Clinicopathologic Features and Genomic Signature of De Novo CD5+ Diffuse Large B-Cell Lymphoma A Multicenter Collaborative Study

De novo CD5(+) diffuse large B-cell lymphoma (DLBCL) has poor survival in the era of immunochemotherapy. Accurate gene-based typing and prognostic stratification can enhance the development of effective individualized treatments. Therefore, we conducted a multicenter retrospective study to evaluate the clinicopathologic characteristics, genomic profiles, and prognostic parameters of 61 patients with CD5(+) DLBCL and 60 patients with CD5(-) DLBCL, with the goal of facilitating accurate prognostic stratification and potential individualized treatment strategies. Compared with patients with CD5(-) DLBCL, older age, advanced stage, higher incidence of central nervous system involvement, and MYC/BCL-2 and p53 overexpression were more prevalent in CD5(+) DLBCL. Most patients with CD5(+) DLBCL had lymph nodes with non-germinal center B-cell-like or activated B-cell-like subtype according to immunohistochemistry or Lymph2Cx assay. Next-generation sequencing showed that the proportion of MCD subtype (based on the co-occurrence of MYD88 and CD79B mutations) in the CD5(+) DLBCL cohort was higher than that in the CD5(-) DLBCL cohort (54.2% vs. 13.0%, P=0.005). Compared with the CD5(-) cohort, CD5(+) DLBCL patients showed poor 5-year overall survival (70.9% vs. 39.0%, P<0.001). Kaplan-Meier survival analysis indicated that cell of origin, MYC/BCL-2, p53, and BCL-6 expression did not have a prognostic impact on patients with CD5(+) DLBCL. Multivariate analysis showed that age above 76 years, advanced stage, higher incidence of central nervous system involvement, and hypoalbuminemia were independent factors for poor prognosis in CD5(+) DLBCL patients. In summary, CD5(+) DLBCL displays poor prognosis, distinctive clinicopathologic characteristics and predominant genetic features of activated B-cell-like and MCD subtypes with worse survival outcome.