Gastrointestinal Pathology. Группа авторов

presence of rings, furrows, plaques, and strictures.

Table 2.6 Conditions associated with esophageal lymphocytosis (lymphocytic esophagitis).

GERD

Medications

Infection

Motility disorders

Immune‐mediated disorders (e.g. CVID)

Lichen planus/lichenoid esophagitis

Crohn's disease (pediatric)

Celiac disease (pediatric)

Figure 2.14 Characteristic histology of lymphocytic esophagitis.

      Microscopic Features

Recently proposed histologic criteria include the presence of dense lymphocytic infiltrates involving esophageal squamous mucosa with marked spongiosis in the absence of significant numbers of neutrophils or eosinophils (Figure 2.14). The findings are most pronounced in the peripapillary epithelium. There is no required or established “minimum” count or density of intraepithelial lymphocytes, and the pattern and distribution of the lymphocytic epithelial injury is most important.

      Immunohistochemical Studies and Molecular Features

      Ancillary testing, including the subtyping of the intraepithelial CD3, CD4, and CD8 T cells is generally noncontributory and not required for the diagnosis. A subset of cases with CD4 predominant T cells and dysmotility has been reported.

      Differential Diagnosis

      The clinical and endoscopic differential diagnosis includes EOE, although by definition eosinophils are rare or absent. If neutrophils are present, special stains for candida may be warranted. Intraepithelial lymphocytes may be prominent in lichen planus esophagitis/lichenoid esophagitis, although the additional presence of a band‐like lymphocytic infiltrate in the lamina propria and necrotic keratinocytes is a distinguishing feature. Characteristic direct immunofluorescence findings of lichen planus DIF may or may not be demonstrated. Lymphocytosis may also be associated with esophageal involvement by Crohn’s disease in children, although other histologic and clinical features of Crohn’s disease are typically present, particularly elsewhere in the gut.

      Prognosis

      Follow‐up clinical and biopsy data are limited, although in some patients sequential biopsies have demonstrated persistent lymphocytosis, suggesting a chronic process.

Drug‐Induced Esophagitis

      Definition, General Features, Predisposing Factors

Medication‐related injury to the esophageal mucosa (“pill esophagitis”) is an increasingly recognized complication of orally administered drugs. Mucosal injury is typically caused by prolonged direct contact and local caustic effects of the offending agent, although mechanisms of toxicity may be complex and multifactorial. Numerous drugs have been implicated (Table 2.7). Most cause a nonspecific injury pattern, and the diagnosis is suggested by the clinical history.

      Elderly patients and women are most commonly affected. The elderly often have multiple underlying risk factors, and the female predominance is attributed to the more common use of certain medications in this group, such as iron supplements and bisphosphonates. Risk factors include pills taken with little or no water or while recumbent, underlying disorders of esophageal motility (e.g. diabetes, strictures, achalasia) and disorders of local anatomy causing external compression (enlarged left atrium, aortic aneurism). However, many patients do not exhibit abnormal esophageal function or other risk factors.

      Clinical and Endoscopic Characteristics

Typically, there is a temporal relationship between the onset of symptoms and ingestion of a potentially injurious drug. Common symptoms include sudden‐onset chest pain, odynophagia and/or dysphagia that occur within a few hours or days after taking the medication. Severe reflux injury is often an initial diagnostic concern. The chest pain may be pleuritic in nature, mimicking a pulmonary embolism, or may suggest an acute cardiac syndrome. Hematemesis and perforation are rare complications.

Table 2.7 Medications implicated in causing esophagitis and histologic features.

Medication	Histologic features
NSAIDs	Nonspecific, ± crystalline debris
Antibiotics (e.g. tetracyclines/doxycycline, clindamycin)	Doxycycline—vascular injury
Potassium chloride	Nonspecific
Iron	Bluish‐brown crystalline debris, Fe stain +
Bisphosphonates (e.g. alendronate)	Nonspecific, ± crystalline debris and multinucleated squamous cells
Quinidine	Nonspecific
Resins (e.g. kayexalate, bile acid sequestrants)	Kayexalate: Basophilic crystals with “fish scales,” AFB (black), PAD, Diff‐quick bile acid sequestrants:Orange‐black crystals, lack “fish scales,” AFB (yellow)
Mycophenolate	Increased apoptosis (GVHD‐like)
Taxanes	Mitotic arrest, ring mitoses

Endoscopically, most lesions occur in the middle third of the esophagus, at the level of the aortic arch, although any level may be involved. Findings include erythema, erosions, ulcers (including “kissing” ulcers), and strictures. Discrete erosions in this region, away from the Z‐line, are an important clue suggesting a drug‐related etiology (Figure 2.15). Occasionally, a diffuse mucosal sloughing pattern has been described.

      Microscopic Features (Table 2.7)

      Biopsies most commonly show nonspecific esophagitis characterized by erosions, ulcers, active inflammation with neutrophils and occasionally eosinophils, surface epithelial damage, and granulation tissue. Adjacent mucosa is relatively normal. A careful search of the exudate and ulcer bed for refractile or polarizable foreign material is warranted, which may be an important diagnostic clue. However, in most cases the clinical history is necessary to make the diagnosis.

Some medications are associated with additional characteristic histologic features. Erosions and ulcers associated with doxycycline injury often exhibit a distinct capillary/vascular