Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
KeywordsBarrett’sGoblet cellsIntestinal metaplasiaDysplasiaEsophagitis
The esophagus is composed of a nonkeratinized squamous epithelium overlying a thin lamina propria and muscularis mucosa. Beneath that, the submucosa contains lymphatics and mucous glands with cuboidal-lined ducts running up to the luminal surface. Under the submucosa is muscularis propria (skeletal muscle proximally, smooth muscle distally), surrounded by the adventitia, which is continuous with mediastinum.
Most esophageal biopsies are performed on patients with symptoms of reflux or dysphagia, and often the goal is to rule out Barrett’s esophagus , a glandular metaplasia that puts the patient at increased risk for adenocarcinoma. Other common findings include reflux changes in the squamous epithelium, ulcers, or infection. Squamous dysplasia is uncommon.
Approach to the Slide
On low power, survey the epithelium. A normal biopsy specimen (Figure 6.1) will have a bland pink squamous epithelium and scant underlying lamina propria; muscularis mucosa is usually not present. Occasional lymphocytes in the epithelium are typical (so-called squiggle cells because of their stretched-out appearance). The epithelium should not be interrupted or undermined by gastric-type glands, although salivary-like mucous glands are okay.
Normal esophageal mucosa. The basal layer (arrow) is seen as a crowded and blue layer at the base. The cells mature into flat nonkeratinizing squamous cells with small nuclei; the clear cytoplasm seen here is glycogen. Vascular pegs penetrate into the epithelium (arrowhead). The vascular lamina propria is visible below the basal layer.
Within the squamous epithelium, look for the following:
Basal cell hyperplasia (an increase over the normal three-cells-deep layer). Basal cells are the deepest layer of squamous cells and are the regenerative cell layer. They are defined by their closely packed nuclei: if you cannot squeeze a new nucleus between two existing nuclei, they are basal cells.
Elongated vascular papillae (into the upper third of the epithelium).
Balloon cell change of epithelium (excess clear glycogen in the cytoplasm).
Intraepithelial neutrophils or eosinophils.
Erosions, fibrinopurulent exudate, granulation tissue.
Columnar cell mucosa or glands.
Squamous debris which has been sloughed from the epithelium.
Eosinophils are not a normal component of the esophageal epithelium, and the presence of even a single eosinophil should prompt you to look for other features of reflux esophagitis. Reflux esophagitis, secondary to gastroesophageal reflux disease (GERD ), is a common condition which is associated with the first four features in the preceding list (Figure 6.2a). Not all features need be present in every case and typically are not. Severe cases may progress to erosions and ulcerations. The inflammation in reflux is mainly lymphocytic, but the presence of scattered eosinophils supports the diagnosis. In reflux esophagitis, the damage is most noticeable distally, close to the gastroesophageal junction.
(Top) Reflux esophagitis. There are inflammatory cells scattered throughout, including eosinophils (circle) and lymphocytes (arrowhead). The vascular peg (arrow) extends nearly to the surface . (Bottom) Eosinophilic esophagitis, low power. The epithelium is very blue due to the high N/C ratio of the reactive squamous cells, and there are dense clusters of eosinophils, including microabscesses at the surface (arrow).
In contrast, there is a distinct condition called eosinophilic esophagitis which shows increasing involvement as you move proximally in the esophagus. Eosinophilic esophagitis is mainly an allergy-induced pediatric disease, and although it shares histologic features with reflux, the eosinophils tend to:
Be more numerous (usually >15 per high power field)
Be grouped into microabscesses (clusters of >4 eosinophils)
Show degranulation of contents
And be clustered at the surface of the epithelium (Figure 6.2b)
Stylistically, as the changes seen in GERD are not specific (nor are they seen in all cases of documented reflux), the diagnosis is often descriptive, such as “reactive epithelial changes of the type seen in reflux esophagitis.” Similarly, there is no magic number of eosinophils that indicates eosinophilic esophagitis over reflux, so clinical findings must always be taken into consideration.
A prominent neutrophilic infiltrate points more to an infection or acute injury than to reflux. A PAS stain can help to find Candida organisms (pseudohyphae and yeast forms in the epithelium or exudate; Figure 6.3). They may be very numerous or extremely scanty. Luminal squamous debris is another hint to look closely for Candida. Candidal infection is typically associated with a superficial neutrophilic infiltrate and parakeratosis (surface squames that are keratinized and have retained nuclei); however, some cases have almost no inflammation and few epithelial changes.
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