by International Association for the Study of Lung Cancer

Credit: CC0 Public Domain

Invasive lung squamous cell carcinoma (LUSC) 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.

In thecurrent issueof theJournal of Thoracic Oncology, the International Association for the Study of Lung Cancer (IASLC) Pathology Committee proposed a simple, prognostically relevant grading system for resected invasive LUSC based on tumor budding. JTO is the official journal of the IASLC.

Tumor grading informs therapy and patient management across many organs; yet no consensus exists for grading invasivesquamous cell carcinomaof the lung (LUSC). This study aimed to develop a globally applicable grading system using international cohorts.

According to the study, 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. 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, tumor budding (2-tiered) was the only variable independently associated with both RFS and overall survival (OS) in both training sets. Therefore, the committee selected tumor budding as the basis for developing a grading system, according to 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 tumor budding incolorectal cancer, the committee evaluated and adopted this cut-off for the proposed two-tiered grading system, classifying tumors 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 tumors 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."

More information: Mari Mino-Kenudson et al, 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 Journal information: Journal of Thoracic Oncology

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International Association for the Study of Lung Cancer