Abstract
High-grade B cell lymphomas with rearrangements on C-MYC and BCL2 and/or BCL6 (HGBL with MYC and BCL2 and/or Bcl6 rearrangement) are associated with worse clinical outcomes and thus were introduced as a separate new category in the recently updated WHO classification. From 2012 to 2016, we analyzed a consecutive cohort of large B cell lymphomas (LBCLs) for C-MYC, BCL2, and BCL6 rearrangements and correlated our results with clinical-pathological parameters. Ten of 78 (13%) cases had a C-MYC and BCL2 and/or BCL6 rearrangement, so-called double or triple hit (DH), while double/triple copy number gains (CNGs) were found in eight (10%) patients. Patients with a high-grade lymphoma with DH or CNG progressed significantly more often after first-line chemotherapy (p = 0.005). When treated with standard chemotherapy, patients with a DH or CNG had a significantly worse overall (OS) and recurrence free survival (RFS) compared with all other patients (p = 0.033 and p < 0.001, respectively). Thus, patients with a diffuse large B cell lymphoma, harboring a double/triple CNG, seem to have a similar poor prognosis than those with a DH. Though our data can only be regarded as preliminary, our results warrant further investigations to fully elucidate the role of CNGs as well as underlying molecular mechanisms resulting in aggressive behavior in LBCL.
Highlights
Large B cell lymphomas (LBCLs) comprise a heterogeneous group of lymphomas
From 2012 to 2016, all LBCLs diagnosed at the Institute of Pathology, Neuropathology, and Molecular Pathology, Medical University of Innsbruck, were upon diagnosis routinely analyzed for the presence of rearrangements on CMYC, as well as BCL2 and BCL6 by means of fluorescence in situ hybridization (FISH), irrespective if they were de novo lymphomas or transformed from an underlying small cell lymphoma
Other specific types of aggressive lymphomas such as Burkitt lymphoma, primary mediastinal large B cell lymphoma, EBV+ DLBCL, or plasmablastic lymphoma were excluded upon diagnosis
Summary
Large B cell lymphomas (LBCLs) comprise a heterogeneous group of lymphomas. While some of them, such as Burkitt lymphoma, have a well-defined morphology and molecular pathology, others are less well defined and disease outcome is highly variable. The group of diffuse large B cell. Beside C-MYC rearrangements, expression of C-MYC protein > 40% together with BCL2 expression in > 50% of lymphoma cells has been reported to be associated with a poor outcome which is better than in HGBL, C-MYC. Several studies point towards a role of copy number gains (CNG) on C-MYC and/or BCL2 and/or BCL6 [13,14,15]. Patients with CNG are reported to have a poor prognosis than those with HGBL with MYC and BCL2 and/or BCL6. Patients with CNG are reported to have a poor prognosis than those with HGBL with MYC and BCL2 and/or BCL6. [13,14,15]
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