Cancer Research and Treatment

Original Articles

Hematologic malignancy

A New Prognostic Index for Extranodal Natural Killer/T-Cell Lymphoma:Incorporation of Serum β-2 Microglobulin to PINK: Sora Kang, Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Eun Hee Kang, Jung Sun Park, Yoon Sei Lee, Chan-Sik Park, Heounjeong Go, Jooryung Huh, Jin Sook Ryu, Sang-Wook Lee, Seok Jin Kim, Won Seog Kim, Sang Eun Yoon, Young Hyeh Ko, Cheolwon Suh; Cancer Res Treat. 2023;55(1):314-324. Published online March 31, 2022; DOI: https://doi.org/10.4143/crt.2022.015

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Purpose
Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model.
Materials and Methods
A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88).
Results
The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort.
Conclusion
Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

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Elevated serum IL-6 and total IgEAb are associated with poor survival in natural killer/T-cell lymphoma
Yun Hui, Yingjun Gao, Jiawei Li, Qingtao Kong, Yuanyuan Duan, Haibo Liu, Fang Liu, Hong Sang
Annals of Hematology.2024; 103(4): 1285. CrossRef
Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients
Theodoros P. Vassilakopoulos, Maria Arapaki, Panagiotis T. Diamantopoulos, Athanasios Liaskas, Fotios Panitsas, Marina P. Siakantaris, Maria Dimou, Styliani I. Kokoris, Sotirios Sachanas, Marina Belia, Chrysovalantou Chatzidimitriou, Elianna A. Konstantin
Cancers.2024; 16(2): 238. CrossRef
Prognostic Value of18F-FDG PET/CT Radiomics in Extranodal Nasal-Type NK/T Cell Lymphoma
Yu Luo, Zhun Huang, Zihan Gao, Bingbing Wang, Yanwei Zhang, Yan Bai, Qingxia Wu, Meiyun Wang
Korean Journal of Radiology.2024; 25(2): 189. CrossRef
A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase
Ziyuan Shen, Xudong Zhang, Yujie Li, Xicheng Chen, Xing Xing, Hao Zhang, Jingjing Ye, Ling Wang, Tao Jia, Taigang Zhu, Yuqing Miao, Chunling Wang, Hui Liu, Liang Wang, Wei Sang
Future Oncology.2024; 20(28): 2071. CrossRef

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Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas: Seok Jin Kim, Yeon Jeong Kim, Sang Eun Yoon, Kyung Ju Ryu, Bon Park, Donghyun Park, Duck Cho, Hyun-Young Kim, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Won Seog Kim; Cancer Res Treat. 2023;55(1):291-303. Published online March 2, 2022; DOI: https://doi.org/10.4143/crt.2022.017

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Purpose
Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods
After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results
Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion
Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

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Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application
Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
Molecular Cancer.2024;[Epub] CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Minimal residual disease detection in lymphoma: methods, procedures and clinical significance
Sijun Zhang, Xiangyu Wang, Zhenzhen Yang, Mengjie Ding, Mingzhi Zhang, Ken H. Young, Xudong Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
Clinical use of circulating tumor DNA analysis in patients with lymphoma
Bettina Bisig, Karine Lefort, Sylvain Carras, Laurence de Leval
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A practical approach to the modern diagnosis and classification of T- and NK-cell lymphomas
Laurence de Leval, Philippe Gaulard, Ahmet Dogan
Blood.2024; 144(18): 1855. CrossRef
In-depth circulating tumor DNA sequencing for prognostication and monitoring in natural killer/T-cell lymphomas
Jin Ju Kim, Hyun-Young Kim, Zisun Choi, So yoon Hwang, Hansol Jeong, Jong Rak Choi, Sang Eun Yoon, Won Seog Kim, Sun-Hee Kim, Hee-Jin Kim, Sang-Yong Shin, Seung-Tae Lee, Seok Jin Kim
Frontiers in Oncology.2023;[Epub] CrossRef
Circulating tumor DNA in NK/T and peripheral T cell lymphoma
Yu-Jia Huo, Wei-Li Zhao
Seminars in Hematology.2023; 60(3): 173. CrossRef
A genetic profiling guideline to support diagnosis and clinical management of lymphomas
Margarita Sánchez-Beato, Miriam Méndez, María Guirado, Lucía Pedrosa, Silvia Sequero, Natalia Yanguas-Casás, Luis de la Cruz-Merino, Laura Gálvez, Marta Llanos, Juan Fernando García, Mariano Provencio
Clinical and Translational Oncology.2023; 26(5): 1043. CrossRef

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Plasma Circulating Tumor DNA in Patients with Primary Central Nervous System Lymphoma: Sang Eun Yoon, Yeon Jeong Kim, Joon Ho Shim, Donghyun Park, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Yeung-Chul Mun, Kyoung Eun Lee, Duck Cho, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2022;54(2):597-612. Published online July 23, 2021; DOI: https://doi.org/10.4143/crt.2021.752

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Purpose
Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL.
Materials and Methods
Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.
Results
Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment.
Conclusion
The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

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Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR
Yujie Zhong, Geok Wee Tan, Johanna Bult, Nick Veltmaat, Wouter Plattel, Joost Kluiver, Roelien Enting, Arjan Diepstra, Anke van den Berg, Marcel Nijland
BMC Cancer.2024;[Epub] CrossRef
Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma
Jin-Hua Liang, Yi-Fan Wu, Hao-Rui Shen, Yue Li, Jun-Heng Liang, Rui Gao, Wei Hua, Chun-Yu Shang, Kai-Xin Du, Tong-Yao Xing, Xin-Yu Zhang, Chen-Xuan Wang, Liu-Qing Zhu, Yang W. Shao, Jian-Yong Li, Jia-Zhu Wu, Hua Yin, Li Wang, Wei Xu
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Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review
Lakshmi Nayak, Chetan Bettegowda, Florian Scherer, Norbert Galldiks, Manmeet Ahluwalia, Alexander Baraniskin, Louisa von Baumgarten, Jacoline E C Bromberg, Andrés J M Ferreri, Christian Grommes, Khê Hoang-Xuan, Julia Kühn, James L Rubenstein, Roberta Rudà
Neuro-Oncology.2024; 26(6): 993. CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas
Jurik A. Mutter, Stefan K. Alig, Mohammad S. Esfahani, Eliza M. Lauer, Jan Mitschke, David M. Kurtz, Julia Kühn, Sabine Bleul, Mari Olsen, Chih Long Liu, Michael C. Jin, Charles W. Macaulay, Nicolas Neidert, Timo Volk, Michel Eisenblaetter, Sebastian Raue
Journal of Clinical Oncology.2023; 41(9): 1684. CrossRef
Clinical applications of circulating tumor DNA in central nervous system lymphoma
Anna Katharina Foerster, Eliza M. Lauer, Florian Scherer
Seminars in Hematology.2023; 60(3): 150. CrossRef
Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
Gloria Figaredo, Alejandro Martín-Muñoz, Santiago Barrio, Laura Parrilla, Yolanda Campos-Martín, María Poza, Laura Rufián, Patrocinio Algara, Marina De La Torre, Ana Jiménez Ubieto, Joaquín Martínez-López, Luis-Felipe Casado, Manuela Mollejo
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Rafael Colmenares, Noemí Álvarez, Santiago Barrio, Joaquín Martínez-López, Rosa Ayala
Cancers.2022; 14(5): 1310. CrossRef

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Hematologic Malignancy

Prognostic Stratification of Patients with Burkitt Lymphoma Using Serum β2-microglobulin Levels: Hyung-Don Kim, Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Eun Hee Kang, Jung Sun Park, Chan-Sik Park, Jooryung Huh, Jin Sook Ryu, Sang-Wook Lee, Dok-Hyun Yoon, Seok Jin Kim, Young Hyeh Ko, Won Seog Kim, Cheolwon Suh; Cancer Res Treat. 2021;53(3):847-856. Published online December 17, 2020; DOI: https://doi.org/10.4143/crt.2020.1060

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to investigate the prognostic value of serum β2-microglobulin for patients with Burkitt lymphoma (BL) and to propose a risk-stratifying classification system.
Materials and Methods
A prospective registry-based cohort study of BL patients treated with dose-intensive or effective dose-adjusted chemotherapies (n=81) was conducted. Survival outcomes were compared based on previously reported risk groups and/or serum β2-microglobulin levels. A risk-stratifying classification system incorporating serum β2-microglobulin levels was proposed and validated in an independent validation cohort (n=60).
Results
The median age was 47 years, and 57 patients (70.4%) were male. Patients with high serum β2-microglobulin levels (> 2 mg/L) had significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.01 for both). Serum β2-microglobulin levels further stratified patients in the low-risk and high-risk groups in terms of PFS (p=0.010 and p=0.044, respectively) and OS (p=0.014 and p=0.026, respectively). Multivariate analyses revealed that a high serum β2-microglobulin level (> 2 mg/L) was independently associated with a shorter PFS (hazards ratio [HR], 3.56; p=0.047) and OS (HR, 4.66; p=0.043). The new classification system incorporating the serum β2-microglobulin level allowed the stratification of patients into three distinct risk subgroups with 5-year OS rates of 100%, 89.5%, and 62.5%. In an independent cohort of BL, the system was validated by stratifying patients with different survival outcomes.
Conclusion
Serum β2-microglobulin level is an independent prognostic factor for BL patients. The proposed β2-microglobulin–based classification system could stratify patients with distinct survival outcomes, which may help define appropriate treatment approaches for individual patients.

Citations

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The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients
Ze Jin, Yi Miao, Jie Zhang, Jing Zhang, Chunling Wang, Xuzhang Lu, Yuqing Miao, Miao Sun, Yunping Zhang, Yun Zhuang, Haiwen Ni, Jingyan Xu, Wanchuan Zhuang, Min Zhao, Jianfeng Zhu, Min Xu, Guoqiang Lin, Haiying Hua, Xiaoyan Xie, Maozhong Xu, Tao Jia, Liji
Annals of Hematology.2024; 103(7): 2257. CrossRef
Prognostic Value of18F-FDG PET/CT Radiomics in Extranodal Nasal-Type NK/T Cell Lymphoma
Yu Luo, Zhun Huang, Zihan Gao, Bingbing Wang, Yanwei Zhang, Yan Bai, Qingxia Wu, Meiyun Wang
Korean Journal of Radiology.2024; 25(2): 189. CrossRef
The Role of Beta2-Microglobulin in Central Nervous System Disease
Zhen-Yuan Liu, Feng Tang, Jin-Zhou Yang, Xi Chen, Ze-Fen Wang, Zhi-Qiang Li
Cellular and Molecular Neurobiology.2024;[Epub] CrossRef
Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study
Zhen-Yuan Liu, Feng Tang, Jing Wang, Jin-Zhou Yang, Xi Chen, Ze-Fen Wang, Zhi-Qiang Li
BMC Cancer.2024;[Epub] CrossRef
Serum beta2-microglobulin and peripheral blood eosinophils for the assessment of severity and prognosis with omicron variant COVID-19 infection
Jie Tan, Hanxi Fang, Xiao Hu, Ming Yue, Junling Yang
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Zhentian Wu, Chenyi Wang, Yao Lyu, Zheshen Lin, Ming Lu, Shixiong Wang, Bingxuan Wang, Na Yang, Yeye Li, Jianhong Wang, Xiaohui Duan, Na Zhang, Jing Gao, Yuan Zhang, Miaowang Hao, Zhe Wang, Guangxun Gao, Rong Liang
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Beta2-microglobulin is a valuable marker and identifies a poor-prognosis subgroup among intermediate-risk patients with diffuse large B cell lymphoma
Ning-Chun Chen, Hung Chang, Hsiao-Wen Kao, Che-Wei Ou, Ming-Chung Kuo, Po-Nan Wang, Tung-Liang Lin, Jin-Hou Wu, Yu-Shin Hung, Yi-Jiun Su, Yuen-Chin Ong, Hsuan-Jen Shih
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Jian-Nan Hu, Mu-Qing Yu, Li-Juan Hua, Chen Bao, Qian Liu, Chao Liu, Zi-Ling Li, Xi Wang, Shu-Yun Xu
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Yajiao Liu, Li Sheng, Haiying Hua, Jingfen Zhou, Ying Zhao, Bei Wang
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Leukemia & Lymphoma.2022; 63(1): 124. CrossRef

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Efficacy of Brentuximab Vedotin in Relapsed or Refractory High-CD30–Expressing Non-Hodgkin Lymphomas: Results of a Multicenter, Open-Labeled Phase II Trial: Seok Jin Kim, Dok Hyun Yoon, Jin Seok Kim, Hye Jin Kang, Hye Won Lee, Hyeon-Seok Eom, Jung Yong Hong, Junhun Cho, Young Hyeh Ko, Jooryung Huh, Woo-Ick Yang, Weon Seo Park, Seung-Sook Lee, Cheolwon Suh, Won Seog Kim; Cancer Res Treat. 2020;52(2):374-387. Published online August 13, 2019; DOI: https://doi.org/10.4143/crt.2019.198

Abstract PDF PubReader ePub

Purpose
The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expression in previous studies enrolling patients with a wide range of CD30 expression level. Thus, this study explored the efficacy of BV in high-CD30–expressing non-Hodgkin lymphoma (NHL) patients most likely to benefit.
Materials and Methods
This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30–expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks. The primary endpoint was > 40% disease control rate, consisting of complete response (CR), partial response (PR), or stable disease. We defined high CD30 expression as ≥ 30% tumor cells positive for CD30 by immunohistochemistry.
Results
High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma. The disease control rate was 48.5% (16/33) including six CR and six PR; six patients (4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survival were not associated with CD30 expression levels. Over a median of 29.2 months of follow-up, the median progression-free and overall survival rates were 1.9 months and 6.1 months, respectively. The most common adverse events were fever (39%), neutropenia (30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis for the association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1- negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients (13.3%, 2/15).
Conclusion
BV performance as a single agent was acceptable in terms of disease control rates and toxicity profiles, especially MUM1-negative patients.

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Body Cavity–Based Lymphoma in a Country with Low Human Immunodeficiency Virus Prevalence: A Series of 17 Cases from the Consortium for Improving Survival of Lymphoma: Junghoon Shin, Young Hyeh Ko, Sung Yong Oh, Dok Hyun Yoon, Jeong-Ok Lee, Jin Seok Kim, Yong Park, Ho Jin Shin, Seok Jin Kim, Jong Ho Won, Sung-Soo Yoon, Won Seog Kim, Youngil Koh, On behalf of the Consortium for Improving Survival of Lymphoma investigators; Cancer Res Treat. 2019;51(4):1302-1312. Published online February 14, 2019; DOI: https://doi.org/10.4143/crt.2018.555

Abstract PDF PubReader ePub

Purpose
Primary effusion lymphoma (PEL) is a type of body cavity–based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden.
Materials and Methods
We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea.
Results
Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival.
Conclusion
PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.

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Comparison of Efficacy of Pembrolizumab between Epstein-Barr Virus‒Positive and ‒Negative Relapsed or Refractory Non-Hodgkin Lymphomas: Seok-Jin Kim, Jiyeon Hyeon, Inju Cho, Young Hyeh Ko, Won Seog Kim; Cancer Res Treat. 2019;51(2):611-622. Published online July 20, 2018; DOI: https://doi.org/10.4143/crt.2018.191

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor inhibits the interplay between PD1 of T-cell and programmed cell death ligand 1 (PDL1) on tumor cells. Although pembrolizumab has been tried to various subtypes of non-Hodgkin lymphoma (NHL), realworld data about the efficacy of pembrolizumab in NHL patients are limited.
Materials and methods
We analyzed the outcome of 30 relapsed or refractory NHL patients treated with pembrolizumab, and compared the outcome between Epstein-Barr virus (EBV)‒positive and negative subtypes because EBV infection of tumor cells can upregulate PDL1 expression.
Results
Seven patients with EBV-positive NHL showed a response including NK/T-cell lymphoma (6/14, 44%) and primary mediastinal B-cell lymphoma (1/4, 25%) whereas EBV-negative subtypes did not respond such as diffuse large B-cell lymphoma and T-lymphoblastic lymphoma. We also evaluated PDL1 expression using tumor tissue of 76 patients. High PDL1 expression (positive staining of > 50% of tumor cells) was more frequent in NK/T-cell lymphoma and primary mediastinal B-cell lymphoma than other subtypes. Thus, PDL1 expression was significantly higher in EBV-positive (18/32, 56%) than EBV-negative NHL (4/38, 11%, p < 0.001). Furthermore, NK/T-cell lymphoma patients with high PDL1 expression showed a higher response (4/6, 67%) than those with low PDL1 expression (1/5, 20%).
Conclusion
Pembrolizumab could be useful as a salvage treatment for relapsed or refractory EBV-positive NHL, especially NK/T-cell lymphoma. However, its efficacy in EBV-negative NHL with low or absent PDL1 expression is still not clear although pembrolizumab could be a potential treatment option for relapsed or refractory NHL.

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Radiation Therapy Outcome and Clinical Features of Duodenal-Type Follicular Lymphoma: Hansang Lee, Dongryul Oh, Kyungmi Yang, Young Hyeh Ko, Yong Chan Ahn, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2019;51(2):547-555. Published online July 10, 2018; DOI: https://doi.org/10.4143/crt.2018.190

Abstract PDF Supplementary Material PubReader ePub

Purpose
Duodenal-type follicular lymphoma (FL) is a rare variant of FL. There is still no consensus on the initial treatment, and clinical features including endoscopic findings are not familiar to most physicians. The objective of this study was to evaluate the outcome of patients who were initially treated with radiation therapy for duodenal-type FL.
Materials and Methods
We retrospectively analyzed 20 patients who were consecutively diagnosed with duodenaltype FL between 2008 and 2017. All patients received radiation therapywith curative intent.
Results
The median age of the patients was 52 years (range, 26 to 66 years), and females were predominant. Most patients (n=18, 90%) had stage I disease, and were diagnosed by a regular health examination in an asymptomatic state. The histological grade was one in 19 patients (95%), and the endoscopic findings were diffuse nodular (n=8), whitish granular (n=8), and mixed pattern (n=4). Radiation therapy was delivered to 17 patients with 24 Gy in 12 fractions, and to three patients with 30.6-36 Gy in 18 fractions. All patients were evaluated with endoscopy for response to radiation therapy, and complete response was achieved in 19 patients (95%). At the time of analysis, all patients survived without any evidence of late toxicities related with radiation therapy.
Conclusion
Taken together, radiation therapy alone could be effective in controlling duodenal lesion. A further study with longer follow-up duration is warranted to confirm our findings.

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Clinical characteristics and outcomes of Brazilian patients with duodenal-type follicular lymphoma: a multicenter retrospective study
Guilherme Duffles, Arthur Braga, Talita Silveira, Yana Novis, Celso Arrais, Luciana Tucunduva, Ana Rita Fonseca, Davimar Borducchi, Pedro Neffa, Fernando Blumm, Marianne de Castro Gonçalves, Frederico Moreira, Fabio Nucci, Eduardo Rego, Vanderson Rocha
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The Role of Small Bowel Capsule Endoscopy in Determining the Treatment Strategy for Duodenal Follicular Lymphoma: A Single-Center Retrospective Study
Donghoon Kang, Gi-June Min, Tong Yoon Kim, Young-Woo Jeon, Yukyung Cho, Jae Myung Park, Joo Hyun O, Byung-Ock Choi, Gyeongsin Park, Seok-Goo Cho
Diagnostics.2025; 15(2): 193. CrossRef
Recent updates on treatment options for primary follicular lymphoma of the gastrointestinal tract
Masaya Iwamuro, Takehiro Tanaka, Daisuke Ennishi, Motoyuki Otsuka
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Duodenal-type follicular lymphoma: comprehensive insights into disease characteristics and established treatment strategies
Ahmed Alnughmush, Riad El Fakih, Ruah Alyamany, Nasir Bakshi, Saud Alhayli, Mahmoud Aljurf
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Jan Bosch-Schips, Xenia Parisi, Fina Climent, Francisco Vega
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Rachael Hagen, Jasmine Tidwell, Emily Weng, Steven A Goldenberg, Anjiya Shaikh
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Judith A. Ferry
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Development of diffuse large B-cell lymphoma from duodenal type follicular lymphoma: a retrospective study of 23 cases
Masuho Saburi, Yoshiyuki Kondo, Masao Ogata, Yasuhiro Soga, Miyuki Abe, Kuniko Takano, Kazuhiro Kohno, Takayuki Nagai, Toshiyuki Nakayama
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Kyu Hye Choi, Han Hee Lee, Seung-Eun Jung, Kyung-Sin Park, Joo-Hyun O, Young-Woo Jeon, Byung-Ock Choi, Seok-Goo Cho
Radiation Oncology.2020;[Epub] CrossRef

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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Low-Dose Radiation Therapy for Primary Conjunctival Marginal Zone B-Cell Lymphoma: Ga-In Lee, Dongryul Oh, Won Seog Kim, Seok Jin Kim, Young Hyeh Ko, Kyung In Woo, Yoon-Duck Kim, Yong Chan Ahn; Cancer Res Treat. 2018;50(2):575-581. Published online June 16, 2017; DOI: https://doi.org/10.4143/crt.2017.182

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate the clinical features and the long-term outcomes of primary conjunctival marginal zone B-cell lymphoma (MZBCL) patients who were treated with radiation therapy (RT).
Materials and Methods
Retrospective data of 79 patients with 121 primary conjunctival MZBCL lesions were collected from January 1, 2001 till June 30, 2014. All lesions were treated by local RT (26 Gy) with patient-specific customized lens-shielding device.
Results
The current Korean patients’ cohort showed younger median age at diagnosis (38 years), great female preponderance (78.5%) and more frequent bilateral involvement (53.2%) than the previous studies. Following 26 Gy’s RT, excellent clinical outcomes were achieved: 5-year rates of overall survival, local relapse-free survival, and contralateral relapse-free survival were 100%, 98.1%, and 91.5%, respectively. Two patients (2.5%) developed local relapse and five (6.3%) developed relapse at initially uninvolved contralateral conjunctiva with median interval of 52.9 months, and late adverse events of grade 2 and 3 occurred in seven (8.8%) and two (2.5%) patients, respectively.
Conclusion
26 Gy’s RT was highly effective and safe, with the use of lens-shielding device, in treating patients with primary conjunctival MZBCL.

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Yuka Suimon, Satoru Kase, Rumiko Kinoshita, Susumu Ishida
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Dose-Response.2018;[Epub] CrossRef

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Comparison of Total Body Irradiation (TBI) Conditioning with Non-TBI for Autologous Stem Cell Transplantation in Newly Diagnosed or Relapsed Mature T- and NK-Cell Non-Hodgkin Lymphoma: Chi Hoon Maeng, Young Hyeh Ko, Do Hoon Lim, Eun Suk Kang, Joon Young Choi, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2017;49(1):92-103. Published online May 9, 2016; DOI: https://doi.org/10.4143/crt.2015.476

Abstract PDF PubReader ePub

Purpose
This retrospective study was conducted for comparison of survival outcomes and toxicities of autologous stem cell transplantation (ASCT) based on the use of total body irradiation (TBI) as a part of the conditioning regimen in patients with mature T- and natural killer (NK)-cell lymphomas.
Materials and Methods
Patients who underwent ASCT in the upfront or salvage setting between January 2000 and December 2013 were analyzed. Patients were dichotomized according to the TBI group (n=38) and non-TBI group (n=60) based on the type of conditioning regimen for ASCT.
Results
Patients with responsive disease underwent upfront ASCT (TBI, n=16; non-TBI, n=29) whereas patients with refractory disease (TBI, n=9; non-TBI, n=12) or relapsed disease (TBI, n=13; non-TBI, n=19) underwent ASCT after salvage treatment. Hematologic and non-hematologic toxicities were manageable, and the median cumulative toxicity score according to Seattle criteria was estimated as 2 (range, 0 to 7) in both groups. No significant difference in 100-day mortality was observed between the TBI (13%, 5/38) and non-TBI (12%, 12/60) groups, and most deaths were related to disease progression. There was no difference in overall and progression-free survival; however, the TBI group showed a trend of better survival in upfront and salvage ASCT than the non-TBI group. However, patients with refractory disease showed the worst outcome regardless of the use of TBI. Patients who showed complete response before ASCT showed better progression-free survival than thosewho showed partial response.
Conclusion
TBI could be used as an effective part of conditioning for ASCT in patients with mature T- and NK-cell lymphomas.

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Mümtaz Köksal, Jonathan Baumert, Danny Jazmati, Felix Schoroth, Stephan Garbe, David Koch, Davide Scafa, Gustavo R. Sarria, Christina Leitzen, Gregor Massoth, Achilles Delis, Annkristin Heine, Tobias Holderried, Peter Brossart, Thomas Müdder, Leonard C. S
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Journal of Radiation Research.2018; 59(4): 477. CrossRef

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Association between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma: Hae Su Kim, Ji Yun Lee, Sung Hee Lim, Keunchil Park, Jong-Mu Sun, Young Hyeh Ko, Chung-Hwan Baek, Young-ik Son, Han Sin Jeong, Yong Chan Ahn, Min-Young Lee, Mineui Hong, Myung-Ju Ahn; Cancer Res Treat. 2016;48(2):527-536. Published online September 15, 2015; DOI: https://doi.org/10.4143/crt.2015.249

Abstract PDF PubReader ePub

Purpose
Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance.
Materials and Methods
Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed.
Results
Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis.
Conclusion
PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.

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Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Philippe Deron, Fréderic Duprez, Debby Laukens, Jo Van Dorpe, Liesbeth Ferdinande, Sylvie Rottey
Oncotarget.2017; 8(46): 80443. CrossRef
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Gustavo Dix Junqueira Pinto, Luciano de Souza Viana, Cristovam Scapulatempo Neto, Sérgio Vicente Serrano
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Current clinical immunotherapeutic approaches for head and neck cancer
Carolina Soto Chervin, Bruce Brockstein
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Oncotarget.2016; 7(47): 77010. CrossRef

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Cross-sectional Study of Patients with Diffuse Large B-Cell Lymphoma: Assessing the Effect of Host Status, Tumor Burden, and Inflammatory Activity on Venous Thromboembolism: Sung Hee Lim, Sook-young Woo, Seonwoo Kim, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2016;48(1):312-321. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.266

Abstract PDF PubReader ePub

Purpose
The risk factors for venous thromboembolism (VTE) in diffuse large B-cell lymphoma (DLBCL) are not clear although thrombosis can be associated with host status, tumor burden, and inflammatory activity. We assessed the effect of those factors on VTE in a cross-sectional study of patients enrolled in a prospective cohort study. Materials and Methods We analyzed the occurrence of VTE in 322 patients with newly diagnosed DLBCL who received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) between 2008 and 2011. Serum levels of inflammatory cytokines were measured from serum samples archived at diagnosis.
Results
With a median follow-up duration of 41.9 months, VTE was documented in 34 patients (10.6%). A comparison of baseline characteristics indicated the group with VTE had higher percentage of old age, stage III/IV and extranodal involvements than the group without VTE (p < 0.05). Thus, the International Prognostic Index was significantly associated with VTE, but the Khorana score was not. A univariate competing risk factor analysis for VTE revealed that increased levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 were also associated with VTE (p < 0.05) in addition to host and tumor burden. However, a multivariate analysis showed that two host factors including age (≥ 60 years) and poor performance were independent risk factors for VTE. Conclusion Among potential risk factors for VTE including tumor burden and inflammatory activity, age and performance status had a strong impact on the occurrence of VTE in patients with DLBCL who received R-CHOP.

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Case Report

Unusual Manifestation of Intravascular Large B-Cell Lymphoma: Severe Hypercalcemia with Parathyroid Hormone-Related Protein: Jung Min Ha, Eun Kim, Woo Joo Lee, Ji-Won Hwang, Sehyo Yune, Young Hyeh Ko, Joon Young Choi, Seok Jin Kim, Won Seog Kim; Cancer Res Treat. 2014;46(3):307-311. Published online July 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.3.307

Abstract PDF PubReader ePub

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/ computed tomography scan and bone marrow examination, which may be useful for early diagnosis.

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Silvia Uccella, Francesca Magnoli, Cristina Amaglio, Fausto Sessa, Stefano La Rosa
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Kosei Matsue, Yoshiaki Abe, Kentaro Narita, Hiroki Kobayashi, Akihiro Kitadate, Masami Takeuchi, Daisuke Miura, Kengo Takeuchi
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Jin Sae Yoo, Juwon Kim, Hyeong Ju Kwon, Jung Soo Lim
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Klinische und pathologische Charakteristika intravaskulärer Lymphome
Lara Abraham, Hans H. Kreipe, Peter Raab, Kais Hussein
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Original Articles

Correlation between VEGF Expression and Prognostic Factors in Breast Cancer: Jung Eun Jang, Sang Yun Choi, Chan Hyung Park, Young Hyeh Ko, Ki Hyun Kim, Hyun Sik Jeong, Kwang Sung Ahn, Jung Hyun Yang, Seok Jin Nam, Sung Soo Yoon; J Korean Cancer Assoc. 1999;31(3):483-491.

Abstract PDF: PURPOSE
Archival tissues of breast cancer patients were examined for VEGF expression to evaluate the relationship with other clinicopathologic factors and prognostic significance of VEGF in breast cancer.
MATERIALS AND METHODS
Paraffin sections from 76 patients with invasive breast cancer who have been treated at Samsung Medical Center from December, 1994 to April, 1998 were examined for VEGF expression by immunohistochemical staining using anti-VEGF antibody. We analyzed relationships between VEGF expression and tumor size, tumor stage, metastasis, steroid honnone receptors, p53, disease recurrence and survival.
RESULTS
Immunostaining showed variable VEGF positivity in the malignant cells and VEGF was detected more frequently in tumors than in adjacent non-tumorous breast tissues. 74 out of 76 (97.4%) was positive for VEGF. We found that the expression of VEGF was strongly correlated with the stages of breast tumor (P=0.020), lymph node metastasis (P=0.043) and PR (P=0.016). However, we could not find statistically significant relationship between VEGF expression and tumor size, ER, p53 and distant metastasis.
CONCLUSION
VEGF may be a useful prognostic indicator in patients with breast cancer, especially correlated with tumor stage and lymph node metastasis. This result warrants further study to confirm our findings.

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A Study on the p53 Mutations in Korean Breast Cancer Tissues: Hong Kyu Baik, Pah Jong Jung, Youl Hee Cho, Young Hyeh Ko; J Korean Cancer Assoc. 1998;30(5):921-934.

Abstract PDF: PURPOSE
The role of mutation of p53 gene on the carcinigenesis was studied since 1991. There were some relationships of p53 mutation and clinicopathologic factors. This sutudy was designed for the clinicopathologic and genetic factor relation in Korean breast cancer.
MATERIALS AND METHOD
A retrospective study on the clinicopathologic findings such as age, menopausal status, TNM stage, histologic grade, estrogen receptor, DNA ploidy and S-phase fraction was camed out on 47 breast cancer tissues which had been resected at the Department of Surgery, Hanyang University Hospital. Forty-seven tissues were grouped into 3 groups. Group 1 was ductal carcinoma in situ, Group 2 was invasive ductal carcinoma without axillary lymph node metastasis and Group 3 was invasive ductal carcinoma with axillary lymph node metastasis. The numbers of tissues in each groups were 14, 15 and 18, respectively. Mutation screening on the p53 tumor suppressor gene was also performed with PCR-SSCP-direct sequencing method from the genomic DNA extracted from formalin fixed and paraffin-embedded pathologic tissue blocks. The results were as followings; RESULT: p53 mutations were detected in 12 cases(25.5%) of 47. In Group 1, 4 cases(28.6%) had mutations, and in Group 2, 5 cases(33.3%), and in Group3, 3 cases(16.7%). There was no significant differences in mutation rate between three groups. In 12 mutations detected, 6 cases were transition, 5 of which were missense mutation in coding sequences, and one of which was splicing mutation at acceptor site. One case was transversion and five cases were deletions or insertions of various lengths resulting in frameshift mutations. There was no statistically significant difference between groups and clinicopathologic factors except the strong relationship between the negative estrogen receptor and p53 mutation(p< 0.001).
CONCLUSIONS
From the above findings, p53 gene could be considered to be inactivated at the all stage of multistep carcinogenesis processes. The nature of mutations and genetic background of Korean breast cancers may be somewhat different from those of Caucasians. And the p53 mutation status may be used as one of the useful prognostic factors in addition to the estrogen receptor status.

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Subtypes of Epstein - Barr Virus in Malignant Lymphoma in Korea: Kyung Eun Choi, Eun Yoon Cho, Chan Kum Park, Won Keun Lee, Young Hyeh Ko; J Korean Cancer Assoc. 1998;30(2):338-349.

Abstract PDF: PURPOSE
Epstein-Barr virus(EBV) exists in the human population in two genetic forms, usually referred to as type 1 and type 2 which have been defined on the basis of sequence divergence in the EBNA-2 and EBNA-3 family genes. In this study, we were intended to investigate whether the subtypes of EBV in malignant lymphoma in Korea were associated with specific disease entities and geographical distribution.
MATERIALS AND METHODS
Biopsy samples obtained from 18 Korean patients with malignant lymphoma including Hodgkin's disease(3 cases), B cell lymphoma(1 case), and NK/T cell lymphoma(14 cases) were analyzed to determine the subtype of EBV infected therein. DNA was extracted from formalin-fixed, paraffin-embeded tissues by ordinary method and specific viral sequences were sought using the polymerase chain reaction(PCR) and Southern blot hybridization assay. Oligonucleotide primers used for examination of EBV strain type were derived from the EBNA-3B and EBNA-3C coding regions. As a control, four cases of reactive hyperplasia were analyzed.
RESULTS
The two of four reactive hyperplasia cases were associated with type 1 and the rest of two cases with both types. Among the 18 cases with malignant lymphoma, thirteen cases(72%) had type 1, one(6%) had type 2, and four(22%) had dual infections with both types. In case of NK/T cell lymphoma(14 cases) occupying 78% of 18 biopsy samples, 86%(12 cases) were associated with type 1, 7%(1 case) with type 2, and 7%(1 case) with both types. In case of Hodgkin's disease, all of three cases had both types. B cell lymphoma taking only one case of twenty two cases was determined as type 1.
CONCLUSION
These observations indicated that type 1 EBV was predominant in Korean patients with malignant lymphoma, especially NK/T cell lymphoma and showed high frequency of dual viral infections(22%) in Hodgkin's disease as well as in reactive hyperplasia.

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2 Cases of Primary Uterine Lymphoma: Seok Nam Yoon, Young Yiul Lee, In Soon Kim, Kyung Tai Kim, Byung Hee Ko, Young Hyeh Ko; J Korean Cancer Assoc. 1994;26(6):1005-1013.

Abstract PDF: Primary Uterine lymphoma is a rare presentation of extranoal lymphoma: therefore, informations regarding histologic type, immunophenotype of tumor cell and etiologic factors are limited. Usually uterine cervix was predominant 1ocation in primary uterine lyphoma and most patients reported abnormal vaginal bleeding as a initial presentation in uterine lymphoma. Histologically, approximately 70% of all uterine lymphoma were diffuse large cell type by Working Formulation. Recently We experienced two cases of uterine lymphoma, one from uterine cervix, the other from uterine corpus. A uterine cervix lymphoma was diagnosed by colposcopic punch biopsy. A uterine corpus lymphoma was suggested by MRI findings; diffuse uterine enlargement without contour alteration of endometrium, and confirmed by deep cervical punch biopsy. Two cases were found to have diffuse large cell lymphoma and immunologically one was Bll lineage, the other T-cell lineage. Two case were treated with chemotherapy only. We report these cases with literature review.

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Correlation of Tumor DNA Ploidy , Axillary Lymph Node Changes with Other Prognostic Factors in Breast Cancer: Hong Chan Lee, Pah Jong Jung, Young Hyeh Ko; J Korean Cancer Assoc. 1995;27(1):52-61.

Abstract PDF: Flow cytometric DNA analysis has been applied as an important factor for decision of postoperative therapeutic regimen and prediction of prognosis of breast cancer. Sinus histiocytosis had been recognized as a better prognosic factor in axillary lymph nodes than negative sinus histiocytosis. It represents not only the presence of metastases, but also their immunologic potential and cell mediated immunity against the tumor. This study examined DNA ploidy pattern, S-phase fraction and sinus histiocytosis in axillary lymph nodes of breast cancer in 131 patients who underwent operation at the Department of Surgery, Hanyang University Hospital during the period of January 1990 through February 1993. On the basis of these datas, we analysed the correlation of tumor DNA ploidy and axillary lymph node changes with other prognostic factors which are TNM status, histologic grade and estrogen receptor in breast cancer. Authors obtained the following results; 1) In 131 patients, aneuploidy was 63(48.1%) and high S-phase fraction was 89(68%) 2) Incidence of aneuploidy and high S-phase fraction was increased according to the aggravation of T factor, N factor and poor histiologic grade. The rate of negative estrogen receptor was high in aneuploidy and high S-phase fraction group. 3) Among 102 patients, 53(50.1%) had positive sinus histiocytosis, 49(49.9%) had negative sinus histiocytosis. The positive rate of sinus histiocytosis in axillary lymph nodes was highly related with negative axillary lymph node metastases and small size of tumor and it was lower in aneuploidy and high S-phase fraction. 4) Among the patients as a whole postoperative early recurrence were present in 8 cases, they had poor TNM staging and high correlation to aneuploidy, high S-phase fraction and sinus histiocytosis seem to be useful prognostic factors. And additional follow up studies for survival is required.

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A case of Multicentric Castleman's Disease: Yong Ho Song, Seon Ho Hwang, Jae Woong Lee, In Soon Kim, You Hern Ahn, Ho Joong Kim, Young Hyeh Ko; J Korean Cancer Assoc. 1995;27(4):696-703.

Abstract PDF: Multicentric Castleman's disease is a systemic lymphoproliferative disorder, characterized by generalized lymphadenopathe, multisystem involvement, disordered immunity and an in- creased incidence of malignant tumors, particularly Kaposis sarcoma and lymphoid neoplasia. The clinical presentation and laboratory features of this syndrome are similar to those of an- other atypical lymphorliferative disorder, angioimmunoblastic lymphadenopathy with dysproteinemia, although this is histologically different from Castleman's disease. A 21-year old male presented ta us with complaints of arthralgia and myalgia of 4 months duration, followed by 2weeks of high fever. Initial physical findings showed small, generalized lymphadenopathies in cervical, axillary and inguinal areas. He developed hepatosplenomegaly and pleuropericardial effusions rapidly. Lymph node biopsy from left inguinal area was consistent with angiofollicular lymph node hyperplasia, plasma cell type.

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A Case of Well - Differentiated Thymic Carcinoma with Severe Aplastic Anemia: Jung Ah Kim, Gi Hyeon Seo, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Keun Chil Park, Young Hyeh Ko, Chan Hyung Park; J Korean Cancer Assoc. 1996;28(5):897-903.

Abstract PDF: Thymoma is occasionally associated with hematologic disorders such as pure red cell aplasia, agranulocytosis, and thrombocytopenia and several cases have been associated with pancytopenia. In contrast, thymic carcinoma has rarely been associated with aplastic anemia except one case reported by Thomas et aL. This case report concerns a patient in whom we have observed simultaneous occurrence of a well differentiated thymic carcinoma and a severe marrow aplasia for which we describe our therapeutic approach. Our patient did not benefit from thymectomy. We then tried antilymphocyte globulin and cyclosporine and the patient had a partial response with hematologic improvements.

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