Spread through air spaces (STAS) in lung adenocarcinoma: Prognostic impact of morphologic patterns, density, and...

Spread through air spaces (STAS) has emerged as a distinct invasion pattern in lung adenocarcinoma, but the prognostic implications of its morphologic features remain incompletely defined. In this study, we analyzed STAS presence, morphologic subtypes, density, and extent with clinicopathologic parameters and survival. We analyzed 184 surgically resected lung adenocarcinomas. We histopathologically examined the presence of STAS, STAS morphological subtypes (solid nests, micropapillary clusters, and single-cell spread), STAS extension, STAS density and evaluated the relationship of the findings with clinicopathological parameters. STAS was detected in 67.9 % of the tumors. The most common STAS subtype was solid (53.6 %), followed by micropapillary (30.4 %) and single-cell (16.0 %) subtypes. STAS density was categorized as low (1-4 tumor cell clusters) or high (≥5 clusters) at ×200 magnification, and STAS extent was classified as limited (≤3 alveolar spaces) or extensive (>3 spaces). High-density STAS was observed in 56 %, low-density STAS in 44 %; limited-STAS in 57.6 %, and extensive-STAS in 42.4 %. STAS positivity was significantly associated with predominant tumor pattern (p = 0.002), tumor grade (p < 0.001), pleural invasion (p = 0.004), lymphovascular invasion (LVI) (p < 0.001), recurrence (p < 0.001), metastasis (p < 0.001), pN (p = 0.003), overall survival (OS) (p < 0.001) and recurrence-free survival (DFS) (p < 0.001). Among morphologic subtypes, significant correlations were found with predominant tumor pattern (p < 0.001), grade (p = 0.001) and LVI (p = 0.005). We found STAS density to show a significant difference in OS (p = 0.009). Extensive STAS correlated with surgical resection type (p = 0.002), necrosis (p = 0.049), pN (p = 0.033), OS (p = 0.016) and DFS (p = 0.037). Our study shows that STAS and its features have prognostic significance with clinically meaningful differences in lung adenocarcinomas. These results highlight the potential clinical relevance of STAS subtype, density, and extent in risk stratification.