Lipomas are benign, slow-growing tumors composed of mature lipocytes. On endoscopy, they usually present as soft, solitary lesions with a yellowish color and they often exhibit a pillow (or cushion) sign when pressed with biopsy forceps [4]. Intensely hyperechoic, homogeneous, well-circumscribed lesions arising from the third layer of the gastric wall are unique EUS features of lipomas. If these features are observed, no further evaluation is needed (Fig. 2A, B) [4].

Heterotopic pancreas is defined as ectopic pancreatic tissue with no anatomic or vascular connection to the pancreas. It is typically located in the gastric antrum and may have central umbilication. Heterotopic pancreas commonly arises from the submucosal layer of the gastric wall, but lesions may involve multiple layers (second, third, and/or fourth layers) with disruption of the layers [8]. Hypoechoic or mixed echogenic lesions with internal structures suggesting ducts or anechoic microcysts are features indicative of heterotopic pancreas (Fig. 3).

Gastric inflammatory fibroid polyps are rare, benign lesions presenting as semipedunculated protrusions with occasional erythematous depression, ulceration, or a white cap on their central surface. They are located in the antrum or prepyloric region [9]. On EUS, inflammatory fibroid polyps are hypoechoic, homogeneous lesions with indistinct margins located in the second or third layer of the gastric wall, without involvement of the muscularis propria (Fig. 4) [10].

Gastric varices appear as hypoechoic or anechoic, tubular, or serpiginous structures with smooth margins located in the submucosal layer of the gastric wall, accompanied by perigastric collateral vessels (Fig. 2C, D). They can be differentiated from submucosal cysts according to the patient’s medical history, the shape of the structure, and if the structure can be easily compressed. Doppler examination can demonstrate flow within the structure, which is a definitive diagnostic clue.

Gastric carcinoid tumors are neuroendocrine tumors that originate from enterochromaffin-like cells. These slow-growing tumors with malignant potential arise from the mucosal layer of the gastric wall and can invade into deeper structures [11,12]. On endoscopy, carcinoid tumors appear as small, round, sessile, or polypoid lesions with occasional central erythematous depression or ulceration. On EUS, carcinoids are mildly hypoechoic or isoechoic, homogeneous lesions with distinct smooth margins located in the second or third layer of the gastric wall (Fig. 5). Carcinoid tumors can be diagnosed by endoscopic biopsy even when the overlying mucosa appears normal, whereas the yield of mucosal biopsies from other subepithelial lesions is usually low.

Leiomyomas are benign tumors that arise from either the muscularis mucosa or the muscularis propria. The location of the lesion may be important in the clinical diagnosis as leiomyoma are frequently found in the esophagus, but rarely occur in the stomach [13]. These tumors present as hypoechoic, homogeneous, well-circumscribed lesions in the second or fourth layer of the gastric wall on EUS examination (Fig. 6A, B).

GISTs are the most commonly identified mesenchymal tumors in the stomach and have malignant potential [14]. GISTs arise from the interstitial cells of Cajal and can be identified using immunohistochemical staining for CD117, the protein product of the c-kit proto-oncogene [15]. The risk of malignancy in GISTs varies widely and depends on tumor size and mitotic count [15]. Endoscopically, GISTs appear as round or dumbbell-shaped lesions and occasionally present with central umbilication or ulceration. On EUS, they are generally hypoechoic, relatively homogeneous masses originating from either the second or fourth layer of the gastric wall (Fig. 6C, D). Many features observed on EUS, including size, irregular margins, intratumoral cystic spaces, presence of echogenic foci, and presence of peritumoral lymphadenopathy, are recognized as predictors of malignancy [16,17]. Although the accuracy of EUS in the diagnosis of small subepithelial lesions is limited, this approach can be useful in differentiating GISTs from other benign tumors based on changes in echogenicity or an increase in size during follow-up [18,19]. Nevertheless, none of these features are specific for the prediction of malignant potential, and histopathological diagnosis remains the gold standard.

Schwannomas are benign S100 protein-positive spindle cell tumors usually located in the proximal part of the stomach [20]. They appear as hypoechoic, heterogeneous tumors originating from the fourth layer of the gastric wall, and their endosonographic appearance is similar to that of leiomyomas or GISTs. Comparing the echogenicity of suspected lesions with that of the muscularis propria may be helpful for the differential diagnosis; the echogenicity of schwannomas is lower than that of the normal muscularis propria, whereas that of leiomyomas and GISTs is similar or higher (Fig. 6E, F) [21-23].

Glomus tumors are mesenchymal tumors originating from modified smooth muscle cells of the glomus body. These tumors are commonly observed in the dermis or subcutis but are rarely found in the gastrointestinal tract. Most gastric glomus tumors are benign. On EUS, they usually appear as well-circumscribed, hypoechoic masses with an internal heterogeneous echo pattern mixed with hyperechogenic spots located in the third and/or fourth layer of the gastric wall [24,25]. Although EUS may help identify the layer-of-origin, there are no specific EUS findings to establish a diagnosis of glomus tumor [26].

Granular cell tumors are rare lesions of neural origin that are most commonly found in the esophagus, but rarely in the stomach [27,28]. Granular cell tumors arising in the stomach are generally considered benign, and only a small number of cases are malignant [29]. Endoscopically, granular cell tumors are small (usually less than 20 mm in diameter), sessile nodules or polyps with a yellowish-white color resembling molar teeth and, when they occur in the stomach, they are most commonly located in the proximal stomach [28,30]. On EUS, they appear as hypoechoic, homogeneous lesions with smooth margins arising from the second or third layer of the gastric wall (Fig. 2E, F).

Malignant tumors such as adenocarcinomas, lymphomas, and metastatic carcinomas can present as subepithelial lesions. Endoscopic and EUS features of these lesions are not diagnostic, even though they have been previously reported as such, and thus histopathologic diagnosis is necessary [31-33]. Gastric carcinomas mimicking subepithelial lesions are rare and tend to have irregular circumferential margins where the tumor is elevated. On EUS, they are usually well-demarcated masses originating from the third layer of the gastric wall [31,32]. Gastric lymphomas may appear as subepithelial lesions with various features such as erosion and ulceration. On EUS, lymphomas appear as hypoechoic, homogeneous lesions located between the second and fourth layers with layer disruption, and the presence of adjacent lymphadenopathy can be helpful in their diagnosis. The most frequent primary tumors with gastrointestinal metastasis are breast carcinoma, melanoma, and lung cancer [33]. On EUS, metastatic carcinomas appear as hypoechoic, heterogeneous lesions in any or all of the EUS layers of the gastric wall [33].