Tumor Spread Through Air Spaces Identifies a Distinct Subgroup With Poor Prognosis in Surgically Resected Lung Pleomorphic Carcinoma

BACKGROUND: Tumor spread through air spaces (STAS) has recently been reported as a novel form of lung adenocarcinoma invasion that can negatively affect survival; however, its role in pleomorphic carcinoma remains unclear. The goal of this study was to characterize tumor STAS in pleomorphic carcinoma, including its association with clinicopathologic features and prognosis. METHODS: Tumor specimens obtained from 35 consecutive patients with pleomorphic carcinoma who underwent surgical resection between 2009 and 2015 were reviewed. Tumor STAS was defined as tumor cells spreading within the air spaces in the surrounding lung parenchyma beyond the edge of the primary tumor. RESULTS: Fourteen patients (40%) had evidence of STAS-positive pleomorphic carcinomas. Three types of morphologic findings were observed: single cells, small tumor cell clusters, and tumor nests. Tumor necrosis tended to be more prevalent in STAS-positive tumors than in STAS-negative tumors (P = .094). Patients with STAS experienced significantly worse recurrence-free survival (P = .005) and overall survival (P = .002) rates than those without STAS. Moreover, multivariate analysis revealed that tumor STAS was an independent risk factor for both recurrence (P = .014) and poor overall survival (P = .042). CONCLUSIONS: In this first study of its kind, tumor STAS in patients with pleomorphic carcinoma was shown to be associated with high recurrence rates and poor survival after surgical resection. Hence, tumor STAS can serve as a predictor of postoperative survival; this information will enable better risk stratification and more effective clinical management of patients with this rare type of tumor.