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CD, or not CD, that is the question: a digital interobserver agreement study in coeliac disease
James Denholm1,2,3, Benjamin A Schreiber1,2, Florian Jaeckle4,3
1Department of Pathology, University of Cambridge, Cambridge, UK.
Insights
Digital pathology improves coeliac disease (CD) diagnosis concordance. Including serological data like immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) significantly enhances diagnostic accuracy in virtual slide reviews.
Area of Science:
- Gastroenterology and Hepatology
- Digital Pathology
- Diagnostic Accuracy
Background:
- Coeliac disease (CD) diagnosis traditionally relies on histological examination of duodenal biopsies.
- Digital pathology offers a novel approach to reviewing these biopsies using whole-slide images (WSIs).
Purpose of the Study:
- To evaluate the concordance of coeliac disease diagnosis using digitised whole-slide images (WSIs) of duodenal biopsies.
- To determine if incorporating serological data (immunoglobulin A tissue transglutaminase [IgA tTG] and haemoglobin [Hb]) improves interobserver agreement in CD diagnosis.
Main Methods:
- A study involving 13 pathologists examining 100 duodenal biopsies (normal, CD, indeterminate enteropathy) using digitised WSIs in a virtual setting.
- Phase 1: pathologists reviewed WSIs without clinical data. Phase 2: pathologists reviewed WSIs with IgA tTG and Hb data.
Main Results:
- Initial concordance without additional data was a mean probability of 0.73 (Cohen's kappa: 0.59).
- Inclusion of IgA tTG and Hb data increased concordance to a mean probability of 0.80 (Cohen's kappa: 0.67).
Conclusions:
- Serological data significantly enhances the quality and agreement of coeliac disease diagnosis from duodenal biopsies.
- Limited interobserver agreement with WSIs highlights the need for clinical context and suggests potential for AI-driven automated analysis for objective diagnosis.
Objective:
Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.
Design:
We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.
Results:
We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen's kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen's kappa coefficient of 0.67 (±0.09).
Conclusion:
We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

