Hypersensitivity pneumonitis, also known as hypersensitivity pneumonia and extrinsic allergic alveolitis, is a diffuse interstitial granulomatous pneumonia secondary to inhalation of organic antigens. Other synonyms used for this disease represent the causative antigen, and terms such as farmer’s lung, bagassosis, bird fancier’s lung, and pigeon breeder’s disease have been used. Hypersensitivity pneumonitis most likely represents a combination of an immune complex-mediated (type III) and T-cell-mediated, delayed (type IV) immunologic mechanisms. In advanced lesions, a picture of nonspecific interstitial pneumonia (NSIP) fibrotic pattern or of end-stage fibrosis may be found. Differential diagnosis includes sarcoidosis, NSIP, usual interstitial pneumonia, lymphoid interstitial pneumonia, and infections. The granulomas seen in hypersensitivity pneumonitis are loose and “poorly formed” and consist of aggregates of lymphocytes, plasma cells, and occasional multinucleated cells. They are usually bronchiolocentric and show extension into adjacent alveolar septa. In contrast, the sarcoidal granuloma is well developed and usually well circumscribed and tends to follow the lymphatic routes (pleura, interlobular septa, and bronchovascular bundles).

Lymphoid interstitial pneumonia is a rare entity characterized by a much more prominent interstitial lymphoid infiltrate than hypersensitivity pneumonia, but sometimes the differential diagnosis between these entities is difficult and history of exposure should be correlated. The cellular pattern of NSIP resembles the changes seen in hypersensitivity pneumonitis, and it is well recognized that some cases diagnosed as NSIP are found to be hypersensitivity pneumonitis. The presence of granulomas and an exposure history help distinguish between the two conditions. The final diagnosis depends on good clinical, radiologic, and histopathologic correlation.