Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients

Abstract

P lasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma commonly associated with Epstein-Barr virus co-infection that most often occurs in the context of human immunodeficiency virus infection. Therefore, its immune escape strategy may involve the upregulation of immune-checkpoint proteins allowing the tumor immune evasion. However, the expression of these molecules was poorly studied in this lymphoma. We have investigated 82 plasmablastic lymphoma cases of whom half were Epstein-Barr virus positive. Although they harbored similar pathological features, Epstein-Barr virus positive plasmablastic lymphomas showed a significant increase in MYC gene rearrangement and had a better 2-year event-free survival than Epstein-Barr virus negative cases (P=0.049). Immunostains for programmed cell death-1, programmed cell death-ligand 1, indole 2,3-dioxygenase and dendritic cell specific C-type lectin showed a high or moderate expression by the microenvironment cells in 60%-72% of cases, whereas CD163 was expressed in almost all cases. Tumor cells also expressed programmed cell death-1 and its ligand in 22.5% and 5% of cases, respectively. Both Epstein-Barr virus positive and negative plasmablastic lymphomas exhibited a high immune-checkpoint score showing that it involves several pathways of immune escape. However, Epstein-Barr virus positive lymphomas exhibited a higher expression of programmed cell death-1 and its ligand in both malignant cells and microenvironment as compared to Epstein-Barr virus negative cases. In conclusion, plasmablastic lymphoma expresses immune-checkpoint proteins through both malignant cells and the tumor microenvironment. The expression of programmed cell death-1 and its ligand constitutes a strong rationale for testing monoclonal antibodies in this often chemoresistant disease.

Plasmablastic lymphoma mimicking carcinomatosis: A case report and review of the literature

“…The pathogenesis of plasmablastic lymphoma remains poorly understood. Rearrangements of the MYC gene are common, presenting in approximately 70% of all cases . MYC rearrangements have also been described in the progression/transformation of plasma cell myeloma as well as in low‐grade lymphoid neoplasms, and may be related to the development of plasmablastic morphology .…”

“…Rearrangements of the MYC gene are common, presenting in approximately 70% of all cases. 5 MYC rearrangements have also been described in the progression/transformation of plasma cell myeloma as well as in low-grade lymphoid neoplasms, and may be related to the development of plasmablastic morphology. 6 As EBV is only rarely seen in plasma cell myeloma; a history of immunodeficiency or tumor EBV-positivity may be helpful in narrowing the differential diagnosis.…”

CD117 (KIT) is a useful marker in the diagnosis of plasmablastic plasma cell myeloma

“…As mentioned earlier, both PPCM and PBL are associated with MYC aberrations. In fact, these gene aberrations have been shown to be present in 30–70% of all PBL cases, leading some to claim that a MYC aberration could be useful for PBL diagnosis. However, MYC aberrations are not useful for differentiating PBL from PPCM, and, in fact, are thought to contribute to the plasmablastic morphology of both of these entities .…”

Checkpoint Inhibition in Non-Hodgkin's Lymphoma

“…Plasmablastic lymphoma, which is a rare but very dismal aggressive lymphoma, is associated with a high expression rate of PD-L1. In this entity, PD-L1 expression is found in tumor cells and in the microenvironment; e.g., in one series, PD-L1 was expressed in 44% of the patient samples analyzed [41,42]. Interestingly PD-L1 expression did not differ in EBV-positive and -negative cases of posttransplant lymphoproliferative disorder (PTLD).…”