MYC Rearrangement Prediction From LYSA Whole Slide Images in Large B-Cell Lymphoma: A Multicentric Validation of Self-supervised Deep Learning Models.

Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
PMID:

Abstract

Large B-cell lymphoma (LBCL) is a heterogeneous lymphoid malignancy in which MYC gene rearrangement (MYC-R) is associated with a poor prognosis, prompting the recommendation for more intensive treatment. MYC-R detection relies on fluorescence in situ hybridization method which is time consuming, expensive, and not available in all laboratories. Automating MYC-R detection on hematoxylin-and-eosin-stained whole slide images of LBCL would decrease the need for costly molecular testing and improve pathologists' productivity. We developed an interpretable deep learning algorithm to detect MYC-R considering recent advances in self-supervised learning and providing an extensive comparison of 7 feature extractors and 6 multiple instance learning models, themselves. Four different multicentric cohorts, including 1247 patients with LBCL, were used for training and validation. The best deep learning model reached an average area under the receiver operating characteristic curve score of 81.9% during crossvalidation on the largest LBCL cohort, and area under the receiver operating characteristic curve scores ranging from 62.2% to 74.5% when evaluated on other unseen cohorts. In addition, we demonstrated that using this model as a prescreening tool (with a false-negative rate of 0%), fluorescence in situ hybridization testing would be avoided in 35% of cases. This work demonstrates the feasibility of developing a medical device to efficiently detect MYC gene rearrangement on hematoxylin-and-eosin-stained whole slide images in daily practice.

Authors

  • Charlotte Syrykh
    Institut Universitaire du Cancer-Oncopole, Pathology Department, F-31059 Toulouse, France.
  • Valentina Di Proietto
    Owkin, New York, New York.
  • Eliott Brion
    Owkin, New York, New York.
  • Christiane Copie-Bergman
    Department of Pathology, Henri Mondor Hospital, APHP, Paris Est-Créteil (UPEC) University Faculty, UMR-S 955, INSERM, Créteil, France.
  • Fabrice Jardin
    INSERM U1245, Centre Henri Becquerel, UNIROUEN, University of Normandie, Rouen, France.
  • Peggy Dartigues
    Department of Pathology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
  • Philippe Gaulard
    Department of Pathology, Henri Mondor Hospital, APHP, Paris Est-Créteil (UPEC) University Faculty, UMR-S 955, INSERM, Créteil, France.
  • Thierry Jo Molina
    Department of Pathology, Necker-Enfants Malades Hospital, AP-HP, Centre-Université de Paris, Paris, France.
  • Josette Briere
    Department of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Diderot, Paris, France.
  • Lucie Oberic
    Department of Hematology, IUCT - Oncopole, Toulouse, France.
  • Corine Haioun
    Department of Hematology, University Hospital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France.
  • Hervé Tilly
    INSERM U1245, Centre Henri Becquerel, UNIROUEN, University of Normandie, Rouen, France.
  • Charles Maussion
    OWKIN Paris, France.
  • Mehdi Morel
    Owkin, New York, New York.
  • Jean-Baptiste Schiratti
    Owkin Lab, Owkin, Inc, New York, NY, USA.
  • Camille Laurent
    Department of Pathology, IUCT Oncopole, Toulouse, France; INSERM, U1037, Research Center In Cancer of Toulouse, laboratoire d'excellence TOUCAN, Toulouse, France. Electronic address: laurent.camille@iuct-oncopole.fr.