CHAPTER 18
Gastritis and gastropathy

M. Blanca Piazuelo, Richard M. Peek, Jr, and M. Kay Washington

Vanderbilt University Medical Center, Nashville, TN, USA

Normal gastric mucosa

The stomach may be divided into two morphologically and functionally different compartments: the corpus/fundus, lined by oxyntic mucosa, and the antropyloric region, lined by mucous glands (Figure 18.1).

Autoimmune gastritis

Autoimmune gastritis is a corpus‐predominant chronic atrophic gastritis induced by antiparietal cell and anti‐intrinsic factor autoantibodies. Most clinical manifestations result from the loss of parietal and chief cells of the oxyntic mucosa, and only become apparent in the advanced stages of the disease. Major effects include achlorhydria, hypergastrinemia, loss of pepsin and pepsinogens, iron deficiency with macrocytic anemia, vitamin B₁₂ deficiency with megaloblastic anemia, and increased risk of gastric neoplasms, particularly neuroendocrine tumors.

Endoscopic appearance

The corpus mucosa is usually thinner than normal; this explains why few folds are left and fine submucosal vessels are easily recognized at endoscopic examination, especially in advanced stages of disease (Figure 18.2). Although the atrophic changes predominate in the oxyntic mucosa, they may be observed in the antrum (Figure 18.3).

Histopathological aspects

The main histopathological features of advanced autoimmune gastritis are the diffuse involvement of the oxyntic mucosa by chronic atrophic gastritis (Figure 18.4), with pseudopyloric or intestinal metaplasia and a gastric antrum that may either be normal or show features of atrophy. Enterochromaffin‐like cell hyperplasia (linear and micronodular) (Figure 18.5), and neuroendocrine tumors are commonly found in the advanced stages of the disease. Hyperplasia of gastrin cells, secondary to achlorhydria, is also often seen.

Helicobacter pylori gastritis

Helicobacter pylori is the most common cause of gastritis. Unless eradicated, this bacterium triggers a series of histological lesions known as the Correa cascade that may lead to gastric cancer after decades of infection. Nonneoplastic lesions (pertinent to this chapter) may be grouped into two main categories: nonatrophic gastritis and atrophic gastritis. The term “atrophic gastritis” encompasses a wide spectrum of morphological manifestations; the main variants are atrophic gastritis without metaplasia, pseudopyloric metaplasia, and intestinal metaplasia. Intestinal metaplasia is found most frequently in patients with either current or past H. pylori infection. However, similar to the other variants of atrophy, the presence of intestinal metaplasia is not exclusive to this infection, but rather a manifestation of chronic injury to the gastric mucosa. The clinical significance of gastric atrophy, and especially of intestinal metaplasia, is related to its association with dysplasia and gastric cancer. The risk of progression to cancer is related to the extension and topographic localization of the atrophic‐metaplastic changes.

Endoscopic appearance

Hyperemia, erosions, ulcerations, hypertrophy, and atrophy may coexist in various combinations in the same stomach, juxtaposed to one another and to apparently normal areas, and none of these features has been proven useful for predicting the presence or absence of chronic H. pylori gastritis. Although there is no distinct endoscopic pattern of chronic H. pylori gastritis, the uncommon pattern of follicular gastritis (Figure 18.6) is almost invariably associated with this infection. The presence of peptic ulcers or gastric cancer, both caused by H. pylori gastritis, also suggests the presence of the infection. Endoscopic manifestations of atrophy are similar to those described for autoimmune gastritis, although atrophic changes related to H. pylori predominate in the antral mucosa (see Figure 18.3).

Intestinal metaplasia is usually difficult to diagnose endoscopically. The endoscopic feature most commonly associated with intestinalization is an irregular surface with patchy pink and pale areas (Figure 18.7). A technique that has gained much favor in Japan, but which has not been found to be very reliable in either the United States or Europe, is spraying of the gastric mucosa with indigo carmine, toluidine blue, or methylene blue. After the metaplastic mucosa sample is washed with saline, it maintains the characteristic blue color and may be differentiated from the nonmetaplastic areas.

Photo depicts normal gastric mucosa. — **Figure 18.1** Normal gastric mucosa. **(a)** Oxyntic mucosa composed of tightly packed glands lined mainly by parietal and chief cells, and mucous cells in the foveolar (superficial) epithelium. **(b)** Normal antral mucosa composed of mucous glands.

Source: M. Blanca Piazuelo.

Photo depicts endoscopic view of the corpus with severe atrophy. — **Figure 18.2** Endoscopic view of the corpus with severe atrophy. The mucosa appears thin and the underlying vasculature is prominent.

Prolonged use of proton pump inhibitors (PPIs), a very common practice in patients with H. pylori gastritis, may lead to development of fundic gland polyps. They appear endoscopically as small smooth polyps in the oxyntic mucosa.

Photo depicts an endoscopic picture from a case similar to that depicted in Figure 18.1 with clearly visible mucosal and submucosal vessels seen in a patient with antral atrophy. — **Figure 18.3** An endoscopic picture from a case similar to that depicted in Figure 18.1 with clearly visible mucosal and submucosal vessels seen in a patient with antral atrophy. The bluish discoloration is the shade of the liver seen through the thin distended gastric wall.

Histopathological features

In infected patients, the gastric mucosa often contains large numbers of H. pylori organisms characteristically attached to the foveolar epithelium (Figure 18.8). The lamina propria shows lymphoplasmocitary infiltration of variable intensity and lymphoid follicles (Figures 18.9 and 18.10). The presence of neutrophils characterizes the “active” component of chronic gastritis. Neutrophils are seen both in the lamina propria and within the foveolar epithelium (Figure 18.11). They are almost never found in areas of intestinal metaplasia (typically not colonized by H. pylori) and disappear rapidly after successful eradication therapy. In nonatrophic gastritis, the original glands are preserved (see Figure 18.9). Lymphocytic gastritis, a special type of gastritis with abundant intraepithelial lymphocytes, may be observed in patients with H. pylori infection (Figure 18.12).

Photo depicts gastric corpus mucosa in autoimmune gastritis showing marked loss of the normal architecture. — **Figure 18.4** Gastric corpus mucosa in autoimmune gastritis showing marked loss of the normal architecture. The normal tightly packed acid‐secreting oxyntic glands have been progressively destroyed by the inflammatory process and some of them are replaced by mucus‐secreting glands similar to those found in the distal antrum (pseudopyloric metaplasia). The lamina propria shows fibrosis and infiltration of mononuclear leukocytes.

Source: M. Blanca Piazuelo.

Atrophic gastritis without metaplasia is characterized by loss of glands (Figures 18.13 and 18.14), inflammatory infiltrate, and in some cases fibrosis of the lamina propria. Pseudopyloric metaplasia is the replacement of oxyntic glands with glands of antropyloric appearance (Figure 18.15). In the absence of adequate topographic information of the biopsy specimen, extensive pseudopyloric metaplasia may be indistinguishable from antropyloric mucosa, unless special stains are performed.

Intestinal metaplasia is the replacement of epithelial cells that line the normal gastric mucosa with an epithelium of intestinal phenotype. It is considered a precancerous lesion, but is also very heterogeneous and some variants are associated with higher risk of progression to gastric cancer. One of the most commonly used classifications of intestinal metaplasia recognizes two types: complete (or small intestinal) and incomplete (or colonic). The incomplete type is associated with a higher risk of cancer. In most cases, intestinal metaplasia can be subtyped based on morphology on H&E‐stained sections (Figure 18.16). Additional histochemical stains, such as Alcian blue at pH 2.5/periodic acid–Schiff (AB‐PAS), may be useful (Figure 18.17).