Original contributionMYC single-hit large B-cell lymphoma: clinicopathologic difference from MYC-negative large B-cell lymphoma and MYC double-hit/triple-hit lymphoma☆,☆☆
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.
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Patient selection and clinical information
A total of 2102 consecutive large B-cell lymphoma cases from August 2004 to July 2017 were selected from the tissue archives of Samsung Medical Center, Seoul, Republic of Korea. Among these cases, 480 cases were available for MYC FISH results. Of the 480 cases, we selected 241 cases after the exclusion of 239 cases. Cases excluded were those with follow-up of less than 6 months (N = 14), lymphomas transformed from low grade to high grade (N = 10), DLBCL of the CNS (N = 94), immune
Morphology and immunohistochemistry
All 241 cases were positive for CD20 and negative for CD3. One hundred twenty-three of 241 cases (51.0%) were negative for CD10 and positive for both BCL6 and MUM1. These cases were of non–germinal center B-cell-like (GCB) phenotype as per the modified Hans’ algorithm [13]. The other 118 cases were of GCB phenotype (Table 1). Among 241 cases, 48 cases showed high-grade morphology including 7 cases with BL-like morphology, 32 cases with features intermediate between DLBCL and BL, and 9 cases
Discussion
MYC contributes to tumorigenesis via its transcriptional and nontranscriptional roles in cell growth, differentiation, proliferation, apoptosis, and metabolism [17]. A translocation of MYC to an IG locus leads to the highest levels of MYC mRNA and MYC protein because of constitutively active transcription driven by the IG promoter [1,18]. Concurrent translocation of MYC with BCL2 or BCL6 can involve large B-cell lymphomas classified as HGBCL-DH or -TH in the recent WHO classification [5].
Acknowledgment
This study was supported by the Samsung Medical Center intramural grant, 20 × 20 Project.
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2022, Pathology Research and PracticeCitation Excerpt :More recently, the prognostic role of Bcl2 and Bcl6 has been reconsidered in the light of MYC-rearrangements. In particular, the coexistence of BCL2 and/or BCL6 gene rearrangements with MYC-rearrangement in B-cell lymphoma is defined as "double-hit" or "triple-hit"; these cases are termed "high-grade B-cell lymphoma" and typically show poorer prognosis than non-rearranged or "single-hit" (i.e., only MYC-rearranged) cases [52]. Cases with high expression of Bcl2 and Myc proteins, with or without gene rearrangements, are termed "double expressors" and are associated with poor prognosis in nodal DLBCL; however, these cases are not included in the "high-grade B-cell lymphoma" category if the MYC gene is not rearranged [53].
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Competing interests: The authors have no competing financial interests to declare.
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Funding/Support: This study was supported by the Samsung Medical Center intramural grant, 20 × 20 Project.
- 1
These authors contributed equally.
- 2
Present address: Department of Pathology, Korea University Guro hospital, 148 Kurodongro, Kurodong, Kuro-gu, Seoul, Republic of Korea.
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Present address: Department of Pathology, Hanyang University hospital, 222-1 Wangsimni-ro, Sageundong, Seongdong gu, Seoul, Republic of Korea.