GIST occurs at every level of the tubular gastrointestinal tract and rarely occurs at the omentum and mesentery. The most common site of GIST is the stomach (60 ~ 70 %), followed by small bowel (20 ~ 30 %), colorectum (<10 %), and esophagus (<5 %) (Fenoglio-Preiser et al. 2000). GIST is the most common mesenchymal tumor of the stomach and accounts for 2.2 % of malignant gastric tumors. All GISTs are potentially malignant and, therefore, cannot be classified as benign versus malignant. Instead, the risk of an aggressive clinical behavior of gastric GISTs is stratified based on tumor size and mitotic count (Fletcher et al. 2002). Microscopically, GISTs typically have spindle cell morphology, but epithelioid morphology may be seen. Immunohistochemically, CD117 (c-kit) protein is a specific marker for GISTs with 95 % positivity for the protein (Miettinen and Lasota 2001).

On barium study, small GISTs commonly present with smooth borders forming right or obtuse angles with the nearby gastric wall. The mucosal surface is usually intact except for areas of ulceration, which are generally present in 50 % of GISTs. Ulcerations fill with barium causing a bull’s eye or target appearance. As the tumor grows, it may project outside the stomach, showing an exophytic or mixed growth pattern. If the tumor outstrips its blood supply, it can necrose internally, creating a central fluid-filled cavity with hemorrhage and cavitation that can eventually communicate into the lumen of the bowel (Gastrointestinal stromal tumor 2013). The presence of bridging fold or slow fade-out of gastric folds at both ends of the mass is known to be one of several characteristics that may permit correct differentiation of a subepithelial tumor from a mucosal lesion. However, barium studies are limited to evaluate exophytic masses, and in staging and detection of small or exophytic GISTs, this method is of little value. On CT, small GISTs are seen as smooth, sharply demarcated subepithelial mass with an intact overlying mucosal layer and with homogeneous attenuation. Large GISTs appear as heterogeneous masses with a low-attenuating focus due to areas of hemorrhage or necrosis.

Malignancy is characterized by local invasion or distant metastasis, usually to the liver, omentum, and peritoneum. Contrary to adenocarcinoma or lymphoma, lymph node metastasis is uncommon (<5 %) and therefore, imaging usually shows absence of lymph node enlargement. If metastases are not present, other CT or MRI features suggesting malignancy include size (>5 cm), heterogeneous enhancement, and necrosis (Kim et al. 2004). The absence of lymphadenopathy and the presence of necrosis can be used as differential point of GIST from gastric schwannoma which is the second most common mesenchymal tumor of the stomach (Choi et al. 2012).

Gastrointestinal schwannoma is a rare mesenchymal tumor and it consists of 3 % of all gastrointestinal mesenchymal tumors. The ratio of incidence between GIST and schwannoma is reported to be 8 ~ 14:1 (Voltaggio et al. 2012). Gastric schwannoma differs histologically from soft tissue schwannoma in several ways. Gastric schwannomas lack encapsulation as a result of their origin from the dispersed autonomic nerve Schwann cells, as opposed to being encased by epineurium, as seen in soft tissue schwannomas. In addition, nuclear palisading, xanthoma cells, and vascular hyalinization and dilation, which are commonly seen in soft tissue schwannomas, are rare in gastric schwannoma. On the other hand, prominent lymphoid infiltration and peripheral lymphoid cuffing are the unique histological features of gastric schwannoma. S-100 protein positivity is a unique IHC feature of gastric schwannoma (Voltaggio et al. 2012).

On CT, gastric schwannoma usually appears as a homogeneous, iso- or low-attenuating subepithelial mass with intact or ulcerated overlying mucosa. On the contrary to GISTs, intratumoral necrosis is rare even in large gastric schwannomas. The presence of enlarged lymph nodes at perigastric or distant areas is known to be a differential point from GIST in which lymphadenopathy is rare (Choi et al. 2012).

Leiomyoma or leiomyosarcoma is a true smooth muscle tumor which can be differentiated from GISTs or other mesenchymal tumors by their positive immunoreactivity for desmin and smooth muscle actin. Leiomyoma occurs frequently in the esophagus or colorectum, but rarely in the stomach. Gastric leiomyoma is mainly located at gastric cardia and appears as a homogeneous low-attenuating subepithelial lesion on CT (Lee et al. 2007). Surface ulceration or calcification is rarely found.

Lipomas composed of mature adipose tissue may be observed in the stomach. They typically protrude into the lumen and appear as a compressible, round, well-circumscribed subepithelial nodule on endoscopy. On barium study, it appears as a well-demarcated nodule with intact overlying layer. Easy compressibility and change in shape during peristaltic movement can be a suggestive feature of gastric lipoma. On CT, typical fat attenuation of the tumor makes the diagnosis of a lipoma easy.

Glomus tumors originate from modified smooth muscle cells of perivascular glomus bodies, which are specialized arteriovenous communications that regulate skin temperature (Hur et al. 2011). Although the most common location of glomus tumor is the subungual region, this tumor can occur elsewhere in the body. Gastrointestinal glomus tumor is very rare with a female predominance and consists of <1 % of all gastrointestinal subepithelial tumor. Gastric glomus tumor is usually located at gastric antrum and shows surface ulceration as the tumor enlarges (Hur et al. 2011). Immunohistochemically, it shows positivity for smooth muscle actin and synaptophysin and negativity for chromogranin A and c-kit.

On CT, predominant antral location, hemangioma-like enhancement pattern on dynamic imaging, strong and persistent enhancement on portal phase, and thick overlying mucosal layer can be used as differential features of glomus tumor from other gastric subepithelial tumors (Hur et al. 2011).

Various kinds of nonneoplastic lesions may manifest themselves as a subepithelial lesion and thus easily mimic tumorous conditions. They include ectopic pancreas, gastritis cystica profunda, and amyloidoma. Ectopic pancreas, also referred to as heterotopic, accessory, or aberrant pancreas, is defined as pancreatic tissue lacking anatomic and vascular continuity with the main body of the gland; an ectopic pancreas is usually located in the stomach, duodenum, or jejunum (Kim et al. 2009). A combination of five CT findings such as prominent enhancement of the overlying mucosa, antral or duodenal location, large long diameter/short diameter ratio, endophytic growth pattern, and ill-defined lesion border may be helpful for the differentiation from subepithelial tumors including GIST and leiomyoma (Kim et al. 2009). Gastritis cystica profunda is an ectopic proliferation of gastric glandular elements, typically located beneath a normal mucosal layer. Gastritis cystica profunda is a rare submucosal lesion that is often reported in the setting of a prior gastroenterostomy. However, it can occasionally be found in the stomach without previous surgery. Histologically, the lesion extends into the gastric submucosal layer and is composed of elongated hyperplastic gastric foveolae with hyperplasia and cystic dilation of the gastric glands. This lesion presents as giant gastric folds, a submucosal tumor, or an isolated polyp (gastritis cystica polyposa). CT findings of gastritis cystica profunda may vary from a homogeneously enhancing polypoid lesion all the way to a purely cystic subepithelial lesion.