Low risk of lymph node metastasis in 495 early gastric cardiac carcinomas: a multicenter clinicopathologic study of 2101 radical gastrectomies for early gastric carcinoma

Abstract

Clinical decision-making on endoscopic vs. surgical resection of early gastric cardiac carcinoma remains challenging because of uncertainty on risk of lymph node metastasis. The aim of this multicenter study was to investigate risk factors of lymph node metastasis in early gastric cardiac carcinoma. Guided with the World Health Organization diagnostic criteria, we studied 2101 radical resections of early gastric carcinoma for risk factors associated with lymph node metastasis, including tumor location, gross pattern, size, histology type, differentiation, invasion depth, lymphovascular, and perineural invasion. We found that the risk of lymph node metastasis was significantly lower in early gastric cardiac carcinomas (6.7%, 33/495), compared with early gastric non-cardiac carcinomas (17.1%, 275/1606) (p < 0.0001). In early gastric cardiac carcinoma, no lymph node metastasis was identified in intramucosal carcinoma (0/193) and uncommon types of carcinomas (0/24), irrespective of the gross pattern, size, histologic type, differentiation, and invasion depth. Ulceration, size > 3 cm, and submucosal invasion were not significant independent risk factors for lymph node metastasis. In 33 early gastric cardiac carcinomas with lymph node metastasis, either lymphovascular invasion or poor differentiation was present in 16 (48.5%) cases and together in six cases. By multivariate analysis, independent risk factors of lymph node metastasis in early gastric cardiac carcinoma included lymphovascular invasion (Odds Ratio (OR): 7.6, 95% Confidence Interval (CI): 2.8-20.2) (p < 0.0001) and poor differentiation (OR: 6.0, 95% CI: 1.4-25.9) (p < 0.05). In conclusion, lymph node metastasis was not identified in early gastric cardiac intramucosal carcinoma and uncommon types of carcinoma. The risk of lymph node metastasis was also significantly lower in tumors with submucosal invasion, especially for cases without lymphovascular invasion or poor differentiation. These results lend support to the role of endoscopic therapy in the treatment of patients with early gastric cardiac carcinoma.

Emerging evidence supports grouping by location of early gastric carcinoma for appropriate clinical management in Chinese patients

“…Histopathologically, EGC located in the fundus‐corpus displays a high fraction (34.2%) of pure and mixed poorly cohesive and signet‐ring cell carcinomas in Chinese patients (Fig. C), which is over 5‐fold higher than that (6.4%) in the cardia . Interestingly, intramucosal poorly cohesive and signet‐ring cell EGCs show a very low prevalence of lymphovascular invasion and lymph node metastasis, which is similar to well‐differentiated intramucosal intestinal EGC .…”

“…Surprisingly, the risk of lymph node metastasis in EGC of the cardia is significantly lower compared with that in EGC of the distal stomach . In a multicenter clinicopathological study of 495 Chinese patients with EGC of the cardia, lymph node metastasis was not detected in 193 intramucosal (M2 [tumor limited to the lamina propria, without involving the muscularis mucosae] and M3 [tumors involving the muscularis mucosae]) carcinomas, 14 mixed mucinous adenocarcinomas with intestinal adenocarcinomas, and 10 rare carcinoma variants .…”

“…C), compared with those in the distal stomach . In contrast, pure and mixed poorly cohesive and signet‐ring cell carcinomas are uncommon and account for about 6% (32/495) . Rare EGC variants, such as early adenosquamous and neuroendocrine carcinomas, and carcinomas with lymphoid stroma, have been found almost all in the cardia .…”

“…It has been well documented in almost all ethnic populations investigated that gastric cardiac mucosa is present at birth and thus it is deemed to be congenital in nature . It is primarily composed of mucous cells, some parietal cells, rare endocrine cells, undifferentiated cells, and importantly, residual embryonic stem cells, which may be responsible for the high heterogeneity of histopathologic patterns of EGC in the cardia . The most recent genomic studies have also revealed the predominance of the instable chromosomal carcinoma molecular subtype and Epstein–Barr virus (EBV) infection‐related carcinomas with lymphoid stroma, but the infrequent presence of instable microsatellite and stable genomic subtypes of gastric carcinoma .…”

“…The gross appearance of EGC in the fundus‐corpus of Chinese patients shows a substantial percentage (26.6%) of cases with the flat erosive (0–IIb/0–IIc) pattern (Figs. A,B), whereas the hereditary CDH1 gene mutation‐associated diffuse gastric carcinoma of primarily Caucasian patients may exhibit flat, pale discoloration, erosion, or a nodular appearance . The flat and slightly depressed (29.3%) growth patterns in EGC of the fundus‐corpus were more commonly observed than EGC from any other location in Chinese patients, based on a recent multicenter study (Table ) …”