Learning to detect lymphocytes in immunohistochemistry with deep learning.

Journal: Medical image analysis
Published Date:

Abstract

The immune system is of critical importance in the development of cancer. The evasion of destruction by the immune system is one of the emerging hallmarks of cancer. We have built a dataset of 171,166 manually annotated CD3 and CD8 cells, which we used to train deep learning algorithms for automatic detection of lymphocytes in histopathology images to better quantify immune response. Moreover, we investigate the effectiveness of four deep learning based methods when different subcompartments of the whole-slide image are considered: normal tissue areas, areas with immune cell clusters, and areas containing artifacts. We have compared the proposed methods in breast, colon and prostate cancer tissue slides collected from nine different medical centers. Finally, we report the results of an observer study on lymphocyte quantification, which involved four pathologists from different medical centers, and compare their performance with the automatic detection. The results give insights on the applicability of the proposed methods for clinical use. U-Net obtained the highest performance with an F1-score of 0.78 and the highest agreement with manual evaluation (κ=0.72), whereas the average pathologists agreement with reference standard was κ=0.64. The test set and the automatic evaluation procedure are publicly available at lyon19.grand-challenge.org.

Authors

  • Zaneta Swiderska-Chadaj
    Department of Pathology, Radboud University Medical Center, The Netherlands. Electronic address: zaneta.swiderska@radboudumc.nl.
  • Hans Pinckaers
    Artera, Inc., Los Altos, CA.
  • Mart van Rijthoven
    Department of Pathology, Radboud University Medical Center, The Netherlands.
  • Maschenka Balkenhol
    Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Margarita Melnikova
    Department of Pathology, Radboud University Medical Center, The Netherlands; Department of Clinical Medicine, Aarhus University, Denmark; Institute of Pathology, Randers Regional Hospital, Denmark.
  • Oscar Geessink
    Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Quirine Manson
    Department of Pathology, University Medical Center, Utrecht, The Netherlands.
  • Mark Sherman
    Mayo Clinic, Jacksonville, Florida, USA.
  • António Polónia
    Laboratório de Anatomia Patológica, Ipatimup Diagnósticos, Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.
  • Jeremy Parry
    Fiona Stanley Hospital, Murdoch, Perth, Western Australia.
  • Mustapha Abubakar
    Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA.
  • Geert Litjens
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Jeroen van der Laak
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Francesco Ciompi
    Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: francesco.ciompi@radboudumc.nl.