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

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.

Treatment of gastric carcinoma with lymphoid stroma by immunotherapy: A case report

“…Programmed cell death (PD)-1/PD-L1 immunotherapy has been widely approved for treatment of lung cancer, liver cancer and other malignant tumors[ 12 ] but there are few reports on GCLS. PD-1/PD-L1 are known to be highly expressed in GCLS, often at higher rates than in gastric adenocarcinoma[ 13 ]. The TCGA study identified some characteristics to suggest that EBV tumors are potential candidates for immunotherapy with PD-1/PD-L1 pathway inhibitors.…”

Collision of Epstein–Barr virus-positive and -negative gastric cancer, diagnosed by molecular analysis: a case report

“…The frequency of nodal metastasis is lower in EBV-positive GCs than in EBV-negative GCs [ 1 , 17 , 18 ]; however, for deeply invasive GCs, the frequency of lymph node metastasis is fairly high, even in EBV-positive GCs [ 17 ]. In the present case, the EBV-positive component invaded up to the serosa, while the EBV-negative component invaded up to the subserosa; only the EBV-positive component involved the lymph nodes.…”

Immune Microenvironment and Immunotherapeutic Management in Virus-Associated Digestive System Tumors

“…EBVaGC is regularly removed by surgical resection since it is an undifferentiated-type cancer. Early EBVaGC has a low risk of lymph node metastasis [ 123 ]. A study presented that EBV-associated GC has a significantly low incidence of lymph node metastasis and a better prognosis compared with EBV-negative GC.…”