Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features

Patients with diffuse large B-cell lymphoma (DLBCL) rarely show relapse after 4 years of complete remission (CR). In this study, we addressed the following questions: (1) Does late-relapsing DLBCL represent clonally related disease or a second malignancy; and (2) is there a characteristic biologic background? in 10 of 13 DLBCL patients with relapse after 4 to 17 years, a clonal relationship was established based on identical IgH-sequences and/or identical bcl2-IgH translocation. Most (77%) showed features of germinal center (GC) cells, as defined by expression of CD10, bcl-2, and bcl-6 protein and ongoing immunoglobulin heavy chain variable region (VH) hypermutation. A GC phenotype was seen in 8 (20%) of 38 control patients matched for age, stage, and (extra)nodal localization with relapse within 2.5 years (P = .005). In conclusion, we have found evidence that late-relapsing DLBCL represents truly clonally related disease episodes in most cases and that this clinical behavior may be related to the biologic features of GC cells. (C) 2003 by The American Society of Hematology.