Cui-Yun Zuo, Center for Interventional Pulmonology, The Second Affiliated Hospital of Xiamen Medical College

•This study aimed to apply real‐time EBUS and nCLE technologies for the diagnosis of benign and malignant HMLN lesions and to further explore the diagnostic potential of EBUS, nCLE, and the combination of EBUS and nCLE for these lesions.

•We recruited 107 patients with HMLN lesions who were examined by EBUS and nCLE. A pathological examination was performed, and the diagnostic potential of EBUS, nCLE, and combined EBUS‐nCLE approach was analyzed according to the results.

•Among the 107 cases of HMLN lesions, 43 cases were benign and 64 cases were malignant on pathological examination, 41 cases were benign and 66 cases were malignant on EBUS examination; 42 cases were benign and 65 cases were malignant on nCLE examination; 43 cases were benign and 64 cases were malignant on combined EBUS‐nCLE examination.
•The combination approach had 93.8% sensitivity, 90.7% specificity, and 0.922 area under the curve, which was higher than those of EBUS (84.4%, 72.1%, and 0.782, respectively) and nCLE diagnosis (90.6%, 83.7%, and 0.872, respectively).
•The combination approach had a higher positive predictive value (0.908), negative predictive value (0.881), and positive likelihood ratio (10.09) than that of EBUS (0.813, 0.721, and 3.03, respectively) and nCLE (0.892, 0.857, and 5.56, respectively), whereas, the negative likelihood ratio was lower than that for EBUS (0.22) and nCLE (0.11).
•No serious complications occurred in patients with HMLN lesions.

•The diagnostic efficacy of nCLE was better than EBUS. The EBUS‐nCLE combination is a suitable approach for diagnosing HMLN lesions.