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.

Citations

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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
Journal of Digestive Cancer Research.2023; 11(1): 15. CrossRef
Histopathology of Gastric Cancer
Baek-hui Kim, Sung Hak Lee
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2023; 23(2): 143. CrossRef
Endoscopic submucosal dissection hands-on training with artificial mucosal layer EndoGEL
Tae-Se Kim, Jun Haeng Lee
Journal of Innovative Medical Technology.2023; 1(1): 5. CrossRef

Original Articles

Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters: Mee-Yon Cho, Jin Hee Sohn, So Young Jin, Hyunki Kim, Eun Sun Jung, Mi-Jung Kim, Kyoung-Mee Kim, Woo Ho Kim, Joon Mee Kim, Yun Kyung Kang, Joon Hyuk Choi, Dae Young Kang, Youn Wha Kim, Eun Hee Choi; Korean J Pathol. 2013;47(3):227-237. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.227

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Abstract PDF

Background

There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients.

Methods

We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report.

Results

Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms.

Conclusions

A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.

Citations

Citations to this article as recorded by

Analysis of Prognostic Risk Factors of Endoscopic Submucosal Dissection (ESD) and Curative Resection of Gastrointestinal Neuroendocrine Neoplasms
Yuan Si, ChaoKang Huang, JingBin Yuan, XianHui Zhang, QingQiang He, ZhiJin Lin, Ling He, ZhongXin Liu, Yuvaraja Teekaraman
Contrast Media & Molecular Imaging.2022; 2022: 1. CrossRef
Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms
Dong-Wook Kang, Baek-hui Kim, Joon Mee Kim, Jihun Kim, Hee Jin Chang, Mee Soo Chang, Jin-Hee Sohn, Mee-Yon Cho, So-Young Jin, Hee Kyung Chang, Hye Seung Han, Jung Yeon Kim, Hee Sung Kim, Do Youn Park, Ha Young Park, So Jeong Lee, Wonae Lee, Hye Seung Lee,
Journal of Pathology and Translational Medicine.2021; 55(4): 247. CrossRef
Preoperative diagnosis of well‐differentiated neuroendocrine tumor in common hepatic duct by brush cytology: A case report
Jiwoon Choi, Kyong Joo Lee, Sung Hoon Kim, Mee‐Yon Cho
Diagnostic Cytopathology.2019; 47(7): 720. CrossRef
Primary renal well-differentiated neuroendocrine tumors: report of six cases with an emphasis on the Ki-67 index and mitosis
Bohyun Kim, Han-Seong Kim, Kyung Chul Moon
Diagnostic Pathology.2019;[Epub] CrossRef
Primary low‐grade neuroendocrine carcinoma of the skin: An exceedingly rare entity
Tiffany Y. Chen, Annie O. Morrison, Joe Susa, Clay J. Cockerell
Journal of Cutaneous Pathology.2017; 44(11): 978. CrossRef
Prognostic Validity of the American Joint Committee on Cancer and the European Neuroendocrine Tumors Staging Classifications for Pancreatic Neuroendocrine Tumors
Jae Hee Cho, Ji Kon Ryu, Si Young Song, Jin-Hyeok Hwang, Dong Ki Lee, Sang Myung Woo, Young-Eun Joo, Seok Jeong, Seung-Ok Lee, Byung Kyu Park, Young Koog Cheon, Jimin Han, Tae Nyeun Kim, Jun Kyu Lee, Sung-Hoon Moon, Hyunjin Kim, Eun Taek Park, Jae Chul Hw
Pancreas.2016; 45(7): 941. CrossRef
Early diagnosis and treatment of gastrointestinal neuroendocrine tumors
Hong Shen, Zhuo Yu, Jing Zhao, Xiu-Zhen Li, Wen-Sheng Pan
Oncology Letters.2016; 12(5): 3385. CrossRef
Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts
Joo Young Kim, Seung-Mo Hong
Archives of Pathology & Laboratory Medicine.2016; 140(5): 437. CrossRef
Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade
Koji Takumi, Yoshihiko Fukukura, Michiyo Higashi, Junnichi Ideue, Tomokazu Umanodan, Hiroto Hakamada, Ichiro Kanetsuki, Takashi Yoshiura
European Journal of Radiology.2015; 84(8): 1436. CrossRef
Tumeurs neuroendocrines du tube digestif et du pancréas : ce que le pathologiste doit savoir et doit faire en 2014
Jean-Yves Scoazec, Anne Couvelard
Annales de Pathologie.2014; 34(1): 40. CrossRef
Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic
Václav Mandys, Tomáš Jirásek
Gastroenterology Research and Practice.2014; 2014: 1. CrossRef
p27 Loss Is Associated with Poor Prognosis in Gastroenteropancreatic Neuroendocrine Tumors
Hee Sung Kim, Hye Seung Lee, Kyung Han Nam, Jiwoon Choi, Woo Ho Kim
Cancer Research and Treatment.2014; 46(4): 383. CrossRef

Galectin-3 Expression and BRAF Mutation in Cases of Cytologically Suspicious Papillary Thyroid Carcinoma.: Dokyung Kim, Hyunki Kim, Jinyoung Kwak, Minju Kim, Hyung Jae Jung, Ja Seung Koo, Beom Jin Lim, Chankwon Jung, SoonWon Hong; Korean J Pathol. 2010;44(2):191-198.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.191

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Abstract PDF: BACKGROUND
Fine needle aspiration, which is known as the most accurate and cost-effective method for diagnosis of thyroid nodule, still may result in indeterminate cases that are pauci-cellular and show minor nuclear atypia, but most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs and galectin-3 was expressed by malignant tumors, helping us to differentiate malignancies from benign lesions.
METHODS
Cases studied included histologically 44 confirmed PTC cases and 18 benign cases previously diagnosed as suspicious of PTC using cytologic examination. Cases were analyzed for galectin-3 expression by immunohistochemical staining and BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme.
RESULTS
All 44 cases of PTC and 8 of 18 benign controls expressed galectin-3. BRAF mutations were found in only 9 of the 44 PTC cases. Assessment of galectin-3 expression demonstrated high sensitivity but low specificity. Evaluation of BRAF mutation revealed high specificity and low sensitivity.
CONCLUSIONS
This study suggests that the combined application of these two methods for PTC of suspicious cytology is complementary.

The Expression of Hypoxia Inducible Factor-1alpha and Its Correlation with the Expressions of Cyclin A1 and Cyclin B1 and the Clinicopathologic Factors of Uterine Cervical Carcinoma.: Ju Yeon Pyo, Jae Ho Cho, Hyunki Kim, Jong Pil Park, Young Tae Kim, Nam Hoon Cho; Korean J Pathol. 2009;43(1):13-19.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.13

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Abstract PDF: BACKGROUND
Hypoxia inducible factor-1alpha(HIF-1alpha) is a transcription factor for various target genes that are involved in adapting cells to hypoxia. It promotes cell proliferation and survival via modulation of such cell cycle regulators such as cyclin A1 and cyclin B1 in response to hypoxia. This is associated with local failure of radiotherapy, which renders a poor prognosis for cervical carcinoma.
METHODS
Using the tissue histologic sections and a tissue microarray of the archived biopsy and surgical specimens of uterine cervical carcinoma from 57 patients who were treated with radiation therapy alone, we performed immunohistochemical staining for HIF-1alpha and cyclin A1 and B1 to evaluate the correlations between the expressions of these proteins in tumors and the clinicopathologic parameters associated with the prognosis.
RESULTS
The large tumor cell nests and invasive front margins of the tumors showed comparatively intense immunoreactivity of HIF-1alpha. There was no significant correlation between the HIF-1alpha, cyclin A1 and cyclin B1 expressions and the clinicopathologic factors.
CONCLUSIONS
The HIF-1alpha expression showed marked intra-tumoral heterogeneity. The HIF-1alpha expression is neither a powerful predictor of resistance to radiotherapy nor is it a poor prognostic marker in cervical carcinoma patients who are treated with radiotherapy. The expressions of cyclin A1 and cyclin B1 are neither independently associated with the response of radiation therapy nor are they associated with the prognostic parameters of uterine cervical carcinoma.

Case Report

Salivary Duct Carcinoma with Mucin Containing Cells: Report of a Case Misdiagnosed as Mucoepidermoid Carcinoma on Fine Needle Aspiration Cytology.: Haeryoung Kim, Hyunki Kim, Hoguen Kim, Jin Kim, Soon Won Hong, Se Hoon Kim; Korean J Cytopathol. 2006;17(1):56-62.

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Abstract PDF: Salivary duct carcinoma (SDC) is a rare primary salivary gland malignancy characterized by histological features similar to those of ductal carcinomas of the breast. It is regarded as a high-grade malignancy associated with frequent local recurrences and early distant metastases that require aggressive treatment. The typical fine needle aspiration cytology (FNAC) findings in SDC include cellular smears showing tumor cells with eccentric pleomorphic nuclei and a granular cytoplasm arranged in flat sheets or cribriform patterns against a necrotic background. However, the presence of mucin-containing cells in SDC has been rarely described. We report the FNAC findings in a patient with histologically confirmed SDC that demonstrated numerous mucin-containing cells and was subsequently misdiagnosed as a high-grade mucoepidermoid carcinoma. Here we discuss the problems involved in distinguishing SDC from high-grade mucoepidermoid carcinoma on the basis of cytologic findings alone.

Original Article

Progressive Suppression of Selenium Binding Protein 1 in Gastric Adenoma and Adenocarcinoma.: Hyunki Kim, Hyun Ju Kang, Jong Pil Park, Ju Yeon Pyo, Hoguen Kim; Korean J Pathol. 2008;42(6):344-350.

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Abstract PDF: BACKGROUND
Human selenium binding protein 1 (SELENBP1) is a protein that binds selenium as a cofactor. The decreased expression of SELENBP1 in several types of carcinomas and its association with a poor prognosis have previously been reported on. In this study, we evaluated the expression of SELENBP1 in low-grade and high-grade epithelial dysplasia/ adenomas and adenocarcinomas. METHODS: We analyzed 45 cases of low-grade epithelial dysplasia/adenomas, 42 cases of high-grade epithelial dysplasia/adenomas and 64 cases of adenocarcinomas and all of them were obtained from endoscopic mucosal resection or endoscopic submucosal dissection. We analyzed all of them for their SELENBP1 expression by immunohistochemistry. Eight triple-paired cases of gastric mucosa, adenoma and adenocarcinoma from the same patient were selected for RT-PCR analysis. RESULTS: There was a progressive decrease in the expression of SELENBP1 from the low-grade dysplasia/adenomas (42/45, 93%) to the high-grade dysplasia/adenomas (29/42, 69%) and finally to the adenocarcinomas (24/64, 37%), (p<0.001). The progressive decrease in the SELENBP1 expression was also evident in the eight paired cases that were analyzed by RT-PCR. CONCLUSIONS: Our findings demonstrate that the SELENBP1 expression is suppressed in gastric epithelial dysplasia/adenomas and adenocarcinomas. The suppression of SELENBP1 was significantly more frequent and severer in the adenocarcinomas than that in the low-grade dysplasia/ adenomas, and this implies that the suppression of SELENBP1 is a late event in gastric carcinogenesis.

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