Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• The role of lung biopsy in suspected sarcoidosis

  Lung biopsy can provide tissue-level evidence when respiratory symptoms, high-resolution computed tomography findings and lymphadenopathy leave meaningful diagnostic uncertainty. Its value in suspected sarcoidosis lies less in producing a label than in testing whether a compatible clinical pattern has a pathological basis that can guide treatment.

  Sarcoidosis is not established by a chest image alone, and granulomas are not unique to it. The role of lung biopsy therefore depends on the presentation, alternative diagnoses, urgency and the likelihood that tissue will change management. In classic Löfgren syndrome, for example, a carefully interpreted clinical syndrome may support diagnosis without biopsy.

  When tissue diagnosis adds value

  Histological confirmation is most useful when imaging is atypical, symptoms suggest another process, or the diagnosis will lead to systemic treatment with meaningful consequences. It can also provide a baseline for later comparison if disease is expected to progress. Pulmonary sarcoidosis may show noncaseating granulomas, but this finding supports rather than independently proves sarcoidosis.

  Some patients do not need tissue. Typical bilateral hilar lymphadenopathy with erythema nodosum and ankle arthritis, consistent with Löfgren syndrome, can have a high probability of sarcoidosis in an appropriate setting. A biopsy may add little when the clinical and radiological pattern is secure, the patient is stable, and treatment is unlikely to change.

  The strongest reason to sample tissue is often the need to exclude a mimic. Granulomatous inflammation can occur with tuberculosis, endemic fungal infection, chronic beryllium disease, drug reactions, foreign material and some cancers. Pathology must therefore be interpreted alongside microbiology, medication history, exposure history and the distribution of disease.

  Building the pre-biopsy assessment

  Before tissue sampling, the respiratory physician should map the abnormality and decide what question the biopsy must answer. High-resolution CT can distinguish airway lesions, lymphadenopathy, parenchymal nodules and pleural disease. Pulmonary function tests, including diffusing capacity, provide a safety baseline and help gauge disease severity.

  The assessment should also cover relevant systemic features. A focused examination for skin, eye, joint, neurological and cardiac involvement may reveal a diagnosis or alter the urgency of treatment. Baseline ECG, blood pressure, oxygen saturation and blood tests are commonly considered. Medication review is essential, particularly for anticoagulants, antiplatelets and drugs associated with granulomatous reactions.

  A multidisciplinary team improves the choice and interpretation of investigation. Radiologists can identify the safest target; pathologists and infectious-disease specialists can advise specimen handling; and rheumatologists or ophthalmologists may help assess extrapulmonary disease. Bronchoscopy and EBUS availability varies by centre, so planning should begin before referral.

  Selecting the safest informative procedure

  Flexible bronchoscopy can combine airway inspection with bronchoalveolar lavage, endobronchial biopsy and transbronchial lung biopsy. Visible endobronchial lesions may yield a diagnosis through endobronchial sampling. Transbronchial lung biopsy reaches parenchymal lesions, although diagnostic yield varies with lesion size, number of samples and operator experience.

  When hilar or mediastinal lymph nodes are the principal target, EBUS-guided transbronchial needle aspiration or biopsy is often preferable to surgical node sampling. CT-guided percutaneous biopsy can be considered for a peripheral pulmonary nodule when less invasive approaches are unsuitable. Mediastinoscopy and surgical lung biopsy provide larger specimens but are rarely required for a straightforward suspicion of sarcoidosis.

  Safety depends on patient selection and the site sampled. Clinicians should check platelet count, haemoglobin, anticoagulant use, lung function and procedural sedation risk. Potential complications include bleeding, hypoxaemia, pneumothorax, arrhythmia and, rarely, respiratory failure. After bronchoscopy, observation and chest imaging may be needed according to local protocol.

  Adapting the pathway for Australian practice

  Australian pathways are shaped by Medicare, the public hospital system and the geography of specialist services. Respiratory and interventional pulmonology teams in Sydney, Melbourne, Brisbane, Perth and Adelaide perform bronchoscopy and EBUS; people in regional and remote areas may need transfer to a tertiary centre and sometimes interstate travel. Eligible specialist consultations and some outpatient procedures attract Medicare rebates, while public hospital treatment is generally provided without a Medicare charge for eligible patients.

  National and state protocols, supported by Thoracic Society of Australia and New Zealand guidance, can structure the work-up and follow-up. Histology and microbiology specimens should be coordinated with hospital or state reference laboratories so that tissue is available for stains, cultures and molecular testing where appropriate. Private providers also offer bronchoscopy and procedural services, and out-of-pocket costs depend on the setting and Medicare coverage.

  The local context makes exposure history particularly important. Mining, construction and manufacturing work can raise the possibility of silicosis or chronic beryllium disease, while travel and environmental histories may prompt exclusion of tuberculosis or fungal infection. These alternatives can produce granulomas or nodular opacities that resemble sarcoidosis on imaging. No single sampling method is best for every patient, so the chosen target should match both the diagnostic question and the available expertise.

  Biopsy method	Main target	Main advantage	Important limitation	Typical role
  Endobronchial biopsy	Visible bronchial mucosal lesions	Direct sampling of affected airway tissue	May miss disease when the mucosa appears normal	Airway-predominant presentations
  Transbronchial lung biopsy	Lung parenchyma	Avoids surgical biopsy and can sample several sites	Variable yield; bleeding or pneumothorax can occur	Common flexible bronchoscopy approach
  EBUS-guided needle sampling	Hilar or mediastinal lymph nodes	High diagnostic value with less morbidity than surgical node biopsy	Operator dependent; abnormal nodes may represent malignancy	Preferred approach when nodes are the principal target
  CT-guided percutaneous biopsy	Peripheral pulmonary nodule	Precise sampling of a peripheral lesion	Pneumothorax and bleeding risk	Considered when less invasive routes are unsuitable
  Mediastinoscopy or surgical lung biopsy	Selected deep or unresolved abnormalities	Provides substantial tissue for pathology	Greater morbidity and inpatient requirements	Uncommon in straightforward suspected sarcoidosis

  Practical recommendations and final messages

  For teams managing suspected sarcoidosis, biopsy should be planned around a specific clinical question rather than used as a routine investigation. The least invasive procedure that can obtain an adequate, representative sample should be selected.

  • Reserve lung biopsy for presentations in which diagnostic uncertainty is consequential and tissue could plausibly change management.
  • Use the least invasive method capable of sampling a radiologically mapped target and obtaining enough material.
  • Coordinate sampling with pathology and microbiology teams, preserving material for cultures and molecular testing where indicated.
  • Explain procedural risks, sedation, alternatives and the possibility of a non-diagnostic result before consent.
  • Review unexpected granulomatous findings in a multidisciplinary setting before committing to sarcoidosis or systemic corticosteroids.

  Results should be reconciled with imaging, microbiology and the systemic assessment. Noncaseating granulomas can support sarcoidosis only after infection and exposure-related mimics have been addressed; an alternative diagnosis may instead require urgent treatment. Most patients with suspected sarcoidosis do not automatically require lung biopsy. The essential lesson is to sample selectively, choose the safest informative target and interpret tissue as part of the whole clinical picture.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)