Dilated Intercellular Spaces as Markers of Reflux Disease: Histology, Semiquantitative Score and Morphometry upon Light Microscopy

Abstract

Background and Aims: A recent electron microscopy study suggested that dilated intercellular spaces (DIS) are specific for acid reflux-damaged esophageal epithelium. Electron microscopy is, however, expensive and difficult to apply to routine biopsies. The aims of this study are to establish a method for assessing DIS on light microscopy of esophageal biopsies and to estimate its association with current clinicopathological parameters of esophagitis. Materials and Methods: 21 patients with reflux symptoms were investigated. Light microscopy biopsies were assessed for DIS size by a semiquantitative method and computer-assisted, static morphometry. A DIS score accounting for DIS size and distribution was assigned to each patient and its association with 30 clinicopathological variables investigated by univariate and multivariate logistic regression. Results: Both the semiquantitative method and static morphometry identified 4 different classes of DIS size. The DIS score was significantly and independently associated with the esophageal symptoms score, the histological score of esophagitis and the relevant morphometry data. Conclusions: DIS may be efficiently assessed during light microscopy of routine esophageal biopsies. Since correlation with both the histology and the symptoms of esophagitis, the DIS score may be considered a novel parameter of esophagitis and is suggested for the routine evaluation of esophageal biopsies in patients with reflux disease.

The normal gastric cardia: fact or fiction?

“…1); this picture is in a 63-year-old woman! In the squamous epithelium of the esophagus, there are no signs of reflux in particular, no dilated intercellular spaces (DIS) that, as we have shown, are the more precocious expression of GERD also in routine biopsies [12]. Chandrasoma's theory is confirmed in this case.…”

Diagnosis and Management of Non-Erosive Reflux Disease – The Vevey NERD Consensus Group

“…The dilated intercellular spaces occur preferentially in the stratum below the surface squamous epithelium and may allow hydrogen ions to interact with sensory nerves in patients with NERD [75]. Dilated intercellular spaces may be useful in the objective diagnosis of NERD though there is some uncertainty left concerning their functional role [50, 76, 77]. There are also concerns regarding the specificity of dilated intercellular spaces as they are also found in association with psychological stress in animal models [78].…”

Microscopic esophagitis in gastro-esophageal reflux disease: individual lesions, biopsy sampling, and clinical correlations

“…More recently, dilatation of intercellular spaces (DIS) has been proposed as a sensitive marker of acid-induced damage in the squamous epithelium. The description of this individual lesion, identifiable both by electron [13][14][15] and light microscopy [16,17], has provided a stimulus for clinicians to reconsider histology in the diagnosis of GERD.…”