Deep Learning-Based Nuclear Morphometry Reveals an Independent Prognostic Factor in Mantle Cell Lymphoma.

Journal: The American journal of pathology
PMID:

Abstract

Blastoid/pleomorphic morphology is associated with short survival in mantle cell lymphoma (MCL), but its prognostic value is overridden by Ki-67 in multivariate analysis. Herein, a nuclear segmentation model was developed using deep learning, and nuclei of tumor cells in 103 MCL cases were automatically delineated. Eight nuclear morphometric attributes were extracted from each nucleus. The mean, variance, skewness, and kurtosis of each attribute were calculated for each case, resulting in 32 morphometric parameters. Compared with those in classic MCL, 17 morphometric parameters were significantly different in blastoid/pleomorphic MCL. Using univariate analysis, 16 morphometric parameters (including 14 significantly different between classic and blastoid/pleomorphic MCL) emerged as significant prognostic factors. Using multivariate analysis, Biologic MCL International Prognostic Index (bMIPI) risk group (P = 0.025), low skewness of nuclear irregularity (P = 0.020), and high mean of nuclear irregularity (P = 0.047) emerged as independent adverse prognostic factors. Additionally, a morphometric score calculated from the skewness and mean of nuclear irregularity (P = 0.0038) was an independent prognostic factor in addition to bMIPI risk group (P = 0.025), and a summed morphometric bMIPI score was useful for risk stratification of patients with MCL (P = 0.000001). These results demonstrate, for the first time, that a nuclear morphometric score is an independent prognostic factor in MCL. It is more robust than blastoid/pleomorphic morphology and can be objectively measured.

Authors

  • Wen-Yu Chuang
    Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Wei-Hsiang Yu
  • Yen-Chen Lee
    School of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Qun-Yi Zhang
    aetherAI, Co, Ltd, Taipei, Taiwan.
  • Hung Chang
    School of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Lee-Yung Shih
    School of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Chi-Ju Yeh
    Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Samuel Mu-Tse Lin
    aetherAI, Co, Ltd, Taipei, Taiwan; Taipei American School, Taipei, Taiwan.
  • Shang-Hung Chang
    School of Medicine, Chang Gung University, Taoyuan, Taiwan; Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Shir-Hwa Ueng
    Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
  • Tong-Hong Wang
    Tissue Bank, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Chuen Hsueh
    Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
  • Chang-Fu Kuo
    Department of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital, Taipei, Taiwan, ROC.
  • Shih-Sung Chuang
    Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan. Electronic address: cmh5301@mail.chimei.org.tw.
  • Chao-Yuan Yeh