Artificial Intelligence–Aided Diagnosis of Breast Cancer Lymph Node Metastasis on Histologic Slides in a Digital Workflow

Abstract

Identifying lymph node (LN) metastasis in invasive breast carcinoma can be tedious and time-consuming. We investigated an artificial intelligence (AI) algorithm to detect LN metastasis by screening hematoxylin and eosin (H&E) slides in a clinical digital workflow. The study included 2 sentinel LN (SLN) cohorts (a validation cohort with 234 SLNs and a consensus cohort with 102 SLNs) and 1 nonsentinel LN cohort (258 LNs enriched with lobular carcinoma and postneoadjuvant therapy cases). All H&E slides were scanned into whole slide images in a clinical digital workflow, and whole slide images were automatically batch-analyzed using the Visiopharm Integrator System (VIS) metastasis AI algorithm. For the SLN validation cohort, the VIS metastasis AI algorithm detected all 46 metastases, including 19 macrometastases, 26 micrometastases, and 1 with isolated tumor cells with a sensitivity of 100%, specificity of 41.5%, positive predictive value of 29.5%, and negative predictive value (NPV) of 100%. The false positivity was caused by histiocytes (52.7%), crushed lymphocytes (18.2%), and others (29.1%), which were readily recognized during pathologists’ reviews. For the SLN consensus cohort, 3 pathologists examined all VIS AI annotated H&E slides and cytokeratin immunohistochemistry slides with similar average concordance rates (99% for both modalities). However, the average time consumed by pathologists using VIS AI annotated slides was significantly less than using immunohistochemistry slides (0.6 vs 1.0 minutes, P = .0377). For the nonsentinel LN cohort, the AI algorithm detected all 81 metastases, including 23 from lobular carcinoma and 31 from postneoadjuvant chemotherapy cases, with a sensitivity of 100%, specificity of 78.5%, positive predictive value of 68.1%, and NPV of 100%. The VIS AI algorithm showed perfect sensitivity and NPV in detecting LN metastasis and less time consumed, suggesting its potential utility as a screening modality in routine clinical digital pathology workflow to improve efficiency.