The Diagnostic yield and safety of pleural cryobiopsy using a flexible bronchoscope: a retrospective cohort study

Authors

  • Thamayanthy Murugesu Medical Department, Hospital Selayang
  • Syahrinnaquiah Samsuddin
  • Zahrah Tawil
  • Jen Lye Wan

Keywords:

Pleural effusion, Cryobiopsy, Pleuroscopy, Flexible bronchoscope, Diagnostic yield

Abstract

Abstract

Background
Pleuroscopy is a well-established diagnostic tool for undiagnosed exudative pleural effusion, conventionally performed with rigid or semi-rigid thoracoscopes when less invasive methods fail. Pleural cryobiopsy improves diagnostic yield and tissue quality, but data on its use with a flexible bronchoscope remain limited. In this study, we assessed the diagnostic yield, adequacy for molecular testing, safety, and feasibility of pleuroscopic cryobiopsy using a flexible bronchoscope.

Methods
We conducted a retrospective cohort study of consecutive adult patients with undiagnosed exudative pleural effusion despite thoracocentesis who underwent pleuroscopic cryobiopsy using a flexible bronchoscope at Selayang Hospital, Malaysia, between November 2023 and September 2025.

Results
Thirty patients underwent pleuroscopic cryobiopsy via a flexible bronchoscope. The diagnostic yield was 90.0% (95% confidence interval (CI): 73.5–97.9%), and malignancy was the most common diagnosis (56.7%), with lung adenocarcinoma being the most frequent. 88.9% of lung adenocarcinoma biopsy samples were sufficient for Epidermal Growth Factor Receptor (EGFR) mutation analysis. 30% of the specimens showed granulomatous inflammation, while 10% were non-diagnostic. Median cryoprobe activation time was 5 seconds (interquartile range (IQR) 3-5), procedure duration was 45 minutes (IQR 30 – 46), and biopsy size was 10 mm (IQR 8-16). Minor bleeding occurred in 23.3% (95% CI: 9.9–42.3%) of patients, and moderate bleeding in 6.7% (95% CI: 0.8–22.1%). No major bleeding events occurred. No significant associations were observed between procedural variables and clinical outcomes.

Conclusion
Pleural cryobiopsy performed via a flexible bronchoscope is an effective and feasible diagnostic modality for undiagnosed exudative pleural effusion, with a low bleeding risk, providing high diagnostic yield and adequacy for molecular testing.

Keywords
Pleural effusion; Cryobiopsy; Pleuroscopy; Flexible bronchoscope; Diagnostic yield; Malaysia

References

Liam C, Lim K, Wong CM. Causes of pleural exudates in a region with a high incidence of tuberculosis. Respirology. 2000;5:33–8. doi: 10.1046/j.1440-1843.2000.00223.x

Boutin C, Viallat JR, Cargnino P, et al. Thoracoscopy in malignant pleural effusions. Am Rev Respir Dis. 1981;124:588–92. doi: 10.1164/arrd.1981.124.5.588

Medical Thoracoscopy/Pleuroscopy. Chest. 2003;123:1712–3. doi: 10.1016/S0012-3692(15)33721-1

Murthy V, Bessich JL. Medical thoracoscopy and its evolving role in the diagnosis and treatment of pleural disease. J Thorac Dis. 2017;9:S1011–21. doi: 10.21037/jtd.2017.06.37

Pathak V, Shepherd RW, Hussein E, et al. Safety and Feasibility of Pleural Cryobiopsy Compared to Forceps Biopsy During Semi-rigid Pleuroscopy. Lung. 2017;195:371–5. doi: 10.1007/s00408-017-9998-0

Giri M, Huang G, Puri A, et al. Efficacy and Safety of Cryobiopsy vs. Forceps Biopsy for Interstitial Lung Diseases, Lung Tumors, and Peripheral Pulmonary Lesions: An Updated Systematic Review and Meta-Analysis. Front Med. 2022;9:840702. doi: 10.3389/fmed.2022.840702

Cheng T-L, Huang Z-S, Zhang J, et al. Comparison of cryobiopsy and forceps biopsy for the diagnosis of mediastinal lesions: A randomised clinical trial. Pulmonology. 2024;30:466–74. doi: 10.1016/j.pulmoe.2023.12.002

Freund O, Wand O, Schneer S, et al. Transbronchial Cryobiopsy Is Superior to Forceps Biopsy for Diagnosing both Fibrotic and Non-Fibrotic Interstitial Lung Diseases. Respiration. 2023;102:852–60. doi: 10.1159/000533197

Thomas R, Karunarathne S, Jennings B, et al. Pleuroscopic cryoprobe biopsies of the pleura: A feasibility and safety study. Respirology. 2015;20:327–32. doi: 10.1111/resp.12441

Aktas Z, Gunay E, Hoca N, et al. Endobronchial cryobiopsy or forceps biopsy for lung cancer diagnosis. Ann Thorac Med. 2010;5:242. doi: 10.4103/1817-1737.69117

Montero MA, De Gracia J, Culebras Amigo M, et al. The role of transbronchial cryobiopsy in lung transplantation. Histopathology. 2018;73:593–600. doi: 10.1111/his.13656

Arimura K, Kondo M, Nagashima Y, et al. Comparison of tumor cell numbers and 22C3 PD-L1 expression between cryobiopsy and transbronchial biopsy with endobronchial ultrasonography-guide sheath for lung cancer. Respir Res. 2019;20:185. doi: 10.1186/s12931-019-1162-3

Haentschel M, Boeckeler M, Ehab A, et al. Cryobiopsy increases the EGFR detection rate in non-small cell lung cancer. Lung Cancer. 2020;141:56–63. doi: 10.1016/j.lungcan.2019.12.008

Udagawa H, Kirita K, Naito T, et al. Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single‐arm study. Cancer Science. 2020;111:2488–98. doi: 10.1111/cas.14489

Johannson KA, Marcoux VS, Ronksley PE, et al. Diagnostic Yield and Complications of Transbronchial Lung Cryobiopsy for Interstitial Lung Disease. A Systematic Review and Metaanalysis. Ann Am Thorac Soc. 2016;13:1828–38. doi: 10.1513/AnnalsATS.201606-461SR

Bondue B, Schlossmacher P, Allou N, et al. Trans-bronchial lung cryobiopsy in patients at high-risk of complications. BMC Pulm Med. 2021;21:135. doi: 10.1186/s12890-021-01503-9

Giri M, Dai H, Guo S, et al. Efficacy and Safety of Pleural Cryobiopsy vs. Forceps Biopsy for Evaluation of Undiagnosed Pleural Effusion: A Systematic Review and Meta-Analysis. Front Med. 2022;9:847146. doi: 10.3389/fmed.2022.847146

Shafiq M, Sethi J, Ali MS, et al. Pleural Cryobiopsy. Chest. 2020;157:223–30. doi: 10.1016/j.chest.2019.09.023

Shamsuddin AR, Mohamad Jailaini MF, Azmel AA, et al. Comparison of diagnostic yield and complication of medical thoracoscopy using Flexible Bronchoscope versus Semi-Rigid Pleuroscope among Hospitalized Patients with Pleural Effusion (FLEXPLEUR): a retrospective observational study. J Thorac Dis. 2025;17:3631–42. doi: 10.21037/jtd-2025-135

Mohan BVM, Dutt TS, Tousheed SZ. Diagnostic and Therapeutic Pleuroscopy Using a Flexible Fiberoptic Bronchoscope for Resource-poor Environments: A Case Series. The Indian Journal of Chest Diseases and Allied Sciences. 2022;59:173–6. doi: 10.5005/ijcdas-59-4-173

Lee P, Colt HG. Rigid and semirigid pleuroscopy: The future is bright. Respirology. 2005;10:418–25. doi: 10.1111/j.1440-1843.2005.00737.x

Lentz RJ, Argento AC, Colby TV, et al. Transbronchial cryobiopsy for diffuse parenchymal lung disease: a state-of-the-art review of procedural techniques, current evidence, and future challenges. J Thorac Dis. 2017;9:2186–203. doi: 10.21037/jtd.2017.06.96

Rial MB, Rodríguez IL, Roibás CM, et al. Diagnostic Yield and Safety of Pleural Cryobiopsy during Medical Thoracoscopy to Diagnose Pleural Effusion. A Systematic Review and Meta-Analysis. Arch Bronconeumol. 2020;56:784–91. doi: 10.1016/j.arbr.2020.10.003

Ahmed MM, AlSharkawy SH, Shoukri AM, et al. Evaluation of safety and diagnostic yield of pleural cryobiopsies during thoracoscopy. Egypt J Bronchol. 2019;13:63–6. doi: 10.4103/ejb.ejb_48_18

Zamzam MA, Khames AA, El-Dahdouh SS, et al. Role of thoracoscopic pleural lavage and brush in undiagnosed exudative pleural effusion. Egypt J Chest Dis Tuberc. 2015;64:601–5. doi: 10.1016/j.ejcdt.2015.05.001

Kiani A, Abedini A, Karimi M, et al. Diagnostic Yield of Medical Thoracoscopy in Undiagnosed Pleural Effusion. Tanaffos. 2015;14:227–31.

Rozman A, Camlek L, Marc Malovrh M, et al. Feasibility and safety of parietal pleural cryobiopsy during semi-rigid thoracoscopy. Clin Respir J. 2016;10:574–8. doi: 10.1111/crj.12256

Kamatani M, Awano N, Inomata M, et al. Diagnostic yields and safety of thoracoscopic cryobiopsies in Japan: A single-center retrospective observational study. Respiratory Investigation. 2024;62:617–22. doi: 10.1016/j.resinv.2024.05.001

Kho SS, Nyanti LE, Chai CS, et al. Exploring the optimal freeze time and passes of the ultrathin cryoprobe in transbronchial cryobiopsy of peripheral pulmonary lesions. ERJ Open Res. 2024;10:00506–2023. doi: 10.1183/23120541.00506-2023

Lee C-S, Li S-H, Chang C-H, et al. Comparison of Diagnostic Yield and Safety between Semirigid Pleuroscopic Cryobiopsy and Forceps Biopsy for Undiagnosed Pleural Effusion. Can Respir J. 2019;2019:5490896. doi: 10.1155/2019/5490896

Published

2026-09-30

How to Cite

Murugesu, T., Samsuddin, S., Tawil, Z., & Wan, J. L. (2026). The Diagnostic yield and safety of pleural cryobiopsy using a flexible bronchoscope: a retrospective cohort study. The Interventionalist Journal, 6(3). Retrieved from https://theinterventionalists.com/index.php/journal/article/view/135