Augmented reality microscopy to bridge trust between AI and pathologists.

Diagnostic certainty is the cornerstone of modern medicine and critical for maximal treatment benefit. When evaluating biomarker expression by immunohistochemistry (IHC), however, pathologists are hindered by complex scoring methodologies, unique positivity cut-offs and subjective staining interpretation. Artificial intelligence (AI) can potentially eliminate diagnostic uncertainty, especially when AI "trustworthiness" is proven by expert pathologists in the context of real-world clinical practice. Building on an IHC foundation model, we employed pathologists-in-the-loop finetuning to produce a programmed cell death ligand 1 (PD-L1) CPS AI Model. We devised a multi-head augmented reality microscope (ARM) system overlayed with the PD-L1 CPS AI Model to assess interobserver variability and gauge the pathologists' trust in AI model outputs. Using difficult to interpret regions on gastroesophageal biopsies, we show that AI-assistance improved case agreement between any 2 pathologists by 14% (agreement on 77% vs 91%) and among 11 pathologists by 26% (agreement on 43% vs 69%). At a clinical cutoff of PD-L1 CPS ≥ 5, the number of cases diagnosed as positive by all 11 pathologists increased by 31%. Our findings underscore the benefits of fully engaging pathologists as active participants in the development and deployment of IHC AI models and frame the roadmap for trustworthy AI as a bridge to increased adoption in routine pathology practice.