The stomach is functionally a more complex organ than the rest of the luminal gastrointestinal tract, with variable histology based on anatomic location and physiologic function. Based purely on anatomic landmarks, the stomach can be divided into the cardiac opening, fundus, body, antrum, and pylorus (Fig. 2.1). To a pathologist, however, the organ is best compartmentalized based on physiologic function of the mucosa, which does not always correspond with anatomic landmarks. A basic understanding of gastric mucosal physiology will aid in the diagnosis and understanding of common gastritides.1–14
LAYERS
The layers of the stomach are structurally similar to the rest of the luminal gastrointestinal tract and can be divided into the gastric mucosa, submucosa, muscularis propria, and serosa (Fig. 2.2). The mucosa consists of epithelium, lamina propria, and muscularis mucosae. The epithelial component includes superficial pits (foveolae) that are lined by mucus-secreting foveolar epithelium and line the entire surface of the stomach, regardless of site. Deep to these pits are the gastric glands, which differ in function and epithelial cell type depending on location, and are discussed in detail later (Histology and Function, next subsection). The lamina propria between the pits and glands contains lymphovascular spaces and is normally nearly devoid of inflammatory cells. The muscularis mucosae is composed of a thin layer of smooth muscle cells, separating the mucosa from the underlying submucosa that contains abundant lymphatic and vascular structures. The muscularis propria of the stomach is composed of three sets of smooth muscle fibers&emdash;longitudinal, circular, and oblique. The serosa is derived from the peritoneum and surfaced by mesothelial cells.
FAQ: Are there lymphatic spaces in the gastric lamina propria? Is a gastric intramucosal carcinoma capable of metastasizing to lymph nodes?
Answer: Yes. Lymphatic channels are present in the lamina propria of the gastric mucosa. They are found directly superficial to the muscularis mucosae and connect to larger efferent channels in the submucosa. Even an early gastric carcinoma without submucosal invasion can have lymphatic metastasis, although such superficial tumors usually do not.
Figure 2.1 Anatomic compartments of the stomach. Although the stomach can be compartmentalized based on anatomic landmarks, the histologic compartmentalization of the stomach is based on physiologic function. The gastric fundus and corpus (body) are composed of oxyntic mucosa, whereas the pyloric antrum and pylorus contain pyloric glands.
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.
HISTOLOGY AND FUNCTION
Body/Corpus and Fundus (“Oxyntic Mucosa”)
The largest histologic compartment is the gastric body and fundus, comprising 90% of the gastric mucosa (Fig. 2.1). They share similar histology and function as both contain oxyntic (or fundic) glands and have shallow pits that extend less than 25% of the distance to the base (Fig. 2.3). The superficial isthmus contains intensely pink acid-secreting parietal cells that also produce intrinsic factor, important for absorption of vitamin B12 (Fig. 2.4). By comparison, the base of the glands contains bluish-purple pepsinogen-secreting chief cells and scattered enterochromaffin-like (ECL) endocrine cells. The intervening neck area contains a mixture of chief, parietal, and mucus neck cells, the latter of which are important in mucosal regeneration (Figs. 2.5 and 2.6) and should not be mistaken for signet ring cells.
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.
Antrum and Pylorus (“Antral Mucosa”)
The antrum and pylorus comprise the second largest histologic compartment, and most practitioners regard them as interchangeable, as they are histologically similar (Fig. 2.1). The pits of the gastric antrum comprise approximately 50% of the distance to the base of the glands (Fig. 2.7). Abundant lamina propria separates the purely mucus-secreting tortuous glands of the antral mucosa. These cells have abundant frothy cytoplasm with nuclei that appear flattened against the basal aspect (Fig. 2.8), similar to those seen in Brunner glands and gastric cardiac glands. Importantly, gastrin-producing G cells are exclusively found in the gastric antral glands, and they can be highlighted with a gastrin immunohistochemical stain (Fig. 2.9).
FAQ: Why does my “antrum” biopsy frequently look like oxyntic mucosa?
Answer: More than 90% of the gastric mucosa is oxyntic type, leaving only the distal-most portion of the stomach as true antral-type mucosa. It is not unusual for endoscopists to capture transition zone, or even distal corpus when targeting the gastric antrum.
PEARLS & PITFALLS
By comparison, it would be highly unusual for the endoscopist to miss a targeted biopsy of the body or fundus. If a specimen labeled as “body” or “fundus” shows antral-type histology, consider one of the following scenarios:
• Atrophy of the gastric corpus, such as in autoimmune metaplastic atrophic gastritis
• Mixed specimen or carryover
An immunohistochemical stain for gastrin can be helpful in this scenario by highlighting the antral restricted “G” cells; biopsies from the antrum would have a prominent band of G cells, and those from the body/fundus are nonreactive for gastrin (Figs. 2.10–2.13). See also Chronic Gastritis subsection, this chapter.
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.
Transition Zone (“Transitional Mucosa”)
Histologically, the transition between the oxyntic and antral mucosa is gradual, spanning 1 to 2 centimeters. The histology shows mixed glands in varying proportions (Fig. 2.14).
Cardia
The smallest gastric compartment, the gastric cardia, is composed of mucus-secreting cells and is devoid of acid-secreting chief cells and parietal cells. Histologically, the surface epithelium is lined by foveolar cells and the pits and glands are composed of pyloric-type glandular epithelium. In the absence of a biopsy location provided by the endoscopist, the histology is nearly indistinguishable from that of the gastric antrum (Fig. 2.15).
FAQ: Why do my gastric cardia biopsies frequently contain oxyntic mucosa?
Answer: The length of cardiac mucosa is variable. The cardia typically spans only 1 to 4 mm in most adults. It was originally believed that the gastric cardia developed as people aged; however, autopsy studies have disproven this idea, as some infants have cardiac glands and some elderly persons have none, transitioning directly from squamous mucosa to acid-secreting mucosa (Fig. 2.16). Although controversial, the presence of gastric cardiac-type mucosa has also been regarded by some as a purely metaplastic condition secondary to gastroesophageal reflux, Helicobacter infection, and autoimmune gastritis.
PEARLS & PITFALLS
Chronic inflammation is so ubiquitous a finding in the gastric cardia that many practitioners do not mention this finding in their reports; however, the gastric cardiac mucosa may harbor Helicobacterorganisms (Fig. 2.17). It is prudent to examine closely or perform staining for Helicobacter organisms in the following scenarios:
• If the pattern of the infiltrate is characteristic of Helicobacter infection; specifically active chronic inflammation, superficial lymphoplasmacytic inflammation, and or prominent lymphoid aggregates with well-formed germinal centers, or
• If the inflammation is exuberant and no additional gastric biopsies were obtained from the gastric antrum and body. In this scenario, careful examination of the cardia might be the only opportunity to diagnose an underlying Helicobacter infection.
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).