressions reported in the Pathophysiology section, particularly rearrangement and/or over expression of the MYC proto-oncogene, may also be apparent in these cells.