Comparison of diagnostic yield of EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-MCB) versus EBUS-guided transbronchial needle aspiration (EBUS-TBNA): A systematic review and meta-analysis

II. Abstract Background EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is the preferred first-line technique for mediastinal lymph node sampling. However, its cytological specimens are often insufficient when tissue architecture is critical, such as benign granulomatous and lymphoproliferative disorders. EBUS-guided transbronchial mediastinal cryobiopsy (EBUS-MCB) has emerged as a technique that retrieves larger, histologically preserved tissue samples. Methods This systematic review and meta-analysis followed PRISMA-2020 guidelines (PROSPERO:CRD420251034456). PubMed and Scopus were searched through January 2026 for studies comparing diagnostic yield of EBUS-MCB with EBUS-TBNA in adults with mediastinal lymphadenopathy. Pooled odds ratios with 95% confidence intervals were calculated using a random-effects model. Heterogeneity was assessed by I 2 and Cochran's Q test, and risk of bias by QUADAS-2. Results Twenty-four studies (including five randomized controlled trials) enrolling 2182 patients across 33 centres (11 countries) were included. EBUS-MCB demonstrated significantly higher overall diagnostic yield (90.8%vs74.5%; OR:3.40; 95%CI:2.55–4.54; p < 0.001). The benefit was greatest in lymphoma (OR:6.40; 95%CI:3.07–13.38; p < 0.001) and benign mediastinal diseases (OR 3.37; 95% CI 2.04–5.57; p < 0.001), including sarcoidosis (OR:3.30; 95%CI:1.66–6.55; p < 0.001). In malignant disease the benefit was modest. No significant difference was observed for lung malignancy sub-group. EBUS-MCB rescued diagnosis in one in five patients where EBUS-TBNA had failed. No procedure-related mortality was reported. Conclusion Both EBUS-MCB and EBUS-TBNA establish diagnoses in patients with mediastinal lymphadenopathy; however, EBUS-MCB demonstrated superior diagnostic yield, particularly in lymphoma and benign mediastinal disease. These findings support selective incorporation of EBUS-MCB into EBUS bronchoscopy practice, especially when histologic tissue architecture is essential for diagnosis.