Original ArticlesThe IASLC Proposed Grading System Accurately Predicts Prognosis and Mediastinal Nodal Metastasis in Patients With Clinical Stage I Lung AdenocarcinomaXu, Long MD*; Su, Hang MD*; Hou, Likun MD†; Wang, Fang MD*; Xie, Huikang MD†; She, Yunlang MD*; Gao, Jiani MD*; Zhao, Shengnan MD†; Dai, Chenyang MD, PhD*; Xie, Dong MD, PhD*; Zhu, Yuming MD*; Wu, Chunyan MD†; Zhao, Deping MD*; Chen, Chang MD, PhD*,‡,§; and on behalf of the Surgical Thoracic Alliance of Rising Star Group Author Information Departments of *Thoracic Surgery †Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine ‡Clinical Center for Thoracic Surgery Research, Tongji University, Shanghai, People’s Republic of China §The First People's Hospital of Linhai, Taizhou, Zhejiang, China L.X., H.S., L.H., and F.W. contributed equally to this work. Supported by the General Program of Xinjiang Natural Science Foundation (2018D01C027), Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR1021B & SHDC22020218), National Natural Science Foundation of China (NSFC91959126 & NSFC81770091), Shanghai Municipal Health Commission (202040322), Clinical Research Project of Shanghai Pulmonary Hospital (FK18001). L.X., H.S., L.H., D.Z. and C.C.: conception and design. C.C., C.W., and D.Z.: administrative support. C.C., C.W., and Z.D.P.: provision of study materials or patients. H.X., Y.S., J.G., F.W., S.Z., C.D., D.Z., and Y.Z.: collection and assembly of data. L.X., H.S., and L.H.: data analysis and interpretation. All authors involved in manuscript writing and final approval of manuscript. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Chang Chen, MD, PhD, Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China (e-mail: [email protected]). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.ajsp.com. The American Journal of Surgical Pathology: December 2022 - Volume 46 - Issue 12 - p 1633-1641 doi: 10.1097/PAS.0000000000001876 Buy SDC Metrics Abstract The International Association for the Study of Lung Cancer (IASLC) recently proposed a new grading system for lung adenocarcinoma (LUAD). We aimed to validate the prognostic performance of the grading system and explore its role in guiding the strategy of lymph node (LN) dissection. We retrospectively reviewed 1029 patients with clinical stage I LUAD who underwent surgery between 2011 and 2013. The association between mediastinal nodal metastasis and grading system was evaluated. To investigate the value of the grading system in guiding LN dissection strategies, 3 pathologists evaluated the feasibility of identifying the grading system using frozen section (FS). The differences in prognosis between all neighboring grades were highly significant based on the grading system (P<0.001). Notably, almost no grade 1 LUAD (1.4%) had pN2 disease, whereas higher rates were found in grade 2 LUAD (9.6%) and grade 3 LUAD (18.3%) (P<0.001). Multivariate logistic regression analysis revealed that higher tumor grade was an independent predictor of mediastinal nodal metastasis (P=0.002). Moreover, limited mediastinal LN dissection had equivalent prognosis in grade 1 LUAD, but significantly worse prognosis in grade 2 and grade 3 LUAD than systematic mediastinal LN dissection. The overall accuracy of using intraoperative FS to identify the IASLC grading system was 85.4% (κ=0.765) with substantial agreement. The IASLC grading system could accurately stratify prognosis and predict mediastinal nodal metastasis in patients with clinical stage I LUAD. FS was feasible for identifying the IASLC grading system. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.