Breast cancer histopathology image classification is critical for early detection and improved patient outcomes. 1 This study introduces a novel approach leveraging EfficientNetV2 models, to improve feature extraction and focus on relevant tissue regions. The proposed models were evaluated on the BreakHis dataset across multiple magnification scales (40X, 100X, 200X, and 400X). 2 Among them, the EfficientNetV2-XL with CBAM achieved outstanding performance, reaching a peak accuracy of 98.96 percent and an F1-score of 98.31 percent at 400X magnification, outperforming state-of-the-art methods. 3 By integrating Contrast Limited Adaptive Histogram Equalization (CLAHE) for preprocessing and optimizing computational efficiency, this method demonstrates its suitability for real-time clinical deployment. 3 The results underscore the potential of attention-enhanced scalable architectures in advancing diagnostic precision for breast cancer detection.

Computational analysis of whole slide images (WSIs) has seen significant research progress in recent years, with applications ranging across important diagnostic and prognostic tasks such as survival or cancer subtype prediction. Many state-of-the-art models process the entire slide - which may be as large as $150,000 \times 150,000$ pixels - as a bag of many patches, the size of which necessitates computationally cheap feature aggregation methods. However, a large proportion of these patches are uninformative, such as those containing only healthy or adipose tissue, adding significant noise and size to the bag. We propose Pathology Transformer with Hierarchical Selection (PATHS), a novel top-down method for hierarchical weakly supervised representation learning on slide-level tasks in computational pathology. PATHS is inspired by the cross-magnification manner in which a human pathologist examines a slide, recursively filtering patches at each magnification level to a small subset relevant to the diagnosis. Our method overcomes the complications of processing the entire slide, enabling quadratic self-attention and providing a simple interpretable measure of region importance. We apply PATHS to five datasets of The Cancer Genome Atlas (TCGA), and achieve superior performance on slide-level prediction tasks when compared to previous methods, despite processing only a small proportion of the slide.

Its mortality rate is considered high, with respect to its incidence rate, as this tumor is typically asymptomatic at the early stages for many patients [1, 2]. This leads to a late diagnosis of the tumor, where the curability likelihood is lower. RCC can be categorized into multiple histological subtypes, mainly: Clear Cell Renal Cell Carcinoma (ccRCC) forming 75% of RCCs, Papillary Renal Cell Carcinoma (pRCC) accounting for 10%, and Chromophobe Renal Cell Carcinoma (chRCC) accounting for 5%. Some of the other sutypes include Collecting Duct Renal Cell Carcinoma (cdRCC), Tubulocystic Renal Cell Carcinoma (tRCC), and unclassified [1]. Approximately 10% of renal tumors belong to the benign entities neoplasms, being Oncocytoma (ONCO) the most frequent subtype with an incidence of 3-7% among all RCCs [3, 2]. These subtypes show different cytological signature as well as histological features [2], which ends up in significantly different prognosis. The correct categorization of the tumor subtype is indeed of major importance, as prognosis and treatment approaches depend on it and on the disease stage. For instance, the overall 5-year survival rate significantly differs among the different histological subtypes, being 55-60% for ccRCC, 80-90% for pRCC and 90% for chRCC.

We present a pioneering investigation into the application of deep learning techniques to analyze histopathological images for addressing the substantial challenge of automated prognostic prediction. Prognostic prediction poses a unique challenge as the ground truth labels are inherently weak, and the model must anticipate future events that are not directly observable in the image. To address this challenge, we propose a novel three-part framework comprising of a convolutional network based tissue segmentation algorithm for region of interest delineation, a contrastive learning module for feature extraction, and a nested multiple instance learning classification module. Our study explores the significance of various regions of interest within the histopathological slides and exploits diverse learning scenarios. The pipeline is initially validated on artificially generated data and a simpler diagnostic task. Transitioning to prognostic prediction, tasks become more challenging. Employing bladder cancer as use case, our best models yield an AUC of 0.721 and 0.678 for recurrence and treatment outcome prediction respectively.

Whole Slide Images (WSI), obtained by high-resolution digital scanning of microscope slides at multiple scales, are the cornerstone of modern Digital Pathology. However, they represent a particular challenge to AI-based/AI-mediated analysis because pathology labeling is typically done at slide-level, instead of tile-level. It is not just that medical diagnostics is recorded at the specimen level, the detection of oncogene mutation is also experimentally obtained, and recorded by initiatives like The Cancer Genome Atlas (TCGA), at the slide level. This configures a dual challenge: a) accurately predicting the overall cancer phenotype and b) finding out what cellular morphologies are associated with it at the tile level. To address these challenges, a weakly supervised Multiple Instance Learning (MIL) approach was explored for two prevalent cancer types, Invasive Breast Carcinoma (TCGA-BRCA) and Lung Squamous Cell Carcinoma (TCGA-LUSC). This approach was explored for tumor detection at low magnification levels and TP53 mutations at various levels. Our results show that a novel additive implementation of MIL matched the performance of reference implementation (AUC 0.96), and was only slightly outperformed by Attention MIL (AUC 0.97). More interestingly from the perspective of the molecular pathologist, these different AI architectures identify distinct sensitivities to morphological features (through the detection of Regions of Interest, RoI) at different amplification levels. Tellingly, TP53 mutation was most sensitive to features at the higher applications where cellular morphology is resolved.

Driven by the recent advances in deep learning methods and, in particular, by the development of modern self-supervised learning algorithms, increased interest and efforts have been devoted to build foundation models (FMs) for medical images. In this work, we present our scalable training pipeline for large pathology imaging data, and a comprehensive analysis of various hyperparameter choices and training techniques for building pathology FMs. We release and make publicly available the first batch of our pathology FMs (https://github.com/kaiko-ai/towards_large_pathology_fms) trained on open-access TCGA whole slide images, a commonly used collection of pathology images. The experimental evaluation shows that our models reach state-of-the-art performance on various patch-level downstream tasks, ranging from breast cancer subtyping to colorectal nuclear segmentation. Finally, to unify the evaluation approaches used in the field and to simplify future comparisons of different FMs, we present an open-source framework (https://github.com/kaiko-ai/eva) designed for the consistent evaluation of pathology FMs across various downstream tasks.

Histopathology image embedding is an active research area in computer vision. Most of the embedding models exclusively concentrate on a specific magnification level. However, a useful task in histopathology embedding is to train an embedding space regardless of the magnification level. Two main approaches for tackling this goal are domain adaptation and domain generalization, where the target magnification levels may or may not be introduced to the model in training, respectively. Although magnification adaptation is a well-studied topic in the literature, this paper, to the best of our knowledge, is the first work on magnification generalization for histopathology image embedding. We use an episodic trainable domain generalization technique for magnification generalization, namely Model Agnostic Learning of Semantic Features (MASF), which works based on the Model Agnostic Meta-Learning (MAML) concept. Our experimental results on a breast cancer histopathology dataset with four different magnification levels show the proposed method's effectiveness for magnification generalization.

Breast cancer is one of the leading causes of death by cancer for women. Early detection can give patients more treatment options. In order to detect signs of cancer, breast tissue from biopsies is stained to enhance the nuclei and cytoplasm for microscopic examination. Then, pathologists evaluate the extent of any abnormal structural variation to determine whether there are tumors. Since the majority of biopsies find normal and benign results, most of the manual labelling of these microscopic images is redundant.