Pb2161: characteristics of aggressive b-cell lymphomas with myc rearrangement

Background:MYC rearrangements (MYC-R), genetic hallmark of Burkitt lymphoma (BL), have been identified in 5-15% of DLBCL and 30-60% of high-grade B-cell lymphomas (HGL). MYC-R in BL always involve an immunoglobulin (IG) gen (IGH, IGK, IGL), whereas in DLBCL and HGL non-IG partners are frequent. The prognostic significance of the MYC partner gene in non-BL is controversial. Aims: We aimed to describe the histobiological features of the aggressive B-cell lymphomas (aBCL) with MYC-R identified in our center and explore their clinical and outcome differences within the context of MYC partner gene (IGH vs non-IGH). Methods: We retrospectively collected data from all adult patients with a MYC-R aBCL diagnosed in our center between 2010-2021. Diagnostic samples were reviewed by 2 expert hematopathologists. Fluorescence in situ hibridation (FISH) studies were performed either on paraffin tissue sections or bone marrow smears using Vysis LSI MYC, BCL2, BCL6 Dual color break apart probes and Vysis IGH/MYC/CEP 8 Tri-Color Dual Fusion probes (Abbott Molecular, USA). The study was approved by the local ethics committee. Results: We identified 61 cases of MYC-R aBCL. Tissue sections were available for MYC-IGH FISH analysis in 57/61 cases, MYC partner was evaluable in 52 patients. The morphologic distribution was: 34 (64.5%) cases with diffuse large B-cell histology, 3 (5.8%) with intermediate-cell or high-grade features and 15 (29%) with Burkitt histology. According to the current WHO classification (Table 1a) 28/34 large-cell morphology cases corresponded to double/triple hit (DH/TH) HGL because of additional BCL2 and/or BCL6-R and 6/34 were DLBCL NOS. 2/3 intermediate-cell cases were DH/THL and 1/3 was a HGL NOS. 14/15 cases with Burkitt histology were diagnosed as BL and one case was reclassified into DHL due to concurrent BCL6-R. Excluding BL, 38 cases (6 DLCBL NOS and 32 HGL) were selected for further analysis. Among this subset MYC-IGH-R was detected in 17/38 (44.7%) cases: 14 DH/THL and 3 DLBCL NOS (Table 1a). Noteworthy, 14/31 (45.2%) of all DH/THL and 3/6 (50%) of LBDCG NOS had an IGH partner. Considering cell of origin (COO) by Hans algorithm, MYC-IGH fusion was detected in 40% of Germinal center-derived (GC) lymphomas and in 62.5% of non-GC. Comparing clinico-biological data and outcome depending on MYC partner (Table 1b) our results show that patients with MYC-IGH fusion were significantly younger (p=0.019) and more likely to have multiple (≥2) extranodal (EN) sites (p=0.023). No other variable was significant. Referring to treatment, 33 patients (92%) received R-CHOP or R-EPOCH regimens, with no differences between groups. First line complete remission (CR) rates were 52% in both MYC-IGH and MYC-non-IGH groups. With a median follow up of 62 months (37-114), no significant association was observed between MYC-R partner and duration of response (p=0.784), event free survival (EFS) (p=0.933) or overall survival (OS) (p=0.706). At last follow-up 15 patients remain alive in CR. Image:Summary/Conclusion: Excluding BL, most patients with MYC-IGH rearrangement had diffuse large B-cell histology (93.8%) and were classified as DH/THL (82.3%). Among all DH/THL cases, 14/31 (45.2%) had IGH partner. MYC-IGH patients were younger and had more EN site involvement as MYC-non-IGH, but no differences in EFS and OS were noted. We are working to incorporate molecular techniques for a more precise analysis of BCL2, BCL6 and MYC translocations and their partners that permit a better understanding of the behavior of patients with aBCL.