Clinicopathological features and prognostic factors of pulmonary pleomorphic carcinoma

OBJECTIVES: The objective of this study was to clarify the clinicopathological features and prognostic factors of pulmonary pleomorphic carcinoma (PPC) in a multicenter setting. PATIENTS AND METHODS: We conducted a retrospective study of PPC patients across four hospitals between 2000 and 2021. Among 4425 resected cases of non-small cell lung cancer (NSCLC), 84 cases (1.9%) were diagnosed as PPC. Clinical records and pathological specimens were reviewed. RESULTS: PPC patients had significantly poorer recurrence-free survival (RFS) and overall survival (OS) than those with other NSCLC subtypes (5-year RFS: 33.0% vs. 59.7%, P < 0.001; 5-year OS: 45.1% vs. 69.7%, P < 0.001). Multivariate analysis identified two independent adverse prognostic factors for RFS: sarcomatoid component ≥50% and tumor necrosis ≥30%. Based on these two factors, PPC patients were stratified into three prognostic risk groups: high-risk (both factors), intermediate-risk (one), and low-risk (neither). The high-risk group demonstrated significantly worse RFS and OS compared with the low-risk group. Furthermore, PD-L1 expression was significantly higher in the high-risk group (median PD-L1 expression: 20% in low-risk, 70% in intermediate-risk, 80% in high-risk; P = 0.026). CONCLUSION: This study identified sarcomatoid component ≥50% and necrosis ≥30% as significant adverse prognostic indicators for RFS in PPC. Stratification into three prognostic risk groups based on these two features may aid in risk assessment and treatment planning. Notably, the high-risk group showed markedly elevated PD-L1 expression, suggesting its potential as a predictor of response to immune checkpoint inhibitors. Further large-scale prospective studies are warranted to validate these findings and improve therapeutic strategies for PPC. SHORT ASBSTRACT: This study analyzed 84 cases of pulmonary pleomorphic carcinoma (PPC). Multivariate analysis identified a sarcomatoid component ≥50% and tumor necrosis ≥30% as independent adverse prognostic factors for recurrence-free survival (RFS). Based on these two factors, PPC patients were stratified into three prognostic risk groups. Notably, the high-risk group exhibited significantly higher PD-L1 expression than the low-risk group, suggesting its potential as a predictor of response to immune checkpoint inhibitors.