Small Sample Lung Biopsy Techniques in the Diagnosis of Airway and Parenchymal Lung Diseases

  • Rafael L. PerezEmail author


Nonsurgical approaches to sample focal or diffuse, solid, or infiltrative pathology of the lung offer the advantages of lower risk, comfort, and cost compared to surgical biopsy techniques. However, tissue size obtained by nonsurgical techniques is in the sub-centimeter range increasing the chance of sampling error and compromising the specificity of interpretation. We focus in this chapter on the various small sample biopsy techniques applied to pathology of the airways and lung parenchyma. Selection of which technique to use depends on the location of the lesion and its consistency, predominantly solid or diffuse. The techniques used are described from the perspective of the operating clinician in the diagnosis of diseases of the airways and lung parenchyma.


Flexible fiberoptic bronchoscopy Navigational bronchoscopy Transbronchial biopsy Cryobiopsy Endobronchial ultrasound 


  1. 1.
    Ikeda S, Yanai N, Ishikawa S. Flexible bronchofiberscope. Keio J Med. 1968;17(1):1–16. PubMed PMID: 5674435. Epub 1968/03/01. eng.CrossRefPubMedGoogle Scholar
  2. 2.
    Bolliger CT, Mathur PN, Beamis JF, Becker HD, Cavaliere S, Colt H, et al. ERS/ATS statement on interventional pulmonology. European Respiratory Society/American Thoracic Society. Eur Respir J. 2002;19(2):356–73. PubMed PMID: 11866017. Epub 2002/02/28. eng.CrossRefPubMedGoogle Scholar
  3. 3.
    Rath GS, Schaff JT, Snider GL. Flexible fiberoptic bronchoscopy. Techniques and review of 100 bronchoscopies. Chest. 1973;63(5):689–93. PubMed PMID: 4703621. Epub 1973/05/01. eng.CrossRefPubMedGoogle Scholar
  4. 4.
    Zavala DC. Diagnostic fiberoptic bronchoscopy: techniques and results of biopsy in 600 patients. Chest. 1975;68(1):12–9. PubMed PMID: 168036. Epub 1975/07/01. eng.CrossRefPubMedGoogle Scholar
  5. 5.
    Cooley ME. Symptoms in adults with lung cancer: a systematic research review. J Pain Symptom Manage. 2000;19(2):137–53.CrossRefPubMedGoogle Scholar
  6. 6.
    Hirshberg B, Biran I, Glazer M, Kramer MR. Hemoptysis: etiology, evaluation, and outcome in a tertiary referral hospital. Chest. 1997;112(2):440–4.CrossRefPubMedGoogle Scholar
  7. 7.
    Oberg K, Castellano D. Current knowledge on diagnosis and staging of neuroendocrine tumors. Cancer Metastasis Rev. 2011;30 Suppl 1:3–7. PubMed PMID: 21311954. Epub 2011/02/12. eng.CrossRefPubMedGoogle Scholar
  8. 8.
    Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72. PubMed PMID: 18565894. Epub 2008/06/21. eng.CrossRefPubMedGoogle Scholar
  9. 9.
    Borczuk AC. Benign tumors and tumorlike conditions of the lung. Arch Pathol Lab Med. 2008;132(7):1133–48. PubMed PMID: 18605767. Epub 2008/07/09. eng.PubMedGoogle Scholar
  10. 10.
    Kraft M, Cassell GH, Henson JE, Watson H, Williamson J, Marmion BP, et al. Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma. Am J Respir Crit Care Med. 1998;158(3):998–1001. PubMed PMID: 9731038. Epub 1998/09/10. eng.CrossRefPubMedGoogle Scholar
  11. 11.
    Yamaya M. Virus infection-induced bronchial asthma exacerbation. Pulm Med. 2012;2012:834826. PubMed PMID: 22966430. Pubmed Central PMCID: PMC3432542. Epub 2012/09/12. eng.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Rikimaru T. Endobronchial tuberculosis. Expert Rev Anti Infect Ther. 2004;2(2):245–51. PubMed PMID: 15482190. Epub 2004/10/16. eng.CrossRefPubMedGoogle Scholar
  13. 13.
    Xue Q, Wang N, Xue X, Wang J. Endobronchial tuberculosis: an overview. Eur J Clin Microbiol Infect Dis. 2011;30(9):1039–44. PubMed PMID: 21499709. Epub 2011/04/19. eng.CrossRefPubMedGoogle Scholar
  14. 14.
    Sulavik SB. Bronchocentric granulomatosis and allergic bronchopulmonary aspergillosis. Clin Chest Med. 1988;9(4):609–21. PubMed PMID: 3069292. Epub 1988/12/01. eng.PubMedGoogle Scholar
  15. 15.
    Greenberger PA. Chapter 18: allergic bronchopulmonary aspergillosis. Allergy Asthma Proc. 2012;33 Suppl 1:S61–3. PubMed PMID: 22794691. Epub 2012/07/20. eng.CrossRefPubMedGoogle Scholar
  16. 16.
    Liebow AA. The J. Burns Amberson lecture—pulmonary angiitis and granulomatosis. Am Rev Respir Dis. 1973;108(1):1–18. PubMed PMID: 4577269. Epub 1973/07/01. eng.PubMedGoogle Scholar
  17. 17.
    Clee MD, Lamb D, Clark RA. Bronchocentric granulomatosis: a review and thoughts on pathogenesis. Br J Dis Chest. 1983;77(3):227–34. PubMed PMID: 6351887. Epub 1983/07/01. eng.CrossRefPubMedGoogle Scholar
  18. 18.
    Iannuzzi MC, Fontana JR. Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA. 2011;305(4):391–9. PubMed PMID: 21266686. Epub 2011/01/27. eng.CrossRefPubMedGoogle Scholar
  19. 19.
    Harrison BD, Shaylor JM, Stokes TC, Wilkes AR. Airflow limitation in sarcoidosis—a study of pulmonary function in 107 patients with newly diagnosed disease. Respir Med. 1991;85(1):59–64. PubMed PMID: 2014359. Epub 1991/01/01. eng.CrossRefPubMedGoogle Scholar
  20. 20.
    Ernst A, Silvestri GA, Johnstone D. Interventional pulmonary procedures: Guidelines from the American College of Chest Physicians. Chest. 2003;123(5):1693–717. PubMed PMID: 12740291. Epub 2003/05/13. eng.CrossRefPubMedGoogle Scholar
  21. 21.
    Yarmus L, Feller-Kopman D. Bronchoscopes of the twenty-first century. Clin Chest Med. 2010;31(1):19–27. Table of Contents. PubMed PMID: 20172429. Epub 2010/02/23. eng.CrossRefPubMedGoogle Scholar
  22. 22.
    Austin JH, Muller NL, Friedman PJ, Hansell DM, Naidich DP, Remy-Jardin M, et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology. 1996;200(2):327–31. PubMed PMID: 8685321. Epub 1996/08/01. eng.CrossRefPubMedGoogle Scholar
  23. 23.
    de Groot P, Munden RF. Lung cancer epidemiology, risk factors, and prevention. Radiol Clin North Am. 2012;50(5):863–76. PubMed PMID: 22974775. Epub 2012/09/15. eng.CrossRefPubMedGoogle Scholar
  24. 24.
    Gazzoni FF, Severo LC, Marchiori E, Irion KL, Guimaraes MD, Godoy MC, et al. Fungal diseases mimicking primary lung cancer: radiologic-pathologic correlation. Mycoses. 2013;57(4):197–208. PubMed PMID: 24147761. Epub 2013/10/24. Eng.CrossRefPubMedGoogle Scholar
  25. 25.
    Ribeiro M, Fritscher LG, Al-Musaed AM, Balter MS, Hoffstein V, Mazer BD, et al. Search for chronic beryllium disease among sarcoidosis patients in Ontario, Canada. Lung. 2011;189(3):233–41. PubMed PMID: 21400234. Epub 2011/03/15. eng.CrossRefPubMedGoogle Scholar
  26. 26.
    Marin C, Robles R, Lopez Conesa A, Torres J, Flores DP, Parrilla P. Outcome of strict patient selection for surgical treatment of hepatic and pulmonary metastases from colorectal cancer. Dis Colon Rectum. 2013;56(1):43–50. PubMed PMID: 23222279. Epub 2012/12/12. eng.CrossRefPubMedGoogle Scholar
  27. 27.
    Descombes E, Gardiol D, Leuenberger P. Transbronchial lung biopsy: an analysis of 530 cases with reference to the number of samples. Monaldi Arch Chest Dis. 1997;52(4):324–9. PubMed PMID: 9401359. Epub 1997/08/01. eng.PubMedGoogle Scholar
  28. 28.
    National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395–409.CrossRefGoogle Scholar
  29. 29.
    Viggiano RW, Swensen SJ, Rosenow 3rd EC. Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med. 1992;13(1):83–95. 19920617 DCOM-19920617(0272-5231 (Print)). eng.PubMedGoogle Scholar
  30. 30.
    Leong S, Ju H, Marshall H, Bowman R, Yang I, Ree AM, et al. Electromagnetic navigation bronchoscopy: a descriptive analysis. J Thorac Dis. 2012;4(2):173–85. PubMed PMID: 22833823. Pubmed Central PMCID: PMC3378214. Epub 2012/07/27. eng.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Eberhardt R, Anantham D, Ernst A, Feller-Kopman D, Herth F. Multimodality bronchoscopic diagnosis of peripheral lung lesions: a randomized controlled trial. Am J Respir Crit Care Med. 2007;176(1):36–41. 20070625 DCOM- 20071123(1535-4970 (Electronic)). eng.CrossRefPubMedGoogle Scholar
  32. 32.
    Gilman MJ, Wang KP. Transbronchial lung biopsy in sarcoidosis. An approach to determine the optimal number of biopsies. Am Rev Respir Dis. 1980;122(5):721–4. PubMed PMID: 7447156. Epub 1980/11/01. eng.PubMedGoogle Scholar
  33. 33.
    Shim HS, Park MS, Park IK. Histopathologic findings of transbronchial biopsy in usual interstitial pneumonia. Pathol Int. 2010;60(5):373–7. PubMed PMID: 20518887. Epub 2010/06/04. eng.CrossRefPubMedGoogle Scholar
  34. 34.
    Wall CP, Gaensler EA, Carrington CB, Hayes JA. Comparison of transbronchial and open biopsies in chronic infiltrative lung diseases. Am Rev Respir Dis. 1981;123(3):280–5. PubMed PMID: 7224338. Epub 1981/03/01. eng.PubMedGoogle Scholar
  35. 35.
    Garwood S, Judson MA, Silvestri G, Hoda R, Fraig M, Doelken P. Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis. Chest. 2007;132(4):1298–304. PubMed PMID: 17890467. Epub 2007/09/25. eng.CrossRefPubMedGoogle Scholar
  36. 36.
    von Bartheld MB, Dekkers OM, Szlubowski A, Eberhardt R, Herth FJ, in’t Veen JC, et al. Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial. JAMA. 2013;309(23):2457–64. PubMed PMID: 23780458. Epub 2013/06/20. eng.CrossRefGoogle Scholar
  37. 37.
    Hirschmann JV, Pipavath SN, Godwin JD. Hypersensitivity pneumonitis: a historical, clinical, and radiologic review. Radiographics. 2009;29(7):1921–38. PubMed PMID: 19926754. Epub 2009/11/21. eng.CrossRefPubMedGoogle Scholar
  38. 38.
    Selman M, Pardo A, King Jr TE. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med. 2012;186(4):314–24. PubMed PMID: 22679012. Epub 2012/06/09. eng.CrossRefPubMedGoogle Scholar
  39. 39.
    Babiak A, Hetzel J, Krishna G, Fritz P, Moeller P, Balli T, et al. Transbronchial cryobiopsy: a new tool for lung biopsies. Respiration. 2009;78(2):203–8. PubMed PMID: 19246874. Epub 2009/02/28. eng.CrossRefPubMedGoogle Scholar
  40. 40.
    Caminati A, Harari S. Smoking-related interstitial pneumonias and pulmonary Langerhans cell histiocytosis. Proc Am Thorac Soc. 2006;3(4):299–306. PubMed PMID: 16738193. Epub 2006/06/02. eng.CrossRefPubMedGoogle Scholar
  41. 41.
    Raghu G, Nicholson AG, Lynch D. The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias. Eur Respir Rev. 2008;17(109):108–15.CrossRefGoogle Scholar
  42. 42.
    Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824. PubMed PMID: 21471066. Epub 2011/04/08. eng.CrossRefPubMedGoogle Scholar
  43. 43.
    Park IN, Jegal Y, Kim DS, Do KH, Yoo B, Shim TS, et al. Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia. Eur Respir J. 2009;33(1):68–76. PubMed PMID: 18829672. Epub 2008/10/03. eng.CrossRefPubMedGoogle Scholar
  44. 44.
    Elliot TL, Lynch DA, Newell Jr JD, Cool C, Tuder R, Markopoulou K, et al. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr. 2005;29(3):339–45. PubMed PMID: 15891504. Epub 2005/05/14. eng.CrossRefPubMedGoogle Scholar
  45. 45.
    Devakonda A, Raoof S, Sung A, Travis WD, Naidich D. Bronchiolar disorders: a clinical-radiological diagnostic algorithm. Chest. 2010;137(4):938–51. PubMed PMID: 20371529. Epub 2010/04/08. eng.CrossRefPubMedGoogle Scholar
  46. 46.
    Marten K. [Smoking-related interstitial lung diseases]. Rofo. 2007;179(3):268–75. PubMed PMID: 17325994. Epub 2007/02/28. Interstitielle Lungenerkrankungen bei Rauchern. ger.CrossRefPubMedGoogle Scholar
  47. 47.
    Myers JL, Colby TV. Pathologic manifestations of bronchiolitis, constrictive bronchiolitis, cryptogenic organizing pneumonia, and diffuse panbronchiolitis. Clin Chest Med. 1993;14(4):611–22.PubMedGoogle Scholar
  48. 48.
    Cordier JF. Organising pneumonia. Thorax. 2000;55(4):318–28. PubMed PMID: 10722773. Pubmed Central PMCID: PMC1745738. Epub 2000/03/18. eng.CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Drakopanagiotakis F, Paschalaki K, Abu-Hijleh M, Aswad B, Karagianidis N, Kastanakis E, et al. Cryptogenic and secondary organizing pneumonia: clinical presentation, radiographic findings, treatment response, and prognosis. Chest. 2011;139(4):893–900. PubMed PMID: 20724743. Epub 2010/08/21. eng.CrossRefPubMedGoogle Scholar
  50. 50.
    Greenberg-Wolff I, Konen E, Ben Dov I, Simansky D, Perelman M, Rozenman J. Cryptogenic organizing pneumonia: variety of radiologic findings. Isr Med Assoc J. 2005;7(9):568–70. PubMed PMID: 16190479. Epub 2005/09/30. eng.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of MedicineUniversity of Louisville School of MedicineLouisvilleUSA

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