Comparative Diagnostic Utility of EBUS Mediastinal Cryobiopsy (EBUS-MCB) and EBUS-TBNA in Granulomatous Mediastinal Lymphadenopathy: The CRYO-GRANULOMA Study

Background Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the investigation of choice for mediastinal lymphadenopathy. However, its limited tissue yield can hinder the diagnosis of granulomatous disorders such as tuberculosis and sarcoidosis. EBUS-guided mediastinal cryobiopsy (EBUS-MCB) is a novel technique that enables collection of larger tissue samples. This study aimed to compare the diagnostic performance of EBUS-MCB and EBUS-TBNA in patients with granulomatous mediastinal lymphadenopathy (GML), focusing on the Xpert MTB/RIF Ultra assay and histopathologic parameters. Methods In this prospective observational study conducted from March 2024 to March 2025, patients ≥12 years with undiagnosed mediastinal lymphadenopathy and granulomas identified on rapid on-site evaluation (ROSE) of EBUS specimens were enrolled. Paired samples of EBUS-TBNA and EBUS-MCB were obtained from the same lymph node and analyzed. Primary objective was comparison of Xpert Ultra positivity rate between EBUS-TBNA and EBUS-MCB. Secondary objectives were comparison of granuloma density, granuloma nature, and Xpert Ultra thresholds. Results Among 167 patients undergoing EBUS, 51 with granulomatous inflammation were included. EBUS-MCB identified granulomas in all 51 cases versus 45 (88.2%) with EBUS-TBNA (P=0.027). EBUS-MCB showed significantly higher granuloma density and a greater proportion of necrotizing granulomas. Xpert Ultra positivity was comparable between EBUS-TBNA and EBUS-MCB (39.5% vs. 36.8%; P=0.826), but trace detection was significantly lower with EBUS-MCB (14.2% vs. 53.3%; P=0.05). Conclusion EBUS-MCB improves histologic characterization of GML with higher granuloma yield and density. While microbiologic yield is similar, EBUS-MCB reduces the proportion of trace-only Xpert Ultra results, enhancing diagnostic confidence.