Prognostic Significance and Classification Value of Tumor Budding, Single Cell Invasion, and Spread Through Airspaces (STAS) in Lung Squamous Cell Carcinoma.

ObjectiveLung squamous cell carcinomas (LSCC) currently lack a standardized histopathological grading system, unlike their adenocarcinoma counterparts. In this retrospective study, we examined the prognostic significance and classification value of tumor budding (TB), single-cell invasion, tumor budding nest size (TBNS) grading system, and spread through airspaces (STAS).MethodsAbout 268 patients who underwent surgical resection for LSCC between November 2011 and December 2021 were evaluated. TB was assessed in hematoxylin and eosin-stained sections at ×200 magnification from the area showing the most prominent budding activity. A 3-tier TBNS grading system was established by combining the number of tumor buds and the size of tumor cell nests. STAS presence was also evaluated.ResultsOur analysis revealed significant associations between high TBNS scores and adverse pathological features, including higher tumor stage, pleural and lymphovascular invasion, increased stromal fibrosis, and lymph node metastasis. Furthermore, survival analysis demonstrated that high TB, single-cell invasion, elevated TBNS scores, and the presence of STAS were all linked to reduced overall and disease-free survival (P < .005).ConclusionThese findings suggest that TB, TBNS, and STAS are valuable histopathological markers that may offer additional prognostic insight beyond traditional staging parameters. Incorporating a standardized assessment of these features into routine pathology reports could improve prognostic stratification and inform clinical decision-making in patients with LSCC.