Benign Gastric Tumors

Practice Essentials

The majority of benign gastric tumors are asymptomatic, but in very rare cases, they present with epigastric pain, gastric outlet obstruction, and bleeding. Adenomatous polyps have a truly neoplastic behavior with the potential for the development of malignancy. Also, gastrointestinal stromal tumors (GISTs) have different behavioral patterns, ranging from benign to malignant. The etiology of benign tumors varies according to the type of tumor and the associated pathology.

Many benign gastric tumors are found incidentally on gastroscopy. Small tumors are usually asymptomatic, but larger ones can ulcerate and cause occult bleeding and anemia. Physical findings are not specific, except in the case of certain underlying conditions. 

With the advent of modern techniques and the widespread use of gastric endoscopy, benign gastric wall lesions are now diagnosed more frequently and can be studied using the tissue obtained by biopsy or polypectomy. In the past, the diagnosis of gastric tumors was based on radiographic examination, but in 1922, Schendler was the first to make an endoscopy-based diagnosis.^[1]

Of the large variety of gastric tumors, GISTs are the only type that has a real systemic medical therapy. Gastric polyps, polyposis syndromes, and nonmucosal intramural tumors are treated surgically or endoscopically.

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Pathophysiology

All layers of the stomach wall have the potential to produce tumorous growths. In 40% of patients with benign gastric tumors, the lesions are mucosal tumors; the remaining 60% are not mucosal-based. Gastric polyps are defined as luminal lesions projecting above the plane of the mucosal surface and are relatively frequent in routine pathology practice. Various subtypes of gastric polyps are recognized and divided into nonneoplastic and neoplastic and are also further classified by their association with polyposis syndromes.^{[2, 3]}

Benign gastric tumors may be classified according to the following schema (see image below):

• 1 - Mucosal tumors
• 1.1 -  Nonneoplastic polyps
• 1.1.1 - Not associated with polyposis syndromes
• 1.1.1.1 - Hyperplastic polyps
• 1.1.1.2 - Inflammatory fibroid polyp (eosinophilic granuloma - Vanek tumor)
• 1.1.1.3 - Xanthoma/xanthelasma
• 1.1.1.4 - Ectopic pancreas
• 1.1.2 - Associated with polyposis syndromes
• 1.1.2.1 - Hamartomatous polyp (Peutz-Jeghers syndrome)
• 1.1.2.2 - Juvenile polyps
• 1.1.2.3 - Cowden disease
• 1.1.2.4 - Cronkhite-Canada syndrome
• 1.1.2.5 - Gardner syndrome
• 1.2 - Neoplastic polyps
• 1.2.1 - Fundic gland polyp
• 1.2.2 - Adenomatous polyp
• 1.2.3 - Gastric carcinoid
• 2 - Nonmucosal tumors
• 2.1 - Mesenchymal
• 2.1.1 - GIST
• 2.1.2 - Lipoma
• 2.1.3 - Fibroma
• 2.1.4 - Glomus tumor
• 2.2 - Vascular
• 2.2.1 - Hemangioma
• 2.2.2 - Lymphangioma

View Image

Classification of benign gastric tumors.

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Epidemiology

Benign tumors of the stomach are uncommon, with an incidence of 0.4% in autopsy series and 3-5% in upper endoscopic series, most of them performed for unrelated reasons. Polyps account for 3.1% of all gastric tumors, and their frequency increases to almost 90% of benign gastric tumors. They can become inflamed or eroded, but bleeding remains unusual. Large distal lesions have been associated with symptoms of gastric outlet obstruction.^[2]

Age and sex distribution depend on the type of tumor. There is no difference in distribution by race.

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History

Many benign gastric tumors are found incidentally on gastroscopy. Small tumors are usually asymptomatic, but larger tumors can ulcerate and cause occult bleeding and anemia. Large antral tumors cause intermittent gastric outlet obstruction, as manifested by nausea, vomiting, and early satiety. If ulcerated, these tumors may cause epigastric pain similar to that caused by a peptic ulcer.

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Physical Examination

Physical findings are not specific, except for underlying conditions, such as Peutz-Jeghers syndrome, in which patients may have abnormal pigmentation of the oral mucosa, lips, and digits. An abdominal mass may be palpable. Palpation may elicit abdominal tenderness.

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Imaging Studies

Air-contrast studies of the stomach are sensitive in delineating mucosal details and lesions. Lesions are often found incidentally on computed tomography (CT) or other radiologic evaluations of the upper gastrointestinal (GI) tract. (See the image below.)

View Image

Benign gastric tumors. CT scan of the abdomen showing a large GIST in the wall of the lesser curvature of the stomach.

Multidectector CT (MDCT) may be useful for evaluating the involvement of the gastric wall and assessing the extragastric extent of the disease.^[4]  A study by Meng et al found quantitative analysis in dual-energy spectral CT (DESCT) imaging parameters to be useful for distinguishing malignant gastric mucosal lesions from benign gastric mucosal lesions.^[5]

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Endoscopy

Endoscopy has become more common for both diagnostic and therapeutic purposes.^[6] (See the image below.) Endoscopic findings that suggest malignancy include red coloring, the presence of surface erosions, and the absence of a pedicle. In a study of endoscopic risk indicators for gastric cancer, Yamashita et al found gastric xanthomas to be positively associated with gastric cancer and fundic gland polyps to be negatively associated.^[7]

View Image

Upper endoscopy showing multiple gastric polyps.

If small superficial lesions are removed endoscopically, follow-up should include a regular annual endoscopy.

Endoscopic biopsies are difficult to interpret and may be misleading because deep layers of the stomach wall or the tumor are not sampled. Snare biopsies that retrieve the whole specimen are preferred whenever technically possible.

Endoscopic ultrasonography (EUS) is helpful in broad-based lesions, where the relation of the tumor to the layers of the stomach is important. Disruption of the normal appearance of five layers on EUS may signify invasion. Contrast enhancement of EUS may prove useful for differentiating various submucosal lesions of the stomach.^[8]

In a prospective blinded study comparing conventional gastroscopy and standing-type magnetically controlled capsule endoscopy (SMCE) with respect to feasibility and safety in detecting gastric lesions, Lai et al found that SMCE was equivalent to gastroscopy and could be useful for screening of gastric illnesses without anesthesia.^[9]

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Histologic Findings

Hyperplastic polyps

There is marked elongation of the pits with branching, resulting in a corkscrew appearance or in cystic dilatation of foveolae. Also, there is an excess of lamina propria with plasma cells, lymphocytes, eosinophils, mast cells, macrophages, and neutrophils. The gastric glands do not normally participate in the formation of the polyps. The surface may be ulcerated and inflamed with regenerative atypia. There may also be invagination of the surface mucosa with budding.^[2]

Inflammatory fibroid polyps

These polyps are centered on the submucosa. Small, thin walled vessels surrounded by spindle cells are arranged in an "onion-skin" pattern. Polyps are CD34-positive and c-Kit-negative.^{[2, 10]}

Hamartomatous polyps of Peutz-Jeghers type

Gastric mucosa is less frequently involved than the small bowel and the colon. The polyps are composed of hyperplastic glands separated by branching cores of smooth muscle with atrophy of deep glandular components. Dysplasia is very uncommon.^[2]

Juvenile polyps

These polyps are very rare and are usually associated with juvenile polyposis. They are composed of edematous and inflamed mucosa with tortuosity of the foveolar zones and are easily confused with hyperplastic polyps. There is an association with an increased risk of cancer.^[2]

Gastric polyps in Cowden disease

The foveolar glands are enlarged and elongated. Smooth-muscle fibers are intermingled within the mucosal components and the cystic structures extend into the submucosa.^[2]

Gastric polyps in Cronkhite-Canada syndrome

These polyps are usually associated with lesions in other parts of the GI tract. They are indistinguishable from juvenile polyps and hyperplastic polyps, and they are diagnosed if in the presence of alopecia, nail atrophy, or hyperpigmentation.^[2]

Fundic gland polyps

These are dilated glands lined by fundic epithelium mixed with normal glands. There is usually no inflammation or atypia, but some disordered muscle fibers may be seen.^[2]

Adenomatous polyps

They are composed of tubules or villi of dysplastic epithelium with some degree of intestinal-type differentiation. They can be low grade or high grade, based on the degree of dysplasia. The risk of malignancy is related to the size, the degree of dysplasia, and the villosity of the growth pattern. About 40-50% of lesions larger than 2 cm contain carcinomatous transformation.^[2]

Gastric carcinoids

Gastric carcinoids are very rare, representing fewer than 0.5% of gastric neoplasms, and are seen in three different settings: autoimmune atrophic gastritis, Zollinger-Ellison syndrome, and multiple endocrine neoplasia (MEN)-1 syndrome, or they may be seen sporadically. They are usually broad-based, yellowish polypoid lesions overlined by normal mucosa. Chromogranin A is positive, but chromogranin B is usually negative. Synaptophysin is positive in 50% of cases.^[2]

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Medical Care

Of the large variety of gastric tumors, the gastrointestinal stromal tumor (GIST) is the only type that has a real systemic medical therapy because of the expression of Kit (tyrosine kinase receptor).^[11]

Imatinib mesylate is a small-molecule receptor inhibitor that targets Kit. Clinical trials have shown partial response rates of 40-69% progression-free survival in patients treated with imatinib for advanced, recurrent, or metastatic GISTs. It has been used in the preoperative treatment of patients with GISTs that are imatinib-responsive to decrease tumor size before surgical resection.^[12]  Imatinib resistance is common, however; thus, therapy generally is not curative.^[13]

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Surgical Care

Gastric polyps

Gastric polyps include the following types:

• Hyperplastic polyps
• Adenomatous polyps
• Fundic gland polyps
• Inflammatory fibroid polyps

Endoscopic excision of gastric polyps provides a minimally invasive approach to diagnosis and treatment.^[14] Polyps smaller than 2 cm are easily snared. Larger polyps or sessile polyps are best removed operatively to obtain a clear margin and complete removal. Occasionally, staged piecemeal endoscopic removal can be performed in patients with severe comorbidities.

Wide, local, or segmental resection of the stomach may be performed for multiple polyps, depending on their histology and location. Gastrectomy is justified in patients with diffuse involvement of the stomach by polyps, which can make detection of a synchronous focus of cancer difficult.

Hyperplastic polyps are by far the most common histologic type, and they can vary in location, number, and size. Most are smaller than 2 cm. Although these polyps harbor no malignancy, they may be accompanied by atrophic gastritis, which predisposes the nonpolypoid mucosa to malignant transformation. Multiple hyperplastic polyps are found in Ménétrier disease. The histology of these polyps is different from that of colorectal polyps in that it shows submucosal edema and faveolar hyperplasia.

Adenomatous polyps (tubular and villous) are usually solitary lesions in the antrum. They have atypical cells and are associated with adenocarcinoma of the stomach. This association is strongest in polyps greater than 2 cm in diameter. The overall incidence of complete malignant transformation in adenomatous polyps is about 3.4%.

Fundic gland polyps contain microcysts that are lined by fundic-type parietal and chief cells, and they are located in the fundus and body of the stomach. They are common in familial polyposis syndromes and have no malignant potential.

Inflammatory fibroid polyps are benign spindle cell tumors that are infiltrated by eosinophils, but they are not associated with a systemic allergic reaction or eosinophilia. Excision of inflammatory fibroid polyps is indicated because of their propensity to enlarge and cause obstruction.

Polyposis syndromes

Sometimes polyps in the stomach are associated with polyposis syndromes. These syndromes include juvenile polyposis, Gardner, Peutz-Jeghers, and Cronkhite-Canada syndromes.

Juvenile polyposis and Cronkhite-Canada syndrome rarely result in gastric cancer.

Peutz-Jeghers syndrome involves gastric hamartomatous polyps. The gastric involvement is generally less than that observed in the small intestine. These polyps can bleed or obstruct the antrum and should be treated accordingly. Although patients with Peutz-Jeghers syndrome may occasionally develop gastric cancer, other nongastrointestinal cancers are more common.

Adenomatous polyps of the stomach and duodenum develop in 50% of cases of familial polyposis and Gardner syndrome. Polyps are usually multiple, and they are best treated endoscopically. Multiple treatments every 3-4 months may be necessary for complete eradication. Routine surveillance endoscopy should be instituted as a life-long program. Patients with Gardner syndrome develop adenomatous polyps in the duodenum as well as in the stomach and should undergo routine esophagogastroduodenoscopy (EGD).

Nonmucosal intramural tumors

Leiomyomas formerly comprised the most common submucosal tumors of the stomach. Many tumors formally designated as leiomyomas (and leiomyosarcomas) are now classified as GISTs and are believed to arise from interstitial cells of Cajal rather than from smooth muscle per se. The overall incidence of GISTs is approximately 4 per 1 million in the general population. These lesions can be found throughout the gastrointestinal (GI) tract from the esophagus to the rectum; however, the stomach is the most common site.

Most patients with GISTs are asymptomatic, but anemia and acute GI bleeding from tumor ulceration can occur.

There is a spectrum from benign to malignant. Histologic characteristics, such as the number of mitotic figures, tumor necrosis, and cellularity, are indicators of malignancy. The only reliable indicator of malignancy in these and other GISTs is evidence of extragastric spread. Lymphatic spread is rare, but hematogenous spread to the liver and the lungs is more common.

These tumors can cause symptoms by obstruction, ulceration, and blood loss or by compressing adjacent organs. They appear as large submucosal lesions on endoscopy, and endoscopic biopsies are invariably not deep enough to be of any diagnostic value.

As defined by the GIST Consensus Conference, the goal of treatment should be complete resection of visible as well as microscopic disease, while avoiding tumor rupture and obtaining negative margins. Because of the adequacy of a narrow margin of resection, there has been significant interest in developing operative techniques that accomplish effective tumor resection but minimize morbidity, preserving stomach parenchyma, and reduce medical costs.

Minimally invasive surgery has proved effective for GIST resection, with shorter hospital stays and comparable operating room time and blood loss in comparison with open techniques.^{[15, 16, 17, 18, 19, 20]}  The GIST Consensus Conference recommended laparoscopic resection for tumors less than 2 cm, and several studies found laparoscopic treatment to be safe and effective in tumors averaging 4.4 cm.^{[21, 22, 20]} The pathologic phenotype and especially the tumor mitosis correlate significantly with patient survival, even if the resected tumor size was relatively small.^[23]

For GISTs located in the fundus, along the greater curvature, a laparoscopic gastric wedge resection may be beneficial. Tumors in the lesser curvature are less likely to be effectively resected via laparoscopy because of the limited mobility of the stomach in this area. For esophagogastric junction tumors, the laparoscopic transgastric procedure can be used successfully.^[21]

Endoscopic resection seems to be an effective and safe method for smaller (≤ 4.0 cm) GISTs originating from the muscularis propria; for some intermediate- or high-risk GISTs, adjuvant therapy or additional surgical procedures might be required to reduce the risk of recurrence or metastasis.^[24]

Patrzyk et al reported increased patient satisfaction with the final cosmetic appearance after single-port resection using a laser-supported diaphanoscopy.^[25]

Lipomas are rare submucosal tumors that are sometimes indistinguishable from GISTs. They represent deposits of adipose tissue in the wall of the stomach, usually in the submucosa. They may cause symptoms when exceeding 2 cm in size. The standard treatment is surgical resection, but endoscopic treatment has been proposed for lesions smaller than 2 cm.^{[26, 27]}

Fibroma and fibromyoma are most commonly observed as small intramural or subserosal lesions during the course of an unrelated surgery. Removal is warranted to confirm their benign nature.

Ectopic pancreas can occasionally cause symptoms by obstructing the pylorus or bleeding. Characteristic findings on endoscopy include a nipplelike appearance and a central ductal orifice. Histologic evaluation can reveal acute and chronic pancreatitis and cystic dilatation of the duct. Asymptomatic lesions require no further treatment. Local full-thickness excision of the gastric wall is adequate for complete removal.

Cystic tumors can be mucocele or intramucosal, and they are the most common benign cystic lesion of the stomach. They develop as a result of obstruction of mucus-secreting glands. Duplication cysts are congenital lesions that share a common wall with the stomach but do not communicate with the lumen. They enlarge because of trapped secretions, resulting in symptoms of obstruction. Treatment of duplication cysts is operative excision.

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