Interstitial granulomatous pulmonary diseases: a diagnostic approach for the general pathologist

Some kinds of interstitial pneumonia present a histopathological pattern dominated by sarcoid - necrotizing or non-necrotizing - granulomas, which can be divided into two main groups: infectious and non-infectious. The infectious causes include tuberculosis, histoplasmosis, fungi in general, paracoccidioidomycosis, ascaridiasis, echinococcosis and dirophilariosis. The non-infectious causes include histiocytosis-X, hipersensitivity pneumonia, vasculitis, lymphomas, sarcoidosis, and pneumoconioses such as silicosis and berylliosis. The purpose of this review is to provide a practical guideline to enable general pathologists to make the differential diagnosis of granulomatous pulmonary diseases. For this purpose, anatomical-clinical-radiological correlations will be presented and targeted to each diagnosis discussed. Whenever a granulomatous inflammatory process is in progress, the search for infective agents by direct observation, by culture, and by histochemical methods should be mandatory. The histological aspects of infectious granulomas to be analyzed should include their random histo-anatomical location, the type of inflammatory reaction, and necrosis. A panel of complementary reactions (immunohistochemistry and PCR) should identify the infectious agent and, whenever their results and the culture are negative, the possibility of non-infectious granulomatous diseases has to be evaluated. In such cases, the histo-anatomical distribution (bronchocentric, lymphangitic, angiocentric, random), the qualitative characteristics of the lesions (type of necrosis and inflammatory reaction), and the correlation with the X-ray findings will help the diagnosis