Introduction
Most biopsy specimens of presumed gastric polyps have distinctive clinical characteristics that enable their easy categorization into one of the major established classes of epithelial or stromal gastric lesions (Table 1). Classic studies and the majority of textbooks on gastrointestinal pathology indicate that although adenomatous polyps1 have a high malignant potential and are frequently associated with synchronous gastric adenocarcinomas, risk of malignant transformation is very low for hyperplastic gastric polyps and is virtually absent in sporadic fundic-gland polyps (FGPs).2 As a consequence, the diagnosis of an adenomatous gastric polyp may trigger inclusion of the patient into an endoscopic surveillance program, whereas only limited follow-up is generally proposed for patients with diagnoses of hyperplastic polyps, inflammatory polyps, or FGPs.3 However, molecular studies contest this long-held management approach. Gastric polyps other than adenomatous polyps display molecular alterations that may lead to neoplastic progression, and might carry unknown risks of malignant transformation.
Clinical and pathological correlations
Substantial information on the etiology of a gastric polyp or lesion and correlations between clinical and pathological findings can be gathered by histological and pathological evaluation of an appropriately representative range of biopsy samples taken from the unaffected gastric mucosa.
Although most gastroenterologists are aware of the value of examining the mucosa that surrounds a gastric polyp or lesion, in our experience a thorough examination of the affected gastric mucosa is not commonly performed at the time a polyp is discovered. The clinical characteristics of gastric polyps or lesions, and the possible pathological findings of the gastric mucosa adjacent to these entities, are highlighted in Tables 2 and 3.
Epidemiology
Published data on the epidemiology of gastric polyps diverge substantially with regard to both absolute and relative prevalence. Among the variables that influence epidemiological data, we must consider the populations studied, which will have wide variations in age and sex, and the prevalence of underlying gastric conditions, such as Helicobacter pylori infection. The methodology of studies and the accuracy of pathological diagnoses should also be considered. Thus, we must be aware that we are comparing unevenly obtained data. A detailed discussion on the effects of these variables is beyond the scope of this Review, but it should be noted that problems exist with the two most common types of studies: pathology-based series and retrospective studies. Pathology-based series, in which the denominator is the total of gastric biopsy samples available, cannot be used to establish the absolute prevalence of gastric polyps, but are adequate to determine the relative frequency of the various types of polyps.4 Retrospective reviews of endoscopic reports are likely to underestimate the true prevalence of gastric polyps, because not all polyps may have been described and excised.5, 6
Similarly to other gastric diseases, important geographical differences in the prevalence of gastric polyps exist. Rates of gastric adenomas and adenocarcinomas are much higher in Eastern Europe and Asia than in Western populations, with figures approaching 27% compared with 0.5–3.75%, respectively.7, 8, 9 A retrospective review of 13,000 endoscopies performed on Greek adults yielded 258 gastric polyps (1.2%).5 Up to 27% of patients had more than one polyp, and 75.6% had hyperplastic polyps. Adenomas (6.6% of all polyps) were predominantly found in males (2:1 male to female ratio), and were found only in patients over 50 years of age. Stromal polyps were present in 5.2% of patients who had previously undergone gastrectomy or gastrojejunostomy. A large, pathology-based, German study analyzed 5,515 gastric polyps collected between 1969 and 1989 and found 47% to be FGPs and 28.3% to be hyperplastic polyps; high representations of gastric adenomas (9.0%) and adenocarcinomas (7.2%) were found.4 A 2007 Brazilian study of the findings of 26,000 endoscopies identified a mere 153 patients with gastric polyps (0.58%). The relative frequency of polyps in this population reflected the high rate of H. pylori infection: 71.3% of polyps were hyperplastic polyps, 16.3% were FGPs, and 12.4% were gastric adenomas.6 Recently, we examined data on gastric polyps obtained over a 12-month period in a nationwide pathology laboratory in the US.10 In approximately 200,000 patients who underwent esophagogastroduodenoscopy (EGD), 8,000 gastric polyps were excised or biopsied from 7,500 patients, with an overall gastric-polyp prevalence of 3.75%—somewhat higher than the amount previously reported for Western populations. In this population with a low prevalence of H. pylori infection (12.3% among the 78,909 patients who had gastric biopsies), the overwhelming majority of gastric polyps (77.2%) were FGPs, 14.4% were inflammatory or hyperplastic polyps, and only 0.7% were gastric adenomas.
Classification and key features
A diverse array of polyps and polypoid lesions may be found in the stomach. Table 1 illustrates the various entities that may appear endoscopically as a polyp or nodule. Epithelial polyps (hyperplastic, fundic gland, and adenomatous) are the classic gastric polyps, but clusters of endocrine cells (carcinoids), infiltrates (xanthomas, lymphoid proliferations) or mesenchymal proliferations (gastrointestinal stromal tumors [GISTs], leiomyoma and inflammatory fibroid polyps) may produce a mucosal protrusion. This Review excludes discussion of carcinomas, lymphomas, and other malignancies.
Fundic-gland polyps
Clinical characteristics
FGPs are the most common type of polyp detected by EGD in Western countries.10 Endoscopically they appear as smooth, glassy, sessile, circumscribed elevations (usually measuring <0.5 cm) in the oxyntic mucosa (Figure 1a). Histologically, the basic lesion consists of one or more cystically dilated oxyntic glands, with the lining cells appearing flattened and difficult to recognize when markedly dilated (Figure 1b,c). FGPs may occur sporadically, in association with PPI use, and in patients with familial adenomatous polyposis (FAP) syndrome.11, 12, 13 Sporadic polyps are either single or few in number, and are found almost exclusively in patients without H. pylori infection.14 In PPI users, large numbers of polyps might exist, but these may regress with cessation of therapy.15 Little is known about the etiology of FGPs. In the past, these polyps were considered to be hamartomatous; however, the recognized association of FGPs with long-term PPI use suggests that mechanisms related to the suppression of acid secretion may be involved in their pathogenesis.16, 17 However, this view is not shared by all researchers.18, 19 Our understanding of the pathogenesis of these polyps has been further complicated by the finding that sporadic FGPs with dysplasia exhibit germ-line mutations in the APC tumor-suppressor gene (a finding also observed in patients with FAP),20 rather than somatic mutations in the 
-catenin gene, which had previously been described in association with these polyps.21, 22
Figure 1 | A fundic-gland polyp.
a | Endoscopically, they appear as glassy, smooth, round polyps (often multiple) in the gastric body and fundus. b | A low-power histological view displaying dilated glands that may be lined by parietal cells (p) or mucous cells (m). c | A high-power histological view showing both flattened parietal cells (thin black arrows) and mucous cells (thick black arrow).
Management
Although dissenting opinions have been expressed, sporadic and PPI-associated FGPs are traditionally believed to have low malignant potential and no ominous associations.23 In patients on PPI therapy with typical, small (<0.5 cm) FGPs, diagnosis is confirmed by taking a biopsy specimen from one polyp. Biopsy specimens are taken from all polyps 0.5–1.0 cm in size. PPI therapy is not discontinued in patients with smaller polyps. Larger polyps (>1 cm) are removed and, if clinically appropriate, PPI therapy is discontinued in these patients. By contrast, a definite risk of dysplasia (between 30% and 50%) is present in FAP-associated FGPs.11 In a 2008 study of 75 patients undergoing surveillance for FAP, 88% had FGPs, 38% had low-grade dysplasia and 3% had high-grade dysplasia.12 Dysplasia in FGPs was associated with large polyp size (>1 cm), increased severity of duodenal polyposis, and antral gastritis. PPI therapy use seemed to have a protective effect against dysplasia in FGPs. Although no official guidelines have been issued, the general consensus is that all pediatric, and perhaps also adult, patients with FAP warrant upper gastrointestinal screening and surveillance endoscopy from the time of initial colonoscopy, irrespective of referable symptoms.13
When multiple FGPs are diagnosed in a young patient, FAP should be considered. The responsibility of alerting the clinician to this possibility and performing a careful search for dysplasia is incumbent upon a conscientious pathologist. No immunohistochemical or molecular studies are warranted outside a research setting.
Hyperplastic polyps
Clinical characteristics
Hyperplastic polyps arise most frequently in patients with an inflamed and often atrophic gastric mucosa.24 In the industrialized world, both their absolute and relative prevalence has decreased along with the declining prevalence of H. pylori infection.25
Hyperplastic polyps are more frequently observed in the antrum than in other parts of the stomach and are often multiple; these polyps are usually smooth, dome-shaped and small in diameter (measuring 0.5–1.5 cm), but they may reach much larger dimensions, wherein they become lobulated and pedunculated (Figure 2a).26 In larger hyperplastic polyps, the surface epithelium is often eroded. This erosion may result in chronic blood loss and iron-deficiency anemia, one of the most common clinical manifestations of hyperplastic polyps. Rarely, patients with large hyperplastic polyps may present with gastric obstruction.27, 28
Figure 2 | A hyperplastic polyp.
a | An endoscopic view showing lobulations with an irregular surface. b | A low-power histological view showing irregular, distorted, branching foveolae, which may form mucous-cell-lined cysts (m); the stroma is vascular and edematous with chronic and active inflammation. c | A high-power histological view showing an eroded branch of a hyperplastic polyp. The epithelial surface is replaced by a thick deposit of fibrin (f), which overlays a richly vascular granulation tissue. Such erosions, which are universal in larger polyps, often result in blood loss and iron-deficiency anemia.
Histologically, hyperplastic polyps consist of elongated, grossly distorted, branching and dilated hyperplastic foveolae lying in an edematous stroma rich in vasculature, and small, haphazardly distributed smooth-muscle bundles; they contain varying degrees of chronic and active inflammation (Figure 2b,c). Owing to this often prominent inflammatory component, some clinicians and researchers prefer the term hyperplastic-inflammatory polyps to hyperplastic polyps, and a few refer to them simply as inflammatory polyps. Some confusion has resulted from these loosely interchanged terms.
A hyperproliferative response to tissue injury (erosions or ulcers) accompanied by increased cellular exfoliation results in the histopathological appearance of foveolar hyperplasia.29 Foveolar hyperplasia has long been recognized as a prominent feature of chemical gastropathy (caused by bile reflux or NSAIDs), and to a lesser extent in H. pylori gastritis.30 Polypoid foveolar hyperplasia, gastric foveolar polyps, gastritis cystica polyposa (characteristic of post-Billroth I and II gastric stumps), and gastric hyperplastic polyps are considered variants of the same basic hyperproliferative disturbance.
Management
Removal of the underlying injury (that is, eradication of H. pylori infection) results in regression of hyperplastic polyps in a high proportion of patients (up to 70% in one study).31, 32
Both isolated hyperplastic polyps and the polypoid lesions found at gastrectomy sites have a low but definite potential for development of malignancy. Between 1% and 20% of hyperplastic polyps have been found to harbor foci of dysplasia; furthermore, mutations of the p53 gene, chromosomal aberrations, and microsatellite instability have been detected in these polyps.33, 34, 35, 36 Molecular studies examining these polyps were designed to acquire insights into possible neoplastic mechanisms, not to develop predictive tests: thus, in the clinical setting, the performance of immunostaining to detect p53 accumulation, microsatellite instability testing (both easily available and accurate) or gene arrays, would yield results whose full clinical implications could not be interpreted. The overall prevalence of dysplasia in hyperplastic polyps is believed to be <2%, and more frequent in large polyps (>2 cm).37, 38 Large, hyperplastic polyps should be completely excised for thorough histological evaluation. If dysplasia, or even intramucosal carcinoma, was present, it will have been removed and most likely will have been cured.
When a hyperplastic polyp of any size, with or without dysplasia, is diagnosed, a full set of topographically defined biopsy specimens ('gastric mapping') should be obtained. If H. pylori gastritis is present, eradication of H. pylori is warranted with a follow-up endoscopy after a few months to monitor not only cure of the infection, but also recurrence or regression of remaining polyps.31, 32 If extensive atrophy and metaplasia are found, the patient should be considered at risk for gastric cancer, as the polyp could be viewed as an alarming lesion, and an individualized surveillance plan (for which guidelines do not yet exist) should be implemented.24 If the polyp is obtained from a gastrectomy site in the absence of dysplasia, optimal management remains uncertain.
Adenomatous polyps
Clinical characteristics
Adenomatous polyps may occur sporadically and in association with FAP. Only the former are discussed in this Review. Endoscopically, adenomatous polyps have a velvety, lobulated appearance, are usually solitary (82%), located in the antrum, and <2 cm in diameter (Figure 3a).1 These polyps are circumscribed lesions, pedunculated or sessile and histology will reveal dysplastic epithelium without detectable invasion of the lamina propria (Figure 3b). Their prevalence varies widely and is estimated to be 0.5–3.75% in Western countries and 9–27% in areas with higher rates of gastric carcinoma, such as China and Japan.4, 7, 39
Figure 3 | An adenomatous polyp.
a | An endoscopic view showing a velvety surface. b | A low-power histological view. Not unlike their colonic counterparts, gastric adenomatous polyps are usually exophytic lesions composed of interlacing sheets of irregular tubular epithelium that may form complex structures with a cribriform architecture (arrows). Cells are crowded in a disorderly arrangement (inset high-power histological view), often elongated, with hyperchromatic nuclei and occasional mitoses. Paneth cells, and rarely oxyntic cells, may be found in various proportions.
Sporadic, gastric adenomatous polyps may be viewed as one of the possible steps in the development of gastric adenocarcinoma. Both conditions arise most often in patients with chronic, atrophic, metaplastic gastritis and they share a common epidemiological pattern. The larger an adenomatous polyp, the greater the probability that it contains foci of adenocarcinoma. A synchronous adenocarcinoma in another area of the stomach has been found in up to 30% of patients with an adenomatous polyp, and up to 50% of adenomatous polyps >2 cm harbor a focus of adenocarcinoma.40, 41
Management
The management of gastric adenomas has not been markedly changed by molecular studies that have confirmed their neoplastic nature. A 2003 molecular study reported that distinction of the type of gastrointestinal adenoma (intestinal versus gastric) might further define the risk of cancer (an increased risk of cancer is associated with intestinal adenomas).41 Gastric mapping is useful to determine the phenotype of gastritis on which an adenoma arises; the finding of metaplastic atrophic gastritis is an indication for surveillance.42 In addition, a thorough search for synchronous adenocarcinoma should be performed and the endoscopist should confirm complete excision of the adenoma with a repeat endoscopy if necessary. The guidelines of the American Society of Gastrointestinal Endoscopy (ASGE) recommend endoscopic surveillance at 1 year follow-up for patients with gastric adenoma, and that specific biopsy techniques be implemented when large or multiple polyps exist.42
Polyposis syndromes
Clinical characteristics
Polyposis syndromes that affect the stomach are rare, and patients with these syndromes often present with clinical manifestations unrelated to gastric polyps. However, some cases of juvenile polyposis may affect the stomach alone.43, 44 The hamartomatous polyps found in juvenile polyposis, Cronkite–Canada Syndrome and Cowden disease have subtle histological findings that closely mimic hyperplastic gastric polyps and might easily be overlooked if the diagnosis is not suggested by the clinical context.45, 46 Patients with FAP can have FGPs with dysplasia as well as adenocarcinoma. Hamartomatous polyps in patients with the Peutz–Jeghers syndrome are easily recognized by their characteristic arborizing pattern of muscle fibers between hyperplastic glands.44
Management
A detailed discussion of the management of different polyposis syndromes is beyond the scope of this Review. However, we will summarize the recommendations for screening and surveillance of the upper gastrointestinal tract for the three most-studied conditions: FAP, Peutz–Jeghers syndrome, and juvenile polyposis. The presence of gastroduodenal polyposis is well recognized in patients with FAP. However, the dearth of published studies prevents an accurate assessment of the potential benefits of surveillance, particularly in light of the relatively low risk of gastric cancer found in these patients in Western countries.47, 48 A reasonable management approach involves the performance of an upper gastrointestinal endoscopy at 3-year intervals from 30 years of age, with the aim of detecting early curable cancers. Patients with large numbers of gastric and duodenal polyps and those with dysplastic polyps (FGPs with epithelial dysplasia and adenomas) are recommended to undergo surveillance yearly.43
Individuals with Peutz–Jeghers syndrome are at risk of a wide variety of cancers at a young age, including cancer of the breast, colon, pancreas, stomach, small intestine, ovaries, uterus, and testes. The lifetime risk for gastric cancer has been estimated to be 
30% in patients with Peutz–Jeghers syndrome;49 most authorities, therefore, suggest surveillance of the stomach and small intestine with upper endoscopy and small-bowel series every 2–3 years, starting at 18 years of age.50 Surveillance should continue every 2–3 years if polyps are noted at baseline evaluation.43, 51
Juvenile polyposis is rare and data regarding gastric malignancy are limited. As the risk of gastric cancer in patients with this condition is estimated to be 15–20%, it seems reasonable to offer gastric endoscopic surveillance at intervals of 1–2 years, with simultaneous colonoscopy.43, 52
Recommendations for the management of Cronkite–Canada syndrome have focused on pharmacological therapy and surgical resection.53 Cowden disease has no documented association with gastrointestinal malignancies; screening is, therefore, aimed at detecting breast and thyroid cancers.54
Inflammatory fibroid polyps
Clinical characteristics
Inflammatory fibroid polyps (also known as Vanek tumors) are rare lesions that represent <1% of all gastric polyps. Although these polyps can form throughout the gastrointestinal tract, 80% arise in the antropyloric region.55 These polyps are firm, solitary, sessile or pedunculated, and are often ulcerated (Figure 4a); they have been associated with hypochlorydia or achlorhydria, as well as with adenomas.55 Inflammatory fibroid polyps are usually found incidentally, although symptoms of bleeding and gastric-outlet obstruction have been reported.56 Histologically, these lesions consist of a submucosal proliferation of spindle cells, small vessels, and a striking inflammatory infiltrate, in which eosinophils predominate (Figure 4b). Owing to the massive eosinophilic infiltrates, these polyps are occasionally referred to as eosinophilic granulomas; however, this term is incorrect, as these polyps are not granulomas and confusion might occur with Langerhan cell histiocytosis (also known as eosinophilic granuloma).
Figure 4 | An inflammatory fibroid polyp.
a | Endoscopic view showing a firm, well-circumscribed, vascular, submucosal polyp. b | A low-power histological view showing a compact aggregate of concentrically organized spindle cell (fibroblasts), prominent vascularity and abundant inflammatory cells, predominantly eosinophils (inset high-power histological view). The surface mucosa might be normal, hyperplastic, or eroded.
The etiology of inflammatory fibroid polyps is unknown. A familial tendency has been suggested by researchers, owing to the finding of a family in Devon, UK, whose female members have a high rate of these polyps.57 The presence of eosinophils in a lesion is sure to elicit allergy-related speculations; however, no supportive evidence is currently available. Immunohistochemical staining suggests these polyps originate in dendritic cells.58 The mucosa adjacent to these polyps is often unremarkable, but associations with chronic atrophic gastritis have been reported. A recent study found that 70% of inflammatory fibroid polyps contain gain-of-function mutations in the gene encoding PDGF-
polypeptide, similar to those found in KIT-negative GISTs, which suggests the possibility of a neoplastic process.59
Management
As most inflammatory fibroid polyps are found incidentally and do not recur after excision, neither further treatment beyond local excision nor surveillance is recommended.60
Gastrointestinal stromal tumors
Clinical characteristics
GISTs are rare tumors of the gastrointestinal tract and comprise 1–3% of gastric neoplasms.61, 62 These tumors are most commonly found in men and in the gastric fundus, although they can be found in other regions of the stomach. The gastric mucosa that surrounds these lesions is usually normal. Microscopic GISTs are common in the upper stomach of Japanese patients who have undergone gastric resection for gastric cancers, which suggests that only a few lesions enlarge and develop malignant potential.63
Endoscopically, GISTs are well-circumscribed submucosal lesions (median diameter 6 cm) that occasionally show an eroded or ulcerated overlying mucosa (Figure 5a). The gastric mucosa tends to slide over benign, submucosal tumors, which might be missed by the biopsy forceps. Thus, representative tissue is best obtained by endosonographic fine-needle aspiration. Histologically, GISTs are composed of spindle cells (Figure 5b), in some cases with an epithelioid (rounding-up) morphology.61 These lesions are believed to originate from the interstitial cells of Cajal, the gut's pacemaker cells. GISTs have unique immunostaining characteristics that allow a specific diagnosis: the stain for KIT gene product, CD117, is positive in approximately 95% of cases.61 On the basis of size and mitotic activity, GISTs are categorized for risk of malignancy (very low risk to high risk).
Figure 5 | A gastrointestinal stromal tumor.
a | An endoscopic view showing a well-circumscribed, hard, submucosal polyp with normal overlying mucosa. These polyps are often large when detected, and their surface may be ulcerated. b | Histological view (low power) of the tumor. A high-power image (inset) shows that the lesion is formed by a compact mass of whirling CD117-positive spindle cells, which usually infiltrate the submucosa. The overlying mucosa is edematous with distorted glands displaced by the infiltrating neoplastic cells.
Management
All GISTs must be considered as having malignant potential, with up to 50% of patients having metastatic disease at presentation, usually of the liver.64 In practice, a strong correlation exists between the mitotic activity, size, and clinical behavior of GISTs. Surgical resection is recommended for lesions >2 cm; endoscopic enucleation followed by surveillance is an option for small GISTs. Endoscopic removal is controversial, however, because of reports of positive resection margins and tumor spillage.65 Tyrosine kinase inhibitors are used as targeted therapy in cases of metastasis and surgically unresectable GISTs.66 Neoadjuvant therapy with use of tyrosine kinase inhibitors after surgical resection of high-risk GISTs deters recurrence, but the optimal duration of therapy remains unknown.67
Carcinoids
Clinical characteristics
Carcinoids comprise less than 2% of gastric polypoid lesions.4, 68 The term carcinoid is used here in the traditional connotation of a type of neuroendocrine tumor derived from enterochromaffin-like (ECL) cells.69 Three types of carcinoids are recognized: type I are associated with chronic autoimmune atrophic gastritis (65–80% of all gastric carcinoid tumors, female predominance, often accompanied by pernicious anemia); type II are associated with Zollinger–Ellison syndrome and multiple endocrine neoplasia type 1 (3–15% of tumors); type III are sporadic (20% of tumors, male predominance).70 Type I carcinoids are associated with hypergastrinemia, which results from loss of negative feedback to the G cells in the antrum secondary to the destruction of parietal cells and increasing gastric pH. Type II carcinoids are also associated with hypergastrinemia, but as a result of a gastrinoma—a gastrin-producing tumor that leads to the development of hypertrophic parietal cells and ECL-cell hyperplasia. Carcinoids associated with hypergastrinemia are usually multiple, broad-based, firm, yellowish lesions located in the body and fundus of the stomach, and rarely measure >2 cm (Figure 6a). Sporadic carcinoid tumors occur in a normal gastric mucosa with no apparent associations; they are typically single, tend to be prepyloric, and are usually >2 cm when detected.71, 72
Figure 6 | A carcinoid.
a | An endoscopic view showing the broad-based appearance of these polyps with a yellowish tinge. b | A low-power histological view showing that these polyps are formed by ribbons and clusters (nests) of small monotonous cells (clearly visible at higher power [inset]) that displace the normal mucosal glands. Larger lesions expand into and beyond the muscularis mucosae.
Histologically, carcinoids are composed of nests or ribbons of endocrine cells (small polygonal cells with round nuclei featuring 'salt and pepper' chromatin) (Figure 6b). Necrosis, anaplasia, increased mitotic activity, and size >2 cm are markers of aggressive behavior, and are found exclusively in sporadic carcinoids.71 The carcinoid syndrome (which is characterized by cutaneous flushing, diarrhea, bronchospasm and cardiac valvular lesions) is present almost exclusively in patients with sporadic carcinoids.70
Management
Prognosis and therapy depend on the type of carcinoid.73 Type I carcinoids rarely metastasize, 5-year survival rates of 95% are reported, and patients may be followed up endoscopically after local excision and biopsy specimens have been obtained from the surrounding mucosa.72, 73, 74 Surveillance is not recommended in patients with pernicious anemia, although according to ASGE guidelines, the performance of one endoscopy is appropriate.42 Antrectomy might be considered if a patient has multiple carcinoids. The prognosis of patients with type II carcinoids is excellent when the underlying gastrinoma can be successfully removed; when this is not possible, endoscopic polypectomy followed by surveillance is the accepted therapy and management.75 Sporadic carcinoids behave like neuroendocrine carcinomas, with a propensity for invasion and metastases. The therapy of choice is gastrectomy, but the 5-year survival rate remains below 50%.68
Xanthomas
Clinical characteristics
Xanthomas (also known as xanthelasmas) are small (<3 mm), yellowish nodules or plaques that barely protrude from the surrounding pink gastric mucosa (Figure 7a). These sessile lesions, which rarely attain the size and shape of a polyp, are often found near the site of mucosal repair, such as gastrectomy stomas, ulcers, or, less commonly, the mucosa adjacent to an adenocarcinoma. Xanthomas are also commonly associated with chronic gastritis and may be found in small clusters along the lesser curvature, antrum, and prepyloric areas of the stomach. Histologically, they consist of aggregates of lipid-laden macrophages that contain cholesterol and neutral fat loosely embedded in the lamina propria (Figure 7b). Their prevalence is low in the West; however, for unknown reasons, possibly related to the high prevalence of chronic gastritis, these lesions are common in Asia.76
Figure 7 | A xanthoma.
a | Endoscopic view. As their name indicates, xanthomas are pale-yellow plaques or nodules, and are often multiple (arrows). b | A low-power histological view showing irregular expansions of the lamina propria (X), which is filled by macrophages laden with foamy-appearing lipids (inset high-power view). The overlying epithelium is usually made of normal mucosa.
Xanthomas represent a reparative response and are not associated with hypercholesterolemia. In cases of chronic gastritis, they might be associated with intestinal metaplasia and hyperplastic polyps.77
Management
Xanthomas are, in themselves, clinically insignificant lesions. However, because of their possible association with other potentially serious conditions of the stomach, the remainder of the gastric mucosa should be examined carefully.77
Pancreatic heterotopia
Clinical characteristics
Pancreatic heterotopia can be found in two clinical settings in the stomach. The first presentation, only rarely seen endoscopically as a polyp, consists of small, submucosal nodules (single or multiple, usually containing only a few glands) of pancreatic tissue at the cardioesophageal junction; this finding is known as pancreatic metaplasia, although whether it represents real metaplasia or heterotopia is unclear. This condition is found in 5–15% of individuals who undergo endoscopy for GERD and have a biopsy specimen taken from the esophageal junction. In some studies, pancreatic metaplasia at the cardioesophageal junction has been related to inflammation at the gastroesophageal junction. The significance of this condition is unclear, but no indication that pancreatic metaplasia has neoplastic potential has been found.78, 79
The other type of pancreatic heterotopia is usually discovered as a submucosal lesion in the antral and prepyloric regions of the stomach, sometimes with a central dimple if a duct is present (Figure 8a). This type is uncommon; it represents <1% of all gastric polyps.80 These lesions are solitary and composed mostly of acinar tissue, often with ducts and seldom with islet cells. The histology resembles normal pancreatic tissue. As is the case with all submucosal lesions, they are easily missed in superficial biopsies (Figure 8b). The gastric mucosa that surrounds these lesions is usually unremarkable.
Figure 8 | A pancreatic heterotopia.
a | Endoscopic view showing a pyloric channel polyp with a central dimple, which may be a draining pancreatic duct. Although considered typical, this endoscopic appearance is by no means the most common. Most pancreatic heterotopias are seen as small, smooth nodules lined by normal gastric mucosa. b | Histological features of a nodule of pancreatic acinar tissue (limited by converging black arrows) completely surrounded by normal oxyntic mucosa. This is the most common microscopic appearance of pancreatic heterotopia in the stomach, with neither ducts nor islets readily visible.
Management
Pancreatic heterotopia is a benign and usually asymptomatic lesion; thus, no therapy is warranted.80 Symptomatic lesions (large enough to cause gastric-outlet obstruction) are rare, and can be treated by resection.81 Ductal adenocarcinomas, islet-cell tumors, and pancreatitis that arises in heterotopic pancreatic tissue have been reported, but the rarity of such occurrences suggests that neither surgical excision nor endoscopic surveillance are warranted.82, 83
When a polyp is not a polyp
In our 2009 series,10 16.1% of 7,925 gastric biopsy specimens identified endoscopically as a polyp or nodule had no histopathological features that could meet the diagnostic criteria of one of the recognized gastric polyps. The overwhelming majority of these specimens consisted of normal or inflamed gastric mucosa. Mucosal folds, edema of the lamina propria, foveolar hyperplasia, and prominent lymphoid follicles might have the endoscopic appearance of a small polyp. The practice, now routine in many centers, to attach an endoscopic picture or a detailed description of the lesion to the pathology requisition is crucial to formulation of an informed report. For example, if endoscopy shows a smooth, round antral nodule and the biopsy specimen reveals a perfectly normal mucosa, a sensible pathologist will add a comment to suggest that the biopsy specimen may not be representative of the lesion, and a submucosal lesion may not have been sampled. If a malignant-looking, necrotic ulcerated lesion is seen endoscopically, but the biopsy specimen shows only dysplastic, but not invasive, epithelium, the pathology report should clearly state that a repeat biopsy is necessary. Gastroenterologists who routinely receive diagnoses of polypoid mucosa, mild hyperplastic features, and similar vacuous expressions should suspect that their pathologist is trying to appease them with a diagnosis that fits the endoscopy. A frank conversation with the pathologist and a few sessions at the microscope could go a long way to improve the specificity of diagnoses and, ultimately, care of patients.
Conclusions
Although no precise epidemiologic data exist, gastric polyps are common, and most often fall into the categories of fundic-gland, hyperplastic, and adenomatous polyps. However, an impressive variety of gastric lesions might present as a polyp, and understanding the need to obtain a biopsy specimen from the gastric mucosa adjacent to a lesion is critical for a cohesive pathological diagnosis. Although polyps are occasionally the cause of symptoms that require endoscopic investigation, they are often a marker of underlying gastritis that may require diagnosis and treatment. Appropriate surveillance protocols, detailed above, exist for polyps with a known neoplastic risk, and the ASGE surveillance recommendations for polyps and polyposis syndromes are also available online.84
Review criteria
The MEDLINE and PubMed databases were searched in October 2008 for English-language articles. The terms "polyp", "fundic-gland polyp", "hyperplastic polyp", "adenoma", "gastrointestinal stromal tumor", "polyposis", "pancreatic heterotopia", "xanthoma", "inflammatory fibroid" and "carcinoid" were combined with "stomach" and "gastric" to locate articles. Reference lists were checked for additional relevant papers.
