Endobronchial Ultrasound Guided Sampling: Diagnostic Yield of Needle Biopsy and Cryobiopsy in Addition to Needle Aspiration

Background: Endobronchial ultrasound (EBUS) guided sampling for evaluation of benign conditions and lymphoma is not standardized. Sampling methods remain under study as new tools become available. Methods: We performed a single center study with protocolized sampling and processing to evaluate the diagnostic utility of transbronchial needle aspiration (TBNA), Franseen needle biopsy (TBNB), and cryobiopsy in patients with mediastinal and hilar abnormality with concern for sarcoid, lymphoma, or undifferentiated lymphadenopathy. Following TBNA, exploratory sampling was performed. A tract was created with a TBNB needle pass followed by cryobiopsy. Sampling was subsequently alternated for a total of 3 passes per tool. The primary outcome was diagnostic yield—using a strict criterion modeled from recent ATS/ACCP guidelines. Secondary outcomes included procedural outcomes and pathologic assessment of TBNB and cryobiopsy samples. Results: Between January and December 2024, 56 nodes were sampled in 51 patients. The overall diagnostic yield per node was 86% (48/56). Regarding individual tools, the yield was 50% for TBNA, 73% for TBNB, and 82% for cryobiopsy (p=0.0001 TBNA vs cryobiopsy; p=0.006 TBNA vs TBNB; p=0.13 TBNB vs cryobiopsy). In subgroup analysis, TBNB and cryobiopsy enhanced diagnostic yield in benign conditions (TBNA- 59%, TBNB-88%, and cryobiopsy-100%; p=0.002 TBNA vs cryobiopsy, p=0.01 TBNA vs TBNB, p=0.11 TBNB vs cryobiopsy). For lymphoma, the diagnostic yield per node was 3/10 for TBNA, 5/10 for TBNB, and 6/10 for cryobiopsy (p=.001 TBNA vs cryobiopsy, p=0.1 TBNA vs TBNB, p=0.1 TBNB vs cryobiopsy). Upon pathology review, TBNB provided larger samples compared to cryobiopsy however TBNB samples contained a larger proportion of blood; these differences translated to similar resultant areas of diagnostic tissue for both tools. Sample usage for immunohistochemistry and special staining was higher for cryobiopsy (61%) vs TBNB (33%). Study sampling was feasible in all patients with a 2% complication rate (1 pneumothorax). Conclusion: Both TBNB and cryobiopsy provide intact histologic sampling that enhance the diagnostic yield of EBUS TBNA in benign conditions. Multiple passes with three biopsy tools at an individual lymph node is safe and feasible. Cryobiopsy provides superior sample quality relative to TBNB and superior yield vs TBNA in lymphoma.