Eosinophil Counts in Mucosal Biopsies of the Ileum and Colon: Interobserver Variance Affects Diagnostic Accuracy

Abstract

Primary eosinophilic gastroenteritis and colitis (EGE) is a rare entity with unspecific clinical and endoscopic findings. Validated histopathologic criteria for confirming the diagnosis are lacking, because numeric values for normal or elevated concentrations of eosinophils in mucosal biopsies are varying between observers. To quantify this interobserver variance, we had the same set of 30 slides of eosinophilic-rich mucosal biopsies from the ileum and colon systematically reviewed by a panel of six independent pathologists, each with more than a ten-year experience in the field. Using a highly standardized biopsy and slide preparation protocol, we ruled out any influence by the preparation, the patient, the endoscopist, the endoscopes and calipers used, the sampling site, the fixation and staining method, and the microscopic field sizes. Still, all numeric results differed between pathologists up to a factor greater than 30. Calculated positive or negative diagnosis of EGE differed up to a factor greater than 8. A theoretical incidence for EGE calculated from these numbers differed by a factor greater than 1500. We conclude that eosinophil counts in mucosal biopsies from the lower gastrointestinal tract are subject to a very high interobserver variance. Until further research provides objective and validated methods for standardization, all epidemiologic numbers derived from histopathologic findings may have to be questioned. When diagnosing individual patients with EGE, overall morphologic picture together with clinical and endoscopic findings is more important than numeric eosinophil count.

A Marked Eosinophilic Infiltration in Mucosa Could Be a Better Predictive Factor for Intractable Non-Esophageal Eosinophilic Gastrointestinal Disorders

“…It is desirable that a prospective study with a large number of cases be designed to confirm our findings and verify the importance of evaluating serum albumin and extensive disease. Second, it was reported that there is a high interobserver variance in counts of EI in the mucosa of the ileum and colon [28]. There is no standardized counting method for EI in the mucosa of the gastrointestinal tract, and this problem has not yet been resolved.…”

Review of Non-Eosinophilic Esophagitis-Eosinophilic Gastrointestinal Disease (Non-EoE-EGID) and a Case Series of Twenty-Eight Affected Patients

“…International consensus concerning the upper cut-off limit of normal eosinophil infiltration has yet to be reached and no international guidelines have been published. Interobserver variance of eosinophil counts in gastrointestinal mucosal biopsy specimens has been reported to be not good enough [ 32 ]. Furthermore, the visual size of the microscopic HPF differs among types of microscopes, with a nearly four-times difference in some cases, which may cause difficulties with determining the eosinophil count for a diagnosis of EGID.…”

Quantity and Distribution of Eosinophils in the Adult Human Gastric Specimens

“…EGE is characterized by clusters of eosinophils in the mucosal lining, eosinophil accumulation, and the presence of intraepithelial eosinophils (9). EGE is distinct from the more well-known EoE for clinical purposes; however, both are thought to be triggered by T2-mediated food hypersensitivity (11). Additionally, because the clinical signs of EGE are non-specific, it might be difficult to diagnose patients (12).…”

“…Additionally, because the clinical signs of EGE are non-specific, it might be difficult to diagnose patients (12). Endoscopic reports are similarly uncharacteristic, mimicking other diseases (13) (11,14) EGIDs are now identified pathologically, practically, and exclusively by endoscopically acquired mucosal biopsies (2), demanding a broader insight into eosinophils' function in GI mucosal health and disease (15)(16)(17).…”