BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin's lymphoma with distinct clinical and molecular heterogeneity. DLBCL that arises in extranodal organs is particularly linked to poor prognosis. This study aimed to determine the clinical and molecular characteristics of extranodal involvement (ENI) in DLBCL and assess the actual survival status of the patients. MethodsIn this population-based cohort study, we investigated the clinical features of 5,023 patients newly diagnosed with DLBCL. Their clinical conditions, eligibility criteria, and sociodemographic details were recorded and analyzed. Gene panel sequencing was performed on 1,050 patients to discern molecular patterns according to ENI. ResultsThe 2-year overall survival (OS) rate was 76.2% [95% confidence interval (CI), 74.0%-78.2%], and the 5-year OS rate was 67.9% (95% CI, 65.2%-70.4%). The primary treatment was immunochemotherapy with rituximab. Specific lymphoma involvement sites, especially the bones, bone marrow, and central nervous system, were identified as independent adverse prognostic factors. A high prevalence of non-germinal center B-cell (non-GCB) phenotype and myeloid differentiation primary response 88 (MYD88)/CD79B mutations were noted in lymphomas affecting the breasts, skin, uterus, and immune-privileged sites. Conversely, the thyroid and gastrointestinal tract showed a low occurrence of non-GCB phenotype. Remarkably, patients with multiple ENIs exhibited a high frequency of MYD88, tet methylcytosine dioxygenase 2 (TET2), CREB binding protein (CREBBP) mutations, increased MYD88L265P and CD79B mutation (MCD)-like subtypes, and poor prognosis. Genetic subtype-guided immunochemotherapy showed good efficacy in subgroup analyses after propensity score matching with 5-year OS and progression-free survival rates of 85.0% (95% CI, 80.6%-89.5%) and 72.1% (95% CI, 67.3%-76.7%). ConclusionsIn the rituximab era, this large-scale retrospective analysis from Asia confirmed the poor prognosis of DLBCL with multiple ENIs and underscored the efficacy of genetic subtype-guided immunochemotherapy in treating extranodal DLBCL.
基金：
Shanghai Clinical Research Center for Cell Therapy, Grant/Award Number:23J41900100; National Natural Science
Foundation of China, Grant/Award
Number: 82130004; Clinical Research
Plan of Shanghai Hospital Development
Center, Grant/Award Number:
SHDC2020CR1032B; National Key
Research and Development Program,
Grant/Award Number: 2022YFC2502600;
Multicenter Clinical Research Project by
Shanghai Jiao Tong University School of
Medicine, Grant/Award Number:DLY201601
第一作者机构：[1]Shanghai Jiao Tong Univ, Shanghai Inst Hematol, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom,Ruijin Hosp,Sch Med, 197 Rui Jin Er Rd, Shanghai 200000, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Shanghai Inst Hematol, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom,Ruijin Hosp,Sch Med, 197 Rui Jin Er Rd, Shanghai 200000, Peoples R China[42]Lab Mol Pathol, Pole Rech Sino Francais Sci Vivant & Genom, Shanghai, Peoples R China
推荐引用方式(GB/T 7714)：
Chen Si-Yuan,Xu Peng-Peng,Feng Ru,et al.Extranodal diffuse large B-cell lymphoma: Clinical and molecular insights with survival outcomes from the multicenter EXPECT study[J].CANCER COMMUNICATIONS.2025,doi:10.1002/cac2.70033.
APA：
Chen, Si-Yuan,Xu, Peng-Peng,Feng, Ru,Cui, Guo-Hui,Wang, Li...&Zhao, Wei-Li.(2025).Extranodal diffuse large B-cell lymphoma: Clinical and molecular insights with survival outcomes from the multicenter EXPECT study.CANCER COMMUNICATIONS,,
MLA：
Chen, Si-Yuan,et al."Extranodal diffuse large B-cell lymphoma: Clinical and molecular insights with survival outcomes from the multicenter EXPECT study".CANCER COMMUNICATIONS .(2025)
医学