The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement Steven Le Gouill, Pascaline Talmant, Cyrille Touzeau, Anne Moreau, Richard Garand, Nadine Juge-Morineau, Fanny Gaillard, Thomas Gastinne, Noël Milpied, Philippe Moreau, Jean Luc Harousseau, Hervé Avet-Loiseau From the Department of Hematology, Hôtel Dieu, University Hospital of Nantes, Place Alexis Ricordeau, 4093 Nantes cedex 01, France (SLG, CT, TG, PM, JLH); Laboratory of Hematology, Clinical Hematology Department, University Hospital, Place Alexis Ricordeau, 44093 Nantes cedex 01, France (PT, RG, H- AL); Laboratory of Anatomopathology, University Hospital, Place Alexis Ricordeau 44093 Nantes cedex 01, France (AM, FG); Centre Catherine de Sienne, 2 rue Eric Tabarly, 44200 Nantes, France (NJ-M); Department of Hematology, University Hospital, Hôpital Haut Lévèque, 3604 Pessac, France (NM). Manuscript received January 25, 2007. Manuscript accepted July 19, 2007. Correspondence: Hervé Avet-Loiseau, MD, PhD, Laboratory of Hematology, Clinical Hematology Department, University Hospital, Place Alexis Ricordeau, 44093 Nantes cedex 01, France. E-mail: herve.avetloiseau@chu- nantes.fr Background and Objectives Diffuse large B-cell lymphomas (DLBCL) are common lymphomas that have been clas- sified into three subgroups on the basis of their patterns of gene expression. The aim of this study was to characterize the clinical, biological, immunophenotypic and cyto- genetic features of DLBCL with concurrent t(14;18) and 8q24/c-MYC rearrangement. Design and Methods Sixteen cases of DLBCL with the dual translocation were identified between 1998 and January 2006. The clinical features of these cases were examined and morpho- logical, immunohistochemical, flow cytometric and cytogenetic analyses were per- formed. Results All patients had aggressive features: B symptoms (81%), ECOG performance status >2 (81%), elevated lactate dehydrogenase (100%), stage IV disease (100%) with at least one extra-nodal localization (bone marrow, blood and central nervous system involvement in 93%, 50% and 50%, respectively) and age-adjusted IPI score of 3 in 81%. Despite intensive chemotherapy regimens (including allogeneic transplants), all patients died of disease progression. Progression-free and overall survival was 4 and 5 months, respectively. Immunophenotyping analysis (CD20, CD10, Bcl-6, Mum-1, Bcl-2 CD138, MIB1, CD19, CD5, CD38 and sIg) was performed and showed DLBCL with a germinal center (GC) profile. Ki-67 staining ranged from 70 to 90%. All cases assessed by cytogenetics analysis [conventional cytogenetic and/or fluorescence in situ hybridization (FISH)] had a complex karyotype. In one case, we identified a 8q24/c-MYC translocation variant never reported in DLBCL before: t(8;9)(q24;p13) and t(14;18)(q32;q21). The BCL-6 rearrangement was investigated by FISH and found to rearranged in four cases. Interpretation and Conclusions In conclusion, DLBCL with concurrent t(14;18) and 8q24/c-MYC rearrangement is a subgroup of GC-DLBCLwith poor outcome. It is worth searching for the coexistence of dual translocations in Bcl-2-positive DLBCL with unusual aggressive presentation. Key words: high grade non-Hodgkin’s lymphoma, bcl-2; c-myc. Haematologica 2007; 92:1335-1342. DOI: 10.3324/haematol.11305 ©2007 Ferrata Storti Foundation Original Article ABSTRACT haematologica/the hematology journal | 2007; 92(10) | 1335 | ©Ferrata Storti Foundation