Clinical application of confocal laser endomicroscopy in the diagnosis of malignant pleural effusion

Our plain-English summary of Clinical application of confocal laser endomicroscopy in the diagnosis of malignant pleural effusion, by S. Ye, M. Yuan, C. Song, et al (Frontiers in Oncology, 2025).

The study

• Authors: S. Ye, M. Yuan, C. Song, Z. Yang, Y. Hu, J. Ni
• Journal: Frontiers in Oncology
• Published: 2025;15:1666259
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Probe-based confocal laser endomicroscopy (pCLE) is an innovative in vivo microscopic imaging technique that enables real-time visualization of tissue cytology during endoscopic examinations. This study aimed to evaluate the clinical utility of pCLE in diagnosing MPE.

Methods: A total of 41 patients with pleural effusion (PE) who underwent pCLE examination were enrolled in this prospective study. The diagnostic performance of pCLE was assessed by calculating sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC), using histopathological results as the reference standard. Additionally, the safety profile of the pCLE procedure was evaluated.

Results: Among the 41 patients, histopathological analysis confirmed MPE in 31 patients and benign pleural effusion (BPE) in 10 patients. Of the 31 MPE cases, 26 were lung adenocarcinoma (LUAD), 2 were lung squamous cell carcinoma (LSCC), 1 was large cell lung cancer (LCLC, a subtype of non-small cell lung cancer [NSCLC]), 1 was pleural malignant mesothelioma (PMM), and 1 was pleural metastasis from other tumors. Compared with histopathology, pCLE demonstrated a sensitivity of 96.77%, specificity of 80%, accuracy of 92.68%, PPV of 93.75%, and NPV of 88.89%. There was substantial agreement between pCLE and histopathological findings (kappa = 0.79, p < 0.001). Furthermore, compared to conventional thoracoscopy, pCLE facilitated targeted biopsy sampling and improved detection of malignant lesions. No adverse events related to pCLE were observed, indicating its favorable safety profile.

Conclusions: Our study demonstrates that pCLE is a valuable tool for enhancing the diagnosis of MPE, with high concordance with histopathological findings (kappa = 0.79, p < 0.001) and significant guidance for thoracoscopic pleural biopsies. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of pCLE were 96.77%, 80%, 92.68%, 93.75%, and 88.89%, respectively, when compared with histopathology. These results indicate that pCLE can effectively differentiate between benign and malignant pleural effusion in patients with undetermined etiology and serves as a robust complementary method to existing diagnostic approaches. However, the small sample size of this study limits the generalizability of the findings, and further large-scale, multicenter clinical trials are needed to validate these results.

Copyright © 2026 Ye, Yuan, Song, Yang, Hu and Ni.

In plain English

This prospective study at a hospital in Wuhan, China, tested whether a microscopic imaging probe (probe-based confocal laser endomicroscopy, pCLE), passed into the chest during medical thoracoscopy, could tell malignant pleural effusions from benign ones. It included 41 adults enrolled from April 2022 to October 2024 whose pleural effusion had no cause found by standard fluid tests. Biopsy results (histopathology) served as the reference. Tissue showed malignancy in 31 patients (26 lung adenocarcinoma, 2 squamous lung cancer, 1 large cell lung cancer, 1 pleural malignant mesothelioma, 1 metastasis from other tumors) and benign disease in 10. pCLE gave 2 false-positive results and 1 false-negative result. That meant a sensitivity of 96.77% (95% confidence interval 81.49 to 99.83) and a specificity of 80% (95% confidence interval 44.22 to 96.46). Agreement with histopathology had a kappa of 0.79. The study did not examine asbestos exposure. The authors concluded that pCLE can serve as a complementary method for distinguishing benign from malignant effusions. They noted the small sample size, the lack of long-term follow-up, and possible reading errors in interpreting pCLE images.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective single-hospital diagnostic accuracy study comparing pCLE readings with histopathology as the reference standard
• Who was studied: 41 adult patients (25 male, 16 female; mean age 59.07 years, range 41 to 86) with pleural effusion of undetermined cause, admitted to the Central Hospital of Wuhan, China, from April 2022 to October 2024
• Exposure: No asbestos or fiber exposure was studied. The study evaluated a diagnostic technique: pCLE imaging of the pleura after intravenous fluorescein sodium, performed during medical thoracoscopy and followed by targeted biopsy.
• Main results:
  • Histopathology found malignant lesions in 31 of 41 patients and benign lesions in 10. Among the malignant cases, 26 were lung adenocarcinoma, 1 was pleural malignant mesothelioma and 1 was a pleural metastasis of other tumors.
  • Lung adenocarcinoma accounted for 26 of the 41 patients (63.41%)
  • Compared with histopathology, pCLE had a sensitivity of 96.77%, specificity of 80%, accuracy of 92.68%, positive predictive value of 93.75% and negative predictive value of 88.89%
  • The 95% confidence interval for sensitivity was 81.49 to 99.83
  • The 95% confidence interval for specificity was 44.22 to 96.46
  • Agreement between pCLE and histopathology had a kappa of 0.79 (p less than 0.001)
  • pCLE gave 2 false-positive results, which the authors attributed mainly to overinterpreting clusters of inflammatory cells
  • pCLE gave 1 false-negative result, which the authors attributed to missing an early small tumor focus
  • On pCLE, malignant pleura appeared as dark black particles of varying size and shape, often clustered
  • The Results section reported no endoscopic complications and no adverse reactions to sodium fluorescein
• The authors' conclusion: The authors concluded that pCLE can serve as a complementary method to existing approaches for telling benign from malignant pleural effusion in patients whose effusion has an undetermined cause, and they called for larger multicenter trials
• Limitations the authors state:
  • Small sample size, so pCLE features of specific types of benign and malignant effusion could not be characterized
  • No long-term follow-up of patients with negative diagnoses
  • The usefulness of pCLE is limited by possible reading errors in both directions (overreading and underreading)
  • The reference standard (pathologic biopsy) depends on where the sample is taken and on the operator
  • A rise in malignancy detection at the hospital after pCLE was introduced could not be directly attributed to pCLE

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Cytology, Lung Adenocarcinoma, Squamous Cell Carcinoma, Lung Cancer, Non-Small Cell Lung Cancer, Mesothelioma, Metastasis.

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• Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications — A. Fiorelli, G. Vicidomini, et al. (2011)

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