Submitted September 16, 2002
Accepted March 6, 2003
Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features
Daphne de Jong*, Annuska M Glas, Lucie Boerrigter, Marie-Christine Hermus, Otilia Dalesio, Els Willemse, Petra M Nederlof, and Marie-Jose Kersten
Department of Pathology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
Department of Biometrics, the Netherlands Cancer Institute, Amsterdam, The Netherlands
Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
* Corresponding author; email: d.d.jong{at}nki.nl.
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). Do late relapsing DLBCL represent clonally related disease or a second malignancy; and 2) is there a characteristic biologic background. In 10/13 DLBCL patients with relapse after 4-17 years, a clonal relationship was established based on identical IgH-sequences and/or identical bcl2-IgH translocation The majority (77%) showed features of germinal center (GC) cells, as defined by expression of CD10, bcl-2 and bcl-6 protein and ongoing VH-hypermutation. A GC-phenotype was seen in 8/38 (20%) control patients matched for age, stage and (extra)nodal localization with relapse within 2.5 years (p=0.005). In conclusion, we have found evidence that late relapsing DLBCL represents truly clonally related disease episodes in the majority of cases and that this clinical behaviour may be related to the biological features of GC cells.
