Respiratory bronchiolitis may uncommonly be associated with a generally mild and generally nonprogressive interstitial lung disease characterized by dyspnea, cough, and radiographic abnormalities referred to as respiratory bronchiolitis-associated interstitial lung disease (RBILD). The histopathologic findings of respiratory bronchiolitis are discussed in Chapter 79. In desquamative interstitial pneumonia (DIP), the alveolar spaces are filled with collections of macrophages containing the same finely granular brown cytoplasmic pigment seen in respiratory bronchiolitis and RBILD. Like respiratory bronchiolitis and RBILD, DIP occurs primarily in smokers. The primary difference between DIP and RBILD is that in DIP the alveolar spaces, alveolar ducts, and respiratory bronchioles are much more diffusely and uniformly involved, whereas in RBILD the lesions are patchy and bronchiolocentric. It seems likely that respiratory bronchiolitis and RBILD are less extensive forms of DIP, either mild forms of the same disease or “precursor” lesions, and increasingly these entities are considered together. Histopathologically, a spectrum of varying degrees of lung involvement between patchy airway-centered respiratory bronchiolitis and diffusely distributed DIP can be observed in different cases.

In DIP the diffuse filling of alveoli, alveolar ducts, and respiratory bronchioles with pigmented macrophages is accompanied by a relatively uniform thickening of alveolar septa by lymphocytes with lesser numbers of plasma cells and occasionally eosinophils. The thickened alveolar septa are lined by prominent cuboidal type 2 pneumocytes.

When originally described, consideration was given to the possibility that the pigmented macrophages in DIP might be pneumocytes shed into the alveolar spaces, although the correct interpretation that these were macrophages was given preference. Focal DIP-like histopathologic patterns and collections of intra-alveolar macrophages are seen adjacent to lung fibrosis and lung nodules of many types, including focal scars, cancers, Langerhans cell histiocytosis, and usual interstitial pneumonia (UIP) (see Chapter 75). Respiratory bronchiolitis and focal DIP-like areas are relatively common in lung tissue from smokers. Therefore, diagnosis of RBILD and DIP should take into account limitations of biopsy sampling and clinical context. The frequent association of focal DIP-like macrophage aggregates in and around areas of UIP probably contributed to earlier speculation that DIP progresses to UIP, a concept that has not been supported by studies over the past decade.