Quantitative histology-based classification system for assessment of the intestinal mucosal histological changes in patients with celiac disease

Abstract

Background/Aims The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies. Methods We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists. Results Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%–85.03%) and interobserver (24.6%–71.5%) agreements. Conclusions Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD.

Celiac disease in duodenal biopsies; 2 year experience at a tertiary care hospital

“…It was much higher than mean of total raised IEL of total cases at 24±15.73. This is similar to S.Pellegegrino et al, Biagi F et al, Jarvinen TT et al, Mokhtar et al and Prasenjit Das et al 8,[15][16][17][18] Thus higher villous tip IEL points towards the suggestive diagnosis of CD. Contrary to this Shmidt et al have observed no correlation between CD and numbers of IELs.…”

Opportunities and challenges in the management of celiac disease in Asia

“…38,39 There has been an increasing interest in quantitative histological reporting, where the crypt depth, villous height, and number of intraepithelial lymphocytes per 100 epithelial cells are measured using a microscope with a calibrated micrometer. 37,38,40 We have recently reported a qualitative assessment of villous abnormalities using a computer-based quantitative assessment. 41 There is a need to increase awareness and training of the pathologists to adapt to the new system, which consumes more time but has higher objectivity, interobserver agreement, and reproducibility.…”

“…As this grading is based on visual impression of the reading pathologist, there is a high degree of interobserver and intraobserver variation in the assessment of the severity of villous abnormalities and, thus, poor reproducibility 38,39 . There has been an increasing interest in quantitative histological reporting, where the crypt depth, villous height, and number of intraepithelial lymphocytes per 100 epithelial cells are measured using a microscope with a calibrated micrometer 37,38,40 . We have recently reported a qualitative assessment of villous abnormalities using a computer‐based quantitative assessment 41 .…”

Case Report: Morphologic and Functional Characteristics of Intestinal Mucosa in a Child With Short Bowel Syndrome After Treatment With Teduglutide: Evidence in Favor of GLP-2 Analog Safety

“…On the other hand, this study could not confirm the existing data about villous and crypt lengthening in patients treated with GLP-2 (6-8). In the routine samples, mechanical artifacts and specimen orientation make a precise measuring of these structures difficult, even if oriented on cellulose acetate strips, as demonstrated by studies on duodenal biopsies in patients with coeliac disease, that recommend quantitative morphometric analysis for a reliable evaluation of villous length on routine biopsies (24)(25)(26)(27). In the same biopsies, we evaluated the immunophenotypic expression of S-phase marker (KI67 Mib-1) and proliferative inhibitors (p21 Kip-1 and p27 Waf-1) in our patient and in a small number of controls with regular morphology.…”