MYC single-hit large B-cell lymphoma: clinicopathologic difference from MYC-negative large B-cell lymphoma and MYC double-hit/triple-hit lymphoma

Summary

MYC-rearranged large B-cell lymphoma with BCL2 and/or BCL6 rearrangement, double-hit (DH) or triple-hit (TH) lymphoma, is associated with poor survival after standard treatment. To investigate the clinical impact of single-hit (SH) MYC rearrangement, we analyzed 241 cases of diffuse large B-cell lymphoma (DLBCL) for MYC, BCL2, and BCL6 rearrangement by fluorescence in situ hybridization. Fifty-five of 241 (22.8%) cases showed MYC rearrangements. Twenty-three cases were diagnosed as DLBCL; 18 as high-grade B-cell lymphoma (HGBCL)-DH; 3 as HGBCL-TH; and 11 as HGBCL, not otherwise specified. Both DH and TH lymphomas showed high-grade morphology (P = 0.002), higher stage (P = 0.022), and more frequent germinal center B-cell-like phenotype (P = 0.008). SH lymphomas displayed high-grade morphology (P = 0.002) but were not different from MYC-negative lymphomas in cell of origin, clinical stage, international prognostic index (IPI), or extranodal involvement. Patients with DH/TH lymphomas had worse overall survival (OS) (P = 0.016) and progression-free survival (PFS) (P < 0.001), while OS and PFS of SH lymphomas were not different from those of MYC-negative lymphomas. There was no survival difference between cases of BCL2 and BCL6 rearrangements. Poorer prognostic factors included higher ECOG class, higher IPI, and DH or TH translocation for OS, and higher IPI and DH or TH translocation for PFS. Higher IPI was an independent prognostic factor for OS and PFS. In conclusion, large B-cell lymphomas with single MYC rearrangement showed high-grade morphology but were otherwise not different from MYC-negative lymphomas.

Introduction

Diffuse large B-cell lymphomas (DLBCLs) are a heterogeneous group of mature B-cell lymphomas that harbor various genetic alterations. The MYC gene is associated with development of B-cell lymphoma and leukemia when coupled with immunoglobulin (IG) genes [1]. MYC controls cell cycle, cell growth, survival, cellular metabolism and biosynthesis, adhesion, mitochondrial function, and other cell-related functions [2]. MYC rearrangements are detected in about 10%–15% of DLBCLs and are often associated with inferior progression-free survival (PFS) and overall survival (OS) [3,4]. In the 2016 revision of the World Health Organization (WHO) classification [5], MYC-rearranged tumors accompanied by BCL2 and/or BCL6 rearrangements are named high-grade B-cell lymphomas (HGBCLs), with MYC and BCL2 and/or BCL6 rearrangements, so-called double-hit (DH) and triple-hit (TH) lymphomas, respectively, regardless of their morphology. DH or TH lymphomas have been associated with a poorer prognosis after standard treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) [6,7]. As a result, fluorescence in situ hybridization (FISH) testing for MYC, BCL2, and BCL6 has become an essential part of the diagnosis of DLBCL [5,8,9].

Despite the necessity of FISH analysis, relatively few studies regarding single-hit (SH) MYC rearrangements in DLBCL have been reported in Asian countries. We previously analyzed the prognostic impact of primary central nervous system (CNS) DLBCL as per MYC status. We found that in CNS, DH/TH lymphomas were rare and that SH MYC rearrangements had no significant clinical impact [10]. In this study, we investigated the clinical and pathological characteristics of non-CNS de novo DLBCL with rearranged MYC in Korean patients and analyzed the clinical differences between SH DLBCL and HGBCL-DH/TH.