Management of Gastric Polyps

An Endoscopy-Based Approach

Yasser H. Shaib; Massimo Rugge; David Y. Graham; Robert M. Genta

Disclosures

Clin Gastroenterol Hepatol. 2013;11(11):1374-1384. 

In This Article

Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are neoplastic proliferations of the interstitial cells of Cajal (or their precursors) that can arise in any segment of the digestive tract as well as, rarely, in the abdominal and pelvic cavity.[51] Of the estimated 4000 GISTs newly diagnosed each year in the United States,[52,53,54,55] 40% to 60% originate in the stomach, where they represent approximately 2% of all tumors.[56] GISTs are more common in men and in the gastric fundus, although they can be found in other regions of the stomach.[57] No predisposing factors are known; thus, the gastric mucosa overlying these tumors may be normal or display any type of gastritis. Interestingly, microscopic GISTs have been found to be common in the upper stomach of Japanese patients who underwent gastric resections for gastric cancer, suggesting that only infrequently does a GIST enlarge and develop malignant potential.[58]

Endoscopically, GISTs are well-circumscribed submucosal lesions; the overlying gastric mucosa is usually normal, but it may have an eroded or ulcerated center (Figure 5A). Biopsy sampling of these tumors is often met with frustration. Because the mucosa tends to slide over benign submucosal tumors, the biopsy forceps often fail to grab an adequate fragment of GIST tissue. In these cases the pathology report often will state that the gastric mucosa is normal, sometimes inducing the clinician to believe that either there was no lesion or the quality of the pathology report was suboptimal. Therefore, the best way to obtain diagnostic tissue is to perform an endosonographic fine-needle aspiration or a tru-cut needle biopsy.

Figure 5.

GIST. (A) Endoscopic view of an ulcerated submucosal mass in the body of the stomach in a patient who presented with upper-gastrointestinal bleeding. (B) The stroma consists of compact bundles of spindle cells, (C) which stain uniformly with CD117. Staining with DOG-1 (not shown) would have an identical appearance to the staining in panel B.

Histologically, GISTs are composed by dense aggregates of fusiform cells (spindle cells) arranged in bundles aligned in different directions (Figure 5B). Two main types of GISTs are recognized in the stomach (spindled and epithelioid), and within each type a number of histologic characteristics (presence of perinuclear vacuoles, numbers of mitoses, necrosis, and tissue invasion) help predict their behavior.[57]

Clinical Approach

The vast majority of GISTs that measure less than 1 cm are asymptomatic and are detected incidentally during an endoscopic examination scheduled for other indications. As GISTs grow, they may cause erosions or ulcerations in the overlaying mucosa or compress adjacent structures; consequently, the 2 more common manifestations are bleeding (occult or overt) and pain.

All GISTs must be considered as having malignant potential: up to 50% of patients with larger GISTs (>2 cm) have metastatic disease at presentation, usually to the liver.[52] In practice, there is good correlation between size, mitotic activity, and clinical behavior of GISTs. Surgical resection is recommended for lesions greater than 2 cm; endoscopic enucleation followed by surveillance is an option for smaller GISTs. Endoscopic removal is controversial, however, because of reports of positive resection margins and tumor spillage.[55] Tyrosine kinase inhibitors are used as targeted therapy in cases of metastasis and surgically unresectable GISTs.[59] Neoadjuvant therapy with use of tyrosine kinase inhibitors after surgical resection of high-risk GISTs deters recurrence, but the optimal duration of therapy has not been determined.[60]

Histopathologic Diagnostic Tips: Special Stains, Immunohistochemistry, and Molecular Studies

Immunohistochemical stains are central to the diagnosis of GISTs. The c-kit proto-oncogene mutation (most often occurring in exon 11) is the key molecular event in gastric GISTs and can be detected by an immunohistochemical stain directed against the KIT protein. The antibody used for the staining, designated as CD117, stains approximately 95% of GISTs (Figure 5C); the remaining 5% (which typically have a more epithelioid morphology) stain with antibodies to the DOG-1 or platelet-derived growth factor α.[56,57,61] If none of these 3 stains is positive on a tumor with morphologic characteristics suggestive of GIST, tumors of smooth muscle (leiomyomas) or neural (neuromas, schwannomas) origin should be considered and immunostaining for actin and S-100 should be performed.

Predictors of behavior that pathologists must evaluate in a GIST include tumor size and mitotic counts. In general, it can be stated that the larger a tumor the greater the likelihood that it has metastasized. Figures most often cited indicate that 15% of GISTs smaller than 2.5 cm metastasize, in contrast to more than 80% of GISTs larger than 6 cm.[57] These data, reproduced in many subsequent studies, emphasize the malignant potential of even small GISTs. Most studies have found that higher mitotic counts are associated with decreased survival; however, the way mitotic counts traditionally are reported (per high-power field) are imprecise, not standardized, and subject to many technical and interpretational variables. Only unequivocally high mitotic counts (eg, >5 mitoses/50 high-power field) obtained under rigorously controlled conditions (details of the methods used to find and count 50 separate fields) and precise information on the exact area of a high-power field (which varies 3-fold in different types of commonly used microscopes) can be used to make a prognostic assessment.[61] Therefore, when clinicians receive a report indicating a high mitotic count in a GIST, they should interpret it cautiously and question the pathologist about the methods used to reach that conclusion.

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