A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee

Andre L. Moreira, Paolo S.S. Ocampo, Yuhe Xia, Hua Zhong, Prudence A. Russell, Yuko Minami, Wendy A. Cooper, Akihiko Yoshida, Lukas Bubendorf, Mauro Papotti, Giuseppe Pelosi, Fernando Lopez-Rios, Keiko Kunitoki, Dana Ferrari-Light, Lynette M. Sholl, Mary Beth Beasley, Alain Borczuk, Johan Botling, Elisabeth Brambilla, Gang ChenTeh Ying Chou, Jin Haeng Chung, Sanja Dacic, Deepali Jain, Fred R. Hirsch, David Hwang, Sylvie Lantuejoul, Dongmei Lin, John W. Longshore, Noriko Motoi, Masayuki Noguchi, Claudia Poleri, Natasha Rekhtman, Ming Sound Tsao, Erik Thunnissen, William D. Travis, Yasushi Yatabe, Anja C. Roden, Jillian B. Daigneault, Ignacio I. Wistuba, Keith M. Kerr, Harvey Pass, Andrew G. Nicholson, Mari Mino-Kenudson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Introduction: A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma. Methods: A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I–III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics. Results: The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617). Conclusions: A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)1599-1610
Number of pages12
JournalJournal of Thoracic Oncology
Issue number10
StatePublished - Oct 2020


  • Adenocarcinoma
  • Lung
  • Model
  • Prognosis
  • Tumor grading

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine


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