title: Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features.
abstract: 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.
authors.affiliation: Department of Pathology, Biomedics and Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. djong@nki.nl
authors.forename: Daphne
authors.initials: D
authors.lastname: de Jong
authors.forename: Annuska M
authors.initials: AM
authors.lastname: Glas
authors.forename: Lucie
authors.initials: L
authors.lastname: Boerrigter
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Hermus
authors.forename: Otilia
authors.initials: O
authors.lastname: Dalesio
authors.forename: Els
authors.initials: E
authors.lastname: Willemse
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Kersten
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002999:Clone Cells / Q000473:pathology; D005260:Female; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013997:Time Factors