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.

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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
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 Study

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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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

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
Frontiers in Oncology.2025;[Epub] CrossRef
A single institution series of intravascular lymphoma: Neurological manifestations and neuroimaging findings
J. Corroza, C. Alburquerque, L. Martínez-Martínez, I. Gastón, L. Torné, M.C. Gil-Alzueta, J. Oteiza, T. Cabada, M.C. Viguria, A. Panizo, M.E. Erro
Neurología.2025;[Epub] CrossRef
A case report and literature review of cutaneous intravascular large B-cell lymphoma presenting clinically as panniculitis: a difficult diagnosis, but a good prognosis
Deniz Bayçelebi, Levent Yıldız, Nilgün Şentürk
Anais Brasileiros de Dermatologia.2021; 96(1): 72. CrossRef
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
Journal of Clinical and Experimental Hematopathology.2021; 61(3): 152. CrossRef
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
Journal of Forensic Sciences.2020; 65(1): 314. CrossRef
Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma
Sylvain Raoul Simeni Njonnou, Bruno Couturier, Yannick Gombeir, Sylvain Verbanck, France Devuyst, Georges El Hachem, Ivan Theate, Anne-Laure Trepant, Virginie De Wilde, Frédéric-Alain Vandergheynst
Case Reports in Hematology.2019; 2019: 1. CrossRef
Accurate Detection of Tumor Infiltration by ¹¹C-Methionine Positron Emission Tomography in a Patient with Central Nervous System Intravascular Lymphoma: A Case Report
Shoji Yomo, Keiji Tsutsumi, Takehiro Yako, Hiromasa Sato, Takao Hashimoto, Kazuhiro Oguchi
Case Reports in Oncology.2018; 11(2): 577. CrossRef

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.

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.

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.

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