Most oncological cases can be detected by imaging techniques, but diagnosis is based on pathological assessment of tissue samples. In recent years, the pathology field has evolved to a digital era where tissue samples are digitised and evaluated on screen. As a result, digital pathology opened up many research opportunities, allowing the development of more advanced image processing techniques, as well as artificial intelligence (AI) methodologies. Nevertheless, despite colorectal cancer (CRC) being the second deadliest cancer type worldwide, with increasing incidence rates, the application of AI for CRC diagnosis, particularly on whole-slide images (WSI), is still a young field. In this review, we analyse some relevant works published on this particular task and highlight the limitations that hinder the application of these works in clinical practice. We also empirically investigate the feasibility of using weakly annotated datasets to support the development of computer-aided diagnosis systems for CRC from WSI. Our study underscores the need for large datasets in this field and the use of an appropriate learning methodology to gain the most benefit from partially annotated datasets. The CRC WSI dataset used in this study, containing 1,133 colorectal biopsy and polypectomy samples, is available upon reasonable request.

Considering the profound transformation affecting pathology practice, we aimed to develop a scalable artificial intelligence (AI) system to diagnose colorectal cancer from whole-slide images (WSI). For this, we propose a deep learning (DL) system that learns from weak labels, a sampling strategy that reduces the number of training samples by a factor of six without compromising performance, an approach to leverage a small subset of fully annotated samples, and a prototype with explainable predictions, active learning features and parallelisation. Noting some problems in the literature, this study is conducted with one of the largest WSI colorectal samples dataset with approximately 10,500 WSIs. Of these samples, 900 are testing samples. Furthermore, the robustness of the proposed method is assessed with two additional external datasets (TCGA and PAIP) and a dataset of samples collected directly from the proposed prototype. Our proposed method predicts, for the patch-based tiles, a class based on the severity of the dysplasia and uses that information to classify the whole slide. It is trained with an interpretable mixed-supervision scheme to leverage the domain knowledge introduced by pathologists through spatial annotations. The mixed-supervision scheme allowed for an intelligent sampling strategy effectively evaluated in several different scenarios without compromising the performance. On the internal dataset, the method shows an accuracy of 93.44% and a sensitivity between positive (low-grade and high-grade dysplasia) and non-neoplastic samples of 0.996. On the external test samples varied with TCGA being the most challenging dataset with an overall accuracy of 84.91% and a sensitivity of 0.996.

Colorectal cancer (CRC) diagnosis is based on samples obtained from biopsies, assessed in pathology laboratories. Due to population growth and ageing, as well as better screening programs, the CRC incidence rate has been increasing, leading to a higher workload for pathologists. In this sense, the application of AI for automatic CRC diagnosis, particularly on whole-slide images (WSI), is of utmost relevance, in order to assist professionals in case triage and case review. In this work, we propose an interpretable semi-supervised approach to detect lesions in colorectal biopsies with high sensitivity, based on multiple-instance learning and feature aggregation methods. The model was developed on an extended version of the recent, publicly available CRC dataset (the CRC+ dataset with 4433 WSI), using 3424 slides for training and 1009 slides for evaluation. The proposed method attained 90.19% classification ACC, 98.8% sensitivity, 85.7% specificity, and a quadratic weighted kappa of 0.888 at slide-based evaluation. Its generalisation capabilities are also studied on two publicly available external datasets.

Human epidermal growth factor receptor 2 (HER2) evaluation commonly requires immunohistochemistry (IHC) tests on breast cancer tissue, in addition to the standard haematoxylin and eosin (H&E) staining tests. Additional costs and time spent on further testing might be avoided if HER2 overexpression could be effectively inferred from H&E stained slides, as a preliminary indication of the IHC result. In this paper, we propose the first method that aims to achieve this goal. The proposed method is based on multiple instance learning (MIL), using a convolutional neural network (CNN) that separately processes H&E stained slide tiles and outputs an IHC label. This CNN is pretrained on IHC stained slide tiles but does not use these data during inference/testing. H&E tiles are extracted from invasive tumour areas segmented with the HASHI algorithm. The individual tile labels are then combined to obtain a single label for the whole slide. The network was trained on slides from the HER2 Scoring Contest dataset (HER2SC) and tested on two disjoint subsets of slides from the HER2SC database and the TCGA-TCIA-BRCA (BRCA) collection. The proposed method attained $83.3\%$ classification accuracy on the HER2SC test set and $53.8\%$ on the BRCA test set. Although further efforts should be devoted to achieving improved performance, the obtained results are promising, suggesting that it is possible to perform HER2 overexpression classification on H&E stained tissue slides.

Immunohistochemistry (IHC) is crucial for the clinical categorisation of breast cancer cases. Deep generative models may offer a cost-effective alternative by virtually generating IHC images from hematoxylin and eosin samples. This review explores the state-of-the-art in virtual staining for breast cancer biomarkers (HER2, PgR, ER and Ki-67) and benchmarks several models on public datasets. It serves as a resource for researchers and clinicians interested in applying or developing virtual staining techniques.

Integrating digital pathology and artificial intelligence (AI) algorithms can potentially improve diagnostic practice and precision medicine. Developing reliable, generalizable, and comparable AI algorithms depends on access to meticulously annotated data. However, achieving this requires robust collaboration among pathologists, computer scientists, and other researchers to ensure data quality and consistency. The lack of standardization and scalability is a significant challenge when generating annotations and annotated data sets. Recognizing these limitations, the Scientific Committee of the European Society of Digital and Integrative Pathology (ESDIP) performed a comprehensive international survey to understand the current state of annotation practices and identify actionable areas to address critical needs in the annotation process. The analysis and summary of the survey results provide several insights for all stakeholders involved in data preparation and ground truthing, ultimately contributing to the advancement of AI in computational pathology.