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Background: Mast cell tumours (MCTs) are frequent neoplasms of dogs, with variable biological behaviour. Internal tandem duplication mutations in c-Kit exon 11 (c-Kit-11-ITD) are associated with poor prognosis but predict therapeutic response to tyrosine kinase inhibitors. In a previous work, a deep learning algorithm managed to predict the presence of c-Kit-11-ITD on digitalized HE-stained histological slides (whole slide images, WSIs) in up to 87% of the cases, suggesting the existence of morphological features characterizing MCTs carrying this mutation.
Materials & Methods: In an ongoing three-stage blinded study, three untrained pathologists were first asked to classify eight WSIs and 200 patches of MCTs as c-Kit-11-ITD positive or negative. Second, they were trained to recognize c-Kit-11-ITD by having access to a set of WSIs with known mutational status and 200 patches of areas highly relevant for algorithmic c-Kit-11-ITD classification. Third, pathologists were asked to classify 16 new WSIs and 200 new patches for c-Kit-11-ITD status. Participants had to report the microscopic features they identified as relevant for their decision.
Results: The participants correctly classified the c-Kit-11-ITD status of 63–88% of the WSIs and 43–55% of the patches without training, but only 25–38% of WSIs and 55–56% of patches after training. Nuclear pleomorphism was commonly named as a potential feature of c-Kit-11-ITD-positive MCTs.
Conclusion: Based on the current results it is assumed that transfer of algorithmic skills to the human observer is difficult. A c-Kit-11-ITD specific morphological feature usable for human observers remains thus to be extracted from the AI model.