A Grading System for Resected Invasive Squamous Cell Carcinoma of the Lung: A Multi-Institutional Study by the IASLC Pathology Committee
Issued Date
2025-01-01
Resource Type
ISSN
15560864
eISSN
15561380
Scopus ID
2-s2.0-105023889177
Pubmed ID
41038316
Journal Title
Journal of Thoracic Oncology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Thoracic Oncology (2025)
Suggested Citation
Mino-Kenudson M., Berezowska S., Minami Y., Chen S., Ray M.A., Rerkpichaisuth V., Hashisako M., Losmanova T., Hayashi T., Shim H.S., Righi L., Gagné A., Kim T.J., Bubendorf L., Lopez-Rios F., Matsubara D., von der Thüsen J., Lantuejoul S., Roden A.C., Nicholson A., Jain D., Han Y., Wynes M.W., Dacic S., Smeltzer M.P., Cooper W.A., Papotti M.G. A Grading System for Resected Invasive Squamous Cell Carcinoma of the Lung: A Multi-Institutional Study by the IASLC Pathology Committee. Journal of Thoracic Oncology (2025). doi:10.1016/j.jtho.2025.09.1761 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113502
Title
A Grading System for Resected Invasive Squamous Cell Carcinoma of the Lung: A Multi-Institutional Study by the IASLC Pathology Committee
Author(s)
Mino-Kenudson M.
Berezowska S.
Minami Y.
Chen S.
Ray M.A.
Rerkpichaisuth V.
Hashisako M.
Losmanova T.
Hayashi T.
Shim H.S.
Righi L.
Gagné A.
Kim T.J.
Bubendorf L.
Lopez-Rios F.
Matsubara D.
von der Thüsen J.
Lantuejoul S.
Roden A.C.
Nicholson A.
Jain D.
Han Y.
Wynes M.W.
Dacic S.
Smeltzer M.P.
Cooper W.A.
Papotti M.G.
Berezowska S.
Minami Y.
Chen S.
Ray M.A.
Rerkpichaisuth V.
Hashisako M.
Losmanova T.
Hayashi T.
Shim H.S.
Righi L.
Gagné A.
Kim T.J.
Bubendorf L.
Lopez-Rios F.
Matsubara D.
von der Thüsen J.
Lantuejoul S.
Roden A.C.
Nicholson A.
Jain D.
Han Y.
Wynes M.W.
Dacic S.
Smeltzer M.P.
Cooper W.A.
Papotti M.G.
Author's Affiliation
Harvard Medical School
Mayo Clinic
Yale School of Medicine
University of Bern
Université Grenoble Alpes
Erasmus MC
University of Tsukuba
Centre Hospitalier Universitaire Vaudois
Yonsei University College of Medicine
University of Pittsburgh Medical Center
Universitätsspital Basel
St. Jude Children's Research Hospital
University of Memphis
Hospital Universitario 12 de Octubre
Royal Prince Alfred Hospital
Siriraj Hospital
Juntendo University School of Medicine
Università degli Studi di Torino, Scuola di Medicina
Institut Universitaire de Cardiologie et de pneumologie de Québec - Université Laval
Royal Brompton & Harefield NHS Foundation Trust
Shanghai Chest Hospital
Kyushu University Hospital
The Catholic University of Korea Yeouido St. Mary's Hospital
National Hospital Organization Ibarakihigashi National Hospital
International Association for the Study of Lung Cancer
Mayo Clinic
Yale School of Medicine
University of Bern
Université Grenoble Alpes
Erasmus MC
University of Tsukuba
Centre Hospitalier Universitaire Vaudois
Yonsei University College of Medicine
University of Pittsburgh Medical Center
Universitätsspital Basel
St. Jude Children's Research Hospital
University of Memphis
Hospital Universitario 12 de Octubre
Royal Prince Alfred Hospital
Siriraj Hospital
Juntendo University School of Medicine
Università degli Studi di Torino, Scuola di Medicina
Institut Universitaire de Cardiologie et de pneumologie de Québec - Université Laval
Royal Brompton & Harefield NHS Foundation Trust
Shanghai Chest Hospital
Kyushu University Hospital
The Catholic University of Korea Yeouido St. Mary's Hospital
National Hospital Organization Ibarakihigashi National Hospital
International Association for the Study of Lung Cancer
Corresponding Author(s)
Other Contributor(s)
Abstract
Introduction: Tumor grading informs therapy and patient management across many organs, yet no consensus exists for grading invasive squamous cell carcinoma of the lung (LUSC). This study aimed to develop a globally applicable grading system using international cohorts. Methods: Histologic features, including tumor budding, smallest tumor nest size, nuclear size, and tumor spread through air spaces (STAS), were evaluated in two training sets comprising 262 and 427 LUSCs resected without neoadjuvant therapy from three institutions. Kaplan-Meier and Cox proportional hazards models were used to identify features associated with recurrence-free survival (RFS) and overall survival (OS). Features significant in both training sets were used to construct a grading system, which was then validated in a test set (n = 827, five institutions). Interobserver agreement was assessed among 10 pathologists on 25 cases. Results: Tumor budding (two-tier: cutoff at 10 buds per 0.785 mm<sup>2</sup>) was the only histologic feature significantly associated with both RFS and OS in multivariable analyses across both training sets. The proposed two-tier grading system—low-grade (0–9 buds), high-grade (≥10 buds)—was validated in the test set, demonstrating median RFS of 4.8 versus 1.6 years for low- versus high-grade tumors in the entire cohort and 7.2 versus 3.4 years within stage I patients. Interobserver agreement was moderate (Fleiss’ kappa = 0.524). Conclusions: The authors propose a simple, prognostically relevant grading system for resected invasive LUSC based on tumor budding. It is reproducible across international data sets and practical for routine pathology, offering a unified framework for clinical and research use.