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Original Article
- Impact of Cell-of-Origin and MYC/BCL2 Status on the Risk of Central Nervous System Relapse in Primary Breast Diffuse Large B-Cell Lymphoma
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Chang-Hoon Lee1,2
, Ga-Young Song3
, Ho-Young Yhim1,2
, Dok Hyun Yoon4, Kyu Yun Jang5, Sang Eun Yoon6, Jin Seok Kim7, Jeong-Ok Lee8, Hyeon-Seok Eom9, Hyewon Lee9, Kyoung Ha Kim10, Ka-Won Kang11, Young Rok Do12, Soon Il Lee13, Han Sang Lee13, Hyo Jung Kim14, Ae Ri Ahn5, Deok-Hwan Yang3, Won Seog Kim6, Jae-Yong Kwak1,2 -
DOI: https://doi.org/10.4143/crt.2025.836 [Epub ahead of print]
Published online: November 5, 2025
1Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
2Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
3Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
4Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5Department of Pathology, Jeonbuk National University Medical School, Jeonju, Korea
6Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
7Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
8Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
9Department of Internal Medicine, Center for Hematologic Malignancies, National Cancer Center, Goyang, Korea
10Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
11Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
12Department of Internal Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea
13Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
14Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
This study was presented in part as an abstract for the 64th American Society of Hematology Annual Meeting, New Orleans, LA, December 10-13, 2022.
2Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
3Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
4Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5Department of Pathology, Jeonbuk National University Medical School, Jeonju, Korea
6Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
7Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
8Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
9Department of Internal Medicine, Center for Hematologic Malignancies, National Cancer Center, Goyang, Korea
10Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
11Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
12Department of Internal Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea
13Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
14Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
This study was presented in part as an abstract for the 64th American Society of Hematology Annual Meeting, New Orleans, LA, December 10-13, 2022.
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Corresponding author:
Ho-Young Yhim
Tel: 82-63-250-2523
Email: yhimhy@jbnu.ac.kr
- Chang-Hoon Lee and Ga-Young Song contributed equally to this work.
Received: 5 August 2025 • Accepted: 3 November 2025
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Abstract
Purpose
Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare entity with a distinct relapse pattern involving the central nervous system (CNS). However, data regarding predictors of CNS relapse in this population remain limited.
Materials and Methods
CNS relapse was retrospectively analyzed in two multicenter cohorts comprising 53 patients with newly diagnosed primary breast DLBCL, including a prospective trial and real-world cohort, all treated with rituximab-based immunochemotherapy. The impact of baseline clinical parameters, cell-of-origin, and MYC/BCL2 dual expression (DE) status on CNS relapse was assessed using a multivariate Cox regression model, separately conducted for the overall study set (n=53) and the immunohistochemical study set (n=36).
Results
By the CNS-International Prognostic Index (CNS-IPI), most patients were classified as low or intermediate risk; no patients were classified as high risk. With a median follow-up of 58.8 months, the 4-year risk of CNS relapse was 15.6% in the overall study set and 14.2% in the immunohistochemical set. MYC/BCL2 DE was identified in 14 patients (38.9%) and was significantly associated with increased risk of CNS relapse (4-year risk, 30.7% vs. 0%, p=0.001). Patients with non-germinal center B-cell–like subtype had a numerically higher risk of CNS relapse. However, in multivariate analysis, only MYC/BCL2 DE status was associated with CNS relapse. Synchronous bilateral involvement was also an independent predictor of CNS relapse in both study sets. CNS-IPI was not discriminatory for CNS relapse.
Conclusion
MYC/BCL2 DE and synchronous bilateral breast involvement may help identify patients at higher risk for CNS relapse. Further studies are warranted.
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