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Mitotic activity is an important feature for grading several cancer types. Counting mitotic figures (MFs) is a time-consuming, laborious task prone to inter-observer variation. Inaccurate recognition of MFs can lead to incorrect grading and hence potential suboptimal treatment. In this study, we propose an artificial intelligence (AI)-aided approach to detect MFs in digitised haematoxylin and eosin-stained whole slide images (WSIs). Advances in this area are hampered by the limited number and types of cancer datasets of MFs. Here we establish the largest pan-cancer dataset of mitotic figures by combining an in-house dataset of soft tissue tumours (STMF) with five open-source mitotic datasets comprising multiple human cancers and canine specimens (ICPR, TUPAC, CCMCT, CMC and MIDOG++). This new dataset identifies 74,620 MFs and 105,538 mitotic-like figures. We then employed a two-stage framework (the Optimised Mitoses Generator Network (OMG-Net) to classify MFs. The framework first deploys the Segment Anything Model (SAM) to automate the contouring of MFs and surrounding objects. An adapted ResNet18 is subsequently trained to classify MFs. OMG-Net reaches an F1-score of 0.84 on pan-cancer MF detection (breast carcinoma, neuroendocrine tumour and melanoma), largely outperforming the previous state-of-the-art MIDOG++ benchmark model on its hold-out testing set (e.g. +16% F1-score on breast cancer detection, p<0.001) thereby providing superior accuracy in detecting MFs on various types of tumours obtained with different scanners.

With the advent of novel cancer treatment options such as immunotherapy, studying the tumour immune micro-environment is crucial to inform on prognosis and understand response to therapeutic agents. A key approach to characterising the tumour immune micro-environment may be through combining (1) digitised microscopic high-resolution optical images of hematoxylin and eosin (H&E) stained tissue sections obtained in routine histopathology examinations with (2) automated immune cell detection and classification methods. However, current individual immune cell classification models for digital pathology present relatively poor performance. This is mainly due to the limited size of currently available datasets of individual immune cells, a consequence of the time-consuming and difficult problem of manually annotating immune cells on digitised H&E whole slide images. In that context, we introduce Immunocto, a massive, multi-million automatically generated database of 6,848,454 human cells, including 2,282,818 immune cells distributed across 4 subtypes: CD4$^+$ T cell lymphocytes, CD8$^+$ T cell lymphocytes, B cell lymphocytes, and macrophages. For each cell, we provide a 64$\times$64 pixels H&E image at $\mathbf{40}\times$ magnification, along with a binary mask of the nucleus and a label. To create Immunocto, we combined open-source models and data to automatically generate the majority of contours and labels. The cells are obtained from a matched H&E and immunofluorescence colorectal dataset from the Orion platform, while contours are obtained using the Segment Anything Model. A classifier trained on H&E images from Immunocto produces an average F1 score of 0.74 to differentiate the 4 immune cell subtypes and other cells. Immunocto can be downloaded at: https://zenodo.org/uploads/11073373.