Tumor-Infiltrating Lymphocyte Recognition in Primary Melanoma by Deep Learning Convolutional Neural Network.

Journal: The American journal of pathology
Published Date:

Abstract

The presence of tumor-infiltrating lymphocytes (TILs) is associated with a favorable prognosis of primary melanoma (PM). Recently, artificial intelligence (AI)-based approach in digital pathology was proposed for the standardized assessment of TILs on hematoxylin and eosin-stained whole slide images (WSIs). Herein, the study applied a new convolution neural network (CNN) analysis of PM WSIs to automatically assess the infiltration of TILs and extract a TIL score. A CNN was trained and validated in a retrospective cohort of 307 PMs including a training set (237 WSIs, 57,758 patches) and an independent testing set (70 WSIs, 29,533 patches). An AI-based TIL density index (AI-TIL) was identified after the classification of tumor patches by the presence or absence of TILs. The proposed CNN showed high performance in recognizing TILs in PM WSIs, showing 100% specificity and sensitivity on the testing set. The AI-based TIL index correlated with conventional TIL evaluation and clinical outcome. The AI-TIL index was an independent prognostic marker associated directly with a favorable prognosis. A fully automated and standardized AI-TIL appeared to be superior to conventional methods at differentiating the PM clinical outcome. Further studies are required to develop an easy-to-use tool to assist pathologists to assess TILs in the clinical evaluation of solid tumors.

Authors

  • Filippo Ugolini
    Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy.
  • Francesco De Logu
    Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
  • Luigi Francesco Iannone
    Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
  • Francesca Brutti
    Department of Mathematics, University of Trento, Trento, Italy.
  • Sara Simi
    Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy.
  • Vincenza Maio
    Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence, Italy.
  • Vincenzo de Giorgi
    Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy.
  • Anna Maria di Giacomo
    Center for Immuno-Oncology, Medical Oncology and Immunotherapy, University of Siena, Siena, Italy.
  • Clelia Miracco
    Center for Immuno-Oncology, Medical Oncology and Immunotherapy, University of Siena, Siena, Italy.
  • Francesco Federico
    Institute of Pathology, Sacred Heart Catholic University, Rome, Italy.
  • Ketty Peris
    Institute of Dermatology, Sacred Heart Catholic University, Rome, Italy.
  • Giuseppe Palmieri
    Unit of Cancer Genetics, Institute of Genetic and Biomedical Research, National Research Council, Sassari, Italy.
  • Antonio Cossu
    Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.
  • Mario MandalĂ 
    Oncology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
  • Daniela Massi
    Section of Pathological Anatomy, Department of Health Sciences, University of Florence, Florence 50139, Italy; Institute of Clinical Physiology, National Research Council, Pisa, Italy. Electronic address: daniela.massi@unifi.it.
  • Marco Laurino
    Institute of Clinical Physiology, National Research Council, Pisa, Italy.