Left: sample view of a slide containing lymph nodes, with multiple artifacts: the dark zone on the left is an air bubble, the white streaks are cutting artifacts, the red hue across some regions are hemorrhagic (containing blood), the tissue is necrotic (decaying), and the processing quality was poor. Right: LYNA identifies the tumor region in the center (red), and correctly classifies the surrounding artifact-laden regions as non-tumor (blue).

In both datasets, LYNA was able to correctly distinguish a slide with metastatic cancer from a slide without cancer 99% of the time. Further, LYNA was able to accurately pinpoint the location of both cancers and other suspicious regions within each slide, some of which were too small to be consistently detected by pathologists. As such, we reasoned that one potential benefit of LYNA could be to highlight these areas of concern for pathologists to review and determine the final diagnosis. In our second paper, 6 board-certified pathologists completed a simulated diagnostic task in which they reviewed lymph nodes for metastatic breast cancer both with and without the assistance of LYNA. For the often laborious task of detecting small metastases (termed micrometastases), the use of LYNA made the task subjectively ?easier? (according to pathologists? self-reported diagnostic difficulty) and halved average slide review time, requiring about one minute instead of two minutes per slide.

Left: sample views of a slide containing lymph nodes with a small metastatic breast tumor at progressively higher magnifications. Right: the same views when shown with algorithmic ?assistance? (LYmph Node Assistant, LYNA) outlining the tumor in cyan.

This suggests the intriguing potential for assistive technologies such as LYNA to reduce the burden of repetitive identification tasks and to allow more time and energy for pathologists to focus on other, more challenging clinical and diagnostic tasks. In terms of diagnostic accuracy, pathologists in this study were able to more reliably detect micrometastases with LYNA, reducing the rate of missed micrometastases by a factor of two. Encouragingly, pathologists with LYNA assistance were more accurate than either unassisted pathologists or the LYNA algorithm itself, suggesting that people and algorithms can work together effectively to perform better than either alone. With these studies, we have made progress in demonstrating the robustness of our LYNA algorithm to support one component of breast cancer TNM staging, and assessing its impact in a proof-of-concept diagnostic setting. While encouraging, the bench-to-bedside journey to help doctors and patients with these types of technologies is a long one. These studies have important limitations, such as limited dataset sizes and a simulated diagnostic workflow which examined only a single lymph node slide for every patient instead of the multiple slides that are common for a complete clinical case. Further work will be needed to assess the impact of LYNA on real clinical workflows and patient outcomes. However, we remain optimistic that carefully validated deep learning technologies and well-designed clinical tools can help improve both the accuracy and availability of pathologic diagnosis around the world.