Esophagus: Normal Structures, Developmental Abnormalities, and Miscellaneous Disorders (2024)

Anatomy

The esophagus is a muscular tube that is lined with stratified squamous epithelium. Its average length is about 11 cm in newborn and about 25 cm in adults. The upper boundary of the esophagus consists of cricopharyngeal muscle that forms the upper esophageal sphincter at the level of the sixth cervical vertebra. The esophagus enters the stomach at an oblique angle (angle of His) several centimeters below the diaphragm.

Endoscopists measure esophageal landmarks as the number of centimeters from the incisors. The upper esophageal sphincter is located 15 to 18 cm from the incisors. The gastroesophageal junction is classically described as being approximately 40 cm (range 37-42 cm) from the incisors, but this location varies considerably according to the individual’s height and whether a hiatal hernia is present (Fig. 9-1). In the latter instance, the gastroesophageal junction is located, on average, 36 cm from the incisors; however, in a short person with a hiatal hernia, it may be located as little as 30 cm from the incisors.

The endoscopic determination of the location of the gastroesophageal junction is based on visualizing the zigzag ora serrata, known more popularly as the Z-line; this is the interface between the pearly, gray-white squamous epithelium of the esophagus and the pink-orange columnar epithelium of the stomach (Fig. 9-2). It straddles the region of the lower esophageal sphincter (LES), which appears endoscopically as an indented or contracted part of the distal esophagus. There may not be a strict correlation between the location of the LES zone and the histologic esophagogastric (squamocolumnar) mucosal
junction. This is reflected in the endoscopic appearance of the Z-line. Gastric mucosa may thus normally extend into the esophagus in this irregular (Z-line) fashion. Endoscopically the junction of tubular esophagus with the saccular stomach is defined by the upper border of convergence of the gastric folds, as neither the squamocolumnar junction nor the lower sphincter defined by manometry is considered reliable or accurate.

Figure 9-1. A: Sketch of the LES region and the proximal stomach. A hiatus hernia is present above the diaphragmatic pinch. B: Endoscopic view (prograde) of the squamocolumnar junction (Z-line). The distal end of the esophagus is defined as the proximal end of the gastric folds. The Z-line is almost straight with very few small indentations. (Courtesy of Steffen Muehldorfer, M.D.)

The blood supply to the esophagus is from the inferior thyroid artery in the upper segment; bronchial arteries, direct aortic branches, accessory branch of subclavian artery, and sometimes branches from the intercostal arteries in the midsegment; and the left gastric artery and the left phrenic artery in the distal segment. The venous drainage arises from intercommunicating plexuses that are both superficial and deep to the muscle coats. The upper third of the esophagus drains through the inferior thyroid veins into the superior vena cava. The middle third of the esophagus drains into the azygous system, and the lower third into gastric veins and ultimately into the portal vein.

The innervation of the esophagus is from both the vagus nerve and the sympathetic nervous system. Most of the esophageal musculature is supplied from the vagus nerve. Its fibers anastomose with short postganglionic fibers in the myenteric (Auerbach’s) plexuses. The sympathetic fibers to the esophagus are derived from cervical and thoracic sympathetic ganglia. As is true throughout the gastrointestinal (GI) tract, regulatory peptides interact with neural and muscle elements in the control of normal function.1

The mucosal and submucosal lymphatics communicate with longitudinal lymphatic channels in the muscle coats. The upper third of the esophagus drains into the cervical nodes, the middle third into the paraesophageal and paratracheal nodes of the mediastinum, and the lower third into the para-aortic nodes, nodes in the celiac axis, or both.

Histology

Mucosa. The mucosal lining consists of stratified squamous epithelium of the nonkeratinized type (Fig. 9-3). Occasionally, keratohyalin particles are present, although a well-developed granular cell layer is absent, which differentiates it from the squamous
epithelium of skin. With electron microscopy the cell layers have been characterized as basal, prickle, and functional, the last referring to the flattened surface cells.2 The epithelium is generally 15 cell layer thick (350-450 µm). In clinical practice, one need to only distinguish between the basal and overlying nonbasal cells. The basal cell zone is one to four cells thick and does not exceed 15% of the thickness of the squamous layer except in the most distal centimeters of the esophagus.3, 4 The cells above the basal zone contain flattened nuclei and a glycogen-rich cytoplasm. The cells at the surface are elongated, with a very narrow margin of cytoplasm surrounding pyknotic-appearing nuclei. Basal cells are distinguished from nonbasal cells by the fact that the former do not contain glycogen. In clinical practice, using conventionally stained sections, basal cells appear juxtaposed. One rule of thumb used to define the upper margin of the basal layer is to determine where nuclei are separated by a distance of at least one nuclear diameter.5 Sometimes the tongues of columnar mucosa of the gastric type normally extend several centimeters on either side of the apparent LES zone. In addition, glands similar to those of the gastric cardia, with mucous glands and scattered fundic gland elements, commonly extend up into the lamina propria of the esophagus for a short distance.

Figure 9-2. Normal histology of the esophagus. A: Low-power view showing the mucosa (M), the submucosa (SM), and the two layers of the muscularis propria (MP). B: High-power view showing that scattered lymphoid aggregates are normally found in the lamina propria (arrow) and that mucous glands are located in the submucosa (proper esophageal glands) (G), here just below the muscularis mucosae.

Mitoses can be observed in the parabasal cell layer and are associated with increased proliferative activity. No mitoses are detected in the basal cell layer, and presumably the cells move higher up once they enter mitotic cycle. The exact time for cells to move from basal zone to surface for shedding is believed to be <10 days, while in mice and rats this is between 4 and 7 days.

Melanocytes have also been described in some esophagi.6 Melanocytes are believed to occur in between 4% and 8% of esophagi. The latter are likely relevant to the rare primary malignant melanomas of the esophagus (see Chapter 12), in which melanosis may surround the neoplasms.7 The number of melanocytes seems to be increased in many esophageal resections (27%-34%) performed for squamous cell carcinoma for yet unclear reasons. Pseudomelanosis of the esophagus has been reported, but the cause is still unknown.8

Endocrine cells can be observed in the esophageal epithelium as well. The incidence is reported to be about 28%. Mostly these cells are found in the basal cell layer of squamous epithelium. There is an ongoing discussion whether these cells contribute to the regulation of esophageal sphincters. Langerhans cells are also present in the esophageal squamous epithelium that can be highlighted with S100 and CD1a immunostains. Their function is likely to be antigen presentation similar to their role in skin, and their
number seems to increase in esophagitis. Merkel cells are also found in the esophageal mucosa.9 Compared to fetuses their numbers are slightly increased in adults (1.2/cm vs. 2.2/cm). The numbers of Merkel cells vary markedly among individuals (Fig. 9-4). Immunohistochemically Merkel cells are positive for CK20. Merkel cells with their long dendritic processes can be identified from the 13th week of gestation onward. They are associated with light touch and in the skin can discriminate shape and textures, but it is unclear if they can do this in the esophagus.

Figure 9-3. A: Normal squamous epithelium with a thin basal cell zone (B) and epithelial papillae (arrows) that extend upwards. B: Biopsy specimen from the gastroesophageal junction. Epithelial papillae close to the Z-line are believed to be more elongated physiologically compared to the upper esophagus. The squamocolumnar junction is rarely abrupt, as illustrated by the alternating columnar and squamous epithelium in the right half of the photograph. The mucous glands (G) in the lamina propria are believed to represent a sign that the biopsy was taken from the esophagus but are almost indistinguishable from cardiac glands. C: Detail of the basal cell zone; the arrows point to mononuclear cells. Sometimes fragments of these cells (squiggle cells) give a false impression of neutrophils.

Lymphocytes may be scattered throughout the squamous cell layer, interspersed between epithelial cells. Their nuclei may be compressed (squiggle cells) or lobulated and thus may be mistaken for neutrophils (Fig. 9-5A). Some tiny cell fragments in the epithelium may defy identification of their origin. Immunocytochemical studies show that these are mostly T lymphocytes10 and are CD8 immunoreactive. Intraepithelial mast cells and B cells can also be found.11

The basal cell zone is invagin*ted by extensions of the lamina propria termed dermal papillae (see Fig. 9-3B). They generally do not extend more than two-thirds of the thickness of the epithelium, except in the distal 2 to 3 cm of the esophagus.3, 4 These papillae contain narrow capillaries; sometimes they are engorged with erythrocytes.

Figure 9-4. Esophageal Merkel cells in the basal layer demonstrated with a CK20 immunostain. (Courtesy of Tilman Schulz, M.D.). These cells likely develop in situ in mammals and do not migrate in, but their precise function in the esophagus remains unclear.

Figure 9-5. Mucosal biopsy specimen of the esophagus illustrating that the muscularis mucosae (arrows) may normally be thickened to the point where the unwary may mistakenly interpret this as muscularis propria. Also seen is a squamous duct from a submucosal gland penetrating the muscularis mucosae and opening onto the luminal surface of the esophagus. These ducts are commonly cuffed by mononuclear cells.

The lamina propria consists of connective tissue, which contains scattered plasma cells and occasional lymphoid nodules (see Fig. 9-3B). Sparsely distributed mucous glands are present in the lamina propria of the distal esophagus. These have been termed esophageal cardiac glands. Near the gastroesophageal junction, these glands may contain oxyntic mucosa glands, such as parietal cells.12

The muscularis mucosae become progressively thicker in the distal part of the esophagus. In biopsy specimens, the unwary morphologist may make the frightening mistake of confusing the thick muscularis mucosae for the muscularis propria (Fig. 9-5). The muscularis mucosa is particularly thick in cases of Barrett’s associated distal esophageal or GE junction cancers and can form multiple layers (duplication of muscularis mucosa).13, 14

Submucosa and muscularis propria. The submucosa consists of loose connective tissue containing blood vessels, nerve fibers, scattered lymphocytes, and small lymphoid follicles. Ganglion cells of Meissner’s submucosal plexus are very sparse in the esophagus. Submucosal esophageal mucous glands are distributed throughout the esophagus (Fig. 9-3B). Ducts from these glands penetrate the muscularis mucosae and end in the epithelium. The ducts are covered with a cuboidal epithelium and then by a stratified epithelium in their terminal parts (Fig. 9-5).15 Focal cystic dilatation of these ducts and glands and surrounding lymphoid collections may be seen in some autopsy specimens of “normal” esophagi.16

The muscle coats that lie outside the submucosa consist of striated muscle in the upper one-quarter to one-third of the esophagus and of smooth muscle in the lower two-thirds of the esophagus. Much of the striated muscle portion (except for the upper esophageal sphincter) is actually a blend of striated and smooth muscles.17 Individual muscle fibers are arranged in a spiral fashion, with inner horizontally curved bands and outer bands with a more longitudinal orientation.15, 17 The ganglion cells of the myenteric plexus (Auerbach’s) are more dense in the distal esophagus. The number of cells of Cajal is related to the plexus density. In achalasia cells of Cajal are more sparse.18 Thus, it is proposed in the esophagus also that cells of Cajal are necessary for a neural-controlled motor function.19, 20

The LES consists of a thickened zone of inner circular fibers in a spiral or oval arrangement. Some of these fibers blend with inner oblique muscle fibers of the stomach.21, 22 The esophagus lacks a serosa, except in the distal few centimeters.

Age-Dependent Changes

The data on age-dependent esophageal changes are very limited. It is known that the smooth musculature does not change with age, but in the elderly the number of ganglia in the Auerbach’s plexus is reduced.23 With age the esophageal lumen is believed to become wider, and the wall consistency and sensitivity to stretching are said to decrease.24

Esophageal Atresia and Tracheoesophageal Fistulas

Esophageal atresia along with tracheoesophageal fistula is the most frequent esophageal anomaly (1:3,000-5,000 births), although isolated esophageal atresia is quite rare.33 It is unclear whether this results from lack of proper separation of foregut into respiratory and intestinal tracts by the growth of tracheoesophageal septum or improper recanalization of the esophagus following esophageal epithelial proliferation.25 The use of teratogenic substances during pregnancy has been implicated in the development of esophageal atresia. Frequently additional anomalies involving other organ systems are also present (Table 9-1; Fig. 9-8).

Esophageal atresia occurs in five different forms (Table 9-2).34, 35 Unfortunately, the terminology in the literature is not consistent and many different classification schemes are in use resulting in some confusion (A-E, Type I-V, Type 1-5, Type I-IIIc). The most common variant is type C (Table 9-2) with a proximal blind esophageal pouch and a fistula between the trachea and the distal esophagus. The fistula often enters the trachea close to the carina. The second most common anomaly is type A—pure esophageal atresia without tracheoesophageal fistula.

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Jun 8, 2016 | Posted by drzezo in | Comments Off on Esophagus: Normal Structures, Developmental Abnormalities, and Miscellaneous Disorders

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