Prognostic significance of intratumoral neutrophil extracellular traps in pulmonary pleomorphic carcinoma: comparison with adenocarcinoma

Pleomorphic carcinoma (PC) of the lung is a rare, aggressive non-small cell lung cancer. Neutrophil extracellular traps (NETs) are linked to tumour progression, but their relevance in pulmonary PC is unknown. We evaluated the prognostic impact of intratumoral NETs and CD66b + neutrophil infiltration in PC versus adenocarcinoma. Among 1148 patients who underwent pulmonary resection for primary lung cancer, 813 patients with adenocarcinoma and 17 with PC were analysed. Clinicopathological factors and survival were compared and propensity score matching was applied. NETs and neutrophils were quantified by CD66b immunohistochemistry and citrullinated histone H3/myeloperoxidase immunofluorescence. PC was associated with heavier smoking, more vascular invasion, and more advanced stage than adenocarcinoma (all p < 0.001). The patient characteristics were comparable after matching. Overall and recurrence-free survival were both worse in the PC group (both p < 0.001) and remained poorer after matching. Cox analysis identified NET-positive area (% per high-power field) as an independent predictor of worse overall survival (hazard ratio 1.14, 95% confidence interval 1.01–1.30; p = 0.033). Pulmonary PC shows intense neutrophil infiltration and abundant intratumoral NETs, both associated with poor survival. Quantitative assessment of NETs may serve as a biomarker and therapeutic target in PC.