Computational Pathology

The rapid digitization of histopathology slides has opened new opportunities for computational tools in clinical and research workflows. Content-based slide retrieval can help pathologists identify morphologically and semantically related precedent cases, supporting expert diagnosis and example-based education. Effective retrieval of whole-slide images (WSIs), however, remains challenging because gigapixel slides contain abundant irrelevant content, focal diagnostic patterns and slide-level semantic information that must be represented at a practicable search cost. Here we present PathSearch, a retrieval framework that combines fine-grained attentive mosaics with slide-level embeddings aligned through vision-language contrastive learning. Trained on 6,926 slide-report pairs, PathSearch captures both fine-grained morphological cues and high-level semantic patterns to enable accurate and flexible retrieval. The framework supports two key functionalities: (1) mosaic-based image-to-image (I2I) retrieval, ensuring accurate and efficient slide search; and (2) multimodal retrieval, where text queries can directly retrieve relevant slides. PathSearch was evaluated on eight tasks comprising 5,021 evaluation slides, spanning malignancy assessment on frozen and hematoxylin and eosin (H&E)-stained slides, lymph-node metastasis detection, tumor subtyping, mixed-gallery rare-cancer retrieval, and hepatocellular carcinoma (HCC) risk stratification. Internal and external experimental results demonstrate that PathSearch consistently outperforms the strongest existing methods without compromising multimodal accuracy. A multi-center reader study further demonstrated increases in task-level mean diagnostic accuracy, confidence, and inter-observer agreement with PathSearch's support. Together, these results support the effectiveness of PathSearch across diverse retrieval tasks and evaluation settings.

Survival analysis plays a vital role in making clinical decisions. However, the models currently in use are often difficult to interpret, which reduces their usefulness in clinical settings. Prototype learning presents a potential solution, yet traditional methods focus on local similarities and static matching, neglecting the broader tumor context and lacking strong semantic alignment with genomic data. To overcome these issues, we introduce an innovative prototype-based multimodal framework, FeatProto, aimed at enhancing cancer survival prediction by addressing significant limitations in current prototype learning methodologies within pathology. Our framework establishes a unified feature prototype space that integrates both global and local features of whole slide images (WSI) with genomic profiles. This integration facilitates traceable and interpretable decision-making processes. Our approach includes three main innovations: (1) A robust phenotype representation that merges critical patches with global context, harmonized with genomic data to minimize local bias. (2) An Exponential Prototype Update Strategy (EMA ProtoUp) that sustains stable cross-modal associations and employs a wandering mechanism to adapt prototypes flexibly to tumor heterogeneity. (3) A hierarchical prototype matching scheme designed to capture global centrality, local typicality, and cohort-level trends, thereby refining prototype inference. Comprehensive evaluations on four publicly available cancer datasets indicate that our method surpasses current leading unimodal and multimodal survival prediction techniques in both accuracy and interpretability, providing a new perspective on prototype learning for critical medical applications. Our source code is available at https://github.com/JSLiam94/FeatProto.

Foundation models (FM) have transformed computational pathology but remain computationally prohibitive for clinical deployment due to their massive parameter counts and high-magnification processing requirements. Here, we introduce XMAG, a lightweight FM developed through corss-magnification distillation that transfers knowledge from state-of-the-art 20x magnification teacher to an efficient 5x magnification student architecture. XMAG employs a compact backbone and operates entirely at 5x, requiring 11.3 times fewer patches per whole slide image (WSI) compared to existing approaches. Our Novel distillation framework incorporates dual-level knowledge transfer, aligning both global image representations and local spatial token mapping. We trained XMAG on 3.49 million images curated from publicly available datasets and evaluated performance across six clinically relevant histopathology analysis tasks spanning multiple cancer types. XMAG achieved diagnostic accuracy within 1% of substantially larger foundation models while delivering 30-fold processing acceleration, reaching 8.8 WSIs per minute processing speed. Our cross-institutional validation confirmed robust generalization. Further, we developed an end-to-end training strategy to further boost our model's performance to approach the larger FMs' performance. These results establish cross-magnification distillation as a viable approach for deploying FM capabilities in resource-constrained clinical environments, potentially enabling real-time pathology AI integration.

Cervical cancer remains a significant global health concern and a leading cause of cancer-related deaths among women. Early detection through Pap smear tests is essential to reduce mortality rates; however, the manual examination is time consuming and prone to human error. This study proposes a deep learning framework that integrates U-Net for segmentation and a classification model to enhance diagnostic performance. The Herlev Pap Smear Dataset, a publicly available cervical cell dataset, was utilized for training and evaluation. The impact of segmentation on classification performance was evaluated by comparing the model trained on segmented images and another trained on non-segmented images. Experimental results showed that the use of segmented images marginally improved the model performance on precision (about 0.41 percent higher) and F1-score (about 1.30 percent higher), which suggests a slightly more balanced classification performance. While segmentation helps in feature extraction, the results showed that its impact on classification performance appears to be limited. The proposed framework offers a supplemental tool for clinical applications, which may aid pathologists in early diagnosis.

Peripheral neuroblastic tumors (pNTs) are among the most common extracranial solid tumors in children, and accurate pathological subtyping is important for risk stratification and treatment planning. However, pNT subtyping on hematoxylin-eosin whole-slide images (WSIs) remains challenging because of limited pediatric tumor cohorts, marked histological heterogeneity, inter-observer variability, and the computational burden of existing WSI classifiers. To address these challenges, we propose CoPath, a framework consisting of CoHisNet and PathVote. CoHisNet is a lightweight multi-scale feature-fusion network for patch-level histopathological classification. By replacing the multilayer perceptron components in Swin Transformer blocks and the classification head with Kolmogorov-Arnold Network layers, CoHisNet improves nonlinear feature modeling under a compact architecture. Its multi-scale interaction and contrast-driven feature-enhancement design enables the model to capture both tissue-level structures and fine-grained cellular morphology. PathVote further incorporates pathology-informed tissue-component priors to aggregate patch-level predictions into WSI-level decisions. We validated CoPath on a private two-branch PpNTs cohort and the public BreakHis breast cancer histopathology dataset. Experimental results show that CoPath achieves competitive or superior performance compared with general image classifiers, pathology foundation models under linear probing, and pathology-specific classification models, while maintaining substantially lower computational complexity. The source code is available at https://github.com/JSLiam94/CoPath.

Breast cancer survival prediction in computational pathology presents a remarkable challenge due to tumor heterogeneity. For instance, different regions of the same tumor in the pathology image can show distinct morphological and molecular characteristics. This makes it difficult to extract representative features from whole slide images (WSIs) that truly reflect the tumor's aggressive potential and likely survival outcomes. In this paper, we present PathoHR, a novel pipeline for accurate breast cancer survival prediction that enhances any size of pathological images to enable more effective feature learning. Our approach entails (1) the incorporation of a plug-and-play high-resolution Vision Transformer (ViT) to enhance patch-wise WSI representation, enabling more detailed and comprehensive feature extraction, (2) the systematic evaluation of multiple advanced similarity metrics for comparing WSI-extracted features, optimizing the representation learning process to better capture tumor characteristics, (3) the demonstration that smaller image patches enhanced follow the proposed pipeline can achieve equivalent or superior prediction accuracy compared to raw larger patches, while significantly reducing computational overhead. Experimental findings valid that PathoHR provides the potential way of integrating enhanced image resolution with optimized feature learning to advance computational pathology, offering a promising direction for more accurate and efficient breast cancer survival prediction. Code will be available at https://github.com/AIGeeksGroup/PathoHR.

Cancer survival prediction from whole slide images (WSIs) is a challenging task in computational pathology due to the large size, irregular shape, and high granularity of the WSIs. These characteristics make it difficult to capture the full spectrum of patterns, from subtle cellular abnormalities to complex tissue interactions, which are crucial for accurate prognosis. To address this, we propose CrossFusion, a novel multi-scale feature integration framework that extracts and fuses information from patches across different magnification levels. By effectively modeling both scale-specific patterns and their interactions, CrossFusion generates a rich feature set that enhances survival prediction accuracy. We validate our approach across six cancer types from public datasets, demonstrating significant improvements over existing state-of-the-art methods. Moreover, when coupled with domain-specific feature extraction backbones, our method shows further gains in prognostic performance compared to general-purpose backbones. The source code is available at: https://github.com/RustinS/CrossFusion

To overcome the black-box nature of predictive AI and the hallucination risks of generative models, retrieval-based models offer an interpretable, evidence-based paradigm for pathology clinical workflow. However, real-world clinical queries are inherently interleaved (e.g., pathology images and text). Current dual-encoders suffer from an Architectural Mismatch, lacking the mechanism to fuse such composed queries. To address this, we formalize the task of Pathology Composed Retrieval (PCR). While Multimodal Large Language Models (MLLMs) offer deep-fusion capabilities, directly applying them exposes a Task Mismatch and a Domain Mismatch. To resolve these challenges, we propose HOMIE, a model-agnostic adaptation framework that transforms any generative MLLM into a specialized pathology retrieval expert. Evaluated on our newly introduced PCR Benchmark, a lightweight 2B-parameter HOMIE variant substantially outperforms existing paradigms, surpassing specialized 7B pathology MLLMs and dual-encoders by large margins on composed retrieval, while maintaining strong performance on traditional simple retrieval. The project page is available at https://qfchou.github.io/HOMIE_page/.

As global life expectancy increases, so does the burden of chronic diseases, yet individuals exhibit considerable variability in the rate at which they age. Identifying biomarkers that distinguish fast from slow ageing is crucial for understanding the biology of ageing, enabling early disease detection, and improving prevention strategies. Using contrastive deep learning, we show that skin biopsy images alone are sufficient to determine an individual's age. We then use visual features in histopathology slides of the skin biopsies to construct a novel biomarker of ageing. By linking with comprehensive health registers in Denmark, we demonstrate that visual features in histopathology slides of skin biopsies predict mortality and the prevalence of chronic age-related diseases. Our work highlights how routinely collected health data can provide additional value when used together with deep learning, by creating a new biomarker for ageing which can be actively used to determine mortality over time.