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Ruini, Cristel; Schlingmann, Sophia; Jonke, Zan; Avci, Pinar; Padron-Laso, Victor; Neumeier, Florian; Koveshazi, Istvan; Ikeliani, Ikenna U.; Patzer, Kathrin; Kunrad, Elena; Kendziora, Benjamin; Sattler, Elke; French, Lars E. und Hartmann, Daniela (2021): Machine Learning Based Prediction of Squamous Cell Carcinoma in Ex Vivo Confocal Laser Scanning Microscopy. In: Cancers, Bd. 13, Nr. 21, 5522

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Abstract

Simple Summary: Squamous cell carcinoma is the second most common type of skin cancer, with incidence rates rising each year. Micrographic urgery is the treatment of choice for large, aggressive, or recurrent lesions. To ensure complete removal, excised tissue is frozen or embedded in paraffin, cut by a microtome, and stained for examination by an expert Mohs surgeon or a dermatopathologist. Thus, resection of tumor is performed in multiple steps, resulting in delayed wound closure, patient discomfort, longer hospital stay, and in turn, higher healthcare costs. In the last few years, ex vivo confocal laser scanning microscopy (CLSM) has shown promising results in intraoperative almost-real-time detection of skin cancers. This technology is not yet widespread in part due to necessity of training for laboratory technicians, surgeon and dermatopathologists. To increase efficiency and objectivity in the image interpretation process, we have built a machine learning model to detect squamous cell carcinoma lesions in excised tissues. Image classification with convolutional neural networks (CNN) offers an unprecedented opportunity to medical imaging. Regulatory agencies in the USA and Europe have already cleared numerous deep learning/machine learning based medical devices and algorithms. While the field of radiology is on the forefront of artificial intelligence (AI) revolution, conventional pathology, which commonly relies on examination of tissue samples on a glass slide, is falling behind in leveraging this technology. On the other hand, ex vivo confocal laser scanning microscopy (ex vivo CLSM), owing to its digital workflow features, has a high potential to benefit from integrating AI tools into the assessment and decision-making process. Aim of this work was to explore a preliminary application of CNN in digitally stained ex vivo CLSM images of cutaneous squamous cell carcinoma (cSCC) for automated detection of tumor tissue. Thirty-four freshly excised tissue samples were prospectively collected and examined immediately after resection. After the histologically confirmed ex vivo CLSM diagnosis, the tumor tissue was annotated for segmentation by experts, in order to train the MobileNet CNN. The model was then trained and evaluated using cross validation. The overall sensitivity and specificity of the deep neural network for detecting cSCC and tumor free areas on ex vivo CLSM slides compared to expert evaluation were 0.76 and 0.91, respectively. The area under the ROC curve was equal to 0.90 and the area under the precision-recall curve was 0.85. The results demonstrate a high potential of deep learning models to detect cSCC regions on digitally stained ex vivo CLSM slides and to distinguish them from tumor-free skin.

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