title: Hepatitis B virus-associated diffuse large B-cell lymphoma: unique clinical features, poor outcome, and hepatitis B surface antigen-driven origin.
abstract: 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.
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Lijuan
authors: L
authors: Deng
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Yuqin
authors: Y
authors: Song
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Ken H
authors: KH
authors: Young
authors: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Shimin
authors: S
authors: Hu
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Ning
authors: N
authors: Ding
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Weiwei
authors: W
authors: Song
authors: Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Xianghong
authors: X
authors: Li
authors: Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Yunfei
authors: Y
authors: Shi
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Huiying
authors: H
authors: Huang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Weiping
authors: W
authors: Liu
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Wen
authors: W
authors: Zheng
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Xiaopei
authors: X
authors: Wang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Yan
authors: Y
authors: Xie
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Ningjing
authors: N
authors: Lin
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Meifeng
authors: M
authors: Tu
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Lingyan
authors: L
authors: Ping
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Zhitao
authors: Z
authors: Ying
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Chen
authors: C
authors: Zhang
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Yingli
authors: Y
authors: Sun
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
authors: Jun
authors: J
authors: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D002648:Child; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006509:Hepatitis B / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000401:mortality; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015995:Prevalence; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region
keywords: B-cell receptor; complementarity determining region 3; diffuse large B-cell lymphoma; hepatitis B surface antigen; hepatitis B virus