Sarcoidosis: the lung
- Lesion
Sarcoidosis is a disease of tight, non-caseating granulomas of unknown cause, mostly in hilar nodes and lungs, but also eyes, skin and heart.
What it is
Sarcoidosis is a systemic granulomatous disease of unknown cause. Its lesion is the well-formed non-necrotising granuloma, a response of CD4 Th1 cells to an unidentified antigen. Bilateral hilar lymphadenopathy or lung involvement occurs in about nine of ten patients, followed by eyes and skin. Because tuberculosis, fungi and beryllium can produce the same granuloma, it is a diagnosis of exclusion.
Structure
- Nodes: enlarged, discrete, rubbery, sometimes calcified hilar and mediastinal nodes.
- Lung: usually no gross change; in advanced cases small grey nodules; late fibrosis with upper-zone honeycombing.
- H&E: well-formed non-necrotising granulomas with Langhans and foreign-body giant cells; fibrous rims and hyalinised scars with time.
- Special stains and cultures for mycobacteria and fungi are negative.
Step by step
- In genetically prone people (HLA associations) an unidentified antigen is presented to CD4 T cells.
- Th1 cells release IL-2 and IFN-γ; macrophages release TNF.
- Activated macrophages turn into epithelioid cells and fuse into giant cells: the granuloma.
- Chemokines keep recruiting T cells and monocytes, so granulomas persist along lymphatics.
- Granulomas heal by fibrosis; extensive disease leaves upper-zone scarring and pulmonary hypertension.
- Peripheral anergy: tuberculin tests are often negative despite active local immunity.
Sarcoid granuloma vs tuberculous granuloma
| Feature | Sarcoidosis | Tuberculosis |
|---|---|---|
| Central necrosis | Absent or minimal | Caseous necrosis common |
| Granuloma shape | Tight, well-formed, often confluent | Well-formed with necrotic centre |
| Organisms | None on stains or culture | Acid-fast bacilli |
| Distribution in lung | Along lymphatics; nodes | Apical cavities, Ghon focus |
| Tuberculin test | Often negative (anergy) | Usually positive |
Markers
- Serum ACE
- High CD4/CD8 in lavage
- Hypercalcaemia
Clinical notes
- Often found by chance as bilateral hilar adenopathy; others have cough, dyspnoea, fever or weight loss.
- Eye (uveitis), skin (erythema nodosum, lupus pernio), heart (conduction block, cardiomyopathy) and salivary glands can be involved.
- Most patients improve; a minority progress to fibrosis.
- In Colombia, tuberculosis and histoplasmosis must be excluded first.
Test yourself
Think of the answer, then tap the question to see it.
What are Schaumann and asteroid bodies, and are they specific for sarcoidosis?
Laminated calcium-protein concretions and stellate inclusions inside giant cells; they are characteristic but also occur in other granulomatous diseases.
Why can sarcoidosis cause hypercalcaemia?
Activated granuloma macrophages express 1-α-hydroxylase and make active vitamin D (calcitriol), which raises calcium absorption.
Why is sarcoidosis a diagnosis of exclusion?
Mycobacteria, fungi and beryllium also cause non-caseating granulomas, so these must be ruled out.
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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Sarcoidosis (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.