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3 "Diffuse large B-cell lymphoma"
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Original Article
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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AbstractAbstract 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.
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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  • 2 Web of Science
  • 2 Crossref
AbstractAbstract 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.

Citations

Citations to this article as recorded by  
  • 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 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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  • 16 Download
AbstractAbstract 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.

J Pathol Transl Med : Journal of Pathology and Translational Medicine