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Pathology of Non-Necrotising Granulomatous Inflammation of the Lung

Dr Sampurna Roy MD

 

                                                                                                                      

 

If the lung shows granulomas which lack central necrosis, and infection has not been proven, then the two principal differential diagnoses are: 

 

-Sarcoidosis  and

-Extrinsic Allergic Alveolitis -EAA (Hypersensitivity Pneumonitis)

 

Clinical history and radiology are essential in making the diagnosis but these conditions are usually very different histologically. 

Sarcoidosis:  

Sarcoidosis is characterized by interstitial, well formed, compact, usually non-necrotizing granulomas of variable size, little surrounding lymphocytic infiltrate and minimal associated interstitial pneumonitis (so-called Ďnakedí granulomas).

Some granulomas are surrounded by concentric fibrosis,and giant cells with or without polarisable inclusions are variable.

Large granulomas may show a hyalinized degenerate center, but true necrosis is rare and should always raise the suspicion of infection.

The granulomas are distributed predominantly lymphatics and so are found in septa , around bronchovascular bundles and in the pleura.

A granulomatous vasculitis is common.

Granulomas are usually are scattered and discrete but may be aggregated into larger masses (so called nodular sarcoidosis).

In a patient with pulmonary infiltrsates on chest radiograph,multiple (5-6) transbronchial biopsies (TBB) will show granulomas in up to 90% of cases.

In a patients with enlarged mediastinal nodes but no pulmonary infiltrates on chest radiograph (Stage I disease), up to 10 TBB specimens may be needed.

Even bronchial biopsy will show granulomatous inflammation in around 50% of cases where pulmonary infiltration is visible radiologically.

There is nothing diagnostic about the granulomas in this disease.

Although a positive lung biopsy may infer the diagnosis, confirmation requires evidence of granulomatous disease at more than one site.

By definition, sarcoidosis is a multisystem disorder of unknown etiology.

All reasonable efforts should be made to exclude other possible causes of multisystem granulomatous disease before the diagnosis of sarcoidosis is accepted.

Extrinsic Allergic Alveolitis (EAA)  :

There is major clinical and radiological differences between EEA and sarcoidosis.

Extrinsic Allergic Alveolitis (EAA) differs from sarcoidosis in the distribution of disease and pattern of inflammation.

Extrinsic Allergic Alveolitis (EAA) reflects a combined  type III / IV hypersensitivity reaction to inhaled organic antigen, such as thermophilic actinomycetes in Farmerís Lung and feather/faecal proteins in Bird Fancierís Lung.

Extrinsic Allergic Alveolitis (EAA) is characterized by non-specific interstitial  chronic inflammation with a peribronchiolar / centriacinar accentuation. Loose poorly formed non-necrotizing granulomas are present.

Foci of organizing air-space exudates (a Boop-like reaction) may be noted.

The distribution of the interstitial chronic inflammation is essential to the differential diagnosis - it is uniform in cellularity and usually lacks fibrosis.

Indistinct granulomas (well formed sarcoid-like granulomas may occur, but are rare) are admixed in the infiltrate.

Sometimes there are occasional clumps of foamy histiocytes and in some cases solitary giant cells.

If the patient has had no recent exposure to antigen, granulomas may be absent, but interstitial inflammation will remain in its characteristic distribution, allowing at least a tentative diagnosis.

Extrinsic Allergic Alveolitis (EAA) is a much more difficult diagnosis than sarcoidosis on transbronchial biopsies since more lung is needed to appreciate the architectural distribution.

In the appropriate context, a good set of TBB may allow a "consistent with" diagnosis to be made, but a specific diagnosis may require open / throracoscopic lung biopsy.

Most patients with Extrinsic Allergic Alveolitis (EAA) are diagnosed without recourse to biopsy.

In many cases pathologists make a diagnosis on open lung biopsy which may be clinically / radiologically atypical.

Visit:

Infectious Granuloma of the Lung;

Pathological Diagnosis of Granulomatous Lung Diseases;

An approach to Histopathological examination of Pulmonary Granulomatous Inflammation.

 

Further reading

Pathology of sarcoidosis

Histologic,microbiologic, and clinical correlates of the diagnosis of sarcoidosis by transbronchial biopsy.

[A study of epithelioid cell granulomas in transbronchial lung biopsy specimens of sarcoidosis patients--correlation between granulomas and clinical activity or chest X-ray lesions].

Pulmonary granulomatous inflammation: From sarcoidosis to tuberculosis.

 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)

 

 


 

 

 

 

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