Shahid Mehmood, Muzammil Hussain, Muhammad Adnan Khan
{"title":"Uncertainty-aware and interpretable deep learning in cytopathology: toward trustworthy AI-powered diagnostics.","authors":"Shahid Mehmood, Muzammil Hussain, Muhammad Adnan Khan","doi":"10.1007/s00428-026-04727-4","DOIUrl":null,"url":null,"abstract":"<p><p>Deep learning has shown remarkable success in cytopathology, particularly in cervical cancer screening and thyroid nodule classification. Yet, most models remain \"black boxes,\" offering deterministic predictions without indicating uncertainty or explaining their reasoning, limiting clinical adoption. This review systematically examines uncertainty quantification (UQ) and explainable AI (XAI) techniques for trustworthy deep learning in cytology-the first to do so in this domain. We review state-of-the-art methods such as Bayesian neural networks, Monte Carlo dropout, and deep ensembles for uncertainty estimation, alongside Grad-CAM, attention mechanisms, and surrogate models for interpretability. Applications span cervical, thyroid, urinary, and hematological cytopathology. UQ methods help identify model limitations, flagging cases that need human review, while studies show improved accuracy for high-confidence predictions and better detection of misclassified cases. Visual explanation tools, especially Grad-CAM, highlight diagnostically relevant cellular features that align with pathologists' reasoning. Integrating UQ and XAI fosters effective human-AI collaboration, enabling systems to communicate both confidence levels and diagnostic rationale. This addresses the clinical trust gap, positioning AI as an assistive colleague rather than a black box, ultimately enhancing diagnostic accuracy and efficiency in cytopathology workflows.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virchows Archiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00428-026-04727-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Deep learning has shown remarkable success in cytopathology, particularly in cervical cancer screening and thyroid nodule classification. Yet, most models remain "black boxes," offering deterministic predictions without indicating uncertainty or explaining their reasoning, limiting clinical adoption. This review systematically examines uncertainty quantification (UQ) and explainable AI (XAI) techniques for trustworthy deep learning in cytology-the first to do so in this domain. We review state-of-the-art methods such as Bayesian neural networks, Monte Carlo dropout, and deep ensembles for uncertainty estimation, alongside Grad-CAM, attention mechanisms, and surrogate models for interpretability. Applications span cervical, thyroid, urinary, and hematological cytopathology. UQ methods help identify model limitations, flagging cases that need human review, while studies show improved accuracy for high-confidence predictions and better detection of misclassified cases. Visual explanation tools, especially Grad-CAM, highlight diagnostically relevant cellular features that align with pathologists' reasoning. Integrating UQ and XAI fosters effective human-AI collaboration, enabling systems to communicate both confidence levels and diagnostic rationale. This addresses the clinical trust gap, positioning AI as an assistive colleague rather than a black box, ultimately enhancing diagnostic accuracy and efficiency in cytopathology workflows.
期刊介绍:
Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.