Semantic Segmentation-Driven Image-Level Diagnosis of Liver Cancers in Hematoxylin and Eosin Histopathology Images

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.