Mesenchymal tumors include stromal cell tumors such as gastrointestinal stromal tumors (GISTs), myogenic tumors (leiomyoma or leiomyosarcoma), and neurogenic tumors (mostly schwannomas in the stomach), lipomas, hemangiomas, lymphangiomas, and granular cell tumors. Mesenchymal tumors sometimes form central ulceration, and biopsies of these areas are often nondiagnostic. Lymphomas and carcinomas mimicking SMT-like tumors sometimes demonstrate slight mucosal changes. Most carcinoma-forming SMT-like tumors are poorly differentiated carcinomas. Congenital diseases include aberrant pancreas and gastric duplication, in which ductal components or cystic lesions are sometimes found in the submucosal area. Aberrant pancreas is most frequently found in the lower third, but may also be located in the body, of the stomach. Gastric submucosal tumors are frequently asymptomatic until they become large. When symptomatic, most patients suffer from hematemesis and/or melena, iron-deficiency anemia, a palpable abdominal mass, and dull abdominal pain. Gastric SMTs form three types of growth: intraluminal, extragastric, and combined. Large tumors tend to form extragastric or combined growth.

The most frequent gastric mesenchymal tumors (70% to 80%) forming submucosal tumors are GISTs; the rest are myogenic tumors (leiomyoma or leiomyosarcoma) and schwannomas. GISTs are preferentially located in the upper and middle stomach, myogenic tumors in the upper third of the stomach around the gastroesophageal junction, and neurogenic tumors along the lesser curvature. GISTs demonstrate the most aggressive behavior compared to the other two mesenchymal tumors. These three stromal tumors in the gastrointestinal tract, however, show very similar macroscopic appearances and they cannot be discriminated from each other by conventional radiographic or endoscopic examinations. They can be differentiated primarily by pathologic examination.