Application of confocal laser endomicroscopy in the diagnosis of peripheral pulmonary lesions: a narrative review.

Background and Objective: Despite continued advances in navigational bronchoscopy, the diagnosis of peripheral pulmonary lesions (PPLs) remains challenging. Although contemporary bronchoscopic techniques have improved lesion accessibility, important limitations persist in instrument position confirmation, and representative tissue sampling. Confocal laser endomicroscopy (CLE) is an emerging real-time microscopic imaging technique that enables in vivo visualization of tissue microarchitecture and cellular morphology during bronchoscopic procedures. Its imaging modalities mainly include autofluorescence imaging and exogenous contrast-enhanced imaging. This review aimed to summarize the CLE features of these two imaging modes in PPLs, with particular emphasis on the differences between normal and lesional tissue, in order to clarify the potential role of CLE in lesion confirmation and biopsy guidance. Methods: A literature search was performed using PubMed/MEDLINE, Embase, and Web of Science from inception to December 2025 for studies evaluating CLE in PPLs. The following terms were used in searching: (endomicroscopy or microendoscopy or fibered confocal fluorescence microscopy or confocal laser microscopy) and (lung or pulmonary or respiratory or bronch* or airway). Studies were excluded if they were non-PPLs, animal-only, or duplicate publications. Key Content and Findings: Autofluorescence CLE primarily visualizes elastin-rich alveolar microstructures and can effectively distinguish normal lung tissue from abnormal lesional areas, although it remains difficult for differentiating benign from malignant lesions. In contrast, exogenous contrast-enhanced CLE provides clearer visualization of cellular morphology and tissue architecture, and may facilitate the detection and differentiation of lung cancer. In the diagnosis of PPLs, CLE has the potential clinical value of providing real-time lesion diagnosis and guiding sampling location. Future studies are needed to further refine and validate CLE interpretation criteria for common benign and malignant PPLs, and to determine its clinical value in transbronchial biopsy of PPLs through randomized controlled trials. Conclusions: CLE is a promising adjunctive bronchoscopic imaging technology with potential value in the evaluation of PPLs, particularly for lesion confirmation and biopsy guidance.