Figure 2.2 Layers of the stomach. This resection specimen illustrates the four main layers of the stomach: mucosa, submucosa, muscularis propria, and serosa. The mucosa consists of epithelium (E), lamina propria (L), and muscularis mucosae (MM). The submucosa sits between the muscularis mucosae and the muscularis propria (MP). The MP consists of three muscle layers: the inner oblique, middle circular and outer longitudinal, which function in gastric contraction and peristalsis. The outermost layer is the serosa.

Figure 2.3 Pits and glands in oxyntic mucosa. The gastric pits are lined by foveolar epithelium, a finding that is common throughout the gastric mucosa, independent of site. The deeper glands of the oxyntic mucosa can be divided into (1) the superficial isthmus, composed primarily of the bright pink parietal cells, (2) the transitional neck area, containing a mixture of parietal cells, mucus neck cells, and chief cells, and (3) the base, composed almost entirely of the more basophilic chief cells.

Figure 2.4 Physiology of the parietal cell. The parietal cell has a number of important functions, including production of intrinsic factor (IF) which binds vitamin B12 (cobalamin), thus, allowing the complex to be transported across the small bowel wall. In addition, parietal cells are stimulated to produce acid (H+) by gastrin (produced in the antrum by the “G” cell) and histamine (secreted predominantly in the oxyntic mucosa by ECL cells). Whereas high acid levels inhibit gastrin secretion, conversely, hypoacidic states, such as those with parietal cell atrophy or loss, result in uninhibited secretion of gastrin.

Figure 2.5 Neck of oxyntic glands. There are three cells types within the neck area of the oxyntic glands. The pink parietal cells and the blue chief cells are easily discernible on routine H&E. Harder to appreciate are the mucous neck cells (arc), which are the proliferative stem cell of the gastric glands.

Figure 2.6 Normal oxyntic mucosa cut in cross section. In tissue sections that are oriented tangentially, the oxyntic glands have a mixture of pink parietal and blue chief cells arranged around a central lumen (arrows). Note the abundant capillaries (arrowheads) at the basal aspect of each gland, and the scant lamina propria.

Figure 2.7 Normal antral mucosa. The pits of the antrum are much deeper as compared to the oxyntic mucosa, comprising sometimes greater than 50% of the mucosal thickness. The deeper pyloric glands are composed of mucus secreting cells.

Figure 2.8 Pyloric glands. The pyloric glands are composed of mucus secreting cells with abundant clear foamy cytoplasm and basally located nuclei, which are sometimes flattened, similar to those seen in Brunner glands and the gastric cardia.

Figure 2.9 G cells (gastrin immunostain). A gastrin immunohistochemical stain highlights a band of G cells, which are exclusively found in the gastric antrum. Their presence can be exploited to identify site of tissue origin.

Figure 2.10 Gastric antrum mislabeled as gastric body. This tissue was received in a jar labeled “stomach, body.” There is a complete lack of oxyntic glands, suggesting this tissue likely originated from the gastric antrum.

Figure 2.11 Gastric antrum mislabeled as gastric body (gastrin immunostain). A gastrin stain of the previous figure highlights a band of G cells, confirming the antral origin of this tissue (oxyntic mucosa lacks G cells).

Figure 2.12 Gastric body with total oxyntic gland atrophy. This tissue fragment was received in a jar labeled “stomach, body.” Similar to the previous case (Fig. 2.10), there is a total lack of oxyntic glands. Note the extensive background intestinal metaplasia.

Figure 2.13 Gastric body with total oxyntic gland atrophy (gastrin immunostain). A gastrin stain of the previous figure fails to highlight any G cells, confirming that this biopsy fragment originated from the gastric body or fundus. The total atrophy of oxyntic glands and presence of intestinal metaplasia raises the suspicion for autoimmune metaplastic atrophic gastritis (AMAG). See also Chronic Gastritis, this chapter.

Figure 2.14 Transitional mucosa. The junction of the body and antrum contains a transition zone that includes a mixture of both the clear pyloric glands of the antrum (left bracket), and the mixed pink and blue oxyntic glands of the body (right bracket).

Figure 2.15 Gastric cardia. The gastric cardia is lined by surface foveolar epithelium and the glands are composed of mucous-secreting cells which are histologically identical to those found in the gastric antrum. It is not unusual to see some inflammatory cells in the lamina propria of the gastric cardia.

Figure 2.16 Minimal gastric cardia. Seen here is the gastroesophageal junction, with squamous epithelium on the far left, gastric cardiac mucosa composed of a few clear pyloric-like glands (arrow) and an immediate transition into the mixed pink and blue oxyntic glands (arrowhead) of the fundus. The cardia differs from the antrum in lacking G cells.

Figure 2.17 Helicobacter pylori carditis. This biopsy of the gastric cardia was performed in evaluation of Barrett esophagus. Although the gastric cardia may have some mild chronic inflammation, the presence of a lymphoid aggregate, expanded lamina propria, and superficial infiltrate should prompt a careful search for Helicobacter organisms. Indeed, Helicobacter organisms were identified on H&E (not shown).

Figure 2.18 Reactive gastritis/gastropathy pattern. Reactive gastritis/gastropathy is another example of an entity that is best appreciated at scanning magnification. At low power, the surface epithelium appears dark because of the mucin loss, and it is easy to appreciate the corkscrew-like appearance of the gastric pits (arrowheads). As true for most cases of reactive gastritis/gastropathy, the background inflammation is minimal.

Figure 2.19 Reactive gastritis/gastropathy pattern. On higher power, the mucin loss is apparent: the surface foveolar epithelium has tiny apical caps of mucin, instead of the normal tall mucin-rich cytoplasm seen in normal apical epithelium. At this power, it is also easy to appreciate the smooth muscle bundles (arrows) between the corkscrew-like gastric pits (arrowheads) which extend toward the surface.

Figure 2.20 Reactive gastritis/gastropathy pattern. Again, the key features of reactive gastritis/gastropathy “jump off the slide” at scanning magnification: gastric surface foveolar mucin cell depletion, a corkscrew-like appearance of the gastric pits, lamina propria edema, smooth muscle bundles splaying foveolar epithelium, and little to no inflammation. If you have to go to 40× to appreciate the key features of reactive gastritis/gastropathy, it is not reactive gastritis/gastropathy! These features should be apparent at scanning magnification.

Figure 2.21 Reactive gastritis/gastropathy pattern. This case manifests all the key features of reactive gastritis/gastropathy: surface foveolar mucin cell depletion, a corkscrew-like appearance of the gastric pits, lamina propria edema, smooth muscle bundles extending to toward the surface, and little to no inflammation.

Figure 2.22 Reactive gastritis/gastropathy pattern. This case is a bit more subtle than the previous cases (Figs. 2.18–2.21) since the gastric foveolar epithelium is not quite as dark or corkscrew-like and lamina propria edema is not seen. Instead, this case features prominent smooth muscle hypertrophy (arrowheads) as it splays and envelopes the involved gastric pits. Gastric foveolar mucin cell depletion and a smattering of chronic inflammation are seen.

Figure 2.23 Reactive gastritis/gastropathy pattern with occasional congested vessels. This case illustrates that congested vessels are occasionally seen in the reactive gastritis/gastropathy pattern (arrowheads). In this case, a quick chart review was helpful to assess for a history of portal hypertension (as would be expected if these congested vessels were a part of portal hypertensive gastropathy) or if a striped watermelon endoscopic appearance was seen (to suggest a diagnosis of gastric antral vascular ectasia). A chart review was noncontributory in this case.

Figure 2.24 Reactive gastritis/gastropathy pattern and erosion. Erosions (blue bracket) are denudations limited to the mucosa and are often accompanied by fibrino-inflammatory debris. The fibrin deposition is “biologic proof” that true tissue damage has occurred prior to the biopsy, that is this is not a histologic artifact of tissue mishandling. The mucosa consists of the E, epithelium; L, lamina propria; MM, muscularis mucosae.

Figure 2.25 Reactive gastritis/gastropathy pattern with erosion. This example of reactive gastritis/gastropathy features an erosion with focal fibrin deposition (arrowhead).

Figure 2.26 Reactive gastritis/gastropathy pattern and ulceration. In contrast to erosions which are confined to the mucosa, ulcerations extend through and beyond the muscularis mucosae and involve at least the submucosa (red bracket). The mucosa consists of the E, epithelium; L, lamina propria; MM, muscularis mucosae and the submucosa is between the muscularis mucosae and the muscularis propria.

Figure 2.27 Reactive gastritis/gastropathy pattern, iron deposition. Reactive gastritis/gastropathy is a nonspecific injury pattern, that can be caused by a variety of unrelated entities. Careful scrutiny of the background can occasionally uncover clues to the etiologic injury, such as iron deposition in this case.

Figure 2.28 Reactive gastritis/gastropathy pattern, iron deposition (Prussian blue). A Prussian blue iron stain highlights the iron deposition.

Figure 2.29 Reactive gastritis/gastropathy pattern, portal hypertensive gastropathy. This case shows the usual features of reactive gastritis/gastropathy in addition to a prominence of congested mucosal vessels. A careful chart review uncovered the red flags of cirrhosis, portal hypertension, and endoscopic abnormalities suggestive of portal hypertensive gastropathy. These features support the clinicopathologic diagnosis of portal hypertensive gastropathy.

Figure 2.30 Reactive gastritis/gastropathy pattern, gastric antral vascular ectasia. Reactive gastritis/gastropathy can be an important clue to the diagnosis of gastric antral vascular ectasia. Other diagnostic features include mucosa thrombi (arrowhead) and an endoscopic image showing a striped-watermelon-like pattern.

Figure 2.31 Active chronic reactive gastritis/gastropathy. In exceptionally striking examples of reactive gastritis/gastropathy, sometimes a prominence of acute and chronic inflammation is seen, as in this case.

Figure 2.32 Active chronic reactive gastritis/gastropathy. The acute inflammation is best appreciated on higher power (arrowheads). The prominent pattern is reactive gastritis/gastropathy with a minimal amount of acute and chronic inflammation.

Figure 2.33 Acute gastritis example. An acute gastritis pattern refers to neutrophils in the gastric epithelium of the stomach (arrows). Acute gastritis pattern is an etiologically nonspecific pattern. This case features a single epithelial cell with nuclear and cytomegaly and smudged chromatin (arrowhead). A confirmatory CMV immunostain was reactive (not shown).

Figure 2.34 Nonspecific pill fragments. Pill fragments not otherwise specified can be easy to miss on H&E because of their transparent appearance (arrowheads).

Figure 2.35 Nonspecific pill fragments. When the substage condenser is flipped, the outline of the pill fragments is often better appreciated (arrowheads) due to increased light refraction. Occasionally, pill fragments are refractile.

Figure 2.36 Nonspecific pill fragments (PAS). Often, these pill fragments are bright pink on PAS staining, which sometimes raises concern for swallowed parasitic ova; however, parasitic ova are exceptionally uncommon, if not reportable. Moreover, parasitic ova are expected to be more uniform is size and shape, associated with a tissue reaction, and seen in the clinical setting of pertinent clinical symptoms.

Figure 2.37 Acute gastritis pattern, Helicobacter pylori. This prototypic example of Helicobacter pylori gastritis shows prominent lymphoid aggregates with a germinal center and a superficial lymphoplasmacytosis that appears band-like and snug beneath the surface foveolar epithelium (bracket). These characteristic features are highly suggestive of Helicobacter gastritis at scanning magnification. Helicobacter pylori was identified on higher-power (not shown).

Figure 2.38 Acute gastritis pattern, Helicobacter pylori. This example shows features highly suggestive of Helicobacter gastritis at scanning magnification: prominent lymphoid aggregates and a band-like superficial lymphoplasmacytosis (bracket) are seen.

Figure 2.39 Acute gastritis pattern, Helicobacter pylori. On high power, a superficial lymphoplasmacytosis is seen along with scattered pockets of acutely inflamed pits (arrowheads). This histologic appearance is highly suggestive of Helicobacter, requiring a thorough “bug hunt” for the organism. Helicobacter pylori were identified on higher-power (not shown).

Figure 2.40 Lymphocytic gastritis pattern, Helicobacter pylori. A lymphocytic gastritis pattern can be an important red flag to the diagnosis of Helicobacter gastritis, as seen in this case. This case also features the usual characteristics of Helicobacter, namely a band-like superficial lymphoplasmacytosis and scattered pockets of acute inflammation (arrowheads). Intestinal metaplasia is seen at the far right (arrow).

Figure 2.41 Lymphocytic gastritis pattern, Helicobacter pylori. On higher power, the intraepithelial lymphocytosis is easily appreciated. Also seen are the superficial lymphoplasmacytosis and pockets of acute inflammation (arrowheads) characteristic of Helicobacter. Helicobacter pylori was identified on higher-power (not shown).

Figure 2.42 Lymphocytic gastritis pattern, Helicobacter pylori. This case originated from a patient with Celiac disease. A Helicobacter immunostain was negative.

Figure 2.43 Acute gastritis pattern, Helicobacter pylori. Unfortunately, most of the time the diagnosis of Helicobacter requires usage of the dreaded 40× objective. Thankfully, only one organism is needed for the diagnosis, and efficient “bug hunts” can speed the diagnostic process by targeting acutely inflamed tissue fragments, particularly those cases that feature superficial, mucin-rich foci, as seen here (arrowheads). Characteristically, the bacilli are helical, slightly curved, or cinched in the midpoint.

Figure 2.44 Acute gastritis pattern, Helicobacter pylori. Note the close association of the Helicobacter pylori organisms to the foveolar epithelium (arrowheads) and their position within the gastric pit (arrow); these are important points of distinction from the normal gastrointestinal tract and oral flora to be discussed below.

Figure 2.45 Acute gastritis pattern, Helicobacter pylori (arrowheads).

Figure 2.46 Acute gastritis pattern, Helicobacter pylori (Warthin-Starry). The organisms appear a bit plumper on a Warthin-Starry since this process coats the organism with the silver compound.

Figure 2.47 Acute gastritis pattern, Helicobacter pylori (Diff–Quik). A Diff–Quik special stain can highlight the organisms (arrowheads).

Figure 2.48 Gastrointestinal tract and oral bacteria. Unlike H. pylori, the gastrointestinal tract and oral bacteria are not found in intimate association with the surface epithelium, and, instead, are more commonly found amidst luminal debris and mixed bacterial flora with rods and cocci, as seen here (arrowheads). Compare with Figure 2.44.

Figure 2.49 Acute gastritis pattern, Helicobacter pylori. Unlike the gastrointestinal tract and oral bacteria, Helicobacter pylori can be found within the gastric pits (arrowheads).

Figure 2.50 Acute gastritis pattern, Helicobacter pylori (Diff–Quik).

Figure 2.51 Acute gastritis pattern, partially treated Helicobacter pylori (Helicobacter pylori immunostain). In partially treated cases, the organisms can be exceedingly difficult to find because of their altered morphology. In this case, the organisms appear small and rounded, requiring the aid of the Helicobacter pylori immunohistochemical stain for confirmation.

Figure 2.52 Acute gastritis pattern, partially treated Helicobacter pylori (Helicobacter pylori immunostain). Note the coccoid morphology, which results from partial treatment effect. These organisms are usually rare and almost impossible to detect on H&E alone.

Figure 2.53 Acute gastritis pattern, Helicobacter heilmannii. At low power, Helicobacter heilmannii and Helicobacter pylori gastritis look similar with antral predominant active chronic inflammation and prominent lymphoid aggregates. Helicobacter heilmannii was identified on higher power (not shown). Compare with Figure 2.37.