Anil Parwani

Yixin Chen, Ziyu Su, Lingbin Meng et al.

Metastatic Progression remains the leading cause of cancer-related mortality, yet predicting whether a primary tumor will metastasize and where it will disseminate directly from histopathology remains a fundamental challenge. Although whole-slide images (WSIs) provide rich morphological information, prior computational pathology approaches typically address metastatic status or site prediction as isolated tasks, and do not explicitly model the clinically sequential decision process of metastatic risk assessment followed by downstream site-specific evaluation. To address this research gap, we present a decision-aware, concept-aligned MIL framework, HistoMet, for prognostic metastatic outcome prediction from primary tumor WSIs. Our proposed framework adopts a two-module prediction pipeline in which the likelihood of metastatic progression from the primary tumor is first estimated, followed by conditional prediction of metastatic site for high-risk cases. To guide representation learning and improve clinical interpretability, our framework integrates linguistically defined and data-adaptive metastatic concepts through a pretrained pathology vision-language model. We evaluate HistoMet on a multi-institutional pan-cancer cohort of 6504 patients with metastasis follow-up and site annotations. Under clinically relevant high-sensitivity screening settings (95 percent sensitivity), HistoMet significantly reduces downstream workload while maintaining high metastatic risk recall. Conditional on metastatic cases, HistoMet achieves a macro F1 of 74.6 with a standard deviation of 1.3 and a macro one-vs-rest AUC of 92.1. These results demonstrate that explicitly modeling clinical decision structure enables robust and deployable prognostic prediction of metastatic progression and site tropism directly from primary tumor histopathology.

Tianyang Wang, Ziyu Su, Abdul Rehman Akbar et al.

Vision foundation models (VFMs), such as DINOv3, provide rich semantic representations that are promising for computational pathology. However, many current adaptations pair frozen VFMs with lightweight decoders, creating a capacity mismatch that often limits boundary fidelity for infiltrative tumor bulk segmentation. This paper presents Dino-NestedUNet, a framework that couples a pre-trained DINOv3 encoder with a Nested Dense Decoder. Instead of sparse skip connections and linear upsampling, the proposed decoder forms a dense grid of intermediate pathways to enable continuous feature reuse and multi-scale recalibration, aligning high-level semantics with low-level morphological textures during reconstruction. We evaluate Dino-NestedUNet on three histopathology cohorts (multi-center CHTN, institutional OSU, and CAMELYON16) and observe consistent improvements over UNet++ and standard Dino-UNet variants, particularly under cross-domain shift. To further assess external generalization, we perform zero-shot evaluation by training on CHTN and directly testing on unseen TIGER WSIBULK and OSU CRC cohorts without fine-tuning. These results suggest that dense decoding is a key ingredient for unlocking foundation encoders in boundary-sensitive pathology segmentation.

Hikmat Khan, Usama Sajjad, Metin N. Gurcan et al.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Accurate survival prediction is essential for treatment stratification, yet existing pathology foundation models often overlook organ-specific features critical for CRC prognostication. Methods: We propose MorphDistill, a two-stage framework that distills complementary knowledge from multiple pathology foundation models into a compact CRC-specific encoder. In Stage I, a student encoder is trained using dimension-agnostic multi-teacher relational distillation with supervised contrastive regularization on large-scale colorectal datasets. This preserves inter-sample relationships from ten foundation models without explicit feature alignment. In Stage II, the encoder extracts patch-level features from whole-slide images, which are aggregated via attention-based multiple instance learning to predict five-year survival. Results: On the Alliance/CALGB 89803 cohort (n=424, stage III CRC), MorphDistill achieves an AUC of 0.68 (SD 0.08), an approximately 8% relative improvement over the strongest baseline (AUC 0.63). It also attains a C-index of 0.661 and a hazard ratio of 2.52 (95% CI: 1.73-3.65), outperforming all baselines. On an external TCGA cohort (n=562), it achieves a C-index of 0.628, demonstrating strong generalization across datasets and robustness across clinical subgroups. Conclusion: MorphDistill enables task-specific representation learning by integrating knowledge from multiple foundation models into a unified encoder. This approach provides an efficient strategy for prognostic modeling in computational pathology, with potential for broader oncology applications. Further validation across additional cohorts and disease stages is warranted.

Veronica Thai, Rui Li, Meng Ling et al.

Interpretation of giga-pixel whole-slide images (WSIs) is an important but difficult task for pathologists. Their diagnostic accuracy is estimated to average around 70%. Adding a second pathologist does not substantially improve decision consistency. The field lacks adequate behavioral data to explain diagnostic errors and inconsistencies. To fill in this gap, we present PathoGaze1.0, a comprehensive behavioral dataset capturing the dynamic visual search and decision-making processes of the full diagnostic workflow during cancer diagnosis. The dataset comprises 18.69 hours of eye-tracking, mouse interaction, stimulus tracking, viewport navigation, and diagnostic decision data (EMSVD) collected from 19 pathologists interpreting 397 WSIs. The data collection process emphasizes ecological validity through an application-grounded testbed, called PTAH. In total, we recorded 171,909 fixations, 263,320 saccades, and 1,867,362 mouse interaction events. In addition, such data could also be used to improve the training of both pathologists and AI systems that might support human experts. All experiments were preregistered at https://osf.io/hj9a7, and the complete dataset along with analysis code is available at https://go.osu.edu/pathogaze.

Tianyang Wang, Ziyu Su, Abdul Rehman Akbar et al.

The expanding ecosystem of pathology foundation models has produced powerful but fragmented tile-level representations, limiting their use in clinical tasks that require unified slide-level reasoning and interpretable linkage to clinically meaningful information. We present ASTRA, a pan-cancer framework that integrates heterogeneous foundation-model representations into a shared slide-level representation space and semantically grounds that space using structured pathology annotation fields, including classification category, cancer type, and anatomic site. ASTRA combines sparse mixture-of-experts contextualization, masked multi-model reconstruction, and contrastive alignment to structured pathology prompts to learn slide representations that support 4-category classification, 3-class solid tumor typing, 16-class cancer typing, and text-guided tumor localization without pixel-level supervision. Developed on a CHTN cohort of 10,359 whole-slide images (WSIs) spanning 16 tumor types, ASTRA consistently improves pan-cancer classification across four pathology foundation-model backbones, achieving up to 97.8% macro-AUC for 4-category classification, 99.7% for 3-class solid tumor typing, and 99.2% for 16-class cancer typing. For tumor localization, ASTRA achieves a mean Dice of 0.897 on an annotated in-domain CHTN subset (n = 380) spanning 16 cancer types and 0.738 on an external TCGA cohort (n = 1,686) spanning four cancer types. These results demonstrate that minimal structured pathology annotation fields derived from slide-level metadata can provide effective semantic supervision for unified slide representation learning, enabling both pan-cancer prediction and weakly supervised tumor localization within a single framework.