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Little is known about clinicopathological characteristics of gastric carcinoma (GC) in young (≤40 years) Chinese patients. We aimed in this study to analyze those features along with family history and prognostic factors after resection. We retrospectively reviewed all 4671 GC resections (surgical and endoscopic) performed at our center from 2004 to 2014 and identified 152 (3.2%) consecutive young patients. Patient demographics, clinical results, family history, and endoscopic-pathological findings were analyzed along with the older (>41 years) GC controls recruited in the same study period. Clinicopathological factors related to postresection outcomes were assessed statistically. The trend of GC resections in young patients was not changed over the study period. Compared to old GCs, the young GC cohort was predominant in women, positive family history, middle gastric location, the diffuse histology type, shorter duration of symptoms, and advanced stage (pIII+pIV, 53.3%). Radical resection was carried out in 90.1% (n = 137) with a better 5-year survival rate (70.3%) than palliative surgery (0%, n = 15). There was no significant difference in clinicopathological characteristics between familial GC (FGC, n = 38) and sporadic GC (SGC, n = 114) groups. Very young patients (≤ 30 years, n = 38) showed lower Helicobacter pylori (Hp) infection and significantly higher perineural invasion rates, compared to older (31-40 years) patients. Hp infection was more commonly seen in the Lauren's intestinal type and early pT stages (T1+T2). Independent prognostic factors for worse outcomes included higher serum CA 72-4, CA 125 levels, positive resection margin, and stage pIII-pIV tumors. The 5-year survival rate was significantly higher in patients with radical resection than those without. GCs in young Chinese patients were prevalent in women with advanced stages but showed no significant differences in clinicopathology between FGC and SGC groups. High serum CA 72-4 and CA 125 levels may help identify patients with worse outcomes. Radical resection improved postresection survival.

Early gastric carcinoma (EGC) in Chinese patients remains poorly understood and endoscopic therapy has not been well established. Here, we compared endoscopic and clinicopathologic features between early proximal gastric carcinoma (PGC, n = 131) and distal gastric carcinoma (DGC, n = 307) in consecutive 438 EGCs diagnosed with the WHO criteria. By endoscopy, PGCs showed protruding and elevated patterns in 61.9%, while depressed and excavated patterns in 33.6%, which were significantly different from those (32.6% and 64.5%) in DGCs. PGCs were significantly smaller (1.9 cm in average, versus 2.2 cm in DGCs), invaded deeper (22.9% into SM2, versus 13% in DGCs), but had fewer (2.9%, versus 16.7% in DGCs) lymph node metastases. Papillary adenocarcinoma was significantly more frequent (32.1%, versus 12.1% in DGCs), as were mucinous and neuroendocrine carcinomas, carcinoma with lymphoid stroma (6.9%, versus 1.6% in DGCs); but poorly cohesive carcinoma was significantly less frequent (5.3%, versus 35.8% in DGCs). The overall 5-year survival rate was 92.9% in EGCs, and PGC patients showed shorter (42.4 months, versus 48.3 in DGCs) survival. Papillary and micropapillary adenocarcinomas and nodal metastasis were independent risk factors for worse survival in EGCs. EGCs in Chinese were heterogeneous with significant differences in endoscopy and clinicopathology between PGC and DGC.

Cardiac glands (CG), along with oxyntocardiac glands, in a normal human constitute cardiac mucosa (CM) that is positioned in the proximal stomach with a length of 10-30 mm, according to traditional teaching. This doctrine has been recently challenged. On the basis of studies on autopsy and biopsy materials in the esophagogastric junction region, some investigators have reported the presence of CG in only 50% of the general US population. They believed that CG were an acquired, metaplastic lesion as a result of gastroesophageal reflux disease. Subsequent recent study results from other research groups showed the presence of CG in the proximal stomach in embryos, fetuses, pediatric, and adult patients in most Europeans and Americans, and almost all Japanese and Chinese patients. These new data showed the following important findings: (i) CG are confirmed to be congenital in the proximal stomach; (ii) the length of CM is much shorter, approximately 5 mm in Caucasians in Europe and North America, and approximately 13 mm in Japanese and probably also in Chinese; (iii) CG are also present in the distal superficial esophagus underneath squamous mucosa in almost all Japanese and Chinese patients, but not so common in Caucasians in Europe, and not clear in Caucasians in North America. The recent data indicate a clear difference in the distribution of CG in the proximal stomach among different ethnic populations, and might explain different disease pathogenesis mechanisms among various ethnic patient groups., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Objectives: We followed The Cancer Genome Atlas (TCGA) grouping criteria and conducted a clinicopathological cohort study in a unique patient population to gain insight into the pathobiology of esophageal adenocarcinoma (EAC) and adenocarcinoma of the gastroesophageal junction (AGEJ). Methods: We studied and statistically compared the clinicopathological and prognostic features of both cancers in 303 consecutive patients treated at the Veterans Affairs Boston Healthcare System over a 20‐year period using uniform criteria and standardized routines. Results: Over 99% of patients were white men with a mean age of 69.1 years and an average body mass index (BMI) of 28.0 kg/m2. No significant differences were detected in age, gender, ethnicity, BMI, and history of tobacco abuse between the two groups. Compared to AGEJ patients, a significantly higher proportion of EAC patients had gastroesophageal reflux disease, long‐segment Barrett's esophagus, common adenocarcinoma type, smaller tumor size, better differentiation, more stages I or II but fewer stages III or IV diseases, scarcer lymph node invasion, fewer distant metastases, and better overall, disease‐free, and relapse‐free survival. The 5‐year overall survival rate was significantly higher in EAC patients than in AGEJ patients (41.3% vs 17.2%, P < 0.001). This improved survival among EAC patients remained significant after censoring all cases detected during endoscopic surveillance, suggesting different pathogenesis mechanisms between EAC and AGEJ. Conclusions: EAC patients showed significantly better outcomes than AGEJ patients. Our results require validation in other patient populations. [ABSTRACT FROM AUTHOR]

The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two‐etiology proposal is appealing: in high‐risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low‐risk regions the sequence from reflux toxin‐induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC. [ABSTRACT FROM AUTHOR]

Purpose: Non-curative resection (NCR) remains problematic in some cases of early gastric carcinomas (EGCs) treated by endoscopic submucosal dissection (ESD). The aim of this study was to identify predictors of NCR, especially of eCura C1 and eCura C2 resections, before ESD and study long-term outcomes of EGC patients with NCR. Patients and Methods: A retrospective review of medical records was conducted over an 8-year period for EGCs undergoing ESD. Clinicopathologic and endoscopic characteristics and patients' survival were analyzed. Risk factors for NCR and eCura C1 and C2 resections were assessed by logistic analyses. Survival of patients was estimated with the Kaplan–Meier method with a Log rank test. Results: A total of 463 patients with 472 lesions were qualified. By univariate and multivariate analyses, the predictors for NCR and eCura C2 resections were tumor size > 20 mm, tumors located in cardia-fundus, uneven surface, margin elevation, and mixed and undifferentiated types, and those for eCura C1 resection were tumors located in cardia-fundus, negative lifting sign, and mixed and undifferentiated types. The 5-year cancer-specific and cancer-free survival rates were 100.0% and 94.2%, and 95.3% and 83.4% in the curative resection (CR) and NCR groups, respectively. The 5-year cancer-specific and cancer-free survival rates were significantly greater in the CR group than that in the NCR group (P < 0.0001). Conclusion: In this cohort, we identified various endoscopic and pathologic features of EGCs to predict NCR, especially eCura C1 and eCura C2 resections before ESD. These clinically valuable factors would be very informative to endoscopists and surgeons who perform ESD to resect EGCs. [ABSTRACT FROM AUTHOR]

Objective: To investigate histopathologic changes of muscularis mucosae (MM) and submucosa in the gastric cardia. Methods: We performed a histopathology study of 50 distal esophagectomies with proximal gastrectomies for esophageal squamous cell carcinoma as the study (non‐cancerous cardiac) group and 60 gastrectomies for early gastric cardiac carcinoma as the cancer group. The gastroesophageal junction was defined as the distal end of squamous epithelium, multilayered epithelium, or deep esophageal glands or ducts. Gastric cardia (n = 110) was defined as the presence of cardiac and cardio‐oxyntic mucosae distal to the gastroesophageal junction. Results: The average thickness of MM and submucosa in the cardia was 1.04 and 1.41 mm, respectively, which was significantly thicker than that in distal stomach (n = 34) (0.22 and 0.99 mm) or distal esophagus (n = 92) (0.60 and 1.15 mm). In the cardia, thickened MM displayed frayed muscle fibers (93.3%) with a significantly higher prevalence of entrapped glands, cysts, and lymphoid follicles than in the distal stomach or distal esophagus. In the submucosa fatty changes, cysts, and abnormal arteries were significantly more common in the cardia than in the distal stomach or distal esophagus. Compared with the study group, the cardia in the cancer group showed significantly thicker MM (average 1.31 vs 0.72 mm) and submucosa (average 1.61 vs 1.16 mm), more frequent frayed MM (93.3% vs 60.0%), prolapse‐like changes (50.0% vs 2.0%), and cysts (26.7% vs 4.0%). Conclusion: MM and submucosa of the cardia were significantly thickened, especially in early gastric cardiac carcinomas. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate risk factors of lymph node metastasis (LNM) in early gastric carcinoma (EGC) in four tertiary medical centers in Jiangsu Province, China. METHODS Among 10 097 consecutive combined gastric cancer radical resections, 1903 EGC were identified and reviewed, 283 excluded and 1620 included in the study. All pathological and some endoscopic reports were reviewed for patients' characteristics, tumor location, gross features, and the number of lymph nodes retrieved and involved. Two pathologists independently investigated the pathological features of tumor type, differentiation, invasion depth, lymphovascular invasion (LVI), and perineural invasion. The data were statistically analyzed to identify risk factors for LNM. RESULTS The average number of lymph nodes retrieved was 17.5 per patient. LNM was diagnosed in 15.5%. By univariate analysis, significant risk factors for LNM included age ≥ 41 years, female sex, size over 1 cm, submucosal invasion, poor differentiation, poorly cohesive carcinoma, micropapillary adenocarcinoma, adenocarcinoma mixed with signet-ring cell carcinoma, LVI, perineural invasion, and distal gastric location. By multivariate analysis, independent risk factors for LNM were size ≥ 3 cm (odds ratio [OR] 1.9), poor differentiation (OR 2.5), adenocarcinoma mixed with signet-ring cell carcinoma (OR 1.7), LVI (OR 5.8) and submucosal invasion (OR 2.9). In contrast, size < 3 cm and ulcer were not significant risk factors. Early cardiac carcinoma (OR 0.4) had significantly lower risk. CONCLUSIONS Independent risk factors for LNM in EGC in Chinese patients included tumor size ≥ 3 cm, poor differentiation, submucosal invasion, adenocarcinoma mixed with signet-ring cell carcinoma and LVI. Early cardiac carcinoma had a significantly lower risk for LNM. [ABSTRACT FROM AUTHOR]

Gastric cardiac carcinoma (GCC) was and is considered as a part of esophageal adenocarcinoma (EAC) and staged with the rules for EAC. This may change. Recent comprehensive integrated genomic investigations on gastric and esophageal carcinomas discovered similar chromosomal instability profiles in these two groups of carcinomas with a gradual increasing gradient from the lowest percentage in the distal gastric antrum to a high level in the proximal gastric cardia, and to the peak of almost 100% in EAC. Therefore, most GCCs and EAC share similar chromosomal instable features of gastric carcinoma and should be grouped as a single disease entity because EAC may be the proximal extension of chromosomal instable GCCs. This breakthrough discovery in genomic characteristics of GCC and EAC would dramatically change the strategy on how patients should be appropriately managed clinically and also greatly help future investigation on detailed molecular pathogenetic mechanisms of GCC, leading to cure this fatal cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate risk factors of lymph node metastasis (LNM) in Chinese early gastric carcinoma (EGC) patients diagnosed using the World Health Organization (WHO) criteria and compare the differences in those factors between proximal (PGC) and distal gastric carcinoma (DGC). Methods Among 3 176 gastric cancer resections we identified 379 (11.9%) consecutive EGC (104 PGC and 275 DGC) with lymphadenectomy performed at the Affiliated Nanjing Drum Tower Hospital of Nanjing University (Nanjing, Jiangsu Province, China) between January 2005 and December 2012. Endoscopic and clinicopathological features related to LNM were analyzed. Results LNM occurred in 49 (12.9%) EGC, including three PGC and 46 DGC. In early DGC, middle age (41-60 years), tumor size ≥3.1 cm, submucosal invasion, poorly cohesive carcinoma, micropapillary adenocarcinoma and lymphovascular invasion were risk factors by univariate analysis. In contrast, no risk factors of LNM were identified in early PGC. By multivariate analysis, female sex (odds ratio [OR] 2.4), DGC (OR 8.1), poorly cohesive carcinoma (OR 8.8) and lymphovascular invasion (OR 38.8) were found to be significant independent risk factors for LNM. The risk of LNM was effectively stratified using a scoring model of mild (score ≤3.5), moderate (score 4.0-8.5) and high (score ≥16) risk groups. Conclusions LNM occurred in 12.9% of EGC diagnosed with the WHO criteria in Chinese patients. Independent risk factors of LNM were identified in early DGC only and included female sex, DGC, poorly cohesive carcinoma and lymphovascular invasion. Early PGC has a much lower risk for LNM than early DGC. [ABSTRACT FROM AUTHOR]

The American Joint Committee on Cancer (AJCC) staging scheme requires staging proximal gastric carcinoma (PGC) as esophageal adenocarcinoma (EAC), which has been shown to be controversial by recent research results. To update the current research findings on PGC, we systematically reviewed and analyzed the scientific evidence on key arguments related to PGC. The data of high-quality research articles showed that PGC arised in the cardiac mucosa in the proximal stomach within 3 cm below the gastroesophageal junction. Its incidence is rising in East Asian countries, but decreasing in the West, and plateaued at a low level in the United States. PGC is a slowly progressive cancer with unknown independent risk factors and the mechanisms of pathogenesis. This carcinoma exhibits a wide histopathological spectrum and heterogeneous post-resection patient survival characteristics, and cannot be adequately staged for prognotic stratification by the current AJCC staging classification. The results on PGC genomics reveal unique genetic profiles, especially in East Asian populations. In conclusion, mounting evidence defies a simple placement of PGC in a single category of EAC for disease classification; further investigations on the mechanisms of PGC pathogenesis are urgently needed. [ABSTRACT FROM AUTHOR]

Purpose: Papillary early gastric carcinoma (EGC) is uncommon but shows worse prognosis in our most recent study in a Chinese population with unknown reasons. The aim of the present study was to further investigate risk factors for worse prognosis in patients with papillary adenocarcinoma, compared to those with tubular adenocarcinoma. Methods: We searched the electronic pathology databank for radical gastrectomy cases over an 8-year period at a single medical center in Nanjing, China, and identified consecutive 240 EGC cases that were classified as either papillary (n=59) or tubular (n=181) EGC tumors in accordance with the World Health Organization (WHO) gastric cancer diagnosis criteria. We investigated and compared clinicopathologic risk factors for prognosis between papillary and tubular EGC groups. All patients were followed up and their 5-year survival rate was compared statistically with the Kaplan-Meier method with a log rank test. Results: Compared to tubular EGCs, papillary EGCs were significantly more common in elderly patients, more frequently occurred in the proximal stomach with protruding/elevated growth patterns, submucosal invasion, and a micropapillary component. Although lymphovascular invasion (16.9%), nodal (13.6%) and distant (11.8%) metastases in papillary EGCs were more frequent than those (8.3%, 7.2%, and 3.7%, respectively) in tubular EGCs, the differences approached but did not reach statistically significant levels. Significant risk factors for nodal metastasis included lymphovascular invasion in both EGC groups, but the ulcerative pattern and submucosal invasion only in tubular EGCs. The 5-year survival rate was significantly worse in papillary (80.5%) than in tubular (96.8%) EGCs. Conclusions: Compared to tubular EGCs, papillary EGCs diagnosed with the WHO criteria in Chinese patients were more frequent in elderly patients, proximal stomach and showed the significantly worse 5-year survival rate with more protruding/elevated growth patterns and the micropapillary component. Further studies in larger samples are urgently needed to validate these findings for precision individualized EGC patient management.

Summary: The aim of this study was to systematically investigate clinicopathologic features of the recently described pancreatic acinar-like adenocarcinoma of the proximal stomach invading the esophagus (n = 43). Patient median age was 66 years (range, 51-90 years). The male-to-female ratio was 7.6. Grossly, pancreatic acinar-like adenocarcinoma tumors were nonencapsulated with the median size of 5.5 cm (range, 2-10.5). Bormann''s types 1 to 4 tumors were in 7%, 9%, 67%, and 16% cases, respectively. Frank necrosis, hemorrhage, and cysts were rare or absent. Lymphovascular (81%), perineural (74%), and lymph node (81%) invasions were more common in the pancreatic acinar-like adenocarcinoma than in the non–pancreatic acinar-like adenocarcinoma (n = 94) groups. Microscopically, pancreatic acinar-like adenocarcinoma tumors showed acinar (78%), micropapillary (12%), microcystic, solid, trabecular, and mixed neuroendocrine or signet ring (33%) patterns of growth. No adenosquamous differentiation was noted in the pancreatic acinar-like adenocarcinoma group. Nuclei were round to oval with thickened nuclear membrane, stippled chromatin, and single prominent nucleoli. Mitotic figures were variable. The cytoplasm was moderate, eosinophilic, finely granular, and diffusely immunoreactive to the α1-chymotrypsin antibody in all cases to various degrees. Tumor stroma was nondesmoplastic, delicate, and fibrovascular. Pancreatic acinar-like adenocarcinoma tumors staged pI, pII, pIII, and pIV were in 2%, 21%, 70%, and 7% of cases, respectively. The median number of follow-up months after surgery was 29. The 2-year survival rate was 67%, lower than that (73%) in the non–pancreatic acinar-like adenocarcinoma group. A worse overall survival trend was found for patients in the pancreatic acinar-like adenocarcinoma than in non–pancreatic acinar-like adenocarcinoma groups, but the difference was not statistically significant. Age older than 75 years and overall pathology stage were independent risk factors. [Copyright &y& Elsevier]

AIM: To investigate the clinicopathologic features which predict surgical overall survival in patients with proximal gastric carcinoma involving the esophagus (PGCE). METHODS: Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009. Each retrieved pathology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were selected as PGCE. Each tumor was re-staged, following the guidelines on esophageal adenocarcinoma, according to the 7th edition of the American Joint Commission on Cancer Staging Manual. All histology slides were studied along with the pathology report for a retrospective analysis of 13 clinicopathologic features, i.e., age, gender, Helicobacter pylori (H. pylori) infection, surgical modality, Siewert type, tumor Bormann's type, size, differentiation, histology type, surgical margin, lymphovascular and perineural invasion, and pathologic stage in relation to survival after surgical resection. Prognostic factors for overall survival were assessed with uni- and multi-variate analyses. RESULTS: Patients' mean age was 65 years (range: 47-90 years). The male: female ratio was 3.3. The 1-, 3- and 5-year overall survival rates were 87%, 61% and 32%, respectively. By univariate analysis, age, male gender, H. pylori, tumor Bormann's type, size, histology type, surgical modality, positive surgical margin, lymphovascular invasion, and pT stage were not predictive for overall survival; in contrast, perineural invasion (P = 0.003), poor differentiation (P = 0.0003), > 15 total lymph nodes retrieved (P = 0.008), positive lymph nodes (P = 0.001), and distant metastasis (P = 0.005) predicted poor post-operative overall survival. Celiac axis nodal metastasis was associated with significantly worse overall survival (P = 0.007). By multivariate analysis, ≥ 16 positive nodes (P = 0.018), lymph node ratio > 0.2 (P = 0.003), and overall pathologic stage (P = 0.002) were independent predictors for poor overall survival after resection. CONCLUSION: Patients with PGCE showed worse overall survival in elderly, high nodal burden and advanced pathologic stage. This cancer may be more accurately staged as gastric, than esophageal, cancer.

Aims: To compare the clinical and pathological features of gastro-oesophageal junction (GEJ) carcinomas in Chinese and American patients. Methods and results: Eighty consecutive patients with a GEJ carcinoma (43 from mainland China, and 37 from the USA) were evaluated for association with Barrett oesophagus (BO), chronic Helicobacter pylori gastritis, intestinal metaplasia, and outcome. GEJ carcinomas were defined as tumours that were located within 20 mm of, and crossed, the GEJ. Overall, GEJ carcinomas from Chinese patients revealed significantly more frequent location in the proximal stomach, higher pathological stage, larger size, younger patient age, and association with chronic H. pylori gastritis. In contrast, GEJ cancers from American patients showed a strong association with distal oesophageal location, BO, and associated intestinal metaplasia and dysplasia. Pathologically, GEJ carcinomas from American patients were predominantly adenocarcinomas, whereas Chinese patients showed a higher proportion of mucinous, adenosquamous, acinar or neuroendocrine tumours. Overall, 3- and 5-year survival rates were statistically similar between both patient groups, but upon multivariate analysis, Chinese patients showed statistically better survival rates for stage III tumours. Conclusions: Most GEJ carcinomas in patients from China represent proximal gastric cancers associated with chronic H. pylori gastritis, and BO-associated carcinomas are rare among this patient population.

Background: The genetics of advanced biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined. Methods: To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases. Results: Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra-hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma. Conclusions: The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.

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. [ABSTRACT FROM AUTHOR]