Probe-based confocal laser endomicroscopy imaging features of malignant lung nodules: results from a prospective in vitro study

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Background: Confocal laser endomicroscopy (CLE) can aid in the diagnosis of malignant lung nodules, but there is currently no comprehensive study of the CLE imaging features of malignant lung nodules. This study aims to summarize the CLE image characteristics of malignant lung nodules to assist in clinical diagnosis. Methods: This prospective study included patients scheduled to undergo lung nodule resection surgery from December 2023 to August 2024 at Chinese PLA General Hospital. The patients underwent standard surgical procedures, and CLE images were captured for target normal tissue, tissue adjacent to the lesion, and lesion tissue in the removal of ex vivo lung tissue. The CLE imaging features of the malignant pulmonary nodules were identified and validated through a consistency evaluation. Results: A total of 29 patients with 32 pulmonary nodules were included in the study. The following eight CLE imaging features of malignant pulmonary nodules were identified: (I) thickened alveolar septa; (II) diffuse hyperplasia of elastic fibers (cloud shadows); (III) curled alveolar septa; (IV) destruction of alveolar structures; (V) broken elastic fibers; (VI) fragmented elastin; (VII) defective alveolar structures (loss of elastin); and (VIII) microvascular disruption. As the malignancy of the lesions increased, the CLE images began to show significant destruction of the alveolar structure, including rupture of the elastic fibers, aggregation of the elastic proteins, and large-scale accumulation. The inter-observer agreement (IOA) and intra-observer reliability (IOR) of the CLE imaging features for the identification of malignant pulmonary nodules were 0.811 [95% confidence interval (CI): 0.747–0.874] and 0.869±0.024, respectively. Conclusions: Malignant pulmonary nodules may display a variety of CLE imaging features. A comprehensive CLE imaging feature map summary of malignant lung nodules may aid in the identification of malignant lung nodules.

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