Real-time visualization of lung malignancy with needle-based confocal laser endomicroscopy during shape-sensing robotic-assisted bronchoscopy

Solitary pulmonary nodules (SPNs) are frequently encountered clinically. Robotic-assisted bronchoscopy (RAB) shows promise in improving the diagnostic yield for lung nodules, particularly peripheral ones. Confocal laser endomicroscopy (CLE), an emerging technology, provides high-resolution, in-vivo, real-time tissue assessment at the cellular and subcellular level, offering 'optical biopsies'. Needle-based CLE (nCLE) allows real-time microscopic analysis of peripheral lung lesions during RAB. This case series presents the first reported experience of using nCLE during shape-sensing RAB to diagnose malignancy in SPNs. The increasing incidence of SPNs, driven by broader lung cancer screening guidelines, necessitates improved diagnostic accuracy and adequacy of tissue sampling. While imaging techniques help characterize nodules, tissue sampling remains crucial for malignancy confirmation. Accessing and adequately sampling peripheral nodules presents challenges. RAB offers improved access to lung nodules, but precise target localization remains critical to maximize diagnostic yield. Real-time microscopic visualization with nCLE has the potential to significantly improve the diagnostic accuracy of RAB.

Several studies highlight the benefits of RAB in improving the diagnostic yield of bronchoscopy for peripheral lung lesions. CLE has demonstrated utility in various applications, including characterizing pancreatic lesions and assessing surgical margins in prostate cancer. Studies using probe-based CLE (pCLE) have shown comparable accuracy to standard biopsies in diagnosing esophageal and gastric lesions, and in differentiating pancreatic cystic lesions. The use of nCLE for real-time microscopic analysis of peripheral lung cancer has been previously reported, although not in conjunction with RAB. The lung's intrinsic autofluorescence, primarily due to elastin, makes it suitable for CLE; however, malignant nodules often lack this autofluorescence, necessitating the use of intravenous fluorescein to enhance visualization.

This case series involved three patients with SPNs. For each patient, the procedure followed these steps: 1. Under general anesthesia, RAB was used to reach the target nodule, with localization confirmed using radial-endobronchial ultrasound (R-EBUS). 2. 2.5 ml of 10% fluorescein was administered intravenously 30 seconds before nCLE use. 3. An <1 mm nCLE fiber, inserted through an 18G needle, was advanced into the target under fluoroscopy. 4. nCLE images were acquired. 5. nCLE was removed, and planned tissue sampling proceeded. In all cases, systematic mediastinal staging was performed using linear endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA). Pathologic analysis confirmed the diagnoses.

Three patients (median age 77, 67% male) with SPNs (median minimum size 1.8 cm, maximum 2.1 cm) underwent simultaneous RAB and nCLE. In all three cases, nCLE detected patterns suggestive of malignancy: dark clumps and pleomorphic dark cells. Pathology confirmed the diagnoses: two patients had lung adenocarcinoma, and one patient had squamous cell carcinoma. The nCLE findings paralleled the pathological results, suggesting real-time visualization of malignancy was achieved.

This case series demonstrates the feasibility and potential benefits of combining RAB and nCLE for diagnosing lung malignancy in SPNs. The real-time visualization provided by nCLE allowed for immediate assessment of tissue characteristics, potentially improving sample adequacy and diagnostic accuracy. This approach may help to reduce the need for repeat procedures and improve patient outcomes. The ability to confirm malignancy in real-time during the procedure could be particularly beneficial for guiding treatment decisions and optimizing biopsy strategies. Future studies with larger patient cohorts are needed to validate these findings and assess the clinical impact of this combined approach.

The combined use of RAB and nCLE, as demonstrated in this case series, offers a promising approach for improving the diagnosis of lung malignancy in patients with SPNs. Real-time visualization of malignant cells during the procedure may enhance diagnostic accuracy and efficiency. Further research with larger prospective studies is warranted to confirm these findings and explore the clinical utility of this technique in broader patient populations.

This is a small case series, limiting the generalizability of the findings. Further research is needed to assess the performance characteristics of this technique in a larger, more diverse patient population and to compare it to other diagnostic methods. The applicability of this technique to various types of lung lesions and sizes of SPNs also needs to be evaluated.