Background/Objectives: Superficial esophageal cancer is diagnosed by evaluating the vascular architecture, including dilation, tortuosity, caliber change, and shape, of a lesion. However, this diagnosis is subjective and requires extensive experience. Endoscopically distinguishing squamous intraepithelial neoplasia (SIN) from esophageal cancer is difficult. Thus far, only a few studies have described the endoscopic findings of SIN. Therefore, the present study aimed to investigate whether endoscopic observation of the vascular architecture of tumors is useful in differentiating SIN from superficial esophageal cancer (SCC). Methods: This study included 141 patients who were histopathologically diagnosed with SIN or SCC between 2007 and 2023. Based on endoscopic images, patients were divided into those with a regular vascular arrangement (regular group) and those with an irregular vascular arrangement (irregular group). After evaluating the clinical characteristics, propensity score matching was used to assess the association between the groups and their pathological diagnoses. Results: Of the 141 patients, 44 and 97 were in the regular and irregular groups, respectively, with a ratio of 1:2. After propensity score matching, 33 and 66 patients were included in the regular and irregular groups, respectively. There were no significant differences between the groups after matching for age, alcohol consumption, smoking status, lesion site, sex, or lesion size. The regular group had significantly more patients with SIN, whereas the irregular group had significantly more patients with esophageal cancer (p < 0.001). Conclusions: The regularity of the vascular architecture may be useful for endoscopically distinguishing between SIN and esophageal cancer.
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