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GI mesenchymal tumors (stromal tumors, leiomyomas, and schwannomas) derive from mesenchymal stem cells and have an epithelioid or spindle cell histologic pattern, resembling smooth muscle. The most common are GI stromal tumors (GISTs), which originate from interstitial cells of Cajal, which are cells that are interposed between the intramural neurons and the smooth muscle cells of the digestive tract. GISTs occur most commonly in the stomach (60%) and small intestine (30%), but can occur throughout the digestive tract, and occasionally in the omentum, mesentery, and peritoneum. Most cases are sporadic, but about 5% of cases are part of familial genetic syndromes (such as neurofibromatosis type 1). GISTs are potentially malignant and have an unpredictable evolution. Determination of the GIST molecular subtype upon diagnosis is important because it informs therapeutic decisions in both the adjuvant and metastatic setting. Approximately 80–90% of GISTs have gain-of-function mutations in KIT, a receptor tyrosine kinase that binds stem cell factor, or in PDGFRα, a homologous tyrosine kinase, platelet-derived growth factor alpha, that leads to constitutive kinase activation.

Mesenchymal tumors may cause symptoms (most commonly bleeding, pain, or obstruction) or may be discovered incidentally on imaging studies or endoscopy. At endoscopy, they appear as a submucosal mass that may have central umbilication or ulceration (eFigure 41–6). EUS with guided FNA biopsy is the optimal study for diagnosing gastric mesenchymal tumors and distinguishing them from other submucosal lesions. Percutaneous biopsy is not recommended due to risk of bleeding or intra-abdominal seeding. CT of the abdomen and pelvis with contrast, MRI, and PET imaging are useful in the diagnosis and staging. PET imaging also may be useful to monitor response to treatment.

eFigure 41–6.

A submucosal tumor with central ulceration. Fine-needle aspiration (FNA) confirmed GI stromal tumor (GIST). (Used, with permission, from Yao-Wen Cheng, MD.)

It is difficult to distinguish benign from malignant tumors by EUS appearance or by FNA. In general, lesions are more likely benign if they are smaller than 2 cm, have a smooth border, and have a homogeneous echo pattern on EUS. But all GISTs have malignant potential, and the risk of developing metastasis is increased with tumor size greater than 2 cm, non-gastric location, and mitotic index greater than 5 mitoses per 50 HPF.


A. Localized Treatment

Complete surgical resection, whether by laparotomy or laparoscopy, is the only potentially curative treatment of localized GISTs (even for tumors larger than 5 cm). Surgical resection is recommended for tumors that are 2 cm or larger, or are increasing in size, suspicious for malignancy on EUS, or symptomatic. The management of asymptomatic gastric lesions 2 cm or smaller depends on the EUS features. Tumors with high-risk EUS features can be surgically resected. If no high-risk features are ...

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