Journal of Pathology and Translational Medicine

Review

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; 24(4): 562. 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
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
Journal of Pathology and Translational Medicine.2024; 58(3): 103. CrossRef
Expression of claudin 18.2 in poorly cohesive carcinoma and its association with clinicopathologic parameters in East Asian patients
Moonsik Kim, Byung Woog Kang, Jihyun Park, Jin Ho Baek, Jong Gwang Kim
Pathology - Research and Practice.2024; 263: 155628. 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

Case Study

Heterotopic mesenteric ossification: a report of two cases: Hisham F. Bahmad, Olga Lopez, Tyson Sutherland, Marisa Vinas, Kfir Ben-David, Lydia Howard, Robert Poppiti, Sarah Alghamdi; J Pathol Transl Med. 2022;56(5):294-300. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.07.23

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Abstract PDF

Heterotopic mesenteric ossification (HMO) is abnormal bone formation in tissues which usually do not undergo ossification. There are approximately 75 cases reported worldwide. We present two cases of HMO. The first case is that of a 39-year-old man who presented with abdominal pain and a computerized tomography scan of the abdomen and pelvis revealed an apple core lesion resulting in small bowel obstruction. The second case is that of a 36-year-old woman who presented 2 months after undergoing robotic gastric sleeve resection complaining of weakness and emesis. An esophagogram revealed kinking at the distal esophagus. Surgical resection was performed in both, yielding the diagnosis of HMO. There are various theories as to the pathophysiology of HMO, but no clearly defined mechanism has been established. Management should be conservative whenever possible to prevent further ossification with subsequent surgical intervention.

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Fatal Moans and Bones in Crohn's
Joyce Opara, Heather Jarrell, Nicole R. Jackson
American Journal of Forensic Medicine & Pathology.2024;[Epub] CrossRef
Heterotopic mesenteric ossification caused by trauma: A case report
Bi-Fang Zhang, Jiang Liu, Shuai Zhang, Ling Chen, Jia-Zheng Lu, Ming-Qing Zhang
World Journal of Gastrointestinal Endoscopy.2024; 16(8): 494. CrossRef

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
Gastric-type extremely well-differentiated adenocarcinoma of the stomach: A rare tumor with diagnostic difficulties and high inter-observer variation in endoscopic pinch biopsies
Soomin Ahn, Sujin Park, Hyun Hee Koh, Han Gyeol Kim, Hyunjin Kim, Jae Yeong Son, Boram Lee, Hyunwoo Lee, Soohyun Hwang, Junhun Cho, Yun Kyung Lee, Ryoji Kushima, Amitabh Srivastava, Kyoung-Mee Kim
Pathology - Research and Practice.2024; 263: 155599. CrossRef

Deep learning for computer-assisted diagnosis of hereditary diffuse gastric cancer: Sean A. Rasmussen, Thomas Arnason, Weei-Yuarn Huang; J Pathol Transl Med. 2021;55(2):118-124. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.22

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Abstract PDF

Background
Patients with hereditary diffuse gastric cancer often undergo prophylactic gastrectomy to minimize cancer risk. Because intramucosal poorly cohesive carcinomas in this setting are typically not grossly visible, many pathologists assess the entire gastrectomy specimen microscopically. With 150 or more slides per case, this is a major time burden for pathologists. This study utilizes deep learning methods to analyze digitized slides and detect regions of carcinoma.
Methods
Prophylactic gastrectomy specimens from seven patients with germline CDH1 mutations were analyzed (five for training/validation and two for testing, with a total of 133 tumor foci). All hematoxylin and eosin slides containing cancer foci were digitally scanned, and patches of size 256×256 pixels were randomly extracted from regions of cancer as well as from regions of normal background tissue, resulting in 15,851 images for training/validation and 970 images for testing. A model with DenseNet-169 architecture was trained for 150 epochs, then evaluated on images from the test set. External validation was conducted on 814 images scanned at an outside institution.
Results
On individual patches, the trained model achieved a receiver operating characteristic (ROC) area under the curve (AUC) of 0.9986. This enabled it to maintain a sensitivity of 90% with a false-positive rate of less than 0.1%. On the external validation dataset, the model achieved a similar ROC AUC of 0.9984. On whole slide images, the network detected 100% of tumor foci and correctly eliminated an average of 99.9% of the non-cancer slide area from consideration.
Conclusions
Overall, our model shows encouraging progress towards computer-assisted diagnosis of hereditary diffuse gastric cancer.

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Non-endoscopic Applications of Machine Learning in Gastric Cancer: A Systematic Review
Marianne Linley L. Sy-Janairo, Jose Isagani B. Janairo
Journal of Gastrointestinal Cancer.2024; 55(1): 47. CrossRef
Artificial intelligence applicated in gastric cancer: A bibliometric and visual analysis via CiteSpace
Guoyang Zhang, Jingjing Song, Zongfeng Feng, Wentao Zhao, Pan Huang, Li Liu, Yang Zhang, Xufeng Su, Yukang Wu, Yi Cao, Zhengrong Li, Zhigang Jie
Frontiers in Oncology.2023;[Epub] CrossRef
Deep learning of endoscopic features for the assessment of neoadjuvant therapy response in locally advanced rectal cancer
Anqi Wang, Jieli Zhou, Gang Wang, Beibei Zhang, Hongyi Xin, Haiyang Zhou
Asian Journal of Surgery.2023; 46(9): 3568. CrossRef
Preparing Data for Artificial Intelligence in Pathology with Clinical-Grade Performance
Yuanqing Yang, Kai Sun, Yanhua Gao, Kuansong Wang, Gang Yu
Diagnostics.2023; 13(19): 3115. CrossRef
Using Deep Learning to Predict Final HER2 Status in Invasive Breast Cancers That are Equivocal (2+) by Immunohistochemistry
Sean A. Rasmussen, Valerie J. Taylor, Alexi P. Surette, Penny J. Barnes, Gillian C. Bethune
Applied Immunohistochemistry & Molecular Morphology.2022; 30(10): 668. CrossRef

Case Studies

Gastric crystal-storing histiocytosis with concomitant mucosa-associated lymphoid tissue lymphoma: Mee Joo, Nam-Hoon Kim; J Pathol Transl Med. 2020;54(4):332-335. Published online May 22, 2020; DOI: https://doi.org/10.4132/jptm.2020.04.20

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Abstract PDF

Crystal-storing histiocytosis (CSH) is a rare entity that is characterized by intrahistiocytic accumulation of crystallized immunoglobulins. CSH is not a malignant process per se, but the majority of CSH cases are associated with underlying lymphoproliferative disorder. Although CSH can occur in a variety of organs, gastric CSH is very rare. We present a localized gastric CSH with concomitant mucosaassociated lymphoid tissue (MALT) lymphoma, manifesting as an ulcer bleeding in a 56-year-old man. Histologically, the biopsied gastric mucosa demonstrated expansion of the lamina propria by prominent collections of large eosinophilic mononuclear cells containing fibrillary crystalloid inclusions. Immunohistochemical studies revealed that the crystal-storing cells were histiocytes harboring kappa light chain-restricted immunoglobulin crystals. Within the lesion, atypical centrocyte-like cells forming lymphoepithelial lesions were seen, consistent with MALT lymphoma. Since this entity is rare and unfamiliar, difficulties in diagnosis may arise. Particularly, in this case, the lymphomatous area was obscured by florid CSH, making the diagnosis more challenging.

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Crystal-storing histiocytosis in the stomach: A case report and review of the literature
Linghong Kong, Liyan Xue, Yanfeng Zhong, Shenglan Wang, Danfeng Zheng, Lining Wang, Yang Jiao, Xinpeng Zhang, Huizhong Xue, Xiaogang Liu
Frontiers in Oncology.2022;[Epub] CrossRef
Lambda-Restricted Crystal-Storing Histiocytosis of Stomach: A Case Report and Review of Literature
Nalini Bansal, Pankaj Puri, Nishant Nagpal, Rahul Naithani, Rahul Gupta
Cureus.2021;[Epub] CrossRef
Immunoglobulin-Storing Histiocytosis: A Case Based Systemic Review
Hanne Wiese-Hansen, Friedemann Leh, Anette Lodvir Hemsing, Håkon Reikvam
Journal of Clinical Medicine.2021; 10(9): 1834. CrossRef

Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor: Banumathi Ramakrishna, Rohan Yewale, Kavita Vijayakumar, Patta Radhakrishna, Balakrishnan Siddartha Ramakrishna; J Pathol Transl Med. 2020;54(3):258-262. Published online March 4, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.10

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Abstract PDF

IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.

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Maryam K. Pezhouh, Dora Lam-Himlin, Atif Zaheer, Lysandra Voltaggio
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Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung
Endocrinology and Metabolism.2024; 39(3): 468. CrossRef
Isolated IgG4-related disease of terminal ileum: Report of a rare case and review of literature
Subham Bhowmik, Hemanga K. Bhattacharjee, Joyner Abraham, Raju Sharma, Prasenjit Das
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Suvendu Maji, Jayesh kumar Jha, Vikram Chaturvedi
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Bei Ji, Lili Qiao, Wei Zhai
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IgG4-related diseases of the digestive tract
J.-Matthias Löhr, Miroslav Vujasinovic, Jonas Rosendahl, John H. Stone, Ulrich Beuers
Nature Reviews Gastroenterology & Hepatology.2022; 19(3): 185. CrossRef
Clinicopathological characteristics of gastric IgG4‐related disease: Systematic scoping review
Haruki Sawada, Torrey Czech, Krixie Silangcruz, Landon Kozai, Adham Obeidat, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Yoshito Nishimura
Journal of Gastroenterology and Hepatology.2022; 37(10): 1865. CrossRef
Utility of gastric biopsy in diagnosing IgG4‐related gastrointestinal disease
Kaori Uchino, Kenji Notohara, Takeshi Uehara, Yasuhiro Kuraishi, Junya Itakura, Akihiro Matsukawa
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Review

Tumor immune response and immunotherapy in gastric cancer: Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee; J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.08

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Abstract PDF

Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.

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Survival-associated alternative splicing events interact with the immune microenvironment in stomach adenocarcinoma
Zai-Sheng Ye, Miao Zheng, Qin-Ying Liu, Yi Zeng, Sheng-Hong Wei, Yi Wang, Zhi-Tao Lin, Chen Shu, Qiu-Hong Zheng, Lu-Chuan Chen
World Journal of Gastroenterology.2021; 27(21): 2871. CrossRef
Immunotherapy of gastric cancer: Past, future perspective and challenges
Jun Xie, Liping Fu, Li Jin
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Sumi Yun, Sukmook Lee, Ho-Young Lee, Hyeon Jeong Oh, Yoonjin Kwak, Hye Seung Lee
International Journal of Molecular Sciences.2021; 22(13): 7042. CrossRef
Injectable shear-thinning polylysine hydrogels for localized immunotherapy of gastric cancer through repolarization of tumor-associated macrophages
Yan Yang, Yang Yang, Meili Chen, Jianquan Chen, Jinyan Wang, Yajun Ma, Hanqing Qian
Biomaterials Science.2021; 9(19): 6597. CrossRef
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Sizhe Hu, Xiaokang Zhao, Feng Qian, Cancan Jin, Kaishun Hou, Tao Huang
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Jinji Jin, Jianxin Tu, Jiahuan Ren, Yiqi Cai, Wenjing Chen, Lifang Zhang, Qiyu Zhang, Guanbao Zhu
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Wen-jun Zhang, Ce-gui Hu, Zheng-ming Zhu, Hong-liang Luo
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Case Study

Multiple Neuroendocrine Tumors in Stomach and Duodenum in a Multiple Endocrine Neoplasia Type 1 Patient: Bohyun Kim, Han-Kwang Yang, Woo Ho Kim; J Pathol Transl Med. 2018;52(2):126-129. Published online December 21, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.16

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Abstract PDF

A 67-year-old woman with a history of subtotal parathyroidectomy, distal pancreatectomy, and total splenectomy 23 years prior underwent surgical gastric resection for neuroendocrine tumors of the stomach and duodenum. Meticulous examination of the entire stomach and duodenum revealed multiple scattered, minute neuroendocrine tumors. To the best of our knowledge, this is the first case report of a patient diagnosed with gastroduodenal neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN 1) in whom complete histologic mapping of the whole gastrectomy specimen was performed. The presence of MEN 1–associated neuroendocrine tumors in the stomach is very rare, but should be considered in patients diagnosed with MEN 1 who present with a new tumor in the stomach.

Citations

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A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid
Suk Ki Park, Moon Won Lee, In Sub Han, Young Joo Park, Sung Yong Han, Joon Woo Park, Bong Eun Lee, Gwang Ha Kim, Sang Soo Kim
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2019; 19(1): 65. CrossRef

Original Articles

Extramural Perineural Invasion in pT3 and pT4 Gastric Carcinomas: Alejandro España-Ferrufino, Leonardo S. Lino-Silva, Rosa A. Salcedo-Hernández; J Pathol Transl Med. 2018;52(2):79-84. Published online November 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.01

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Abstract PDF

Background
Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated. Most studies have focused on evaluating the mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis in gastric cancer. We evaluated the prognostic value of ePNI compared with mPNI in gastric cancer in this observational comparative cross-sectional study.
Methods
Seventy-three pT3 and pT4 gastric carcinomas with PNI were evaluated. Forty-eight (65.7%) were in the mPNI group and the remaining in the ePNI group.
Results
Clinicopathologic characteristics between the two groups were similar, except for the outcomes. The 5-year disease-specific survival (DSS) rate was 64% for the mPNI group and 50% for the ePNI group (p=.039), a difference that did not remain significant in multivariate analysis. The only independent adverse prognostic factor in multivariate analysis was the presence of lymph node metastasis (hazard ratio, 1.757; 95% confidence interval, 1.082 to 2.854; p=.023).
Conclusions
We demonstrated the prognostic effect of ePNI for DSS in surgically resected pT3–pT4 gastric cancer patients. ePNI could be considered in the staging and prognostic systems of gastric cancer to stratify patients with a high risk of recurrence.

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Neural control of tumor immunity
Burak Kizil, Francesco De Virgiliis, Christoph Scheiermann
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Spectral CT-based nomogram for preoperative prediction of perineural invasion in locally advanced gastric cancer: a prospective study
Jing Li, Shuning Xu, Yi Wang, Mengjie Fang, Fei Ma, Chunmiao Xu, Hailiang Li
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Meng Huang, Gu Gong, Yicheng Deng, Xinmiao Long, Wenyong Long, Qing Liu, Wei Zhao, Rufu Chen
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Cancer-Associated Neurogenesis and Nerve-Cancer Cross-talk
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Perineural Invasion and Postoperative Adjuvant Chemotherapy Efficacy in Patients With Gastric Cancer
Qing Tao, Wen Zhu, Xiaohui Zhao, Mei Li, Yongqian Shu, Deqiang Wang, Xiaoqin Li
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Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis
Bochao Zhao, Wu Lv, Di Mei, Rui Luo, Shiyang Bao, Baojun Huang, Jie Lin
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Consensus-Expressed CXCL8 and MMP9 Identified by Meta-Analyzed Perineural Invasion Gene Signature in Gastric Cancer Microarray Data
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HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient: Dang Anh Thu Phan, Vu Thien Nguyen, Thi Ngoc Ha Hua, Quoc Dat Ngo, Thi Phuong Thao Doan, Sao Trung Nguyen, Anh Tu Thai, Van Thanh Nguyen; J Pathol Transl Med. 2017;51(4):396-402. Published online June 19, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.24

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Abstract PDF

Background
Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab.
Methods
We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated.
Results
In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+.
Conclusions
HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

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Review

Rare Gastric Lesions Associated with Helicobacter pylori Infection: A Histopathological Review: Mee Joo; J Pathol Transl Med. 2017;51(4):341-351. Published online June 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.03

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Abstract PDF

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. However, some rare gastric lesions exhibiting distinctive histological features may also be associated with H. pylori infection, including lymphocytic gastritis, granulomatous gastritis, Russell body gastritis, or crystal-storing histiocytosis. Although diverse factors can contribute to their development, there is convincing evidence that H. pylori infection may play a pathogenic role. These findings are mainly based on studies in patients with these lesions who exhibited clinical and histological improvements after H. pylori eradication therapy. Thus, H. pylori eradication therapy might be indicated in patients with no other underlying disease, particularly in countries with a high prevalence of H. pylori infection. This review describes the characteristic histological features of these rare lesions and evaluates the evidence regarding a causative role for H. pylori infection in their pathogenesis.

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Zeeshan Umar, Jia-Wei Tang, Barry J. Marshall, Alfred Chin Yen Tay, Liang Wang
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Mousa Mobarki, Alexandra Papoudou-Bai, Jean Marc Dumollard, Abdulaziz H. Alhazmi, Shaqraa Musawi, Mohammed Ali Madkhali, Khalid Y. Muqri, Michel Péoc’h, Georgia Karpathiou
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Elizaveta Flerova, Susan Inniss, Nneamaka Nwaoduah, Richard P. Denicola, Jialing Huang
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Hyemin Jo, Cheol Min Shin
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Igor Brasil-Costa, Cintya de Oliveira Souza, Leni Célia Reis Monteiro, Maria Elisabete Silva Santos, Edivaldo Herculano Correa De Oliveira, Rommel Mario Rodriguez Burbano
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Linghong Kong, Liyan Xue, Yanfeng Zhong, Shenglan Wang, Danfeng Zheng, Lining Wang, Yang Jiao, Xinpeng Zhang, Huizhong Xue, Xiaogang Liu
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Christina A. Arnold, Wendy L. Frankel, Ling Guo, Chandra Krishnan, Sheryl Pfeil, Melinda Schumacher, Lysandra Voltaggio, Martha M. Yearsley, Wei Chen
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Case Study

Perivascular Epithelioid Cell Tumor in the Stomach: Sun Ah Shin, Jiwoon Choi, Kyung Chul Moon, Woo Ho Kim; J Pathol Transl Med. 2017;51(4):428-432. Published online April 4, 2017; DOI: https://doi.org/10.4132/jptm.2016.09.16

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Abstract PDF

Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST), and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.

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Unusual paediatric sigmoid perivascular epithelioid cell tumour with regional lymph node metastasis treated using gemcitabine and docetaxel: a case report and literature review
Hsiu-Chung Cheng, Chia-Yu Kuo, Ching-Wen Huang, Hsiang-Hung Shih, Chih-Hung Lin, Jaw-Yuan Wang
Journal of International Medical Research.2021;[Epub] CrossRef
Gastric Perivascular Epithelioid Cell Tumor (PEComa)
Jinghong Xu, Yu Yan, Xueping Xiang, Peter Jiang, Xiangrong Hu, Wenjun Yang
American Journal of Clinical Pathology.2019; 152(2): 221. CrossRef
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Review

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives: Yoon Young Choi, Sung Hoon Noh, Jae-Ho Cheong; J Pathol Transl Med. 2016;50(1):1-9. Published online October 26, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.10

12,467 View
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Abstract PDF

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

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Oncotarget.2017; 8(16): 26356. CrossRef

Case Studies

IgG4-Related Disease Presented as a Mural Mass in the Stomach: Chang Gok Woo, Jeong Hwan Yook, Ah Young Kim, Jihun Kim; J Pathol Transl Med. 2016;50(1):67-70. Published online September 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.28

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Abstract PDF

Isolated gastric IgG4-related disease (IgG4-RD) is a very rare tumefactive inflammatory condition, with only a few cases reported to date. A 48-year-old woman was incidentally found to have a subepithelial tumor in the stomach. Given a presumptive diagnosis of gastrointestinal stromal tumor or neuroendocrine tumor, she underwent wedge resection. The lesion was vaguely nodular and mainly involved the submucosa and proper muscle layer. Microscopically, all classical features of type I autoimmune pancreatitis including lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and numerous IgG4-positive plasma cells were seen. She had no evidence of IgG4-RD in other organs. Although very rare, IgG4-RD should be considered one of the differential diagnoses in the setting of gastric wall thickening or subepithelial mass-like lesion. Deep biopsy with awareness of this entity might avoid unnecessary surgical intervention.

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Gastric-Type Extremely Well-Differentiated Adenocarcinoma of the Stomach: A Challenge for Preoperative Diagnosis: Mee Joo, Song Hee Han; J Pathol Transl Med. 2016;50(1):71-74. Published online September 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.14

10,850 View
158 Download
10 Web of Science
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Abstract PDF

Gastric-type extremely well-differentiated adenocarcinoma (EWDA) is a rare type of gastric adenocarcinoma characterized by infiltration of well-formed mucinous glands with little or no nuclear atypia, which resemble foveolar epithelium or pyloric glands. Because of its high degree of differentiation, preoperative biopsy diagnosis of gastric-type EWDA is very difficult. We encountered a case of gastric-type EWDA, manifesting as a Borrmann type 4 lesion, in a 47-year-old man. Despite four repeated biopsies, the preoperative biopsy diagnosis was not conclusive due to the scarcity of diagnostic tumor cells and lack of knowledge regarding the unusual histologic findings of gastric-type EWDA. We herein describe the histologic findings of gastric-type EWDA in detail, with the aim of facilitating a preoperative biopsy diagnosis and understanding of this rare type of gastric adenocarcinoma.

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