Esophagogastric junction (EGJ) adenocarcinoma is a relatively common cancer in western countries and its incidence has been low in Asia historically but has been increasing in recent years [[1], [2], [3]]. EGJ adenocarcinoma can occur as a primary malignancy in the distal esophagus or it may be of gastric origin with esophageal invasion [[4], [5], [6]]. Because the biological behavior of EGJ adenocarcinoma differs between cases of esophageal origin and cases of gastric origin in ways that affect treatment planning and prognosis, it is important to distinguish between these two forms of the disease. However, thus far, there are not yet molecular biological or histopathological morphological markers that enable reliable diagnostic differentiation.

The Siewert classification system designates EGJ adenocarcinoma types I, II, and III on the basis of the distance from the tumor epicenter to the EGJ line [7]. In addition to being useful for surgical planning, this typing system is suggestive of whether the tumor originated in the esophagus or the stomach and thus is in broad use. Based on an accumulation of evidence, for the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system published in 2017, the system was simplified such that the previous Siewert type I and II EGJ adenocarcinomas are indicated as esophageal cancer while type III is indicated as gastric cancer; the former three Siewert classifications are no longer used in the new AJCC/UICC classification system [8]. This new classification scheme has not been widely adopted because categorization based on distance alone does not ensure accuracy, especially for cases that would be considered type II in the original scheme. Type II EGJ adenocarcinomas, which are located within 1 cm above and 2 cm below the EGJ line, are often referred to as cardiac adenocarcinomas. There remains a need for more reliable EGJ adenocarcinoma classification methods.

In terms of etiology, esophageal adenocarcinomas develop mainly from Barrett esophagus (BE) lesions caused by gastroesophageal reflux whereas gastric adenocarcinomas develop mainly from Helicobacter pylori (HP)-related atrophic gastritis lesions. Given these distinct etiologies, the characteristics of the background mucosa around these two types of tumor lesions should be distinct from each other [[9], [10], [11], [12], [13]]. The aim of the present study was to explore the possibility that tumor-adjacent background mucosa characteristics evident by pathology and endoscopy may be combined to classify Siewert type II EGJ adenocarcinoma lesions as being of esophageal or gastric origin.