Validation of needle-based confocal laser endomicroscopy

We congratulate Benias et al. for their work on needle-based confocal laser endomicroscopy (nCLE) for the evaluation of malignant lymph nodes [1]. Confocal laser endomicroscopy is a laser-based optical technique that enables real-time visualization of tissue on a microscopic level. In combination with endoscopic ultrasound (EUS), the nCLE technique can possibly be helpful in identifying the optimal sampling location or even evolve to a real “optical biopsy” tool in the diagnosis and staging of pancreatic [2] and lung cancer [3].

At this stage, however, the nCLE technique is still investigational and requires validation in different tissue types. nCLE image interpretation by relating the videos to pathology is essential. Ideally, a one-to-one comparison of the nCLE images with the corresponding histology is indicated.

In the Benias et al. paper, the assessed lymph nodes were punctured using a 19 G needle under EUS guidance and subsequently imaged with nCLE [1]. Several questions remain regarding the actual image interpretation and analysis. In the methods section, it is stated that the reviewers compared the nCLE imaging with histological core biopsies. Was a core biopsy always present, or were cell blocks and cytological smears also used as the reference standard?

Although the histology images of Figs. 1a, 2a, and 6a are very illustrative, they do not seem to correlate directly with the case discussed. A direct comparison of nCLE images to the pathological substrate is a key component in understanding the diagnostic possibilities and limitations of this novel optical imaging technique. Could the authors clarify how they specifically performed this assessment?

Clearly recognizable lymph node structures such as the cortex (Fig. 3a) and the capsule (Fig. 1b) are shown on nCLE imaging. However, the lymphoid follicles (Fig. 3b) and the sarcoid-type granuloma (Fig. 3e) seem very similar on appearance. What criteria are used to distinguish the lymphoid node follicles from epithelioid histiocytes?

An official statement of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the utilization of advanced endoscopic imaging in gastrointestinal endoscopy was recently published in Endoscopy [4]. The development of validated classification systems is advocated to support the use of optical diagnosis in combination advanced endoscopic imaging [4].

The authors have made a first step in describing nCLE characteristics of normal and malignant involved lymph nodes. However, larger sample numbers and validation of the characteristics are essential to evaluate the value of the nCLE technique, as an add-on to EUS-guided fine-needle aspiration, for lymph node analysis.

• References

• 1 Benias PC. D’Souza LS. Papafragkakis H. et al. Needle-based confocal endomicroscopy for evaluation of malignant lymph nodes – a feasibility study. Endoscopy 2016; 48: 923-928
• 2 Giovannini M. Caillol F. Monges G. et al. Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in solid pancreatic masses. Endoscopy 2016; 48: 892-898
• 3 Wijmans L. de Bruin DM. Meijer SL. et al. Real-time optical biopsy of lung cancer. Am J Respir Crit Care Med 2016; 194: e10-e11
• 4 East JE. Vleugels JL. Roelandt P. et al. Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy (ESGE) Technology Review. Endoscopy 2016; 48: 1029-1045