Chapter 2, Page 10  

NORMAL ANATOMY, EMBRYOLOGY, AND HISTOLOGY OF THE ESOPHAGUS HISTOLOGY Mucosa The esophageal mucosa has three components: an outer stratified squamous epithelium; a thin muscle coat, the muscularis mucosae; and the lamina propria which is sandwiched in between the two (fig. 2-6a,b, fig. 2-6c,d). In addition, glands similar to those of the gastric cardia and known as esophageal cardiac glands, consisting of mucous cells that secrete neutral mucin (9), are commonly found in the lamina propria of the distal esophagus (fig. 2-7). The squamous epithelium is nonkeratinized, although occasionally rare keratohyaline granules are present. It is composed of three zones: the basal, prickle, and functional layers; the latter refers to the flattened surface epithelium devoid of nuclei (fig. 2-8). The basal cell layer is about three cells thick and comprises up to 15 percent of the thickness of the squamous epithelium, except for the most distal 3 cm of the esophagus (15, 29). It is composed primarily of basal cells with scattered mitoses, interspersed with rare argyrophilic cells and melanocytes (5, 27). The latter two cells are the sources of the rare primary small cell (oat cell) carcinoma (5) and malignant melanoma of the esophagus in which melanosis often is found around the melanoma (5, 7). Pseudomelanosis of the esophagus has also been reported but the cells of origin are unknown (11). The basal cells have hyperchromatic nuclei and scant cytoplasm, and they blend with the prickle cell layer. A rule of thumb used to define the lower edge of the prickle cell layer is to determine where nuclei are separated by a distance of at least one nuclear diameter (17). The cells of the prickle cell layer contain flattened nuclei and a glycogen-rich cytoplasm; the latter stains with periodic acid-Schiff (PAS) and Lugol's iodine solution. As these cells move up towards the luminal surface, they become progressively flatter and their cytoplasm becomes clearer. In the cervical esophagus, just below the upper esophageal sphincter, may be a patch of heterotopic gastric mucosa known as the "inlet patch." This consists of heterotopic gastric fundic or antral mucosa (fig. 2-9). In most instances this heterotopic mucosa is benign, but on rare occasions may result in peptic ulceration or carcinoma. Phenotypic T-cell lymphocytes are frequently scattered throughout the squamous cell layer (3, 11, 12, 24) and Langerhans cells are occasionally present (11, 24). Sometimes the lymphocytic nuclei are compressed or lobulated and may be mistaken for neutrophils (the so-called squiggle cells) (fig. 2-10) (4). The lamina propria invaginates the basal cell zone to produce dermal papillae that extend one third to half the thickness of the epithelium. These papillae contain capillaries which are sometimes engorged with blood. The lamina propria consists of loose connective tissue containing mononuclear cells, lymphocytes, occasional plasma cells, and rare lymphoid follicles. In the distal esophagus, sparsely distributed mucous glands are present in the lamina propria between the muscularis mucosae and the overlying squamous epithelium. These glands may communicate with the luminal surface and have sometimes been misdiagnosed as Barrett's esophagus. It should be stressed that these glands almost never give rise to esophageal adenocarcinoma (fig. 2-7). The muscularis mucosae consists of a thin band of longitudinally oriented smooth muscle separating the lamina propria from the submucosa (13). It becomes progressively thicker in the distal part of the esophagus and may be mistaken for the muscularis propria in biopsy specimens (fig. 2-11).