Slide-free surface histology enables rapid colonic polyp interpretation across specialties and foundation AI

Abstract Colonoscopy is a mainstay of colorectal cancer screening and has helped to lower cancer incidence and mortality. The resection of polyps during colonoscopy is critical for tissue diagnosis and prevention of colorectal cancer, albeit resulting in increased resource requirements and expense. Discarding resected benign polyps without sending for histopathological processing and confirmatory diagnosis, known as the ‘resect and discard’ strategy, could enhance efficiency but is not commonly practiced due to endoscopists’ predominant preference for pathological confirmation. The inaccessibility of histopathology from unprocessed resected tissue hampers endoscopic decisions. We show that intraprocedural fibre-optic microscopy with ultraviolet-C surface excitation (FUSE) of polyps post-resection enables rapid diagnosis, potentially complementing endoscopic interpretation and incorporating pathologist oversight. In a clinical study of 28 patients, slide-free FUSE microscopy of freshly resected polyps yielded mucosal views that greatly magnified the surface patterns observed on endoscopy and revealed previously unavailable histopathological signatures. We term this new cross-specialty readout ‘surface histology’. In blinded interpretations of 42 polyps (19 training, 23 reading) by endoscopists and pathologists of varying experience, surface histology differentiated normal/benign, low-grade dysplasia, and high-grade dysplasia and cancer, with 100% performance in classifying high/low risk. This FUSE dataset was also successfully interpreted by foundation AI models pretrained on histopathology slides, illustrating a new potential for these models to not only expedite conventional pathology tasks but also autonomously provide instant expert feedback during procedures that typically lack pathologists. Surface histology readouts during colonoscopy promise to empower endoscopist decisions and broadly enhance confidence and participation in ‘resect and discard’. One Sentence Summary Rapid microscopy of resected polyps during colonoscopy yielded accurate diagnoses, promising to enhance colorectal screening. Competing Interest Statement ASKY, GM and KL are inventors on patent filings related to FUSE technology. Other authors have no competing interests. Funding Statement This study was funding by the following grants. Singapore National Research Foundation grant NRFF13-2021-0002 (KL) Agency for Science, Technology and Research grant M22K2c0089 (KL) Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Domain Specific Review Board (DSRB) of the National University Hospital (NUH) gave approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data needed to evaluate the conclusions in the paper are presented. Experimental data underlying the results, and code used for data analysis are available from the corresponding authors upon reasonable request.