Journal of Pathology and Translational Medicine

Case Studies

Concurrent intestinal plasmablastic lymphoma and diffuse large B-cell lymphoma with a clonal relationship: a case report and literature review: Nao Imuta, Kosuke Miyai, Motohiro Tsuchiya, Mariko Saito, Takehiro Sone, Shinichi Kobayashi, Sho Ogata, Fumihiko Kimura, Susumu Matsukuma; J Pathol Transl Med. 2024;58(4):191-197. Published online June 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.05.14

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Abstract PDF: Herein, we report a case of plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL) that occurred concurrently in the large intestine. An 84-year-old female presented with a palpable rectal tumor and ileocecal tumor observed on imaging analyses. Endoscopic biopsy of both lesions revealed lymphomatous round cells. Hartmann’s operation and ileocecal resection were performed for regional control. The ileocecal lesion consisted of a proliferation of CD20/CD79a-positive lymphoid cells, indicative of DLBCL. In contrast, the rectal tumor showed proliferation of atypical cells with pleomorphic nuclei and abundant amphophilic cytoplasm, with immunohistochemical findings of CD38/CD79a/MUM1/MYC (+) and CD20/CD3/CD138/PAX5 (–). Tumor cells were positive for Epstein-Barr virus– encoded RNA based on in situ hybridization and MYC rearrangement in fluorescence in situ hybridization analysis. These findings indicated the rectal tumor was most likely a PBL. Sequencing analysis for immunoglobulin heavy variable genes indicated a common B-cell origin of the two sets of lymphoma cells. This case report and literature review provide new insights into PBL tumorigenesis.

Fibrin-associated large B-cell lymphoma arising in an endovascular graft: first case report in Korea: Min Gyoung Pak, Mee Sook Roh; J Pathol Transl Med. 2024;58(2):87-90. Published online January 24, 2024; DOI: https://doi.org/10.4132/jptm.2023.12.28

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Abstract PDF: Fibrin-associated large B-cell lymphoma (FA-LBCL) is an extremely rare subtype of LBCL that consists of microscopic aggregates of atypical large B cells in the background of fibrin. Here, we report the first case of FA-LBCL in Korea. A 57-year-old male presented with a large amount of thrombus in the thoracic aorta during follow-up for graft replacement of the thoracoabdominal aorta 8 years prior. The removed thrombus, measuring 4.3 × 3.1 cm, histologically exhibited eosinophilic fibrinous material with several small clusters of atypical lymphoid cells at the periphery. The atypical cells were positive for CD20 by immunohistochemistry and for Epstein-Barr virus by in situ hybridization. The Ki-67 proliferation rate was 85%. The patient was still alive with no recurrence at the 7-year follow-up after thrombectomy. Although the diagnosis can be very difficult and challenging due to its paucicellular features, pathologists should be aware of FALBCL, which has likely been underestimated in routine evaluations of thrombi.

Original Articles

Tumor-infiltrating T lymphocytes evaluated using digital image analysis predict the prognosis of patients with diffuse large B-cell lymphoma: Yunjoo Cho, Jiyeon Lee, Bogyeong Han, Sang Eun Yoon, Seok Jin Kim, Won Seog Kim, Junhun Cho; J Pathol Transl Med. 2024;58(1):12-21. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.02

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Abstract PDF

Background
The implication of the presence of tumor-infiltrating T lymphocytes (TIL-T) in diffuse large B-cell lymphoma (DLBCL) is yet to be elucidated. We aimed to investigate the effect of TIL-T levels on the prognosis of patients with DLBCL.
Methods
Ninety-six patients with DLBCL were enrolled in the study. The TIL-T ratio was measured using QuPath, a digital pathology software package. The TIL-T ratio was investigated in three foci (highest, intermediate, and lowest) for each case, resulting in TIL-T–Max, TIL-T–Intermediate, and TIL-T–Min. The relationship between the TIL-T ratios and prognosis was investigated.
Results
When 19% was used as the cutoff value for TIL-T–Max, 72 (75.0%) and 24 (25.0%) patients had high and low TIL-T–Max, respectively. A high TIL-T–Max was significantly associated with lower serum lactate dehydrogenase levels (p < .001), with patient group who achieved complete remission after RCHOP therapy (p < .001), and a low-risk revised International Prognostic Index score (p < .001). Univariate analysis showed that patients with a low TIL-T–Max had a significantly worse prognosis in overall survival compared to those with a high TIL-T–Max (p < .001); this difference remained significant in a multivariate analysis with Cox proportional hazards (hazard ratio, 7.55; 95% confidence interval, 2.54 to 22.42; p < .001).
Conclusions
Patients with DLBCL with a high TIL-T–Max showed significantly better prognosis than those with a low TIL-T–Max, and the TIL-T–Max was an independent indicator of overall survival. These results suggest that evaluating TIL-T ratios using a digital pathology system is useful in predicting the prognosis of patients with DLBCL.

Citations

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Do Pre‐Treatment Biopsy Characteristics Predict Early Tumour Progression in Feline Diffuse Large B Cell Nasal Lymphoma Treated With Radiotherapy?
Valerie J. Poirier, Valeria Meier, Michelle Turek, Neil Christensen, Jacqueline Bowal, Matthew D. Ponzini, Stefan M. Keller
Veterinary and Comparative Oncology.2025; 23(1): 82. CrossRef
Comprehensive Analysis of Tumor Microenvironment and PD-L1 Expression Associations with Clinicopathological Features and Prognosis in Diffuse Large B-Cell Lymphoma
Yun-Li Xie, Long-Feng Ke, Wen-Wen Zhang, Fu Kang, Shu-Yi Lu, Chen-Yu Wu, Huan-Huan Zhu, Jian-Chao Wang, Gang Chen, Yan-Ping Chen
Blood and Lymphatic Cancer: Targets and Therapy.2025; Volume 15: 167. CrossRef
Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL
Chengqian Chen, Wei Guo, Haotian Wang, Luming Cao, Ou Bai
Frontiers in Immunology.2025;[Epub] CrossRef
Integrative analysis of a novel immunogenic PANoptosis‑related gene signature in diffuse large B-cell lymphoma for prognostication and therapeutic decision-making
Ming Xu, Ming Ruan, Wenhua Zhu, Jiayue Xu, Ling Lin, Weili Li, Weirong Zhu
Scientific Reports.2024;[Epub] CrossRef

Prognostic significance of BLK expression in R-CHOP treated diffuse large B-cell lymphoma: Soyeon Choi, Yoo Jin Lee, Yunsuk Choi, Misung Kim, Hyun-Jung Kim, Ji Eun Kim, Sukjoong Oh, Seoung Wan Chae, Hee Jeong Cha, Jae-Cheol Jo; J Pathol Transl Med. 2022;56(5):281-288. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.07.26

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Abstract PDF

Background
The aim of the present study was to evaluate the prognostic significance of B-cell lymphocyte kinase (BLK) expression for survival outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP.
Methods
We retrospectively analyzed the medical records of 89 patients from two tertiary referral hospitals. The expression of BLK, SYK, and CDK1 were evaluated in a semiquantitative method using an H-score, and the proportions of BCL2 and C-MYC were evaluated.
Results
A total of 89 patients received R-CHOP chemotherapy as a first-line chemotherapy. The expression rates of BLK in tumor cells was 39.2% (n = 34). BLK expression status was not significantly associated with clinical variables; however, BLK expression in tumor cells was significantly associated with the expression of both C-MYC and BCL2 (p = .003). With a median follow-up of 60.4 months, patients with BLK expression had significantly lower 5-year progression-free survival (PFS) and overall survival rates (49.8% and 60.9%, respectively) than patients without BLK expression (77.3% and 86.7%, respectively). In multivariate analysis for PFS, BLK positivity was an independent poor prognostic factor (hazard ratio, 2.208; p = .040).
Conclusions
Here, we describe the clinicopathological features and survival outcome according to expression of BLK in DLBCL. Approximately 39% of DLBCL patients showed BLK positivity, which was associated as a predictive marker for poor prognosis in patients who received R-CHOP chemotherapy.

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Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies
Philippe Decruyenaere, Edoardo Giuili, Kimberly Verniers, Jasper Anckaert, Katrien De Grove, Malaïka Van der Linden, Dries Deeren, Jo Van Dorpe, Fritz Offner, Jo Vandesompele
Frontiers in Oncology.2023;[Epub] CrossRef

Case Studies

An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing: Bogyeong Han, Sehui Kim, Jiwon Koh, Jeong Mo Bae, Hongseok Yun, Yoon Kyung Jeon; J Pathol Transl Med. 2022;56(2):92-96. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.15

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Abstract PDF

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.

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Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts
Sophia M. Roush, Mishalan Moodley, Jenny Coelho, Samantha Beck, Amon Chirwa, Edwards Kasonkanji, Marriam Mponda, Maurice Mulenga, Tamiwe Tomoka, Hanri van Zijl, Katherine Hodkinson, Arshad Ismail, Senzo Mtshali, Jonathan Featherston, Satish Gopal, Matthew
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Chimeric and mutant CARD9 constructs enable analyses of conserved and diverged autoinhibition mechanisms in the CARD‐CC protein family
Jens Staal, Yasmine Driege, Femke Van Gaever, Jill Steels, Rudi Beyaert
The FEBS Journal.2024; 291(6): 1220. CrossRef
PD-L1+diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquiredPMS2mutation
Andrew W. Allbee, James Gerson, Guang Yang, Adam Bagg
Molecular Case Studies.2023; 9(4): a006318. CrossRef

Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: Soyeon Choi, Ji Hye Kim, Kyungbin Kim, Misung Kim, Hye Jeong Choi, Young Min Kim, Jae Hee Suh, Min Jung Seo, Hee Jeong Cha; J Pathol Transl Med. 2020;54(4):340-345. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.18

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Abstract PDF

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), is one of the specific type of low-grade B-cell lymphoma not infrequently found worldwide. It typically involves mucosal sites such as stomach and conjunctiva; however, primary hepatic MALT lymphoma has been extremely rarely reported. We describe a case of hepatic MALT lymphoma in a 70-year-old male patient who underwent left hepatectomy due to the incidentally detected liver masses at a medical checkup. The resected specimen revealed multinodular masses consisting of small-to-intermediate-sized lymphoid cells with serpentine pattern and focal lymphoepithelial lesions. The tumor cells were diffusely positive for CD20 and Bcl-2 but negative for CD3, CD10, CD5, CD23, CD43, and cyclinD1. The Ki-67 labeling index was 10% and immunoglobulin heavy chain gene rearrangement study confirmed monoclonal proliferation. In this paper, we discuss several unique clinicopathologic characteristics which will be helpful to the differential diagnosis of hepatic MALT lymphoma.

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Oral administration of Limosilactobacillus reuteri VHProbi® M07 alleviates ovalbumin-induced allergic asthma in mice
Guoqing Meng, Hongchang Cui, Congrui Feng, Chaoqun Guo, Lei Song, Zhi Duan, Misbahuddin Rafeeq
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Shin-Ting Chen, Yu-Guang Chen, Wen-Yen Huang, Cheng-Hsiang Lo
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Primary Hepatic Mucosa-Associated B-Cell Lymphoma in a Patient with Primary Sclerosing Cholangitis—A Case Ultimately Requiring Liver Transplantation
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Tao He, Jieyu Zou
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Yizhen Pang, Long Zhao, Qihang Shang, Tinghua Meng, Haojun Chen
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Original Articles

A Small Case Series of Intravascular Large B-Cell Lymphoma with Unexpected Findings: Subset of Cases with Concomitant Extravascular Central Nervous System (CNS) Involvement Mimicking Primary CNS Lymphoma: Kate Poropatich, Dave Dittmann, Yi-Hua Chen, Kirtee Raparia, Kristy Wolniak, Juehua Gao; J Pathol Transl Med. 2017;51(3):284-291. Published online April 17, 2017; DOI: https://doi.org/10.4132/jptm.2017.02.16

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Abstract PDF

Background
Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal lymphoma with growth mainly in the lumina of vessels. We studied a small series of IVLBCL and focused on its central nervous system (CNS) involvement.
Methods
Searching the medical records of Northwestern Memorial Hospital, we identified five cases of IVLBCL from January 2007 to January 2015. Clinical information, hematoxylin and eosin stained histologic slides and immunohistochemistry studies were reviewed for all cases. Polymerase chain reaction (PCR) analysis for the immunoglobulin (Ig) heavy and light chain gene rearrangement was performed on all five cases.
Results
Three of the five cases of IVLBCL were autopsies. Patients’ age ranged from 56 to 84. CNS involvement was present in two cases—in both patients, the CNS involvement showed an extravascular pattern with confluent sheet-like formation. PCR analysis confirmed that in one case the systemic intravascular and CNS extravascular components were clonally identical.
Conclusions
In a small case series of IVLBCL, we observed that CNS involvement by IVLBCL often has an extravascular morphology, but is clonally identical to the intravascular counterpart by PCR analysis. As IVLBCL can have a rapidly progressing poor outcome, it should be kept in the differential diagnoses for patients presenting with lymphoma of the CNS. The presence of extravascular growth patterns in the CNS should not exclude IVLBCL as a diagnosis.

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Clinical manifestations and outcomes of patients with intravascular large B-cell lymphoma with neurological involvement: highlighting longitudinally extensive myelopathy as a distinct feature
Ekdanai Uawithya, Palakorn Lertsakworakul, Weerapat Owatthanapanich, Jiraporn Jitprapaikulsan
BMJ Neurology Open.2025; 7(1): e000915. CrossRef
Intravascular large B-cell lymphoma of the central nervous system with renal involvement: a case report and literature review
Jun Li, Zhaojiao Li, Yifeng Shi, Jiajie Chen, Heng Zhao, Xueye Mao, Shan Li, Huiying Wang, Qiang Meng, Lingchun Liu
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Diffuse large B-cell lymphoma (DLBCL) with significant intravascular invasion. Close resemblance of its clinicopathological features to intravascular large B-cell lymphoma, but not to DLBCL-not otherwise specified
Hiroe Itami, Hirokazu Nakamine, Masayuki Kubo, Kohei Ogawa, Rina Tani, Shinji Nakamura, Maiko Takeda, Yuji Nitta, Tomoko Uchiyama, Tomomi Fujii, Kinta Hatakeyama, Chiho Ohbayashi
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Unusual and Fatal Case of an Undiagnosed Intravascular Large B‐cell Lymphoma: The Oncologist’s Great Imitator†
Rosario Barranco, Fiorella Caputo, Davide Bedocchi, Francesca Maria Elena Frigiolini, Lara Castelletti, Giulio Fraternali Orcioni, Francesco Ventura
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Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation: Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon; J Pathol Transl Med. 2016;50(5):369-376. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.06

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Abstract PDF

Background
A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs).
Methods
The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs.
Results
The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression.
Conclusions
HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.

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Yun Lin, Zhihong Fang, Zhijuan Lin, Zhifeng Li, Jintao Zhao, Yiming Luo, Bing Xu
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Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma: Chang Hwan Choi, Young Hoon Park, Joo Han Lim, Suk Jin Choi, Lucia Kim, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu; J Pathol Transl Med. 2016;50(2):96-103. Published online February 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.01.12

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Abstract PDF

Background
Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. Methods: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. Results: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. Conclusions: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome.

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Juhyeon Jeong, Eun Ji Oh, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
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Hyang Joo Ryu, Eun Kyung Kim, Su Jin Heo, Byoung Chul Cho, Hye Ryun Kim, Sun Och Yoon
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Diagnostic Utility of a Clonality Test for Lymphoproliferative Diseases in Koreans Using the BIOMED-2 PCR Assay: Young Kim, Yoo Duk Choi, Chan Choi, Jong-Hee Nam; Korean J Pathol. 2013;47(5):458-465. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.458

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Abstract PDF

Background

A clonality test for immunoglobulin (IG) and T cell receptor (TCR) is a useful adjunctive method for the diagnosis of lymphoproliferative diseases (LPDs). Recently, the BIOMED-2 multiplex polymerase chain reaction (PCR) assay has been established as a standard method for assessing the clonality of LPDs. We tested clonality in LPDs in Koreans using the BIOMED-2 multiplex PCR and compared the results with those obtained in European, Taiwanese, and Thai participants. We also evaluated the usefulness of the test as an ancillary method for diagnosing LPDs.

Methods

Two hundred and nineteen specimens embedded in paraffin, including 78 B cell lymphomas, 80 T cell lymphomas and 61 cases of reactive lymphadenitis, were used for the clonality test.

Results

Mature B cell malignancies showed 95.7% clonality for IG, 2.9% co-existing clonality, and 4.3% polyclonality. Mature T cell malignancies exhibited 83.8% clonality for TCR, 8.1% co-existing clonality, and 16.2% polyclonality. Reactive lymphadenitis showed 93.4% polyclonality for IG and TCR. The majority of our results were similar to those obtained in Europeans. However, the clonality for IGK of B cell malignancies and TCRG of T cell malignancies was lower in Koreans than Europeans.

Conclusions

The BIOMED-2 multiplex PCR assay was a useful adjunctive method for diagnosing LPDs.

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CD44s and CD44v6 Are Predominantly Expressed in the Non-germinal Center B-Cell-like Type of Diffuse Large B-Cell Lymphomas.: Kyueng Whan Min, Young Ha Oh, Chan Kum Park, So Dug Lim, Wan Seop Kim; Korean J Pathol. 2011;45(6):589-595.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.589

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Abstract PDF: BACKGROUND
CD44 protein is known as a homing cellular adhesion molecule that is linked to diverse cellular functions such as adhesion, migration and invasion, which are all important in cancer progression and metastasis. The expression of CD44 standard and variant isoforms (CD44 standard isoform [CD44s] and CD44 splice variants containing exon v6 [CD44v6], respectively) is associated with an unfavorable clinical outcome in various neoplasms.
METHODS
Forty patients who were diagnosed with diffuse large B-cell lymphoma (DLBCL) through biopsy at Hanyang University Hospital between 1996 and 2003 were included in this study. CD44 proteins expression was analyzed by immunohistochemical staining on a tissue microarray and the correlation of CD44 with the types of DLBCL and clinical parameters, including the factors defined by the International Prognostic Index, was evaluated.
RESULTS
A high CD44s and intermediate to strong CD44v6 expression, including cytoplasmic membranous staining patterns, was present in 35% (14/40) and 25% (10/40) of DLBCL patients, respectively. High CD44s expression was correlated significantly with non-germinal center B-cell-like types (non-GCB, p=0.004) and patients with old age (p=0.041).
CONCLUSIONS
High CD44s expression may be significantly associated with the non-GCB type compared to the GCB type and may be essential to the prediction of disease outcome in tumor stage III in DLBCL patients.

Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma.: Young Sin Ko, Young Ha Oh, Chan Kum Park, Wook Youn Kim, Hye Seung Han, So Dug Lim, Tae Sook Hwang, Wan Seop Kim; Korean J Pathol. 2011;45(6):573-581.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.573

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Abstract PDF

BACKGROUND
Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity.
METHODS
We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x).
RESULTS
Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score.
CONCLUSIONS
The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.

Citations

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Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies
Pauline Gravelle, Barbara Burroni, Sarah Péricart, Cédric Rossi, Christine Bezombes, Marie Tosolini, Diane Damotte, Pierre Brousset, Jean-Jacques Fournié, Camille Laurent
Oncotarget.2017; 8(27): 44960. CrossRef
Expression of programmed cell death ligand 1 (PD-L1) in advanced stage EBV-associated extranodal NK/T cell lymphoma is associated with better prognosis
Wook Youn Kim, Ho Young Jung, Soo Jeong Nam, Tae Min Kim, Dae Seog Heo, Chul-Woo Kim, Yoon Kyung Jeon
Virchows Archiv.2016; 469(5): 581. CrossRef

Case Report

Diffuse Large B-Cell Lymphoma Associated with Chronic Inflammation Manifested as a Soft Tissue Mass: Incidental Discovery on Histological Examination.: Sang Yun Ha, Yoon La Choi, Sung Joo Kim, Young Hye Ko; Korean J Pathol. 2011;45(4):417-422.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.417

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Abstract PDF

We report an extraordinary case of diffuse large B-cell lymphoma arising in a cystic necrotic mass in a 35-year-old man who presented with a soft tissue mass at the site of previous surgery. A benign mass was surgically removed 17 years ago, after which a cystic lesion gradually developed at the same site. The resected mass appeared as a thick-walled cyst filled with brown necrotic and hemorrhagic material. On microscopic examination, the cyst wall was primarily necrotic tissue with some aggregates of large atypical lymphoid cells. These atypical cells were diffusely positive for CD20 and showed a high proliferation index, Epstein-Barr virus positivity, and clonal rearrangement of the immunoglobulin gene. His present condition was diagnosed as Epstein-Barr virus-associated diffuse large B-cell lymphoma arising from chronic inflammation. It is important to be aware of the clinical manifestations and histological features of this rare disease in light of diagnosis and treatment.

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EBV-negative Fibrin-Associated Large B-Cell Lymphoma Arising in Thyroid Hyperplastic Nodule: Report of a Case and Literature Review
Tin Wai Ho, Wah Cheuk, John K.C. Chan
International Journal of Surgical Pathology.2023; 31(7): 1420. CrossRef
Diffuse Large B Cell Lymphoma in a Prosthetic Aortic Graft
David Bell, David Marshman
Heart, Lung and Circulation.2017; 26(2): e4. CrossRef
Fibrin-associated EBV-positive Large B-Cell Lymphoma
Daniel F. Boyer, Penelope A. McKelvie, Laurence de Leval, Kerstin L. Edlefsen, Young-Hyeh Ko, Zachary A. Aberman, Alexandra E. Kovach, Aneal Masih, Ha T. Nishino, Lawrence M. Weiss, Alan K. Meeker, Valentina Nardi, Maryknoll Palisoc, Lina Shao, Stefania P
American Journal of Surgical Pathology.2017; 41(3): 299. CrossRef
Malignant Lymphoma Mimicking an Infection After Shoulder Surgery
Jabari Ian Justin Martin, Jasmine Bauknight, Vincent Desiderio, Bahman Sadr
Journal of the American Academy of Orthopaedic Surgeons.2017; 25(4): 314. CrossRef
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Korean Journal of Pathology.2014; 48(2): 81. CrossRef

Original Articles

Fine-Needle Aspiration Cytology of the Nodal Marginal Zone Lymphoma.: Seung Kyu Choi, Ji Eun Kwon, Young Hyeh Ko; Korean J Pathol. 2011;45(4):406-411.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.406

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Abstract PDF: BACKGROUND
Nodal marginal zone lymphoma (NMZL) is a rare B-cell neoplasm consisting of heterogeneous cellular components and residual B-cell follicles. Because of such histological features, it is difficult to diagnose NMZL by fine needle aspiration (FNA) cytology. We reviewed FNA cytology of NMZL to identify a cytological clue to avoid misdiagnosing NMZL.
METHODS
Histological, cytological, and clinical findings of seven cases of NMZL were reviewed.
RESULTS
Most cases showed nodular aggregates of lymphohistiocytes derived from the germinal center irrespective of histological pattern. The cellular components were heterogeneous and composed of mature small lymphocytes, intermediate and large lymphocytes, immunoblasts, tingible body macrophages, and follicular dendritic cells. Intermediate-sized neoplastic cells with a pale nucleus were observed but difficult to identify because of admixed non-neoplastic cells, which outnumbered neoplastic cells. Except for one case with a high proportion of intermediate-sized cells, the other six cases were initially diagnosed as reactive hyperplasia. A flow cytometric analysis was performed in two cases and failed to demonstrate a monoclonal B-cell population.
CONCLUSIONS
The FNA showing a reactive hyperplasia-like smear pattern should be carefully observed by experienced cytopathologists to identify intermediate-sized neoplastic cells. Clinical information including the size of the lymph nodes is important to avoid a misdiagnosis.

Association of CD57+ Natural Killer Cells with Better Overall Survival in DLBCL Patients.: Jeong Hyeon Lee, Yoon Jin Kwak, Chul Hwan Kim, Insun Kim; Korean J Pathol. 2011;45(4):361-370.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.361

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Abstract PDF

BACKGROUND
Malignant tumor cells may evoke the innate and adaptive immune systems. Various immune cells are involved in this immune reaction, and tumor infiltrating lymphocytes, macrophages, natural killer (NK) cells are associated with patient prognosis for solid tumors.
METHODS
Seventy-eight patients who were diagnosed with diffuse large B cell lymphoma (DLBCL) between 2001 and 2009 were selected. CD57+ NK cells, CD68+ tumor associated macrophages (TAMs), and CD4+ and CD8+ T cells were evaluated in tissue sections using immunohistochemical staining and compared with clinical parameters including age, gender, performance status, clinical stage, serum lactic dehydrogenase level, number of extranodal sites, international prognostic index score, chemotherapy response, and survival.
RESULTS
Patients with high numbers of CD57+ NK cells had a significantly higher overall survival rate than patients with low numbers of CD57+ NK cells. However, no significant difference was observed between the number of CD57+ NK cells and other prognostic parameters. The number of CD68+ TAMs and CD4+ or CD8+ T cells was not significantly correlated with prognostic factors in patients with DLBCL.
CONCLUSIONS
An evaluation of tumor infiltrating CD57+ NK cells is recommended as a prognostic indicator in patients with DLBCL.

Citations

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The prognostic value of tumor-associated macrophages detected by immunostaining in diffuse large B cell lymphoma: A meta-analysis
Mei Lin, Shupei Ma, Lingling Sun, Zhiqiang Qin
Frontiers in Oncology.2023;[Epub] CrossRef

Expression of P-glycoprotein and Apoptosis in Diffuse Large B-cell Lymphoma.: Ji Eun Kim, Young A Kim, Mee Soo Chang, Yunkyeong Jeon, JinHo Paik, Seon Og Yoon; Korean J Pathol. 2009;43(4):317-320.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.317

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Abstract PDF: BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma which responds well to conventional chemotherapy. However, quite a few patients have a recurrence with more aggressive forms after completion of therapy. Multidrug resistance proteins (MRP) are related to this process in several ways such as cell cycle alteration and modulation of apoptosis. METHODS: We investigated the expression of P-glycoprotein (Gp), one of the well-known MRP, as well as apoptosis associated proteins in DLBCL. Immunohistochemical staining for Gp, p53, Bcl-2, Ki-67, active caspase 3 and FADD was done in forty DLBCL cases. The association between MRP and apoptosis associated proteins to clinical findings was also tested. RESULTS: Twenty-nine patients out of 40 (73%) with DLBCL were positive for Gp, and 26 cases (65%) had a strong positive for Gp. Gp expression was stronger in high-grade lesions than in low-grade lesions and was associated to Bcl-2 expression. However, we could not find an adverse impact of Gp expression on patients' overall survival or relapse free survival rate. CONCLUSIONS: Our study revealed a high frequency of expression for Gp in DLBCL with a possible relationship between the expressions of Gp to apoptosis associated proteins.

Clinicopathologic Study of Chromosomal Aberrations in Gastric Lymphomas of Korean Patients.: Wook Youn Kim, Jung Ho Kim, Hyoungsuk Ko, Young A Kim, Yoon Kyung Jeon, Chul Woo Kim; Korean J Pathol. 2009;43(1):5-12.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.5

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Abstract PDF

BACKGROUND
The incidence and clinical correlation of MALT1 translocation and numerical aberrations in Korean gastric MALT lymphoma patients have been rarely reported. We studied the incidence and clinicopathologic relationship of these chromosomal aberrations in Korean gastric lymphomas.
METHODS
Seventy-six gastric lymphomas, which consisted of 40 low grade MALT lymphoma, 4 high grade MALT lymphoma and 32 diffuse large B-cell lymphoma (DLBCL) cases, were analyzed for the detection of t(11;18) API2-MALT1, t(14;18) IgH-MALT1 and aneuploidies of chromosomes 3 or 18 using fluorescence in situ hybridization.
RESULTS
The t(11;18) was demonstrated in 3 low grade MALT lymphomas (7.5%) and one DLBCL, which was associated with advanced stage, deeper invasion, and disease progression or relapse. The t(14;18) was demonstrated in none of these cases. Trisomy 3 and 18 were detected in 8 (11%) and 11 of 76 cases (12.5%) respectively, and found only in translocation-negative cases. Two of 4 high grade MALT lymphomas showed trisomy 18. All patients survived with successful second treatment after progression or relapse.
CONCLUSIONS
The t(11;18) API2-MALT1 was not quite frequent in Korean low grade gastric MALT lymphomas and was associated with advanced clinical situations. Overall prognosis was good for long-term follow-up regardless of progression or relapse.

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Clinicopathologic Study of Chromosomal Aberrations in Ocular Adnexal Lymphomas of Korean Patients
Hokyung Choung, Young A Kim, Namju Kim, Min Joung Lee, Sang In Khwarg
Korean Journal of Ophthalmology.2015; 29(5): 285. CrossRef

Case Report

Non-Hodgkin's Malignant Lymphoma Arising in the Appendix: A case report.: Yun Sin Kim, Mi Sook Lee, Kwang Seok Lee Lee, Sung Chul Lim, Ho Jong Jeon; Korean J Pathol. 1995;29(4):524-526.

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Abstract PDF: Primary malignant lymphoma of the appendix is an unconnnon neoplasm although the gastrointestinal tract is the most common extranodal site of malignant lymphoma. We report a case of primary malignant lymphoma of the appendix in a 54-year-old male, who presented with pain in the right lower abdomen. An appendectomy was performed. The appendix measured 9.5 cm in length and 5.5 cm in diameter. Cut sections showed a solitary circumferential mass in the appendiceal lumen. Light microscopic features were compatible with malignant lymphoma of diffuse large cell type(Working Formulation) and the immunophenotype was B cell type.

Original Article

Correlation between Clinical Outcome and Proliferation Index in Diffuse Large B-Cell Lymphoma.: Sung Shin Park, Joo ryung Huh, Seung Sook Lee, Yun Koo Kang, Dae Seog Heo, Chul Woo Kim; Korean J Pathol. 1999;33(7):475-482.

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Abstract PDF: The diffuse large B-cell lymphoma category of the Revised European American Classification of Lymphoid Neoplasms (REAL) encompasses different morphologic lymphoma subtypes in a single entity, especially the diffuse large cell (DLC) and the immunoblastic (IBL) subtypes by Working Formulation (WF). The aim of this study is to determine the influence of the morphologic subdivision within this category with respect to clinical outcome and proliferative index using Ki-67 immunostainig combined with image analysis. We retrospectively reviewed 74 patients from 1990 to 1996, who were diagnosed with diffuse large B-cell lymphoma. All cases were reclassified according to REAL and Working Formulation (WF), and Ki-67 immunostaining was performed in all the cases. Fifty-eight cases (78.4%) were classified as DLC and 16 cases (21.6%) as IBL, according to WF. Twenty one cases (28.4%) showed nodal involvement and 53 cases (71.6%), extranodal involvement. All cases were found to display a variable degree of nuclear Ki-67 staining. A proliferative index of 50% or higher identified a group of patients (77%) who had poor clinical results. Overall survival was significantly reduced in these patients displaying high Ki-67 associated proliferative index compared to those with a low proliferative index (p=0.007). 5-year survival estimates were 93% in the low proliferative index group and 55% in the high proliferative index group. A multivariate regression analysis incorporating commonly used clinical prognostic factors confirmed the independent effect of proliferation index on survival. Moreover, all of the 16 IBL cases showed Ki-67 positivity of 50% or higher, which correlates with the poor clinical outcome compared to 70.7% of DLC (p=0.014). We conclude that subdivision of the diffuse large B-cell lymphoma category of the REAL classification is necessary in terms of prognostic significance in correlation with Ki-67 proliferative index.

Case Report

Primary Cerebral B Cell Lymphoma: A "ghost tumor" case report.: Hye Jae Cho, Jung Won Shim, Sang Keun Park, Joon Suk Song, Gham Hur, Hyun Sook Seo; Korean J Pathol. 1991;25(1):68-75.

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Abstract PDF: Primary non-Hodgkin's lymphoma of the brain is a rare malignancy and there are known to occur almost exclusively in brain parenchyme. Recent immunological advances and immunohistochemical techniques have provided new insights into the pathogenesis and diagnosis of the malignant lymphoma even in the small biopsied tissue and the majority of these CNS tumors is thought to be derived from B lymphocytes. A 22-year old man was admitted due to headack, dizziness and walking difficulty for 2 months. On the initial CT scan, there were two enhancing lesion in the suprasellar area and pineal gland which were completely disappeared with steroid therapy and three new lesions appeared on the follow-up CT and MRI studies in corpus callosum, third ventricle and left cerebral peduncle. The serial cytologic smears of cerebrospinal fluid and a stereotaxic biopsy tissue from the corpus callosum mass showed diffusely homogenous infiltration of neoplastic large noncleaved lymphocytes with focal perivascular arrangement. On the immunocytochemical stains, the reaction was negative for GFAP, positive for LCA and MB2, and negative for MT1. After radiation therapy, the masses completely disappeared on the follow-up CT scan and the patient was discharged free of all the clinical symptoms.

Original Articles

Non-Radioactive Detection of Clonality in Malignant Lymphoid Neoplasms using the Polymerase Chain Reaction.: Chan Kum Park, Chul Woo Kim; Korean J Pathol. 1996;30(4):311-317.

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Abstract PDF: The polymerase chain reaction(PCR) was performed to detect clonal rearrangements of the immunoglobulin heavy chain gene(IgH) or T-cell receptor(TCR) genes in 57 lymphoproliferative diseases including 26 B-cell lymphomas and 23 peripheral T-cell lymphomas(PTCL). Using the IgH primers, monoclonality was detected in 19 out of 22(86.4%) cases of diffuse lymphomas and 2 out of 4(50%) follicular lymphomas, respectively, but not in the 23 PTCL cases. Using the V and J regions of the TCRgamma chain primers, monoclonality was detected in 14 out of the 23(60.9%) PTCL cases. TCR beta chain gene rearrangements were observed in 7 out of the 9 cases which did not show TCRgamma chain gene rearrangements. One non-T non-B acute lymphoblastic leukemia was found to have TCR beta chain gene rearrangements. In conclusion, analysis of Ig and TCR gene rearrangements by using the PCR technique can be used as a useful diagnostic adjunct to establish the clonality of various lymphoproliferative diseases.

Immunopathologic Study and Clinical Correlation of Non-Hodgkin's Lymphoma.: Mi Seon Lee, Jin Man Kim, Kwang Sun Suh, Dae Young Kang; Korean J Pathol. 1991;25(5):407-417.

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Abstract: In Korea, the proportion of B-cell and T-cell lymphomas has not yet been clearly estimated. In the present study, we analysed clinicopathologic and immunophenotypic findings in 60 cases of non-Hodgkin's lymphomas(NHL) and in 17 cases of polymorphic reticulosis. Immunohistochemical studies for monoclonal antibodies, such as MB2, UCHL-1, Kappa/Lambda light chains, and IgG/IgM/IgD heavy chains were performed on formaldehyde-fixed paraffin embedded tissue sections. Among 60 cases of NHL, 28 cases(46.7%) expressed B-cell markers, 29 cases(48.3%) T-cell markers, and 3 cases(5.0%) lacked detectable markers, whereas 16 of 17 cases(94.2%) of polymorphic reticulosis reacted with T-cell markers. The mean survival of the 16 cases of T-cell lymphoma group was shorter than that of the lymphoma group positive for B-cell markers.

Establishment and Characterization of an Epstein-Barr Virus-negative B-cell Line from a Patient with Dissemination of Peripheral Blood and Bone Marrow by Malignant Lymphoid Cell.: Ho Jong Jeon, Mi Ja Lee, Yu Kyung Jeong, Yoo Hwan Park, Choon Hae Chung, Yoon Kyung Oh, Chul Heel Choi, Sang Woo Cheong; Korean J Pathol. 1996;30(9):792-809.

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Abstract PDF: A human malignant lymphoid cell line(JeKo-1) was established from a Korean patient with retroperitoneal tumor presenting peripheral blood and bone marrow involvement by malignant lymphoid cells. This cell line was established from peripheral blood, and the cell line had the identical immunophenotypic features as malignant cells from the peripheral blood. The established cell line had features of a mature B-cell phenotype with no evidence for commitment to other lineages. The JeKo-1 grows in suspension with a doubling time of 33 hours. By light and electron microscopic examination, the established cells had a follicular center showing, a small, cleaved, lymphoid appearance, and had a large amount of cytoplasm containing few vacuoles and an irregular cytoplasmic membrane. Immunophenotypic analyses with monoclonal antibodies using flow cytometry showed a monoclonal IgM kappa and CD5- B-cell phenotype. The cells were non-reactive for T-cells and myeloid/monocyte antigens, and no evidence of Epstein-Barr virus nuclear antigen by polymerase chain reaction. DNA analysis showed a hypodiploid stemline with a DNA index of 0.83. The established cells were strongly reactive for bcl-2 and c-myc onco-protein, but lacked expression of multidrug resistance gene protein, p-glycoprotein by Western blot analysis. Karyotypic analysis of JeKo-1 showed 40-41 chromosomes. This cell line should be a valuable tool to study the dissemination of malignant lymphoma into the peripheral blood and bone marrow.

Case Report

High-grade Transformation of Primary Nodal Marginal Zone B-Cell Lymphoma: A Case Report.: Joo Heon Kim, Dong Wook Kang, Mee Ja Park, Jin Man Kim; Korean J Pathol. 2003;37(4):282-286.

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Abstract PDF: Primary nodal marginal zone B-cell lymphoma (MZBCL) is recognized as a rare and distinct entity. The rate of histologic transformation into diffuse large B-cell lymphoma (DLBCL) seems lower than the rate of transformation in follicular lymphoma. We herein report a rare case ofnodal MZBCL showing transformation into DLBCL. The patient was a 73-year-old female withcervical lymphadenopathy. On the initial biopsy, the lymph node architecture was diffuselyeffaced with an extensive interfollicular and parafollicular infiltrate of monocytoid B-cells. Therewere scattered large blastic B-cells without formations of compact sheets. The diagnosis ofnodal MZBCL was made. The patient did not receive chemotherapy and was treated with aconservatively supportive regimen. Forty two months later, the patient developed a new cervicallymphadenopathy and a biopsy was performed. Histologically, the lymph node revealeddiffuse sheets of transformed large B-cells showing prominent nucleoli. The diagnosis ofDLBCL transformed from nodal MZBCL was made. The patient was treated with 3 cycles ofcombined CHOP chemotherapy and she showed clinical improvement. These observationssuggest that an untreated primary nodal MZBCL may undergo high-grade transformation.

Original Article

The Value of Immunohistochemistry on Paraffin Embedded Tissue Sections in the Differentiation of Subgroups of Low Grade B-Cell Lymphomas.: Tae Sook Hwang, Seung Sook Lee, Ji Eun Kim, Hye Seung Han, Chul Woo Kim; Korean J Pathol. 1998;32(12):1066-1073.

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Abstract: There had been a continuous evolution of lymphoma classification and recently a Revised European-American Lymphoma Classification was proposed by the International Lymphoma Study Group. This new classification often requires information on immunophenotypic and molecular biologic markers in addition to the usual histologic findings. Recent advances in the production of commercially available monoclonal antibodies reactive on formalin-fixed paraffin-embedded tissues provide us a great help to classify the non-Hodgkin's lymphoma. We have analyzed 31 low grade B-cell lymphomas by the schemes proposed by the International Lymphoma Study Group using antibodies to CD3, CD5, CD20, CD23, CD43, cyclin D1, and bcl-2 protein, and have analyzed the immunophenotypic features. Among 31 low grade B-cell lymphomas, 8 small lymphocytic lymphomas, 5 mantle cell lymphomas, 7 follicle center lymphomas (2 grade I, 3 grade II, and 2 grade III), and 11 marginal zone B-cell lymphomas (all of which were extranodal) were identified. Among 8 small lymphocytic lymphomas, 5 cases were positive for CD5; 6 cases were positive for CD23; 7 cases were positive for CD43; all 8 cases were negative for cyclin D1; and 7 cases were positive for bcl-2. Among 5 mantle cell lymphomas, 4 cases were positive for CD5 and CD43; all five cases were negative for CD23; 4 cases were positive for cyclin D1 and bcl-2. All 7 follicle center lymphomas were negative for CD5, CD43 and cyclin D1 and 2 cases were positive for CD23; and 6 cases were positive for bcl-2. All marginal zone B-cell lymphomas were negative for CD5, CD23 and cyclin D1; 3 cases were positive for CD43 and 9 cases were positive for bcl-2. Diagnostic utility for CD5 antigen detection on paraffin embedded tissue has a limitation due to weak antigen expression in tumor cells of B-cell lymphomas; however, still be useful in differentiating small lymphocytic lymphoma and mantle cell lymphoma from other B-cell lymphomas when applied in conjunction with CD43. CD23, CD43, and cyclin D1 appear to be of great help in differentiating subgroups of low grade B-cell lymphomas. Bcl-2, as known, is found to be useful to rule out reactive follicular hyperplasia.

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