An Attention-based Weakly Supervised framework for Spitzoid Melanocytic Lesion Diagnosis in WSI

Melanoma is an aggressive neoplasm responsible for the majority of deaths from skin cancer. Specifically, spitzoid melanocytic tumors are one of the most challenging melanocytic lesions due to their ambiguous morphological features. The gold standard for its diagnosis and prognosis is the analysis of skin biopsies. In this process, dermatopathologists visualize skin histology slides under a microscope, in a high time-consuming and subjective task. In the last years, computer-aided diagnosis (CAD) systems have emerged as a promising tool that could support pathologists in daily clinical practice. Nevertheless, no automatic CAD systems have yet been proposed for the analysis of spitzoid lesions. Regarding common melanoma, no proposed system allows both the selection of the tumoral region and the prediction of the diagnosis as benign or malignant. Motivated by this, we propose a novel end-to-end weaklysupervised deep learning model, based on inductive transfer learning with an improved convolutional neural network (CNN) to refine the embedding features of the latent space. The framework is composed of a source model in charge of finding the tumor patch-level patterns, and a target model focuses on the specific diagnosis of a biopsy. The latter retrains the backbone of the source model through a multiple instance learning workflow to obtain the biopsy-level scoring. To evaluate the performance of the proposed methods, we perform extensive experiments on a private skin database with spitzoid lesions. Test results reach an accuracy of 0.9231 and 0.80 for the source and the target models, respectively. Besides, the heat map findings are directly in line with the clinicians’ medical decision and even highlight, in some cases, patterns of interest that were overlooked by the pathologist due to the huge workload.

[1]  Sharath Pankanti,et al.  Deep learning ensembles for melanoma recognition in dermoscopy images , 2016, IBM J. Res. Dev..

[2]  Andrew H. Beck,et al.  Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer , 2017, JAMA.

[3]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[4]  Achim Hekler,et al.  Deep learning outperformed 136 of 157 dermatologists in a head-to-head dermoscopic melanoma image classification task. , 2019, European journal of cancer.

[5]  Rich Caruana,et al.  Multitask Learning , 1998, Encyclopedia of Machine Learning and Data Mining.

[6]  Juan Ye,et al.  Automated identification of malignancy in whole-slide pathological images: identification of eyelid malignant melanoma in gigapixel pathological slides using deep learning , 2019, British Journal of Ophthalmology.

[7]  Rainer Hofmann-Wellenhof,et al.  A deep learning system for differential diagnosis of skin diseases , 2019, Nature Medicine.

[8]  Cuicui Zhang,et al.  Computer-Aided Diagnosis (CAD) of Pulmonary Nodule of Thoracic CT Image Using Transfer Learning , 2019, Journal of Digital Imaging.

[9]  B. van Ginneken,et al.  Deep learning as a tool for increased accuracy and efficiency of histopathological diagnosis , 2016, Scientific Reports.

[10]  A. Madabhushi,et al.  Histopathological Image Analysis: A Review , 2009, IEEE Reviews in Biomedical Engineering.

[11]  Shuji Suzuki,et al.  An Inductive Transfer Learning Approach using Cycle-consistent Adversarial Domain Adaptation with Application to Brain Tumor Segmentation , 2019, ICBBE.

[12]  Rafael Molina,et al.  Going deeper through the Gleason scoring scale: An automatic end-to-end system for histology prostate grading and cribriform pattern detection , 2020, Comput. Methods Programs Biomed..

[13]  Mats Andersson,et al.  Convolutional neural networks for an automatic classification of prostate tissue slides with high-grade Gleason score , 2017, Medical Imaging.

[14]  Fan Yang,et al.  Predicting Lymph Node Metastasis Using Histopathological Images Based on Multiple Instance Learning With Deep Graph Convolution , 2020, 2020 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR).

[15]  Kilian Q. Weinberger,et al.  Densely Connected Convolutional Networks , 2016, 2017 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[16]  Thomas J. Fuchs,et al.  Clinical-grade computational pathology using weakly supervised deep learning on whole slide images , 2019, Nature Medicine.

[17]  Eugenio Vocaturo,et al.  Melanoma Detection by Means of Multiple Instance Learning , 2019, Interdisciplinary Sciences: Computational Life Sciences.

[18]  Ling Shao,et al.  A Benchmark for Studying Diabetic Retinopathy: Segmentation, Grading, and Transferability , 2020, IEEE Transactions on Medical Imaging.

[19]  M. Mihm,et al.  Genomic aberrations in spitzoid melanocytic tumours and their implications for diagnosis, prognosis and therapy. , 2016, Pathology.

[20]  Sebastian Thrun,et al.  Dermatologist-level classification of skin cancer with deep neural networks , 2017, Nature.

[21]  Dayong Wang,et al.  Deep Learning for Identifying Metastatic Breast Cancer , 2016, ArXiv.

[22]  Sergey Ioffe,et al.  Rethinking the Inception Architecture for Computer Vision , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[23]  N. Razavian,et al.  Classification and mutation prediction from non–small cell lung cancer histopathology images using deep learning , 2018, Nature Medicine.

[24]  Ricardo Vilalta,et al.  Inductive Transfer , 2010, Encyclopedia of Machine Learning.

[25]  Andrew Zisserman,et al.  Very Deep Convolutional Networks for Large-Scale Image Recognition , 2014, ICLR.

[26]  Tim Holland-Letz,et al.  Pathologist-level classification of histopathological melanoma images with deep neural networks. , 2019, European journal of cancer.

[27]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[28]  Max Welling,et al.  Attention-based Deep Multiple Instance Learning , 2018, ICML.

[29]  R. Barnhill The Spitzoid lesion: rethinking Spitz tumors, atypical variants, ‘Spitzoid melanoma’ and risk assessment , 2006, Modern Pathology.

[30]  Ce Zhang,et al.  Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features , 2016, Nature Communications.

[31]  Jyotirmoy Chatterjee,et al.  Detection of Breast Cancer From Whole Slide Histopathological Images Using Deep Multiple Instance CNN , 2020, IEEE Access.

[32]  Noureddine Zerhouni,et al.  Spitzoid Lesions Diagnosis Based on SMOTE-GA and Stacking Methods , 2019 .

[33]  Peyman Hosseinzadeh Kassani,et al.  A comparative study of deep learning architectures on melanoma detection. , 2019, Tissue & cell.

[34]  S. Lodha,et al.  Discordance in the histopathologic diagnosis of difficult melanocytic neoplasms in the clinical setting , 2008, Journal of cutaneous pathology.

[35]  Mounim A. El-Yacoubi,et al.  Adversarial Multi-Source Transfer Learning in Healthcare: Application to Glucose Prediction for Diabetic People , 2020, Comput. Methods Programs Biomed..

[36]  Danna Zhou,et al.  d. , 1840, Microbial pathogenesis.

[37]  A. Enk,et al.  Systematic outperformance of 112 dermatologists in multiclass skin cancer image classification by convolutional neural networks. , 2019, European journal of cancer.

[38]  Elizabeth Lazaridou,et al.  Epidemiological trends in skin cancer , 2017, Dermatology practical & conceptual.

[39]  Robert E. Mercer,et al.  The Task Rehearsal Method of Life-Long Learning: Overcoming Impoverished Data , 2002, Canadian Conference on AI.

[40]  Adrián Colomer,et al.  Self-Learning for Weakly Supervised Gleason Grading of Local Patterns , 2021, IEEE Journal of Biomedical and Health Informatics.

[41]  H. Haenssle,et al.  Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[42]  S. W. Lee,et al.  Acral melanoma detection using a convolutional neural network for dermoscopy images , 2018, PloS one.

[43]  Qiang Yang,et al.  A Survey on Transfer Learning , 2010, IEEE Transactions on Knowledge and Data Engineering.

[44]  Alexander Rakhlin,et al.  Deep Convolutional Neural Networks for Breast Cancer Histology Image Analysis , 2018, bioRxiv.

[45]  Enhua Wu,et al.  Squeeze-and-Excitation Networks , 2017, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[46]  D. Massi,et al.  Recognition of Cutaneous Melanoma on Digitized Histopathological Slides via Artificial Intelligence Algorithm , 2020, Frontiers in Oncology.

[47]  Anne L. Martel,et al.  Deep neural network models for computational histopathology: A survey , 2019, Medical Image Anal..

[48]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.