What is a lung granuloma?

What is a Lung Granuloma?

A lung granuloma is an organized collection of inflammatory cells—primarily macrophages that differentiate into epithelioid cells and multinucleated giant cells—surrounded by lymphocytes, forming a nodular structure that represents the immune system's attempt to wall off and contain persistent antigens or pathogens that cannot be eliminated. 1, 2

Formation and Purpose

Granulomas develop when the immune system encounters particles or organisms that persist within phagocytes and cannot be eliminated through normal mechanisms 2. This immune reaction evolved specifically to combat mycobacteria, with the goal of localizing these organisms and preventing their spread throughout the body 1, 2.

The formation process involves:

• Antigen exposure and processing by macrophages 3
• T-cell activation and recruitment 1
• Macrophage differentiation into epithelioid cells 1
• Formation of multinucleated giant cells 1
• Surrounding lymphocytic infiltration 1
• Fibroblast and extracellular matrix deposition to isolate the antigen 3

Radiographic Appearance

On chest imaging, granulomas appear as small nodular densities representing organized collections of inflammatory cells, typically manifesting as calcified nodules, fibrotic scars, or areas of apical pleural thickening. 4

Specific radiographic patterns include:

• Calcified nodular lesions: Discrete, well-defined densities indicating healed disease with lower risk for progression 4
• Fibrotic scars and nodules: May contain slowly multiplying organisms with higher reactivation risk 4
• Upper lobe infiltrates: Patchy or nodular patterns, especially in apical or subapical posterior regions 4

Histologic Classification

Well-Formed vs. Poorly-Formed Granulomas

Well-formed granulomas are tightly organized, sharply circumscribed collections of epithelioid histiocytes that typically indicate:

• Sarcoidosis (in lymphatic distribution) 1
• Mycobacterial infections (especially when necrotizing) 1
• Fungal infections 1
• Berylliosis 1

Poorly-formed granulomas consist of loose, poorly circumscribed clusters of epithelioid cells and multinucleated histiocytes, characteristic of:

• Hypersensitivity pneumonitis (peribronchiolar distribution) 1
• Early or resolving infections 1

Necrotizing vs. Non-Necrotizing

Necrotizing granulomas with central necrosis strongly suggest:

• Mycobacterial infection (tuberculosis or atypical mycobacteria) 1
• Fungal infection 1
• Granulomatosis with polyangiitis (Wegener's) 2, 5

Non-necrotizing granulomas are more consistent with:

• Sarcoidosis 1
• Hypersensitivity pneumonitis 1
• Berylliosis 1

Common Causes

Infectious Causes

• Tuberculosis: Produces nodules, fibrotic scars, calcified granulomas, and apical pleural thickening as healed disease 4
• Nontuberculous mycobacteria (especially MAC): Creates discrete centrilobular and bronchiocentric granulomas 4
• Fungal infections: Robust, frequent necrotizing granulomas 1

Non-Infectious Causes

• Sarcoidosis: Most common granulomatous lung disease with well-formed granulomas in lymphatic distribution 1, 2
• Hypersensitivity pneumonitis: Small, poorly-formed peribronchiolar granulomas 1
• Autoimmune diseases: Rheumatoid arthritis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis 2
• Occupational exposures: Silicosis, berylliosis, hard metal lung 1, 2
• Aspiration: Bronchiolocentric inflammation with foreign material and giant cell reaction 1

Critical Diagnostic Features

Hypersensitivity Pneumonitis Pattern

Granulomas in HP are typically 1:

• Small and poorly formed
• Loose clusters of epithelioid cells and multinucleated histiocytes
• Peribronchiolar distribution
• Situated in interstitium but can extend into airspaces
• May contain nonspecific inclusions (Schaumann bodies, cholesterol clefts, oxalate crystals)

Sarcoidosis Pattern

Granulomas in sarcoidosis are 1:

• Well-formed and may coalesce
• Lymphatic distribution
• Sharply circumscribed borders
• Minimal surrounding inflammation

Clinical Implications and Risk Assessment

Patients with radiographic evidence of prior tuberculosis have approximately 2.5 times higher risk of reactivation compared to those with latent TB infection without radiographic abnormalities. 4

When to Pursue Further Evaluation

Sputum examination is recommended for 4:

• Any respiratory symptoms suggestive of active disease
• Chest radiographic findings consistent with TB disease
• HIV-infected persons with any pulmonary symptoms regardless of radiograph findings
• Uncertain treatment history requiring exclusion of active disease

Follow-Up Recommendations

For patients with granulomas from prior TB 4:

• Clinical monitoring every 3 months during the first year after completing treatment
• Repeat chest imaging only if new symptoms develop
• Calcified lesions indicate lower risk (up to 85% are sterile) 6
• Fibrotic scars pose higher reactivation risk 4

Important Caveats

BCG vaccination does NOT cause internal organ granulomas. 6 BCG causes only local injection site reactions and possible regional lymphadenopathy; calcified granulomas in lungs, liver, or spleen indicate prior TB or fungal infection, not vaccination 6.

The presence or absence of granulomas must be interpreted within the totality of clinical, radiologic, and histologic findings. 1 No specific threshold exists for the number of granulomas required to distinguish between different diagnoses, and granulomas are frequently absent even in confirmed granulomatous diseases 1.