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Histopathology of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE), a chronic relapsing antigen-driven disease, is associated with characteristic esophageal histopathology, including ≥15 intraepithelial eosinophils in at least one high-power field (HPF), and alterations in the epithelium and subepithelial connective tissue. Currently, the pathologic changes in EoE are characteristic but not pathognomonic: the differential diagnosis includes gastroesophageal reflux disease, proton pump inhibitor-responsive esophageal eosinophilia, EoE with significant eosinophilic inflammation in other parts of the gastrointestinal tract (eosinophilic gastrointestinal disorder), etc. EoE biopsy pathology does not vary according to age, sex, or familial predisposition. Genetic analyses of EoE esophageal biopsies have identified a characteristic transcriptome that includes upregulation of several genes that relate to histopathology, such as periostin, thymic stromal lymphopoietin, and desmoglein. Diagnostic pitfalls include the patchy distribution of the characteristic EoE pathology; examining multiple biopsies increases the disease detection rate. The method used to quantitate eosinophils, including the size of the HPF, influences the diagnostic yield, but excellent interobserver variability is achieved among pathologists who agree to a uniform methodology. Therapy for EoE includes diet-based approaches to eliminate offending antigens, topical steroid therapy, and novel biologic agents including monoclonal antibodies. Following appropriate therapy, biopsies may revert to normal histology, but signs and symptoms of esophageal dysfunction may persist. A potential explanation is that endoscopic biopsies obtain very small superficial fragments of tissue from an organ that has complex underlying neuromuscular components; unseen pathology in those loci may influence the clinical state of patients with normal epithelial biopsies.