Journal of Pathology and Translational Medicine

Reviews

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee; Received February 22, 2024 Accepted March 14, 2024 Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15 [Epub ahead of print]

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Abstract PDF: Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

A standardized pathology report for gastric cancer: 2nd edition: Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi, Hee Kyung Chang, Soomin Ahn, Mee Soo Chang, Song-Hee Han, Yoonjin Kwak, An Na Seo, Sung Hak Lee, Mee-Yon Cho; J Pathol Transl Med. 2023;57(1):1-27. Published online January 15, 2023; DOI: https://doi.org/10.4132/jptm.2022.12.23

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The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

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Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis
Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim
Cancer Research and Treatment.2024; 56(1): 219. CrossRef
Microscopic tumor mapping of post-neoadjuvant therapy pancreatic cancer specimens to predict post-surgical recurrence: A prospective cohort study
Yeshong Park, Yeon Bi Han, Jinju Kim, MeeYoung Kang, Boram Lee, Eun Sung Ahn, Saemi Han, Haeryoung Kim, Hee-Young Na, Ho-Seong Han, Yoo-Seok Yoon
Pancreatology.2024;[Epub] CrossRef
Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center
Elliott J. Yee, Danielle Gilbert, Jeffrey Kaplan, Sachin Wani, Sunnie S. Kim, Martin D. McCarter, Camille L. Stewart
Cancers.2024; 16(7): 1428. CrossRef
Pathological Interpretation of Gastric Tumors in Endoscopic Submucosal Dissection
Jung Yeon Kim
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Histopathology of Gastric Cancer
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Endoscopic submucosal dissection hands-on training with artificial mucosal layer EndoGEL
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Original Articles

Extremely well-differentiated adenocarcinoma of the stomach: diagnostic pitfalls in endoscopic biopsy: Jongwon Lee, In-Seob Lee, Ji Yong Ahn, Young Soo Park, Jihun Kim; J Pathol Transl Med. 2022;56(2):63-72. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.12

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Abstract PDF Supplementary Material

Background
Extremely well-differentiated adenocarcinoma (EWDA) is a deceptively bland-looking adenocarcinoma of the stomach. It often causes diagnostic problems, especially in endoscopic biopsy samples. To better recognize this deceptively bland lesion, we carefully reviewed a series of EWDAs treated at our institution.
Methods
A total of 55 specimens from 19 patients were obtained. Endoscopic, gross and microscopic features defining EWDA were described and documented. For comparison, hyperplastic polyp specimens were randomly selected and analyzed.
Results
Most cases (18 of 19, 94.7%) were advanced gastric cancer (AGC) and primarily located in the body of the stomach (15 of 19, 79.0%). The majority of AGCs were non-ulcerated (11 of 18, 61.1%) with an undermining growth pattern and a relatively small mucosal involvement. Specific histologic features included an irregular glandular shape, an undulating apical cytoplasmic border, disproportionately large glands, a variably distended mucinous cytoplasm. Classical features, such as small infiltrating glands or desmoplastic reactions, were barely observed. Identification of irregularly spaced nuclei and disruption of the foveolar epithelial structure, along with atypical features described above were helpful in making a diagnosis especially in gastric forceps biopsies.
Conclusions
Awareness of the histomorphologic characteristics described in this report would lead to timely diagnosis and prevent repeated endoscopic procedures.

Citations

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Unusual or Uncommon Histology of Gastric Cancer
Jinho Shin, Young Soo Park
Journal of Gastric Cancer.2024; 24(1): 69. CrossRef
A case of gastric adenocarcinoma with pyloric gland-type infiltrating submucosa
Kaiho Hirata, Shusuke Yagi, Hideki Miyazaki, Kazuhiko Yamada, Naoki Akazawa, Naoki Enomoto, Kyoko Nohara, Chizu Yokoi, Toru Igari, Norihiro Kokudo
Surgical Case Reports.2024;[Epub] CrossRef

Expression of CD99 in Multiple Myeloma: A Clinicopathologic and Immunohistochemical Study of 170 Cases: Su-Jin Shin, Hyangsin Lee, Geunyoung Jung, Minchan Gil, Hosub Park, Young Soo Park, Dok Hyun Yoon, Cheolwon Suh, Chan-Jeoung Park, Jooryung Huh, Chan-Sik Park; Korean J Pathol. 2014;48(3):209-216. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.209

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Abstract PDF

Background

Multiple myeloma (MM) is a heterogeneous and ultimately fatal disease. Risk stratification using prognostic biomarkers is crucial to individualize treatments. We sought to investigate the role of CD99, a transmembrane protein highly expressed in many hematopoietic cells including subpopulations of normal and neoplastic plasma cells, for MM risk stratification.

Methods

CD99 expression was measured in paraffin samples of bone marrow and extramedullary biopsies of 170 patients with MM. Patients were divided into those with high score (moderately and strongly positive) and low score (negative and weakly positive), with all staining being cytoplasmic and/or membranous.

Results

High anti-CD99 immunostaining was observed in 72 of 136 (52.9%) bone marrow biopsies and 24 of 87 (27.6%) extramedullary biopsies in MM. High CD99 expression of extramedullary specimens was associated with significantly longer overall survival (OS; p=.016). High CD99 expression of extramedullary specimens was also associated with better prognosis in the nonautologous stem cell transplantation group of MM patients (p=.044). In multivariate analysis, International Staging System stage was an independent prognostic factor, whereas CD99 expression was no longer statistically significant.

Conclusions

Expression of CD99 in extramedullary specimens was correlated with longer OS, suggesting that CD99 may be a helpful immunohistochemical marker for risk stratification.

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Cell Adhesion Molecule CD99 in Cancer Immunotherapy
Feng Yu, Guodong Liu, Hailing Zhang, Xiaoyan Wang, Zhi Wu, Qinggang Xu, Yan Wu, Dongfeng Chen
Current Molecular Medicine.2023; 23(10): 1028. CrossRef
Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications
Luzalba Sanoja-Flores, Juan Flores-Montero, Martín Pérez-Andrés, Noemí Puig, Alberto Orfao
Cancers.2020; 12(6): 1499. CrossRef
Tumor suppressor CD99 is downregulated in plasma cell neoplasms lacking CCND1 translocation and distinguishes neoplastic from normal plasma cells and B-cell lymphomas with plasmacytic differentiation from primary plasma cell neoplasms
Qi Gao, Venkata Yellapantula, Maly Fenelus, Janine Pichardo, Lu Wang, Ola Landgren, Ahmet Dogan, Mikhail Roshal
Modern Pathology.2018; 31(6): 881. CrossRef
EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma
Gregory W Charville, Wei-Lien Wang, Davis R Ingram, Angshumoy Roy, Dafydd Thomas, Rajiv M Patel, Jason L Hornick, Matt van de Rijn, Alexander J Lazar
Modern Pathology.2017; 30(9): 1312. CrossRef
Activation of the polycomb repressive complex pathway in the bone marrow resident cells of diffuse large B-cell lymphoma patients
Eun Ji Oh, Eun Kyung Kim, Woo Ick Yang, Sun Och Yoon
Leukemia & Lymphoma.2016; 57(8): 1921. CrossRef
CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some Subpopulations of Appendages: Comparison with Developing Fetal Skin
Gawon Choi, Jin Roh, Chan-Sik Park
Journal of Pathology and Translational Medicine.2016; 50(5): 361. CrossRef
Towards Stratified Medicine in Plasma Cell Myeloma
Philip Egan, Stephen Drain, Caroline Conway, Anthony Bjourson, H. Alexander
International Journal of Molecular Sciences.2016; 17(10): 1760. CrossRef
Human Myeloma Cell Lines Induce Osteoblast Downregulation of CD99 Which Is Involved in Osteoblast Formation and Activity
Angela Oranger, Giacomina Brunetti, Claudia Carbone, Graziana Colaianni, Teresa Mongelli, Isabella Gigante, Roberto Tamma, Giorgio Mori, Adriana Di Benedetto, Marika Sciandra, Selena Ventura, Katia Scotlandi, Silvia Colucci, Maria Grano
Journal of Immunology Research.2015; 2015: 1. CrossRef
CD99 regulates CXCL12-induced chemotaxis of human plasma cells
Minchan Gil, Hyo-Kyung Pak, A-Neum Lee, Seo-Jung Park, Yoonkyung Lee, Jin Roh, Hyunji Lee, Yoo-Sam Chung, Chan-Sik Park
Immunology Letters.2015; 168(2): 329. CrossRef

Brief Case Report

Adenocarcinoma Arising in Gastric Duplication Cyst: Hyo Jeong Kang, Se Jin Jang, Young Soo Park; Korean J Pathol. 2014;48(2):159-161. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.159

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Papillary Adenocarcinoma in a Gastric Duplication Cyst
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Original Article

Expression Pattern of the Cortical Immature Thymocyte Specific Antigen JL1 in Thymomas; a New Adjunctive Diagnostic Marker.: Young Soo Park, Youngji Kim, Yun Hee Lee, Joo Ryung Huh, Chan Sik Park; Korean J Pathol. 2008;42(5):251-259.

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Abstract PDF: BACKGROUND
JL1 is a novel antigen that has been reported to be expressed exclusively in immature CD4 CD8 double positive T-cells in the thymic cortex. Thymomas are often infiltrated with lymphocytes that are mostly immature T-cells. METHODS: We evaluated 67 cases of surgically resected thymomas and reviewed their histological, surgical, and clinical findings. Representative sections were immunostained using anti-JL1 monoclonal antibody and the immunostaining score was evaluated in each case. RESULTS: JL1 was strongly positive in immature T cells infiltrated in various subtypes of thymomas. The mean value of the immunostaining score was 0 for type A, 0.24 for the A areas of type AB, 2.71 for the B areas of type AB, 3 for type B1, 1.87 for type B2, 0.67 for type B3, and 0.13 for type C. The immunostaining score correlated with the histological subtypes according to the WHO classification, and stages according to the modified Masaoka system. CONCLUSION: JL1 was specifically detected in immature thymocytes in thymomas. Therefore, JL1 immunostaining can be useful for subtyping thymomas. JL1 can also serve as an adjunctive marker to diagnose thymomas in small biopsy specimens.

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