iSight: Towards expert-AI co-assessment for improved immunohistochemistry staining interpretation

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's $κ$ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

VISTA-PATH: An interactive foundation model for pathology image segmentation and quantitative analysis in computational pathology

Accurate semantic segmentation for histopathology image is crucial for quantitative tissue analysis and downstream clinical modeling. Recent segmentation foundation models have improved generalization through large-scale pretraining, yet remain poorly aligned with pathology because they treat segmentation as a static visual prediction task. Here we present VISTA-PATH, an interactive, class-aware pathology segmentation foundation model designed to resolve heterogeneous structures, incorporate expert feedback, and produce pixel-level segmentation that are directly meaningful for clinical interpretation. VISTA-PATH jointly conditions segmentation on visual context, semantic tissue descriptions, and optional expert-provided spatial prompts, enabling precise multi-class segmentation across heterogeneous pathology images. To support this paradigm, we curate VISTA-PATH Data, a large-scale pathology segmentation corpus comprising over 1.6 million image-mask-text triplets spanning 9 organs and 93 tissue classes. Across extensive held-out and external benchmarks, VISTA-PATH consistently outperforms existing segmentation foundation models. Importantly, VISTA-PATH supports dynamic human-in-the-loop refinement by propagating sparse, patch-level bounding-box annotation feedback into whole-slide segmentation. Finally, we show that the high-fidelity, class-aware segmentation produced by VISTA-PATH is a preferred model for computational pathology. It improve tissue microenvironment analysis through proposed Tumor Interaction Score (TIS), which exhibits strong and significant associations with patient survival. Together, these results establish VISTA-PATH as a foundation model that elevates pathology image segmentation from a static prediction to an interactive and clinically grounded representation for digital pathology. Source code and demo can be found at https://github.com/zhihuanglab/VISTA-PATH.

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 involving changes in magnification and movement between fields. Although recent pathology foundation models are strong, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. The blocker is data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not written in textbooks or online, and therefore absent from large language model training. We introduce the AI Session Recorder, which works with standard WSI viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands (inspect or peek at discrete magnifications) and bounding boxes. A lightweight human-in-the-loop review turns AI-drafted rationales into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters" supervision produced at roughly six times lower labeling time. Using this behavioral data, we build Pathologist-o3, a two-stage agent that first proposes regions of interest and then performs behavior-guided reasoning. On gastrointestinal lymph-node metastasis detection, it achieved 84.5% precision, 100.0% recall, and 75.4% accuracy, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, this 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.