Clinical Features and Pathogenesis

Numerous synonyms, including inflammatory polyp, regenerative polyp, and hyperplasiogenous polyp, have been used to describe hyperplastic polyps. The diversity of names is not surprising given the prevalence and pathologic diversity of these lesions. Hyperplastic polyps account for approximately 75% of all gastric polyps.^1,11–14

Hyperplastic polyps are detected most often in older patients, with a peak incidence occurring in the sixth and seventh decades of life,¹ and they are diagnosed equally in both genders.^15–20 Because they most often appear in the context of chronic gastritis, hyperplastic polyps are associated with clinical symptoms and signs similar to those in patients with chronic gastritis. In many cases, patients are asymptomatic. Rarely, large lesions can cause obstructive symptoms if located near the pylorus or gastroesophageal junction. Helicobacter pylori infection is common.

More than 85% of hyperplastic polyps occur in a background of chronic gastritis,^13–15 and this observation has led some to conclude that the lesions develop as a consequence of an exaggerated mucosal response to tissue injury and inflammation.^15,21,22 It is thought that gastritis initiates the process of injury and that the mucosal healing response results in a stepwise progression through phases of foveolar hyperplasia and polypoid foveolar hyperplasia to the formation of a hyperplastic polyp.

Conditions associated with the development of hyperplastic polyps include H. pylori gastritis, chronic non–H. pylori gastritis, chemical or reactive gastritis (including gastritis caused by bile reflux), and gastritis related to Billroth II gastrectomy.^1,15–17,23 The H. pylori CagA protein may have a more direct role, because expression of CagA in the gastric mucosa of transgenic mice produces hyperplastic polyps.^1,24 The tendency of hyperplastic polyps to occur more proximally in the stomach in the setting of autoimmune gastritis (which involves the corpus of the stomach) than in other types of gastritis¹⁵ supports the hypothesis that hyperplastic polyps develop as a consequence of chronic mucosal injury.

In one study, 33% of hyperplastic polyps of the gastroesophageal junction were related to Barrett’s esophagus, and they presumably developed in the context of reflux.²⁵ In other instances, a hyperplastic polyp may be the first biopsy finding that leads to a diagnosis of Barrett’s esophagus.²⁵ One study²² suggests that many so-called hyperplastic polyps (as many as 49%) instead represent foveolar hyperplasia resulting from a lack of significant stromal edema or inflammatory changes, cyst formation, muscle hyperplasia, or large-sized vessels. In that study, 51% of originally diagnosed hyperplastic polyps were reclassified as mucosal prolapse polyps. They occurred more commonly in the antral or prepyloric region of the stomach and showed thickened and hyperplastic-appearing bands of muscle extending toward the surface of the polyp and thick-walled blood vessels, both of which are characteristic of prolapse-type polyps in other areas of the GI tract.

Pathologic Features

Almost 50% of hyperplastic polyps are less than 0.5 cm in greatest dimension at the time of diagnosis; most are smaller than 1 cm. However, lesions may rarely grow to as large as 12 cm. Large polyps can easily be misdiagnosed clinically and pathologically as carcinomas. All hyperplastic polyps should be exhaustively sampled and the entire polyp submitted for histologic evaluation.

Hyperplastic polyps occur most commonly in the antrum, but they can be found anywhere in the stomach.²⁰ They may develop as solitary lesions but frequently occur as multiple polyps, particularly in patients with atrophic gastritis. In some studies, fundic gland polyps have been associated with as much as a 7% incidence of hyperplastic polyps.¹ These data may reflect a link between hyperplastic polyps and gastritis, the frequent use of proton pump inhibitors in chronic gastritis, and an association between proton pump inhibitors and fundic gland polyps.

Grossly, hyperplastic polyps are typically ovoid and contain a smooth surface contour, although villiform or pedunculated polyps may develop (Fig. 20.1, A). Surface erosion is often seen. Rarely, patients may have more than 50 polyps, in which case a diagnosis of gastric hyperplastic polyposis should be considered, although specific diagnostic criteria for this syndrome have not been well established.^26–28 In this situation, pathologists should obtain further clinical and endoscopic information to rule out another type of polyposis disorder, such as juvenile polyposis, Peutz-Jeghers syndrome, or familial adenomatous polyposis (FAP).

Microscopically, hyperplastic polyps are characterized by architecturally distorted, irregular, cystically dilated, and elongated foveolar epithelium (see Fig. 20.1, B). Intestinal metaplasia (i.e., goblet cells) may be identified, particularly in polyps located at the gastroesophageal junction and associated with Barrett’s esophagus. Crowding of cells and infolding of the epithelium often impart a corkscrew appearance. Foveolar cells typically have abundant mucinous cytoplasm, but they may be mucin depleted focally and contain slightly enlarged and hyperchromatic nuclei with prominent nucleoli, which are considered to be regenerative features. Mitotic activity may be brisk in areas of active inflammation and surface ulceration.

Pseudogoblet or globoid mucinous cells, which are frequently seen, are cells that contain apically located nuclei and basally oriented mucous vacuoles (see Fig. 20.1, C). These cells were considered to be dysplastic before they were recognized as a reactive change. Therefore, previously used term globoid dysplasia has been discarded in favor of the more descriptive term dystrophic goblet cell. Intestinal metaplasia is identified in less than 25% of hyperplastic polyps and, paradoxically, is more often seen in the surrounding nonpolypoid mucosa than in the polyp itself. The lamina propria of hyperplastic polyps is typically edematous and congested, with various degrees of acute and chronic inflammation and smooth muscle consistent with prolapse (see Fig. 20.1, D). The inflammatory infiltrate is usually most prominent in the superficial aspects of the polyp and is often associated with surface erosions (see Fig. 20.1, E). In rare cases, granulation tissue associated with ulcerations (see Fig. 20.1, F) may show marked atypical pseudosarcomatous changes in reactive stromal fibroblasts and endothelial cells (see Fig. 20.1, G).

Nodular lymphoid aggregates, with or without germinal centers, may be seen in gastric hyperplastic polyps. Most well-developed hyperplastic polyps also contain thick or thin, wispy bundles of smooth muscle that extend upward from the muscularis mucosae toward the polyp surface and have large, thick-walled blood vessels at the base of the polyp, which may indicate prolapse as a pathogenic factor. These polyps tend to occur in the antral or prepyloric region of the stomach. As noted above, H. pylori infection is common, and organisms are found in as many as 76% of hyperplastic polyps.^15,29

Differential Diagnosis

The differential diagnosis of gastric hyperplastic polyps includes polypoid gastritis, polypoid foveolar hyperplasia, gastritis cystica polyposa or profunda, fundic gland polyps, polyps associated with Ménétrier disease, Cronkhite-Canada syndrome, juvenile polyposis, and Peutz-Jeghers polyposis. Features helpful in determining the correct diagnosis are summarized in Table 20.1. Polyps in patients with polypoid gastritis and polypoid foveolar hyperplasia are typically smaller than hyperplastic polyps, and they lack cystically dilated, irregular, and tortuous foveolar epithelium. The lamina propria of polypoid foveolar hyperplasia contains less inflammation and lacks smooth muscle hyperplasia.

Gastritis cystica polyposa or profunda is closely related to hyperplastic polyps in its pathogenesis and morphologic appearance (see Gastritis Cystica Polyposa or Profunda). The surface and intraluminal portions of these lesions may be identical. However, unlike hyperplastic polyps, gastritis cystica polyposa is characterized by cystically dilated, distorted, and irregularly shaped glands or acellular mucin pools located in the muscularis mucosae or the submucosa. Polyps related to gastritis cystica polyposa often develop adjacent to anastamotic sites in patients who have had a partial gastrectomy.

In contrast to hyperplastic polyps, fundic gland polyps show surface and foveolar hypoplasia and contain cystically dilated glands lined predominantly by parietal and chief cells. Occasional cysts may contain mucous cells. Fundic gland polyps do not normally contain prominent inflammation, ulceration, or marked regenerative changes typical of hyperplastic polyps.

Polyps associated with Ménétrier disease, Cronkhite-Canada syndrome, and juvenile polyps are histologically similar to hyperplastic polyps. Appropriate clinical and endoscopic information is essential to establish a correct diagnosis.³⁰

Examination of Peutz-Jeghers polyps of the stomach may reveal a characteristic arborizing pattern of smooth muscle that is more extensive than that of hyperplastic polyps. Peutz-Jeghers polyps also lack significant stromal inflammation and are usually not associated with underlying chronic gastritis. However, other features of Peutz-Jeghers polyps are similar to those of hyperplastic polyps.

Natural History and Treatment

The natural history of hyperplastic polyps is poorly understood, but some data suggest that as many as 67% remain stable, 27% may enlarge, and 5% shrink with time.^31,32 Recurrent polyps develop in as many as 50% of patients after endoscopic resection.^33,34 Conversely, regression of hyperplastic polyps has been documented in as many as 71% of patients with H. pylori infection after eradication of the bacteria.^29,35,36 Because of the risk of dysplasia in larger polyps, resection is recommended for all polyps greater than 1.5 cm in the largest dimension.