The International Association for the Study of Lung Cancer (IASLC) Pathology Committee has proposed a simple, prognostically relevant grading system for resected invasive LUSC based on tumour budding, in a newly published study.
Invasive lung squamous cell carcinoma (LUSC; pictured above) accounts for approximately one-quarter of all lung cancers, but therapeutic options for LUSC remain limited, primarily due to the absence of well-defined, targetable molecular alterations. Therefore, histopathologic features are increasingly being explored as tools to enhance prognostic accuracy and guide treatment decisions.
Tumour grading informs therapy and patient management across many organs; yet no consensus exists for grading invasive LUSC. This study aimed to develop a globally applicable grading system using international cohorts.
According to the study, published in the current issue of the Journal of Thoracic Oncology, histologic features, including tumour budding, smallest tumour nest size, nuclear size, and tumour spread through air spaces (STAS), were evaluated in two training sets comprising 262 and 427 LUSCs resected without neoadjuvant therapy from three institutions. 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.
Of all the pathologic features evaluated, tumour budding (two-tiered) was the only variable independently associated with both RFS and overall survival (OS) in both training sets. Therefore, the committee selected tumour budding as the basis for developing a grading system, according to lead author Mari Mino-Kenudson MD, Department of Pathology, Massachusetts General Hospital and member of the IASLC Pathology Committee.
Given that a cut-off of 10 buds is the threshold recommended by the ITBCC 2016 for defining high tumour budding in colorectal cancer, the committee evaluated and adopted this cut-off for the proposed two-tiered grading system, classifying tumours as low-grade (0-9 buds/0.785 mm²) or high-grade (≥10 buds/0.785 mm²).
The proposed two-tier grading system was validated in the test set, demonstrating median RFS of 4.8 vs. 1.6 years for low- vs. high-grade tumours in the entire cohort and 7.2 vs. 3.4 years within stage I patients. Interobserver agreement was moderate (Fleiss' kappa = 0.524).
"This grading system for resected LUSC is reproducible across international datasets and practical for routine pathology, offering a unified framework for clinical and research use," said Dr Mino-Kenudson. "Importantly, it differs from the standard grading system of the AJCC and UICC, which applies the same framework to all lung cancers, as it is specifically applicable to LUSC."
- Mino-Kenudson M, Berezowska S, Minami Y, et al. A Grading System for Resected Invasive Squamous Cell Carcinoma of the Lung: A Multi-Institutional Study by the IASLC Pathology Committee. J Thorac Oncol. 2025 Sep 30:S1556-0864(25)02845-X.
doi: 10.1016/j.jtho.2025.09.1761.