Skip to main content
Top
Published in: BMC Gastroenterology 1/2020

Open Access 01-12-2020 | Metastasis | Research article

Very low risk of lymph node metastasis in Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma

Authors: Yuqing Cheng, Xiaoli Zhou, Kequn Xu, Jin Huang, Qin Huang

Published in: BMC Gastroenterology | Issue 1/2020

Login to get access

Abstract

Background

Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma (EBV-GCLS) is a rare variant of early gastric carcinomas. Clinicopathological features of this variant remain obscure, especially in Chinese patients. Therefore, we collected EBV-GCLS cases and studied clinicopathology and prognosis.

Methods

By a retrospective review of 595 consecutive radical gastrectomies for early gastric carcinoma from 2006 to 2018, we identified 8 (1.3%, 8/595) EBV-GCLS cases. Clinicopathologic characteristics were compared between EBV-GCLSs and 109 conventional early gastric carcinomas, which were divided into intramucosal, SM1, and SM2 subgroups. The latter 2 subgroups were classified according to the submucosal invasion depth below or over 500 μm.

Results

All 8 EBV-GCLSs occurred in male patients and invaded deep submucosa (SM2) without lymph node metastasis (LNM), four (50%) of which had synchronous non-gastric malignant tumors (3 gastric gastrointestinal stromal tumors and 1 primary clear cell renal cell carcinoma), and four (50%) arose in the proximal stomach. Compared to conventional early gastric carcinomas, EBV-GCLS was significantly more frequent with SM2 invasion, poor differentiation, and synchronous non-gastric carcinoma tumor, but not with age, gender, macroscopic type, location, size, perineural invasion, lymphovascular invasion, and pathologic stage. In invasion-depth stratified comparisons in the SM2 subgroup, the frequency of LNM in EBV-GCLS was significantly lower than that in conventional early gastric carcinomas (p < 0.05) and the 5-year survival rate of patients with EBV-GCLS was better than that with conventional early gastric carcinomas in 3 subgroups (100% vs 91.5, 85.7, 83.9%, respectively), although the differences did not reach a statistically significant level due to the small sample size. Significant differences among 4 subgroups were found in tumor grade, lymphovascular invasion, LNM, pathological stage, and synchronous tumor, but not in age, gender, macroscopic type, tumor size, location, perineural invasion.

Conclusions

Even with poor differentiation and SM2 invasion, EBV-GCLS showed very low risk of LNM and may be a candidate for endoscopic therapy such as endoscopic submucosal dissection.
Literature
2.
go back to reference Lauwers GY, Franceschi S, Carneiro F, et al. Gastric carcinoma. In: Bosman FT, Carneiro F, Hruban RH, et al., editors. WHO classification of tumours of the digestive system. 4th ed. France: International Agency for Research on Cancer; 2010. p. 48–54. Lauwers GY, Franceschi S, Carneiro F, et al. Gastric carcinoma. In: Bosman FT, Carneiro F, Hruban RH, et al., editors. WHO classification of tumours of the digestive system. 4th ed. France: International Agency for Research on Cancer; 2010. p. 48–54.
3.
go back to reference Kim MY, Cho JH, Cho JY. Ever-changing endoscopic treatment for early gastric cancer: yesterday-today-tomorrow. World J Gastroenterol. 2014;20:13273–83.CrossRef Kim MY, Cho JH, Cho JY. Ever-changing endoscopic treatment for early gastric cancer: yesterday-today-tomorrow. World J Gastroenterol. 2014;20:13273–83.CrossRef
4.
go back to reference Herath CH, Chetty R. Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma. Arch Pathol Lab Med. 2008;132:706–9.PubMed Herath CH, Chetty R. Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma. Arch Pathol Lab Med. 2008;132:706–9.PubMed
5.
go back to reference Min BH, Tae CH, Ahn SM, Kang SY, Woo SY, Kim S, et al. Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma. Gastric Cancer. 2016;19:852–9.CrossRef Min BH, Tae CH, Ahn SM, Kang SY, Woo SY, Kim S, et al. Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma. Gastric Cancer. 2016;19:852–9.CrossRef
6.
go back to reference Lim H, Lee IS, Lee JH, Park YS, Kang HJ, Na HK, et al. Clinical application of early gastric carcinoma with lymphoid stroma based on lymph node metastasis status. Gastric Cancer. 2017;20:793–801.CrossRef Lim H, Lee IS, Lee JH, Park YS, Kang HJ, Na HK, et al. Clinical application of early gastric carcinoma with lymphoid stroma based on lymph node metastasis status. Gastric Cancer. 2017;20:793–801.CrossRef
7.
go back to reference Park S, Choi MG, Kim KM, Kim HS, Jung SH, Lee JH, et al. Lymphoepithelioma-like carcinoma: a distinct type of gastric cancer. J Surg Res. 2015;194:458–63.CrossRef Park S, Choi MG, Kim KM, Kim HS, Jung SH, Lee JH, et al. Lymphoepithelioma-like carcinoma: a distinct type of gastric cancer. J Surg Res. 2015;194:458–63.CrossRef
8.
go back to reference Chirieac LR, Chang Y-L, Yatabe Y. Lymphoepithelioma-like carcinoma. In: Travis WD, Brambilla E, Burke AP, et al., editors. WHO classification of tumours of the lung, pleura, thymus and heart. 4th ed. France: International Agency for Research on Cancer; 2015. p. 95–6. Chirieac LR, Chang Y-L, Yatabe Y. Lymphoepithelioma-like carcinoma. In: Travis WD, Brambilla E, Burke AP, et al., editors. WHO classification of tumours of the lung, pleura, thymus and heart. 4th ed. France: International Agency for Research on Cancer; 2015. p. 95–6.
9.
go back to reference Wu MS, Shun CT, Wu CC, Hsu TY, Lin MT, Chang MC, et al. Epstein-Barr virus-associated gastric carcinomas: relation to H. pylori infection and genetic alterations. Gastroenterology. 2000;118:1031–8.CrossRef Wu MS, Shun CT, Wu CC, Hsu TY, Lin MT, Chang MC, et al. Epstein-Barr virus-associated gastric carcinomas: relation to H. pylori infection and genetic alterations. Gastroenterology. 2000;118:1031–8.CrossRef
10.
go back to reference Cheng N, Hui DY, Liu Y, Zhang NN, Jiang Y, Han J, et al. Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms. Gastric Cancer. 2015;18:246–55.CrossRef Cheng N, Hui DY, Liu Y, Zhang NN, Jiang Y, Han J, et al. Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms. Gastric Cancer. 2015;18:246–55.CrossRef
11.
go back to reference Cheng Y, Du M, Wang Y, Liu T, Zhou X, Chen L, et al. Micropapillary early gastric carcinoma with distinct clinicopathological features, high risk for lymph node metastasis, and dismal prognosis: a multicenter clinicopathological study of 29 cases identified in 1890 early gastric carcinoma radical gastrectomies. Hum Pathol. 2019;83:149–58.CrossRef Cheng Y, Du M, Wang Y, Liu T, Zhou X, Chen L, et al. Micropapillary early gastric carcinoma with distinct clinicopathological features, high risk for lymph node metastasis, and dismal prognosis: a multicenter clinicopathological study of 29 cases identified in 1890 early gastric carcinoma radical gastrectomies. Hum Pathol. 2019;83:149–58.CrossRef
12.
go back to reference Participants in the Paris Work. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003;58:S3–43. Participants in the Paris Work. The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest Endosc. 2003;58:S3–43.
13.
go back to reference Ajani JA, In H, Sano T, et al. Stomach. In: Amin MB, Edge SB, Greene FL, et al., editors. AJCC cancer staging manual. 8th ed. New York: Springer; 2017. p. 211–2. Ajani JA, In H, Sano T, et al. Stomach. In: Amin MB, Edge SB, Greene FL, et al., editors. AJCC cancer staging manual. 8th ed. New York: Springer; 2017. p. 211–2.
14.
go back to reference Ramos M, Pereira MA, Dias AR, Faraj SF, Zilberstein B, Cecconello I, et al. Lymphoepithelioma-like gastric carcinoma: clinicopathological characteristics and infection status. J Surg Res. 2017;210:159–68.CrossRef Ramos M, Pereira MA, Dias AR, Faraj SF, Zilberstein B, Cecconello I, et al. Lymphoepithelioma-like gastric carcinoma: clinicopathological characteristics and infection status. J Surg Res. 2017;210:159–68.CrossRef
15.
go back to reference Hissong E, Ramrattan G, Zhang P, Zhou XK, Young G, Klimstra DS, et al. Gastric carcinomas with lymphoid stroma: an evaluation of the histopathologic and molecular features. Am J Surg Pathol. 2018;42:453–62.CrossRef Hissong E, Ramrattan G, Zhang P, Zhou XK, Young G, Klimstra DS, et al. Gastric carcinomas with lymphoid stroma: an evaluation of the histopathologic and molecular features. Am J Surg Pathol. 2018;42:453–62.CrossRef
16.
go back to reference Du M, Chen L, Cheng Y, Wang Y, Fan X, Zhang Y, et al. Tumor budding and other risk factors of lymph node metastasis in submucosal early gastric carcinoma: a multicenter clinicopathologic study in 621 radical gastrectomies of Chinese patients. Am J Surg Pathol. 2019;43:1074–82.CrossRef Du M, Chen L, Cheng Y, Wang Y, Fan X, Zhang Y, et al. Tumor budding and other risk factors of lymph node metastasis in submucosal early gastric carcinoma: a multicenter clinicopathologic study in 621 radical gastrectomies of Chinese patients. Am J Surg Pathol. 2019;43:1074–82.CrossRef
17.
go back to reference Watanabe H, Enjoji M, Imai T. Gastric carcinoma with lymphoid stroma. Its morphologic characteristics and prognostic correlations. Cancer. 1976;38:232–43.CrossRef Watanabe H, Enjoji M, Imai T. Gastric carcinoma with lymphoid stroma. Its morphologic characteristics and prognostic correlations. Cancer. 1976;38:232–43.CrossRef
18.
go back to reference Song HJ, Srivastava A, Lee J, Kim YS, Kim KM, Ki Kang W, et al. Host inflammatory response predicts survival of patients with Epstein-Barr virus-associated gastric carcinoma. Gastroenterology. 2010;139:84–92.e2.CrossRef Song HJ, Srivastava A, Lee J, Kim YS, Kim KM, Ki Kang W, et al. Host inflammatory response predicts survival of patients with Epstein-Barr virus-associated gastric carcinoma. Gastroenterology. 2010;139:84–92.e2.CrossRef
19.
go back to reference Osumi H, Kawachi H, Yoshio T, Ida S, Yamamoto N, Horiuchi Y, et al. Epstein-Barr virus status is a promising biomarker for endoscopic resection in early gastric cancer: proposal of a novel therapeutic strategy. J Gastroenterol. 2019;54:774–83.CrossRef Osumi H, Kawachi H, Yoshio T, Ida S, Yamamoto N, Horiuchi Y, et al. Epstein-Barr virus status is a promising biomarker for endoscopic resection in early gastric cancer: proposal of a novel therapeutic strategy. J Gastroenterol. 2019;54:774–83.CrossRef
20.
go back to reference Murphy G, Pfeiffer R, Camargo MC, Rabkin CS. Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology. 2009;137:824–33.CrossRef Murphy G, Pfeiffer R, Camargo MC, Rabkin CS. Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology. 2009;137:824–33.CrossRef
21.
go back to reference Ribeiro J, Oliveira A, Malta M, Oliveira C, Silva F, Galaghar A, et al. Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal. World J Gastroenterol. 2017;23:7292–302.CrossRef Ribeiro J, Oliveira A, Malta M, Oliveira C, Silva F, Galaghar A, et al. Clinical and pathological characterization of Epstein-Barr virus-associated gastric carcinomas in Portugal. World J Gastroenterol. 2017;23:7292–302.CrossRef
22.
go back to reference van Beek J, zur Hausen A, Klein Kranenbarg E, van de Velde CJ, Middeldorp JM, van den Brule AJ, et al. EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement. J Clin Oncol. 2004;22:664–70.CrossRef van Beek J, zur Hausen A, Klein Kranenbarg E, van de Velde CJ, Middeldorp JM, van den Brule AJ, et al. EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a low frequency of lymph node involvement. J Clin Oncol. 2004;22:664–70.CrossRef
23.
go back to reference Kim YB, Hur H, Lee D. Frequent EBV positivity in conventional adenocarcinomas occurring simultaneously with EBV-associated gastric cancers. Pathology. 2016;48:616–8.CrossRef Kim YB, Hur H, Lee D. Frequent EBV positivity in conventional adenocarcinomas occurring simultaneously with EBV-associated gastric cancers. Pathology. 2016;48:616–8.CrossRef
24.
go back to reference Matsunou H, Konishi F, Hori H, Ikeda T, Sasaki K, Hirose Y, et al. Characteristics of Epstein-Barr virus-associated gastric carcinoma with lymphoid stroma in Japan. Cancer. 1996;77:1998–2004.CrossRef Matsunou H, Konishi F, Hori H, Ikeda T, Sasaki K, Hirose Y, et al. Characteristics of Epstein-Barr virus-associated gastric carcinoma with lymphoid stroma in Japan. Cancer. 1996;77:1998–2004.CrossRef
25.
go back to reference Namikawa T, Fujisawa K, Munekage E, Munekage M, Oki Y, Maeda H, et al. Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma, accompanied with lymph node metastasis. Mol Clin Oncol. 2018;8:561–6. Namikawa T, Fujisawa K, Munekage E, Munekage M, Oki Y, Maeda H, et al. Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma, accompanied with lymph node metastasis. Mol Clin Oncol. 2018;8:561–6.
26.
go back to reference Lee JY, Kim KM, Min BH, Lee JH, Rhee PL, Kim JJ. Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: case series. World J Gastroenterol. 2014;20:1365–70.CrossRef Lee JY, Kim KM, Min BH, Lee JH, Rhee PL, Kim JJ. Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: case series. World J Gastroenterol. 2014;20:1365–70.CrossRef
27.
go back to reference Tamura T, Hamada T, Sako T, Makihara K, Yamada K, Kashima K, et al. Lymphoepithelioma-like carcinoma of the stomach with epithelioid granulomas. Case Rep Gastroenterol. 2010;4:361–8.CrossRef Tamura T, Hamada T, Sako T, Makihara K, Yamada K, Kashima K, et al. Lymphoepithelioma-like carcinoma of the stomach with epithelioid granulomas. Case Rep Gastroenterol. 2010;4:361–8.CrossRef
28.
go back to reference Ji-Hoon K, Dae-Woon E. A case of multifocal EBV associated gastric carcinoma with focal squamous differentiation. Indian J Pathol Microbiol. 2019;62:505–7.CrossRef Ji-Hoon K, Dae-Woon E. A case of multifocal EBV associated gastric carcinoma with focal squamous differentiation. Indian J Pathol Microbiol. 2019;62:505–7.CrossRef
29.
go back to reference Fukayama M, Ushiku T. Epstein-Barr virus-associated gastric carcinoma. Pathol Res Pract. 2011;207:529–37.CrossRef Fukayama M, Ushiku T. Epstein-Barr virus-associated gastric carcinoma. Pathol Res Pract. 2011;207:529–37.CrossRef
30.
go back to reference Shinozaki-Ushiku A, Kunita A, Fukayama M. Update on Epstein-Barr virus and gastric cancer (review). Int J Oncol. 2015;46:1421–34.CrossRef Shinozaki-Ushiku A, Kunita A, Fukayama M. Update on Epstein-Barr virus and gastric cancer (review). Int J Oncol. 2015;46:1421–34.CrossRef
31.
go back to reference Huang Q, Fang C, Shi J, Sun Q, Wu H, Gold JS, et al. Differences in clinicopathology of early gastric carcinoma between proximal and distal location in 438 Chinese patients. Sci Rep. 2015;5:13439.CrossRef Huang Q, Fang C, Shi J, Sun Q, Wu H, Gold JS, et al. Differences in clinicopathology of early gastric carcinoma between proximal and distal location in 438 Chinese patients. Sci Rep. 2015;5:13439.CrossRef
32.
go back to reference Ono H, Yao K, Fujishiro M, Oda I, Nimura S, Yahagi N, et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Dig Endosc. 2016;28:3–15.CrossRef Ono H, Yao K, Fujishiro M, Oda I, Nimura S, Yahagi N, et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Dig Endosc. 2016;28:3–15.CrossRef
33.
go back to reference Huang Q, Cheng Y, Chen L, Mingzhan D, Wang Y, Xu G, et al. Low risk of lymph node metastasis in 495 early gastric cardiac carcinomas: a multicenter clinicopathologic study of 2101 radical gastrectomies for early gastric carcinoma. Mod Pathol. 2018;31:1599–607.CrossRef Huang Q, Cheng Y, Chen L, Mingzhan D, Wang Y, Xu G, et al. Low risk of lymph node metastasis in 495 early gastric cardiac carcinomas: a multicenter clinicopathologic study of 2101 radical gastrectomies for early gastric carcinoma. Mod Pathol. 2018;31:1599–607.CrossRef
34.
go back to reference Shi Y, Xu X, Zhao Y, Qian F, Tang B, Hao Y, et al. Short-term surgical outcomes of a randomized controlled trial comparing laparoscopic versus open gastrectomy with D2 lymph node dissection for advanced gastric cancer. Surg Endosc. 2018;32:2427–33.CrossRef Shi Y, Xu X, Zhao Y, Qian F, Tang B, Hao Y, et al. Short-term surgical outcomes of a randomized controlled trial comparing laparoscopic versus open gastrectomy with D2 lymph node dissection for advanced gastric cancer. Surg Endosc. 2018;32:2427–33.CrossRef
35.
go back to reference Gholami S, Janson L, Worhunsky DJ, Tran TB, Squires MH 3rd, Jin LX, et al. Number of lymph nodes removed and survival after gastric cancer resection: an analysis from the US Gastric cancer Collaborative. J Am Coll Surg. 2015;221:291–9.CrossRef Gholami S, Janson L, Worhunsky DJ, Tran TB, Squires MH 3rd, Jin LX, et al. Number of lymph nodes removed and survival after gastric cancer resection: an analysis from the US Gastric cancer Collaborative. J Am Coll Surg. 2015;221:291–9.CrossRef
36.
go back to reference Kang BW, Seo AN, Yoon S, Bae HI, Jeon SW, Kwon OK, et al. Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer. Ann Oncol. 2016;27:494–501.CrossRef Kang BW, Seo AN, Yoon S, Bae HI, Jeon SW, Kwon OK, et al. Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer. Ann Oncol. 2016;27:494–501.CrossRef
Metadata
Title
Very low risk of lymph node metastasis in Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma
Authors
Yuqing Cheng
Xiaoli Zhou
Kequn Xu
Jin Huang
Qin Huang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2020
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-020-01422-9

Other articles of this Issue 1/2020

BMC Gastroenterology 1/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.