AI summaryⓘ
The authors developed Atlas H&E-TME, an AI system that analyzes standard stained tissue slides to identify tissue quality, regions, and cell types across various cancers at a very detailed level. They addressed the challenge of unclear tissue features by creating a new validation method using more precise molecular data from multiple experts, improving agreement beyond usual methods. Tested on a large and diverse set of samples, their system performed as well or better than pathologists using only traditional slides, showing it works reliably across different cancer types and technical conditions. This tool turns common pathology slides into a powerful resource for research and clinical use without needing extra special tests.
Hematoxylin and eosin (H&E) stainingWhole-slide images (WSIs)Computational pathologyImmunohistochemistry (IHC)Tissue microenvironment (TME)Pathologist annotationAI pathology modelsMulti-pathologist consensusCancer subtypesTissue biomarkers
Authors
Kai Standvoss, Miriam Hägele, Rosemarie Krupar, Julika Ribbat-Idel, Jennifer Altschüler, Gerrit Erdmann, Hans Pinckaers, Evelyn Ramberger, Madleen Drinkwitz, Ádám Nárai, Alexander Möllers, Katja Lingelbach, Sebastian Kons, Lukas Hönig, Recepcan Adigüzel, Joana Baião, Alberto Megina Gonzalo, Marius Teodorescu, Marie-Lisa Eich, Paolo Chetta, Shakil Merchant, Verena Aumiller, Simon Schallenberg, Andrew Norgan, Klaus-Robert Müller, Lukas Ruff, Maximilian Alber, Frederick Klauschen
Abstract
Hematoxylin and eosin (H&E) staining is the cornerstone of histopathology, yet scalable, quantitative analysis of H&E whole-slide images (WSIs) remains a central challenge in computational pathology. We present Atlas H&E-TME, an AI-based system built on the Atlas family of pathology foundation models that predicts tissue quality, tissue region, and cell type labels across multiple cancer types, yielding over 4,500 quantitative readouts per slide at cell-level resolution. A key challenge to validating such systems is overcoming morphological ambiguity inherent to H&E-only ground truth and the limited scalability of more informed references drawing on modalities such as immunohistochemistry (IHC). We address this with a dual validation framework combining biologically grounded depth with technical and morphological breadth. For depth, we propose an IHC-informed multi-pathologist consensus protocol that substantially improves inter-rater agreement over conventional H&E-only annotation. This yields a molecularly grounded reference against which we compare Atlas H&E-TME and pathologists working from H&E alone. For breadth, we benchmark Atlas H&E-TME on over 200,000 high-confidence H&E-only pathologist annotations across 1,500+ cases spanning eight cancer types and their most common metastatic sites, with subtypes covering >90% of clinical cases per cancer type, drawn from 25+ sources and 8+ scanner models. Benchmarked against the IHC-informed consensus, Atlas H&E-TME matches or exceeds pathologist H&E-only performance and generalizes consistently and robustly across this broad morphological and technical scope. In doing so, Atlas H&E-TME turns the H&E slide -- the most ubiquitous data in pathology -- into a scalable, quantitative window into the tumor and its microenvironment, laying a foundation for the next generation of tissue-based biomarkers in translational and clinical research.