Pathology-CoT: Learning Visual Chain-of-Thought Agent from Expert Whole Slide Image Diagnosis Behavior

Diagnosing a whole-slide image is an interactive, multi-stage process of changing magnification and moving between fields. Although recent pathology foundation models demonstrated superior performances, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. Such limitation is largely bottlenecked by data – scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not documented in textbooks or internet, and therefore absent from LLM training. Here we introduce Pathology-CoT, a framework designed to address this challenge through three key breakthroughs. First, the AI Session Recorder seamlessly integrates with standard whole-slide image (WSI) viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect/peek at discrete magnifications) and bounding boxes. Second, a lightweight human-in-the-loop review turns AI-drafted rationales for behavioral commands into the Pathology-CoT dataset, a form of paired “where to look” and “why it matters”, enabling six-fold faster labeling compared to manual constructing such Chain-of-Thought dataset. Using this behavioral data, we build Pathology-o3, a two-stage agent that first proposes important regions of interest and then performs behavior-guided reasoning. On the gastrointestinal lymph-node metastasis detection task, our method achieved 100.0% recall on the internal validation dataset from Stanford Medicine and 97.6% recall on an independent external validation dataset from Sweden, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, Pathology-CoT constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.