Onkológia 4/2023

Bioptic analysis of high-grade B-cell lymphomas with rearrangements of MYC, BCL2 and/or BCL6 genes – our results

Purpose: In this study we analysed an occurance of high-grade B-cell lymphomas with double/triple rearrangements of MYC, BCL2 and/or BCL6 genes (HGBL-DH/TH) in Slovakia. Few selected prognostic markers were assessed together with their impact on overall survival (OS) of patients. Patients and methods: By retrospective analysis 98 DH/TH lymphomas were identified from database covering all FISH tested diffuse large B-cell lymphomas (DLBCL) from 01/2008 until 06/2022. Bioptic specimens were prepared using standard panel of histological, IHC and FISH examinations. OS was evaluated in 97 HGBL-DH/TH patients and compared with control group of 43 DLBCL without DH/TH gene rearrangements. Results: Our study showed predominance of cases with DH gene rearrangements, the most commonly DH with MYC and BCL2 gene rearrangements (55.1%), less of MYC a BCL6 rearranged cases (22.4%) and TH cases (22.4%). There was no significant difference in OS between the three groups (p=0.6138). Median OS of HGBL-DH/TH was 8 months, median OS of DLBCL without DH/TH status was 89 months (p=0.0009). 86.7% of HGBL-DH/TH had simultaneously double/triple expressor (DE/TE) phenotype, the most common were TE (57.1%). The group of DH/ TH lypmphomas without DE/TE showed significantly better outcomes compared to DE/TE (p=0.0353). GCB subtype explicitly outnumbered non-GCB DH/TH in a ratio of 7.8 : 1. Significant difference in OS between the two groups was not observed. Furthermore, our results showed similar OS of MYC-rearranged DLBCL patients with concurrent abberant expression of p53 and OS of DH lymphomas withou aberrant p53. Conclusion: In this study we confirmed the prognostic significance of HGBL-DH/TH identification and indicated a strong need for acute diagnostics and tretment of these patients due to their dismal outcome. We also highlighted some prognostic differences in IHC subtypes of DH/TH, which seem to obscure still unknown biologic heterogeneity of the disease. Therefore, new subclassifications of these lymphomas are to be expected in near future.

Keywords: DLBCL, diffuse large B-cell lymphomas, HGBL, aggressive B-cell lymphomas, double-hit, triple-hit, prognosis, survival