Attention-guided classification and tumor localization of combined hepatocellular-cholangiocarcinoma

Liver cancer, especially hepatocellular carcinoma (HCC), imposes a substantial global disease burden. Accurate diagnosis and prognostic assessment directly influence treatment selection and patient survival, and pathological examination remains the gold standard for liver cancer diagnosis. Identifying diverse tissue components and pathological subtypes on histopathology slides is crucial for estimating postoperative recurrence risk and overall prognosis. However, most publicly available resources are still provided at the whole-slide image (WSI) level, and well-annotated datasets for fine-grained tissue component identification in liver cancer are scarce, which hinders reproducible model development and the deployment of quantitative analysis tools. To address this gap, we release HepatoBench, a patch-level image database for liver cancer with annotations for seven key tissue categories. Based on HepatoBench, we train and open-source a deep learning classification model as a tissue recognition tool. Furthermore, we train a WSI-level tumor/non-tumor segmentation model to automatically localize lesion regions across entire slides. By integrating the patch-level tissue classifier with the WSI-level segmentation model, we build HepatoQuant, an end-to-end, disease-specific regional quantification tool for liver cancer, enabling a unified workflow from WSIs to tissue composition parsing and quantitative statistics. We also open-source HepatoBench, the benchmarking protocol, and supporting tools, providing a solid foundation for automated regional quantification and fair method comparison in liver cancer pathology.

As hematoxylin & eosin (H&E) staining constitutes the primary entry point in routine diagnostic workflows, computer-aided diagnosis from whole-slide H&E images is of particular clinical relevance. However, substantial variability in specimen preparation, staining protocols, and scanning conditions, together with inherent uncertainty in expert pixel-level annotations, makes automated analysis of H&E-stained images challenging. In this study, we propose a semantic segmentation-based framework for image-level diagnosis, grounded in the clinically motivated assumption that each histopathological image corresponds to a single cancer type. Image-level predictions are obtained by assigning the class of the dominant pixel-level label in the segmentation output. To ensure clinical relevance, we adopt the nnU-Net architecture and train it on a publicly available dataset collected in our study with pixel-level annotations for three liver cancer types: hepatocellular cacrcinoma (HCC; 55 images from 30 patients), cholangiocellular carcinoma (CCA; 55 images from 29 patients), and colorectal metastatic adenocarcinoma (CMA; 60 images from 30 patients). Annotations were independently provided by four pathologist. We hypothesize that the combination of stain normalization and semantic segmentation mitigates domain shift and reduces sensitivity to annotation noise. Five-fold cross-validation yielded balanced accuracy of 0.975 (HCC), 0.950 (CCA), and 1.000 (CMA), comparable to results obtained with immunohosthochemical staining and superior to several deep learning models trained on patch-level annotations. The proposed framework has the potential to support pathologists in prioritizing immunohistochemical marker selection, thereby reducing diagnostic costs and turnaround time. Integration with immunohistochemical findings improve overall diagnostic reliability.

Early diagnosis of hepatocellular carcinoma is critical to preserve access to curative treatment options. The Liver Imaging Reporting and Data System (LI-RADS) provides a standardized framework for non-invasive diagnosis on multiphase computed tomography, based on major visual imaging features. However, these features may be difficult to assess consistently, particularly in small liver lesions. We developed dLI-RADS, an interpretable artificial intelligence method designed to estimate the probability of hepatocellular carcinoma from multiphase computed tomography images of manually segmented liver lesions, while remaining aligned with LI-RADS-related imaging concepts. dLI-RADS combines neural network-derived predictions with handcrafted quantitative imaging measurements reflecting LI-RADS major features and integrates these inputs using logistic regression. In this multicenter retrospective study, patients with multiphase computed tomography and at least one liver lesion were included, while lesions larger than 40 mm were excluded. Histology served as the reference standard for hepatocellular carcinoma, and a composite reference standard was used for non-hepatocellular carcinoma lesions. The lesion-level accuracy of dLI-RADS and LI-RADS were compared on the internal evaluation set using 10,000-repetition bootstrap non-inferiority tests, with 5% margins and significance levels. On the external test set, sensitivities were similarly compared. dLI-RADS was non-inferior to LI-RADS for lesion-level accuracy in the internal evaluation set, achieving 80% accuracy compared with 74% for LI-RADS (p = 0.04)...