Intra- and interobserver agreement of histopathological findings in pediatric patients with eosinophilic esophagitis

Abstract Objective: To assess intra- and interobserver agreement among non-expert pathologists in identifying features of the eosinophilic esophagitis histologic scoring system (EoEHSS) in pediatric patients. Patients and methods: The authors used 50 slides from patients (aged 1-15 years; 72% male) with EoE. EoEHSS evaluates eosinophilic inflammation and other features including epithelial basal zone hyperplasia, eosinophilic abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Grade and stage of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Four pathologists determined EoEHSS findings on two occasions. Intra- and interobserver agreement was assessed using Kappa (κ) statistics and intra-class correlation coefficients. Results: Intra- and interobserver agreement for the identification of eosinophil counts ≥ 15/high power field (HPF) was excellent, however varied when assessing additional features of the EoEHSS. For the more experienced pathologist, agreement for most EoEHSS items and the composite scores was substantial to excellent. For the less experienced pathologists, intraobserver agreement ranged from absent to substantial for individual features and ranged from moderate to substantial for the composite scores. Conclusion: Most items of the EoEHSS had substantial to excellent reliability when assessed by a pathologist experienced in the diagnosis of EoE but presented lower repeatability among less experienced pathologists. These findings suggest that specific training of pathologists is required for the identification of EoEHSS characteristics beyond eosinophil count, as these features are considered useful in the evaluation of response to treatment and correlation with clinical manifestations and endoscopic findings.

Intra- and interobserver agreement of histopathological findings in pediatric patients with eosinophilic esophagitis.

OBJECTIVE: To assess intra- and interobserver agreement among non-expert pathologists in identifying features of the eosinophilic esophagitis histologic scoring system (EoEHSS) in pediatric patients. PATIENTS AND METHODS: The authors used 50 slides from patients (aged 1-15 years; 72% male) with EoE. EoEHSS evaluates eosinophilic inflammation and other features including epithelial basal zone hyperplasia, eosinophilic abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Grade and stage of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Four pathologists determined EoEHSS findings on two occasions. Intra- and interobserver agreement was assessed using Kappa (κ) statistics and intra-class correlation coefficients. RESULTS: Intra- and interobserver agreement for the identification of eosinophil counts ≥ 15/high power field (HPF) was excellent, however varied when assessing additional features of the EoEHSS. For the more experienced pathologist, agreement for most EoEHSS items and the composite scores was substantial to excellent. For the less experienced pathologists, intraobserver agreement ranged from absent to substantial for individual features and ranged from moderate to substantial for the composite scores. CONCLUSION: Most items of the EoEHSS had substantial to excellent reliability when assessed by a pathologist experienced in the diagnosis of EoE but presented lower repeatability among less experienced pathologists. These findings suggest that specific training of pathologists is required for the identification of EoEHSS characteristics beyond eosinophil count, as these features are considered useful in the evaluation of response to treatment and correlation with clinical manifestations and endoscopic findings.

The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score.

Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8+) cytotoxic T lymphocytes (CD8+-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8+-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8+-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8+ T cell recognition may provide insights for future pre-clinical studies.