pathology labs

Abstract: Combined hepatocellular-cholangiocarcinomas (cHCC-CCA) are a type of cancer that share components of two other primary liver cancers: hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Accurate diagnosis of cHCC-CCA, of which the behavior may resemble that of either HCC or CCA, remains a challenge due to strong intratumoral heterogeneity. Since the prognoses differ between liver cancer types, it is necessary to improve their morphological characterization and recognition in order to accurately identify cHCC-CCA. In this work, we use whole slide images (WSIs) of the two main types of liver cancer (HCC and CCA) and cHCC-CCA, stained with Hematoxylin-Eosin-Safran (HES), to train a classification model that can distinguish between these subtypes and provides a potential solution for localizing different types of tumors in the combined liver cancer images.

Abstract: Predicting spatial gene expression from standard H&E images could extend molecular analysis to tissues without spatial transcriptomic measurements. A standard Transformer applies self-attention over spots but ignores where each spot sits in the tissue, whereas a spot's molecular state depends on tissue context at multiple spatial scales. Building on this insight, we introduce MIST, a Multi-context Spatial Transformer that augments the self-attention backbone with two context pathways applied in every layer: a coordinate-invariant local pathway that attends over spatial k-nearest-neighbor spots, and a slide pathway that broadcasts a whole-slide summary to every spot; the model predicts all spots in a single forward pass. Because coordinates enter only through pairwise distances, the local pathway is invariant to translations, rotations, and reflections when image features are fixed. In intra-cohort evaluation across six human organ cohorts from HEST-1k, MIST improves mean Pearson correlation over the strongest evaluated baseline by 9.7%, 11.6%, and 11.4% for 10-, 50-, and 100-gene panels, respectively, with the lowest average MSE and MAE. MIST further improves leave-one-organ-out transfer by 6.0% over the next strongest baseline, attains the best expression-derived domain recovery (highest mean ARI and NMI at every clustering resolution, and higher NMI than the closest baseline on 84% of held-out slides), and reproduces spatial expression patterns of selected cancer-marker genes. Together, these results show that adding local and slide context to a vanilla Transformer backbone is an effective approach to spatial gene expression prediction from histology.

Abstract: Spatial transcriptomics enables spatially resolved gene expression analysis from slide-level images while preserving morphological features, providing valuable information for studying disease mechanisms and developing treatments. However, spatial gene expression profiling typically requires expensive and time-consuming tests. While existing image-based prediction optimizations mostly revolve around including positional embeddings and further image-based changes, text-based optimizations remain relatively unexplored. We present GATE-ST, which incorporates text-based inputs into image-based spatial gene expression predictions. With this approach, generated text descriptions of genes are utilized to better spatial transcriptomics prediction results. Gene summaries are put through a text encoder, generating embeddings that integrate with image embeddings through cross-attention layers to align with morphological features. We demonstrate the effectiveness of such text inputs by benchmarking performance against random gene embeddings and multiple other image-text fusion architectures, and show that GATE-ST outperforms these alternatives. Our results demonstrate the effectiveness of GATE-ST in pathology imaging, which may greatly reduce the time and cost of accurate spatial transcriptomic predictions, proving the potential of text-guided spatial gene expression prediction.

Abstract: Background. Agentic AI systems independently decompose tasks such as literature search, data analysis, and programming into subtasks, search the web, access databases, and execute code. This allows them to perform digital research tasks at high speed. Objectives. Under what conditions does the use of agentic systems produce reliable efficiency gains, and which tasks remain with researchers? Materials and methods. Summary of current studies on literature searches, data analysis, software development, and clinical decision support. Results. For digital activities, work shifts from execution to steering and review. Efficiency gains are greatest when expected behavior can be formalized in advance and tested automatically. In complex agentic systems, recorded sequences of reasoning steps and tool calls can quickly become too extensive for human review. Furthermore, explanations generated by the model do not reliably reflect how an output was produced. One possible step toward more reliable systems is the validation of individual components. The limited reviewability extends beyond research itself; the review of scientific articles and grant proposals is also reaching capacity limits. In pathology, curated and annotated data, researchers' own analytical skills, and institutional exchange of experience are becoming increasingly important. Conclusions. Researchers remain responsible for their results. They must determine what to delegate and how to review the results. The importance of a research question to patients, the field, and society cannot be fully assessed using formalized criteria and remains a matter of expert judgment. Agentic systems can free up time for this.

Abstract: Pathology vision-language models are commonly built by pretraining or fine-tuning large encoders on paired image-caption data. We asked whether a pathology vision-language model can instead be assembled by parameter-efficient alignment of frozen unimodal foundation models, leaving their pretrained representations untouched. Here we present Lumen, which aligns frozen Virchow2 and BioMedBERT backbones using rank-4 adapters and projection heads, training only 0.40% of the total parameters on the public QUILT-1M corpus. Across nine public zero-shot patch benchmarks, Lumen achieved the highest mean chance-corrected balanced accuracy, 0.546 versus 0.461 for the strongest baseline (paired difference 0.086, 95% CI 0.042-0.136). On lymph-node metastasis detection, Lumen reached an AUROC of 0.964 (95% CI 0.956-0.971) on 4,214 held-out internal slides and 0.955 (95% CI 0.942-0.966) on 2,368 slides across nine external cohorts and six organs. At the internally calibrated threshold, it outperformed all vision-language baselines, with a balanced accuracy of 0.909 (95% CI 0.896-0.923) internally and 0.915 (95% CI 0.902-0.929) externally. Lumen performed competitively across the evaluations, with the exception of cross-modal retrieval, where it ranked third behind CONCH and PathGen-L/14. Fully fine-tuning both encoders gave Lumen no consistent benefit over low-rank adaptation, although it improved retrieval. Aligning frozen unimodal foundation models therefore yields strong and transferable performance at patch and slide level while training only a small fraction of the parameters.

Abstract: Label-free virtual staining offers a compelling, non-destructive alternative to standard histopathology; however, its clinical adoption is hindered by the computational bottlenecks inherent to processing gigapixel Whole Slide Images (WSIs). Current deep learning approaches require patch-based inference to avoid memory constraints, which disrupts global tissue continuity and introduces tiling artifacts--displaying visible seams and color shifts. To address this, we introduce the Consistency Memory Bank (COMB), a novel label-free virtual staining framework that enforces spatial and channel consistency across tiles without memory bottlenecks. COMB decouples context storage from computation, utilizing a dynamic retrieval mechanism to fetch feature representations from adjacent tiles. This enables a retrieval-based context integration strategy that adopts local padding to resolve spatial discontinuities and neighbor-aware channel attention to stabilize statistical drift. Further optimized with a sliding window schedule to ensure minimal memory overhead, our method demonstrates superior performance over state-of-the-art baselines, achieving significant improvements in both perceptual fidelity and tiling consistency, while suggesting its downstream utility in tumor segmentation. Code is available at https://github.com/dou0000/COMB.