Clinicopathology of Early Gastric Carcinoma: An Update for Pathologists and Gastroenterologists

The WHO defines early gastric carcinoma (EGC) as invasive carcinoma up to the submucosal layer, regardless of nodal metastasis. The recent study results indicate that EGC varies in location, histology, nodal metastasis, and prognosis.

The heterogeneity in EGC may be related to various types of epithelial stem cells. The most important stem cells include Lgr5⁺ cells at the base of a gastric unit in the antrum-pylorus-cardia, Mist1⁺ cells at the isthmus/Troy⁺ cells at the base in the corpus-fundus, and Sox2⁺ cells at the base in almost all regions. Dysregulation of these cells along with environmental factors transform stem cells in different regions into malignancy in genetically susceptible populations.

The 2 most vulnerable regions for EGC have been found along the lesser curvature: the cardia in elderly patients and antrum-angularis in mid-aged and elderly patients. Most hereditary early-onset gastric carcinomas are concentrated in the corpus-fundus of young women. By histology, the most common EGC type is tubular adenocarcinoma in many growth patterns, starting in the neck of a gastric unit. Worse prognosis has been found in early papillary, compared to tubular, adenocarcinoma, related to deeper penetration, more lymphovascular invasion, and more liver and nodal metastases. Contrary to the common belief, intramucosal signet ring cell carcinoma demonstrates low risk of nodal metastasis, comparable to early intestinal-type EGC.

The overall risk for nodal metastasis in EGC is low but significant. It is urgent to organize multicenter studies on risk of nodal metastasis in EGC in order to establish more reliable clinical practice guidelines to treat EGC patients.