Automated Detection and Scoring of Tumor-Infiltrating Lymphocytes in Breast Cancer Histopathology Slides

Abstract

Detection of tumor-infiltrating lymphocytes (TILs) in cancer images has gained significant importance as these lymphocytes can be used as a biomarker in cancer detection and treatment procedures. Our goal was to develop and apply a TILs detection tool that utilizes deep learning models, following two sequential steps. First, based on the guidelines from the International Immuno-Oncology Biomarker Working Group (IIOBWG) on Breast Cancer, we labeled 63 large pathology imaging slides and annotated the TILs in the stroma area to create the dataset required for model development. In the second step, various machine learning models were employed and trained to detect the stroma where U-Net deep learning structure was able to achieve 98% accuracy. After detecting the stroma area, a Mask R-CNN model was employed for the TILs detection task. The R-CNN model detected the TILs in various images and was used as the backbone analysis network for the GUI development of the TILs detection tool. This is the first study to combine two deep learning models for TILs detection at the cellular level in breast tumor histopathology slides. Our novel approach can be applied to scoring TILs in large cancer slides. Statistical analysis showed that the output of the implemented approach had 95% concordance with the scores assigned by the pathologists, with a p-value of 0.045 (n = 63). This demonstrated that the results from the developed software were statistically meaningful and highly accurate. The implemented approach in analyzing whole tumor histology slides and the newly developed TILs detection tool can be used for research purposes in biomedical and pathology applications and it can provide researchers and clinicians with the TIL score for various input images. Future research using additional breast cancer slides from various sources for further training and validation of the developed models is necessary for more inclusive, rigorous, and robust clinical applications.

Enhancing AI Research for Breast Cancer: A Comprehensive Review of Tumor-Infiltrating Lymphocyte Datasets

“…Another helpful method for quantification that is more complex than combining classification and localization involves drawing a box around each TIL and counting the frequency of boxes [48,49]. A variant of the method consists of placing a point over the object instead of a bounding box.…”

Histopathology-based breast cancer prediction using deep learning methods for healthcare applications

“…Pathological images not only include pathological characteristics of growth, tumor form, and distribution but also provide radiomics benefits such as low cost, high speed, and non-invasiveness ( 11 ). Larger size patches that are sampled from a histology image have enough data to be assigned to the patches using the image label ( 12 ). However, it is possible that cell-level patches are taken from high-resolution histology images that do not have enough diagnostic information ( 13 , 14 ).…”