The histological characteristics and clinical outcomes of lung cancer in patients with combined pulmonary fibrosis and emphysema

Combined pulmonary fibrosis and emphysema (CPFE) is an important risk factor for lung cancer (LC), because most patients with CPFE are smokers. However, the histological characteristics of LC in patients with CPFE (LC-CPFE) remain unclear. We conducted this study to explore the clinicopathological characteristics of LC-CPFE. We retrospectively reviewed data from 985 patients who underwent resection for primary LC, and compared the clinicopathological characteristics of patients with LC-CPFE and non-CPFE LC. We identified 72 cases of LC-CPFE, which were significantly associated with squamous cell carcinoma (SqCC) histology (n = 46, P < 0.001) and higher tumor grade (n = 44, P < 0.001), compared to non-CPFE LC. Most LC-CPFE lesions were contiguous with fibrotic areas around the tumor (n = 59, 81.9%), and this association was independent of tumor location. Furthermore, dysplastic epithelium was identified in the fibrotic area for 31 (52.5%) LC-CPFE lesions. Moreover, compared to patients with pulmonary fibrosis alone in the non-CPFE group (n = 31), patients with CPFE were predominantly male (P = 0.008) and smokers (P < 0.001), with LC-CPFE predominantly exhibiting SqCC histology (P = 0.010) and being contiguous with the tumor-associated fibrotic areas (P < 0.001). Multivariate analysis revealed that CPFE was an independent predictor of overall survival (hazard ratio: 1.734; 95% confidence interval: 1.060-2.791; P = 0.028). Our results indicate that LC-CPFE has a distinct histological phenotype, can arise from the dysplastic epithelium in the fibrotic area around the tumor, and is associated with poor survival outcomes.