Plasmablastic Lymphomas (PBL) Are Genetically Characterized by Frequent MYC Translocations
O Balague, S Valera, A Martinez, L Colomo, J Delabie, A Macolscy, E Campo. Hospital Clnic, University of Barcelona, Barcelona, Spain; Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway; Semmelweis University, Budapest, Hungary
Background: PBL is an aggressive lymphoma characterized by a diffuse proliferation of large cells with predominant immunoblastic morphology and a plasma cell phenotype. The clinical and pathological features of this lymphoma have been relatively well characterized but its genetic alterations are not well known. The aim of this study was to identify recurrent cytogenetic aberrations that may be involved in the pathogenesis of PBL.
Design: We investigated 31 PBL, 4 primary effusion lymphomas (PEL) and 5 plasmablastic plasmacytomas (PBL-PC). Genetic alterations involving BCL2, BCL6, MALT1, PAX5, MYC and IGH genes were assessed in paraffin sections by interphase fluorescence in situ hybridization (FISH) using split-apart probes. In cases carrying a MYC translocation FISH for MYC/IGH translocation was additionally investigated with a dual color-dual fusion probe. MYC expression was examined by immunohistochemistry in 12 PBL.
Results: Structural alterations of MYC were detected in 11 of 28 PBL (39%), 9 of them corresponded to split signals (32%) and 2 were additional copies of the locus. The translocation t(8;14) was confirmed in 5 of the 9 cases with a 8q24 rearrangement using the MYC/IGH dual color-dual fusion probe. Two of the four cases in which the fusion probe failed were investigated with the IGH split-apart probe that showed also a rearrangement of the this locus suggesting the presence of a t(8;14). BCL2, BCL6, MALT1 and PAX5 were examined in 26, 25, 23, and 17 cases respectively. No rearrangements were observed but extra copies of these genes were observed in 3 (12 %), 3 (16%), 4 (21%) and 4 (21%) of the cases respectively. Two cases showed gains of BCL2 and MALT1. Two PEL showed a gain of MYC and PAX5, respectively, whereas only a gain of MYC was detected in one of the PBL-PC. No rearrangements in any of these loci were detected in the PEL or PBL-PC cases. Nuclear MYC protein expression was detected in 4 PBL with gene translocations but was negative in 8 cases without genetic alterations.
Conclusions: PBL are genetically characterized by frequent structural alterations of the MYC locus that in most cases correspond to the t(8;14) translocation. The lack of translocations and the low number of gains in the BCL6, MALT1, BCL2 and PAX5 loci distinguishes genetically PBL from other types of diffuse large B-cell lymphomas.
Monday, March 9, 2009 1:30 PM
Platform Session: Section D, Monday Afternoon