PURPOUSE: to assess the clinicopathologic features of a poorly defined subset of diffuse large b-cell lymphoma, which is characterized by the secretion of an IgM paraprotein (IgMs-DLBCL).
EXPERIMENTAL DESIGN: multicentre, retrospective, and comparative study to analyse with an integrated diagnostic approach the IgMs-DLBCL subset.
RESULTS: Overall, 650 DLBCL were enrolled: 102 had an associated serum IgM and 56 other paraproteins (OP), the remaining 492 cases were the reference group (REF). IgMs-DLBCL were characterized by older age, advanced stage, dissemination to extra-nodal organs, elevated LDH and poor PS. As a result, the majority of IgMs had a high IPI, NCC-IPI and CNS-IPI score (p<.001).
Furthermore, IgMs qualified as an independent prognostic factor in multivariate analysis for both PFS and OS (p<.001). Remarkably, the incidence of CNS involvement was higher in the IgMs compared to the OP and the REF subsets, respectively (p<.001). IgMs-DLBCL were characterized by: 1) prevalence of non-GCB/ABC-type; 2) frequent overexpression of BCL-2; 3) preferential IGVH4-34 gene usage; 4) MYD88 and TP53 mutations, both occurringin 30.8% of IgMs cases (95%CI, 14.3-51.8)
CONCLUSION: Our study was carried out on the largest series of IgMs-DLBCL reported so far. This is a sizeable subset of DLBCL (7.9%, 95%CI, 5.9-10.5%),which is worth to detect at diagnosis. Remarkably, IgMs-DLBCL harbours features of a molecular subset that associate with a worse outcome. Indeed, more studies are necessary to fully understand the molecular pathogenesis of IgMs-DLBCL and the biological mechanisms leading to the high rate of CNS spreading.