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)

• Diagnostic Challenges in Pulmonary Sarcoidosis

  Pulmonary sarcoidosis is an inflammatory disorder in which clusters of immune cells, known as granulomas, develop in the lungs and sometimes in lymph nodes, skin, eyes, heart or nervous tissue. Its presentation can range from an incidental chest X-ray finding to progressive breathlessness and respiratory failure. This broad clinical spectrum makes a reliable diagnosis more complex than identifying a single abnormal test.

  The disease can resemble tuberculosis, fungal infection, hypersensitivity pneumonitis, occupational lung disease and several forms of cancer. In Australia, clinicians may also need to consider exposure histories linked to mining, construction, agriculture, bushfires and mould. A careful assessment is essential before immunosuppressive treatment is started, particularly when infection remains a possibility.

  For respiratory physicians, radiologists, pathologists and primary care teams, the diagnostic process depends on combining clinical findings, imaging, tissue sampling and exclusion of alternatives. The experience of specialist centres in Sydney, Melbourne, Brisbane and Perth can be valuable, while telehealth and coordinated referral pathways help extend expertise to patients in regional and remote communities.

  Recognising Atypical Clinical Presentations

  Pulmonary sarcoidosis often produces dry cough, exertional dyspnoea, chest discomfort or fatigue. Some patients have no respiratory symptoms and are referred after bilateral hilar lymphadenopathy is seen on imaging. Others present with erythema nodosum, uveitis, facial lesions, peripheral lymph node enlargement or unexplained constitutional symptoms.

  The presentation may be less typical in older adults, people with coexisting lung disease and those taking immune-modifying medicines. Reduced exercise tolerance can be attributed to asthma, chronic obstructive pulmonary disease, obesity or cardiac disease. In Aboriginal and Torres Strait Islander communities, culturally safe history-taking and access to appropriate follow-up are important when symptoms overlap with infectious or chronic respiratory conditions.

  A full history should cover travel, household contacts, occupation, recreational exposures, medications and family history. Previous residence in areas where tuberculosis or endemic fungal disease is more common may alter the differential diagnosis. In Australia, exposure to silica, metal dust, birds, agricultural materials and bushfire smoke can point towards alternative inflammatory or occupational lung disorders.

  Interpreting Imaging Without Overcalling Disease

  High-resolution computed tomography is central to evaluating suspected sarcoidosis. Typical findings include symmetrical hilar and mediastinal lymph node enlargement, perilymphatic nodules, upper-lobe predominance and bronchovascular distribution. Fibrotic disease may cause architectural distortion, traction bronchiectasis and volume loss.

  Radiological patterns are helpful but not definitive. Lymphoma, metastatic malignancy, tuberculosis, pneumoconiosis and other granulomatous conditions can produce similar appearances. Atypical node distribution, unilateral disease, cavitation or a dominant mass should prompt a broader investigation rather than an assumption of sarcoidosis.

  Pulmonary function testing adds information about severity and progression. A restrictive pattern, reduced diffusing capacity for carbon monoxide or an impaired six-minute walk test may support clinically significant lung involvement. Serial measurements are especially useful because symptoms and imaging can remain stable while functional impairment gradually develops.

  Confirming Granulomatous Inflammation

  A diagnosis usually requires compatible clinical and radiological findings, histological evidence of non-caseating granulomas and reasonable exclusion of other causes. Tissue can be obtained through endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial lung biopsy, endobronchial biopsy, peripheral lymph node sampling or, less often, surgical biopsy.

  The least invasive site with the highest diagnostic yield should generally be chosen. Enlarged mediastinal nodes may be accessible through bronchoscopy, while skin lesions or palpable peripheral nodes can sometimes provide safer tissue. Pathology specimens should be sent for bacterial, mycobacterial and fungal testing where clinically appropriate, rather than being reserved solely for routine histology.

  Granulomas are not specific to sarcoidosis. Their presence must be interpreted alongside microbiology, imaging and the patient’s risk profile. Serum angiotensin-converting enzyme levels, calcium studies and other biomarkers may contribute context, but none can independently establish or exclude the diagnosis.

  Separating Sarcoidosis From Mimicking Conditions

  In Australia, tuberculosis remains an important consideration in people who have lived in or travelled to high-prevalence regions, as well as in close-contact settings. Fungal infection, including less common environmental exposures, may also resemble granulomatous lung disease. Immunosuppression can make these infections more severe and can alter their radiological appearance.

  Malignancy is another major diagnostic concern, particularly when lymphadenopathy is asymmetrical, enlarging or associated with weight loss and night sweats. Berylliosis, silicosis, hypersensitivity pneumonitis and drug-induced granulomatous reactions can create overlapping clinical and pathological patterns. The patient’s work history should therefore be explored in detail, including mining and engineered-stone exposure.

  Tests should be selected according to the individual’s risks rather than applied as a fixed panel. This may include tuberculosis screening, fungal studies, autoimmune testing, bronchoscopy and repeat imaging. A multidisciplinary review involving respiratory medicine, radiology, pathology and infectious diseases can prevent premature diagnostic closure.

  Assessing Extent and Prognostic Risk

  Establishing the diagnosis is only the first stage. Patients should be assessed for extrapulmonary disease involving the eyes, skin, heart, nervous system, liver and kidneys. Baseline blood tests commonly include full blood count, renal and liver function, calcium and vitamin D-related measures, with electrocardiography and ophthalmological review guided by symptoms and local practice.

  Cardiac sarcoidosis deserves particular attention because conduction abnormalities, arrhythmias and myocardial dysfunction may occur even when lung symptoms are modest. Palpitations, syncope, unexplained chest pain or disproportionate exercise limitation warrant prompt cardiac evaluation. An electrocardiogram is a practical starting point, with advanced imaging or rhythm monitoring used when indicated.

  Management decisions depend on symptoms, lung function, radiographic progression and organ threat. Mild, stable disease may be monitored, while progressive pulmonary impairment or critical extrapulmonary involvement may require corticosteroids or steroid-sparing therapy. Australian patients may encounter differences in specialist access and medication pathways between metropolitan hospitals and regional services, making clear communication and shared follow-up particularly important.

  A dependable diagnostic pathway combines exposure history, high-resolution CT, physiological testing, appropriately selected biopsy and systematic exclusion of infection and malignancy. It also recognises that sarcoidosis is a multisystem disorder, not simply a pattern of enlarged chest lymph nodes.

  The practical next step is to refer a patient with suspected pulmonary sarcoidosis for multidisciplinary respiratory review before immunosuppression is commenced, with the CT images, pulmonary function results, exposure history and pathology or microbiology reports assembled for assessment.

  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)