Histo-MExNet: A Unified Framework for Real-World, Cross-Magnification, and Trustworthy Breast Cancer Histopathology

Breast cancer is one of the most common types of cancer among women around the world. Rapid detection and early treatment can hinder its progress to more complex stages and can impede its spread to other parts of the body. Histopathological image classification is the most common task in cancer detection due to its robustness in analyzing cellular data. Breast histopathology classification requires handling both multi-scale tissue morphology and clinically relevant generalization beyond the source domain. This paper presents MagViT, an interpretable multi-magnification transformer framework with scale-gated fusion and patient-level model selection. The model uses four BreakHis magnifications (40X, 100X, 200X, 400X) and extracts per-scale representations with a ViT backbone, and combines them via a learnable gate that masks missing scales. Patient-level five-fold cross-validation with a fixed seed has been run and compared with three architectural branches. The most accurate branch is then selected as the final model due to the strongest patient-level accuracy while retaining the simplest fusion pathway. On BreakHis, our architecture achieves a mean image accuracy of 0.9191, a mean patient accuracy of 0.9643, and a mean macro-F1 of 0.9042. External transfer experiments provide preliminary evidence of cross-dataset generalization under controlled adaptation settings on BUSI (image accuracy 0.8306, macro-F1 0.7480, patient accuracy 0.8291) and IDC (image accuracy 0.8577, macro-F1 0.8191, patient accuracy 0.8372). Grad-CAM visualization indicates that the model focuses on diagnostically significant and meaningful regions across magnifications. Relative to prior ViT-centered BreakHis work, this study emphasizes patient-level selection and cross-dataset robustness under a reproducible protocol.

Magnification shift is a major obstacle to robust histopathology classification, because models trained on one imaging scale often generalize poorly to another. Here, we evaluated this problem on the BreaKHis dataset using a strict patient-disjoint leave-one-magnification-out protocol, comparing supervised baseline, baseline augmented with DCGAN-generated patches, and a gradient-reversal domain-general model designed to preserve discriminative information while suppressing magnification-specific variation. Across held-out magnifications, the domain-general model achieved the strongest overall discrimination and its clearest gain was observed when 200X was held out. By contrast, GAN augmentation produced inconsistent effects, improving some folds but degrading others, particularly at 400X. The domain-general model also yielded the lowest Brier score at 0.063 vs 0.089 at baseline. Sparse embedding analysis further revealed that domain-general training reduced average signature size more than three-fold (306 versus 1,074 dimensions) while preserving equivalent predictive performance (AUC: 0.967 vs 0.965; F1: 0.930 vs 0.931). It also increased cross-fold signature reproducibility from near-zero Jaccard overlap in the baseline to 0.99 between the 100X and 200X folds. These findings show that calibrated, compact, and transferable representations can be learned without added architectural complexity, with clear implications for the reliable deployment of computational pathology models across heterogeneous acquisition settings.

Histopathology remains the gold standard for cancer diagnosis because it provides detailed cellular-level assessment of tissue morphology. However, manual histopathological examination is time-consuming, labour-intensive, and subject to inter-observer variability, creating a demand for reliable computer-assisted diagnostic tools. Recent advances in deep learning, particularly transformer-based architectures, have shown strong potential for modelling complex spatial dependencies in medical images. In this work, we propose DeepHistoViT, a transformer-based framework for automated classification of histopathological images. The model employs a customized Vision Transformer architecture with an integrated attention mechanism designed to capture fine-grained cellular structures while improving interpretability through attention-based localization of diagnostically relevant regions. The framework is evaluated on three publicly available histopathology datasets covering lung cancer, colon cancer, and acute lymphoblastic leukaemia. Experimental results demonstrate state-of-the-art performance across all datasets, with classification accuracy, precision, recall, F1-score, and ROC-AUC reaching 100 percent on the lung and colon cancer datasets, and 99.85 percent, 99.84 percent, 99.86 percent, 99.85 percent, and 99.99 percent respectively on the acute lymphoblastic leukaemia dataset. All performance metrics are reported with 95 percent confidence intervals. These results highlight the effectiveness of transformer-based architectures for histopathological image analysis and demonstrate the potential of DeepHistoViT as an interpretable computer-assisted diagnostic tool to support pathologists in clinical decision-making.