High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements: Biopsy analysis of 70 cases from the Slovak Lymphoma Registry

Katarína Lešková, Peter Szépe, Tomáš Balhárek, Martina Barthová, Ľuboslava Janáková, Anna Farkašová,  Lukáš Plank

Abstract:

We performed a twelve-year retrospective analysis of diffuse large B-cell lymphoma (DLBCL) patients’ biopsies with rearrangements of genes MYC, BCL2, and/or BCL6, commonly referred to as double-hit and triple-hit high-grade B-cell lymphomas (DH/TH HGBL). Our aim was to present complex characteristics of the DH/TH HGBL group of patients diagnosed in the Slovak National Lymphoma Register together with the evaluation of the relationship between immunohistochemical (IHC) protein expressions of c-myc, bcl2, bcl6, and cyclin D1 in tissue specimens and the presence of rearrangements of their protein-coding genes by FISH analysis in order to find a clinically relevant diagnostic algorithm that would be the most time- and cost-efficient. For this study, a standard panel of histomorphological, IHC, and FISH methods was used to analyze the characteristics of 70 DH/TH HGBL patients’ biopsies. Our study showed a predominance of the immunohistochemical GCB subtype over the non-GCB subtype (59:10 cases) in DH/TH lymphomas. The centroblastic morphology was the most commonly observed (30/70 cases; 43%). Furthermore, our study showed a high predominance of DH lymphoma cases with simultaneous MYC and BCL2 genes rearrangements (40/70; 57%), followed by an almost equal incidence of DH lymphomas with rearrangements of MYC and BCL6 genes (16/70; 23%) and of TH lymphomas (14/70; 20%). 15 of 16 FISH-examined DLBCL cases were negative for CCND1 rearrangement. A great majority of DH/TH cases showed also immunohistochemical overexpression of corresponding proteins (62/70; 89%), mostly in a form of triple expressor of c-myc/bcl2/bcl6 proteins (36/70; 51%), followed by c-myc/bcl2 and c-myc/bcl6 double expressor proteins positivity (20/70 and 6/70, respectively). Comparing preferential FISH testing of DE/TE and GCB DLBCL cases for genetic rearrangements we would be able to detect 89% and 84% of our HGBL-DH, TH group of patients, respectively. None of the examined methods for economically rational FISH testing showed enough concordance with IHC analysis results. We might, therefore, advocate the complex testing of all DLBCL patients’ biopsies including FISH analyses.