Broadly defined as a state of exaggerated immune response to a wide variety of antigenic substances, hypersensitivity pneumonitis refers to an inflammatory condition clinically characterized by a flulike illness and histologically typified by a triad of peribronchiolar chronic interstitial pneumonitis, organizing pneumonia, and the formation of loose incomplete granulomas. However, this hypersensitivity pneumonitis triad is seen in only 70% to 80% of the cases. Often only two of the three elements of the triad are seen in biopsy material. Three stages of the disease are recognized both clinically and histopathologically: acute; subacute, the most prevalent; and chronic. The discussion here primarily applies to this subacute form. A variant of hypersensitivity pneumonitis occurring in association with hot tub usage has been termed hot tub lung.

Endobronchial lung biopsies are not useful in the diagnosis of hypersensitivity pneumonitis because they will miss most if not all of the elements of the histopathologic triad just described. Transbronchial lung biopsies, however, are much more helpful. The bronchiolitis or peribronchiolitis of hypersensitivity pneumonitis is chiefly mononuclear, lymphocytic, and not associated with necrosis of the bronchial epithelium. The chronic interstitial inflammation is bronchiolocentric, in continuity with the peribronchial inflammation, and characterized by lymphocytic or lymphoplasmacytic infiltrates. The granulomas of hypersensitivity pneumonitis are poorly formed, often referred to as incomplete, and they are, by definition, nonnecrotizing. Isolated giant cells with or without cholesterol clefts or Schaumann bodies may constitute the only evidence of a granulomatous response. These granulomas of hypersensitivity pneumonitis are really granulomatoid aggregates of multinucleated histiocytes, lymphocytes, and/or plasma cells and blend into the surrounding interstitial inflammatory infiltrate, a feature that assists in differentiating these granulomas from other granulomatous conditions. Granulomas can also be found in the chronic stage of the disease.