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Pulmonary Pathology Online

Pathological Diagnosis of Granulomatous Lung Diseases

Dr Sampurna Roy MD


Pathology Poster of the Day: Granulomatous Pneumonia From Infection




Presence of granulomas in a lung biopsy or at autopsy is a relative common finding.

The differential diagnosis range from sarcoidosis or tuberculosis to various rare conditions. Image

The patient’s history, clinical findings and radiology is essential for making a complete diagnosis. 

A granuloma has been defined by Adams as "a compact (organized) collection of mature mononuclear phagocytes (macrophages and / or epithelioid cells) which may or may not be accompanied by features such as necrosis or the infiltration of inflammatory leucocytes".

Granulomas often arise in circumstances where a stimulating agent persists in the host, resisting the usual mechanisms of removal.

The most common example is the chronic foreign body granuloma, but most granulomatous diseases involve granulomas which comprise mostly epithelioid macrophages, with variable numbers of macrophage giant cells. Image

Many of these granulomas are immune system driven and are a manifestation of a delayed Type IV hypersensitivity reaction.

The compact or organized arrangement of the macrophages in the granuloma is an an important indicator.

A few macrophages lying together in close proximity should not be interpreted as a granuloma.

Most important condition:



Extrinsic Allergic Alveolitis (Hypersensitivity Pneumonitis)


Other conditions are as follows:

Wegener’s granulomatosis                            

Granulomas in Pneumoconiosis (granulomas are main histological features)       

- Includes Talcosis  and

- Berylliosis

Sarcoid-like reactions to tumours                   

Necrotizing sarcoidal granulomatosis (granulomas are main features)      

Drug Reaction (Methotrexate)

Talcosis in drug abusers (granulomas are main histological features)    

Other foreign body reactions (include aspiration pneumonia, in haemosiderosis and

pulmonary veno-occlusive disease).                    

Eosinophilic granuloma (granulomas are a small component)                      

Bronchocentric granulomatosis (granulomas are a small component)         

Churg-Strauss Syndrome                                 

Lymphocytic Interstitial Pneumonitis              

Amyloidosis (tumour), granulomas are a small component of the lesion            


Several conditions may have granulomas of some sort as part of their histological picture.

Many of these, such as drug reaction, is diagnosed on the basis of clinical history, as well as the accompanying histological features.

Examination under polarized light may allow foreign material such as talc to be detected, but inclusions (Schaumann, conchoidal and asteroid bodies) seen in the giant cells in granulomas may also polarize.

These inclusions are neither specific to nor diagnostic of, sarcoidosis.

Granulomas related to identifiable foreign material and situated around bronchioles suggest inhalation of dust or other material while a vascular distribution is seen in IV talcosis in drug abusers.

Granulomas may also be related to other exogenous factors such as inhaled non-refractile foreign material or  aspirated food particles, or to endogenous deposition of amyloid or hemosiderin (as seen in hemosiderosis or pulmonary veno-occlusive disease).

In these conditions the diagnosis will usually be made on the basis of other features present.

Necrotizing sarcoidal granulomatosis (NSG) is a rare disease characterized by masses of sarcoid-like granulomas associated with extensive geographic tissue necrosis and granulomatous vasculitis.

Granulomas may be seen in bronchocentric granulomatosis (BCG) and in the Churg-Strauss syndrome (CSS: asthma, peripheral blood eosinophilia and systemic vascularity), but, both are very rare conditions, and there are other major clinical and histological features, to establish the correct diagnosis.

In bronchocentric granulomatosis acute and chronic inflammation destroys airways and palisaded  histiocytes surround the central necrotic tissue.

Eosinophils are abundant and the setting is often an asthmatic patient with allergic bronchopulmonary aspergillosis.

Scattered discrete granulomas may also be seen in the inflammatory mass lesion.

The BCG is also seen in non-asthmatics, when it poses even more of a diagnostic challenge and distinction from infection can be difficult , and a similar reaction (unrelated to aspergillus sensitivity) may be seen distal to obstructing bronchial tumor.

In CSS, necrotizing and non-necrotizing granulomas are part of a range of pathological features, which may exist in variable combination.

Wegener’s granulomatosis (WG) is much commoner than BCG or CSS and thus worthy of more consideration. 

The characteristic necrotizing vasculitis and tissue necrosis are often associated with a vaguely granulomatous inflammation with small, smudgy multinucleate giant cells.

Sarcoid-like non-necrotizing granulomas are very rare in WG, but the necrotizing granulomatous inflammation may be confused with infection.

Distinction between Wegener’s Granulomatosis (WG) and infection:

(1) lack of positive staining for microorganisms in Wegener’s granulomatosis.

(2) the necrotizing vasculitis in Wegener’s granulomatosis will be found in pulmonary vessels, away from the necro-inflammatory masses, surrounded by normal lung.

Rarely, alveolar walls show capillaries with small collection of neutrophils within the alveolar interstitium. 

In contrast, the vasculitis in infection is seen within areas of florid inflammation or necrosis.


Further reading:

Pathological diagnosis of granulomatous lung disease: a review.

Pulmonary granulomatous inflammation: From sarcoidosis to tuberculosis.

Expression profiling in granulomatous lung disease.

Pulmonary angiitis and granulomatosis revisited.

Pulmonary hyalinizing granuloma.

Pulmonary angiitis and granulomatosis: a review.

Pulmonary hyalinizing granuloma. A limited form of Wegener's granulomatosis?



Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)







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