Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China

Abstract

Background Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. Methods A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. Results Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. Conclusions In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

Plasmablastic Lymphoma in a Human Immunodeficiency Virus-positive Child With a Suspicion of Concomitant Primary Immunodeficiency Disorder

“…However, interestingly, on genetic analysis of the tumors, most of these patients had defects in B-cell receptors and T-cell receptor signaling molecules. Some of them are very well characterized for causing CVID, such as CD19, CD22, BLNK, etc 23 Therefore, even though HIV infection was found in this patient, the main etiological factor in this child was more likely an inherited aberrancy in the immune system. This highlights the importance of studying the course of disease in such patients to help us be better equipped to diagnose and manage these rare but lethal diseases.…”

New insights into the role of macrophages in cancer immunotherapy

“…Therefore, the prevention and treatment of tumors were urgent to further decrease the morbidity and mortality rates. Surgery, radiotherapy, and chemotherapy are three traditional treatment strategies for cancer, but the treatment outcome was still dismal in some patients ( 1 , 2 ). In the recent years, emerging treatment methods were developed, such as Chimeric antigen receptor (CAR)-T cell therapy and immune-checkpoint inhibitors, which were considered as the fourth treatment mode following the traditional therapy.…”

Plasmablastic lymphoma: current knowledge and future directions

“…ARLs account for approximately 3% of non-Hodgkin’s lymphoma ( 15 , 16 ), however, the exact incidence of HIV-positive PBL is still unknown. In the recent years, an increasing number of PBL cases with normal immune function have been reported ( 6 , 17 – 19 ). The clinicopathologic features of PBL were significantly different between HIV positive and HIV negative individuals ( 18 , 20 ).…”

“…A meta-analysis summarized the reported cases of PBL between 1997 and 2015 in China and the results demonstrated that all the patients were HIV negative ( 23 ). Recently, our group reported 56 cases of PBL from China and found that most patients were immunocompetent, and HIV infection was not observed ( 17 ). The above results showed that the immune status of PBL was significantly different between the eastern and western population.…”

“…In HIV-negative PBL, the most common sites of extra-oral lesions were gastrointestinal tract, lymph nodes and skin, and extra-nodal lesions accounted for 82% ( 6 , 17 , 19 ). However, oral cavity is involved more frequently in HIV positive PBL than that in HIV negative PBL ( 6 , 20 ).…”