Hepatitis B virus-associated diffuse large B-cell lymphoma: unique clinical features, poor outcome, and hepatitis B surface antigen-driven origin
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Lijuan Deng1, Yuqin Song1, Ken H. Young2, Shimin Hu2, Ning Ding1, Weiwei Song1, Xianghong Li3, Yunfei Shi3, Huiying Huang1, Weiping Liu1, Wen Zheng1, Xiaopei Wang1, Yan Xie1, Ningjing Lin1, Meifeng Tu1, Lingyan Ping1, Zhitao Ying1, Chen Zhang1, Yingli Sun1, Jun Zhu1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China
2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
Jun Zhu, e-mail: [email protected]
Keywords: hepatitis B virus, diffuse large B-cell lymphoma, hepatitis B surface antigen, B-cell receptor, complementarity determining region 3
Received: April 30, 2015 Accepted: July 09, 2015 Published: July 22, 2015
While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known more than this epidemiologic evidence. We studied a cohort of 587 patients with DLBCL for HBV infection status, clinicopathologic features, and the immunoglobulin variable region in HBV surface antigen (HBsAg)-positive patients. Eighty-one (81/587, 13.8%) patients were HBsAg-positive. Compared with HBsAg-negative DLBCL, HBsAg-positive DLBCL displayed a younger median onset age (45 vs. 55 years), more frequent involvement of spleen or retroperitoneal lymph node (40.7% vs. 16.0% and 61.7% vs. 31.0% respectively, both p < 0.001), more advanced disease (stage III/IV: 76.5% vs 59.5%, p = 0.003), and significantly worse outcome (2-year overall survival: 47% versus 70%, p < 0.001). In HBsAg-positive DLBCL patients, almost all (45/47, 96%) amino acid sequences of heavy and light chain complementarity determining region 3 exhibited a high homology to antibodies specific for HBsAg, and the majority (45/50, 90%) of IgHV and IgLV genes were mutated. We conclude that 13.8% of DLBCL cases are HBV-associated in HBV-endemic China and show unique clinical features and poor outcomes. Furthermore, our study strongly suggests that HBV-associated DLBCL might arise from HBV antigen-selected B cells.
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