Peripheral type squamous cell carcinoma of the lung: Clinicopathologic characteristics in comparison to the central type

Background: Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type. Methods: This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included. Results: Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type. Conclusions: In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.