Two Double-hit Lymphomas Cases: A Molecular Cytogenetic Approach.

Objectives: Double-hit lymphomas represent 5% of cases of diffuse large B-cell lymphomas (DLBCL). They are currently recognized as highgrade B-cell lymphomas (HGBCL) with rearrangements of MYC and BCL2 and/or BCL6 by the 2016 WHO classification. One of these rearrangements is the translocation of the BCL2 gene (18q21.33), which codes for an apoptotic inhibitor, to the immunoglobulin heavy chain gene (14q32). In rarer instances, a translocation of the BCL2 gene to the immunoglobulin light chain gene on 2p11 also occurs. Both of these rearrangements result in consistent expression of the BCL2 protein. Another rearrangement is the translocation of the MYC proto-oncogene (8q24.21) to the IGH gene (14q32), which results in the overactivation of MYC. A t(14;18) can drive a low-grade malignant lymphoma, which is commonly a follicular or DLBCL. However, the presence of a t(8;14) abnormality may result in a highgrade malignant lymphoma, such as Burkitt's lymphoma. Both translocations affecting MYC and BCL2 rarely occur in an identical cell, and this lymphoid malignancy is known as BCL2 and MYC double-hit lymphoma. The incidence of aggressive B-cell lymphomas other than Burkitt's with a MYC breakpoint is difficult to assess, mainly because the published cytogenetics data may be biased toward specific categories of lymphomas and not consider the BCL2 involvement. BCL6/MYC double-hit lymphomas are less common, and most of these cases represent triple-hit lymphomas with involvement of BCL2 as well. In this review, we summarize and discuss the significance of cytogenetic abnormalities found in HGBCL and discuss possible directions for future research. We present two patients with double-hit lymphomas as well as our molecular cytogenetic approach to check the presence of MYC and BCL6 rearrangements as well as a BCL2/ IGH fusion.