Which histologic findings are characteristic of eosinophilic esophagitis (EoE)?

Updated: Jan 03, 2020
  • Author: Nina Tatevian, MD, PhD, FCAP; Chief Editor: Nirag C Jhala, MD, MBBS  more...
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The normal histology of esophageal mucosa shows a nonkeratinizing stratified squamous epithelium, lamina propria, and muscularis mucosae. The basal cell layer is 1-3 cell layers thick and occupies about 10%-15% of the epithelium. The vascular papillae, which are extensions of lamina propria, extend less than two thirds of the distance from base to surface. Among inflammatory cells, intraepithelial lymphocytes are a normal component of esophageal squamous mucosa. However, eosinophils are not normally seen in esophageal squamous mucosa.

Eosinophilic esophagitis. Normal esophagus. Eosinophilic esophagitis. Normal esophagus.

Histopathologic evaluation plays an integral role in diagnosing eosinophilic esophagitis (EoE). A suspected case of EoE requires histologic confirmation on mucosal biopsy samples. On the same note, the presence of esophageal eosinophilia is not a pathognomonic histological feature of EoE. The presence of eosinophils in esophageal squamous mucosa is most commonly seen in GERD and EoE. Esophageal eosinophilia can also be seen various other pathological conditions, such as achalasia, connective-tissue diseases, vasculitis, drug reactions, and inflammatory bowel disease. [48]

In 2006, a multidisciplinary group at First International Gastrointestinal Eosinophil Research Symposium (FIGERS) proposed a histologic criterion of at least 15 eosinophils/hpf for a diagnosis of EoE based on extensive literature review; this criterion, among other recommendations, was published in 2007. [1, 3]

Eosinophilic esophagitis. Increased eosinophils in Eosinophilic esophagitis. Increased eosinophils in squamous mucosa, more than 15 per high power field (hpf).

Subsequently, the updated recommendations for diagnosis of EoE, published in 2011, stated no change in the threshold number of 15 eosinophils/hpf. [2] This was based on the observation that, since the 2007 consensus recommendations, no studies have identified a clear ‘‘lower limit of esophageal eosinophilia’’ or threshold number that would define EoE or have identified other histologic features or pattern of disease distribution that are pathognomonic of EoE.

Importantly, no change in the use of hpf as the unit of measurement for eosinophilia was made in the 2011 guidelines since no studies have yet determined a standardized size of an hpf. This technical issue is critical, because the size of an hpf can alter the reported number of eosinophils per hpf. The size of a hpf, measured in terms of area, varies from less than 0.1 mm2 to greater than 0.4 mm2, depending on the eyepiece used. [48]

Other pathologic features that support the diagnosis of EoE include degranulated eosinophils, eosinophilic microabscesses (defined as clusters of ≥4 eosinophils), presence of eosinophils in superficial layers of squamous mucosa with or without mucosal sloughing, patchy or diffuse distribution of eosinophils through the entire length of esophageal squamous mucosa, and lamina propria fibrosis. [2, 48, 49] Sloughed off squamous epithelial cells mixed with eosinophils are histologic correlates of white exudates observed on endoscopy. [50]

Eosinophilic esophagitis. Superficial layering of Eosinophilic esophagitis. Superficial layering of eosinophils with desquamation.
Eosinophilic esophagitis. Eosinophilic microabsces Eosinophilic esophagitis. Eosinophilic microabscesses.

EoE is a progressive disease with an inflammatory and fibrostenotic presentation. In the presence of ongoing eosinophilic inflammation, there is esophageal remodeling, leading to subepithelial fibrosis causing esophageal strictures. A histopathologic study by Wang et al that assessed for adequate lamina propria for subepithelial fibrosis in pediatric EoE patients reported that lamina propria fibrosis is patchy and more likely to be detected in middle and distal esophageal biopsies. [51] In this study, most newly diagnosed cases of EoE, had subepithelial fibrosis in esophageal biopsies, despite presenting with inflammatory endoscopic features

The updated consensus guidelines also recommended relaxation of the threshold criteria of eosinophils (>15 eosinophils/hpf) for diagnosis of EoE under certain circumstances, such as when there is a strong clinical evidence of EoE and the biopsy samples show above-mentioned supportive histologic features. [2]

Multiple biopsies from the proximal and distal esophagus are recommended for optimal pathologic evaluation. [2] If biopsy samples from two or more sites show squamous mucosal eosinophil counts of more than 15 per hpf, then a diagnosis “compatible with EoE” may be rendered by the pathologist. [48]

Features of basal cell hyperplasia, dilated intercellular spaces, and elongation of vascular papillae are markers of esophagitis and are not very helpful in distinguishing reflux esophagitis from EoE. However, moderate to marked basal cell hyperplasia occupying more than 50% of mucosal thickness and papillary elongation to 75% of epithelial thickness has been associated with increased eosinophils [52, 53] and with eosinophil degranulation. [54] Esophageal subepithelial fibrosis has been observed to be related to the extent of esophageal eosinophil activation, as evidenced by eosinophil degranulation. [55]

Eosinophilic esophagitis. Eosinophil degranulation Eosinophilic esophagitis. Eosinophil degranulation.
Eosinophilic esophagitis. Architectural abnormalit Eosinophilic esophagitis. Architectural abnormalities (basal cell hyperplasia and elongation of vascular papillae).
Eosinophilic esophagitis. Reflux esophagitis. Eosinophilic esophagitis. Reflux esophagitis.

The presence of erosion, ulceration, and neutrophils are not features of EoE and favor an alternate cause such as reflux esophagitis, infections, or drug-related mucosal damage.

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