Tumor spread through air spaces (STAS) has been recognized as a prognostic factor for several types of lung cancers. However, information regarding its clinical significance in pulmonary lymphoepithelial carcinoma is limited. Therefore, this study investigated effects of STAS on the clinical outcomes for patients with pulmonary lymphoepithelial carcinoma. This study retrospectively reviewed 56 surgically resected pulmonary lymphoepithelial carcinomas. The study defined STAS as the presence of tumor cells within air spaces in lung parenchyma beyond the tumor edge. Artifacts were excluded. Recurrence-free survival (RFS) was analyzed using the log-rank test and Cox proportional hazards model. In 18 patients (32.1%), STAS was observed and found to be associated with larger tumor size (>3 cm) (p = 0.009), higher pathologic stage (p = 0.026), and tumor necrosis (p = 0.046). Patients with STAS had a significantly lower 5-year RFS rate (p = 0.025). Multivariate analysis showed that STAS was an independent predictor of worse RFS (hazard ratio, 3.395; p = 0.038). Patients with STAS had a significantly increased risk of locoregional recurrence (p = 0.049). The study findings suggest that STAS is an independent predictor of poor RFS. Based on these findings, a new three-tier grading system based on the patterns of tumor border and STAS was proposed for effective prediction of 5-year RFS in pulmonary lymphoepithelial carcinoma.
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