The idiopathic interstitial pneumonias include usual interstitial pneumonia (UIP, the pathologic correlate of idiopathic pulmonary fibrosis, or IPF), nonspecific interstitial pneumonia (NSIP), respiratory bronchiolitis-associated interstitial lung disease (RBILD), desquamative interstitial pneumonia (DIP), cryptogenic organizing pneumonia (COP), and acute interstitial pneumonia (AIP). Although several of the idiopathic interstitial pneumonias (UIP, RBILD, DIP) have a very strong association with tobacco smoking, the idiopathic interstitial pneumonias are traditionally considered to be of unknown etiology. A review of the clinical and pathologic features of each disease is beyond the scope of this chapter; however, the references to this chapter provide significant information about these diseases. Traditionally, lymphocytic interstitial pneumonia (LIP) and giant cell interstitial pneumonia (GIP) were also considered in the category of idiopathic interstitial pneumonias, but LIP is now recognized to be associated with other conditions in the majority of cases, and GIP is now recognized usually to be a hard metal pneumoconiosis.

The transbronchial biopsy has a role in the diagnosis of the idiopathic interstitial pneumonias primarily in one of two ways. In many cases, the transbronchial biopsy shows a histopathologic pattern for which an idiopathic interstitial pneumonia is a consideration in the differential diagnosis. In other cases, the transbronchial biopsy provides a supportive role for a clinical and radiologic diagnosis because it fails to reveal any histopathologic features that suggest a different diagnosis than the clinically suspected idiopathic interstitial pneumonia. For example, granulomas or hyaline membranes in a transbronchial biopsy indicate that another process besides UIP may be responsible for the clinical and radiologic findings in a suspected case of IPF.

UIP cannot be diagnosed by means of a transbronchial biopsy alone. Transbronchial biopsy may show areas of mature interstitial fibrosis or even fortuitously a fibroblast focus, but provides too small a sample to allow a diagnosis of UIP by itself. Nevertheless, transbronchial biopsy has potential roles in the diagnosis and management of patients with UIP. As already noted, transbronchial biopsy may be used in conjunction with imaging and clinical findings of IPF to help “rule out” other causes of these radiologic and clinical findings and to support a diagnosis of IPF. When patients experience changes in their clinical course, transbronchial biopsy may be used to rule out superimposed infection, diffuse alveolar damage, and so on.

The histopathologic diagnosis of UIP can be rendered on wedge biopsies or larger specimens, although even with wedge biopsies, clinical and radiologic correlation is often important. Currently, patients requiring wedge biopsies for a diagnosis of UIP generally do so because their disease has atypical radiologic or clinical features.

NSIP is most often cellular showing interstitial lymphocytic infiltrates, but it may also be fibrotic or mixed cellular and fibrotic. On transbronchial biopsy, interstitial lymphocytic
infiltrates have a long differential diagnosis including infections, hypersensitivity pneumonitis, collagen vascular disease, and drug reactions, among others. The diagnosis of NSIP requires that the findings not have an identifiable etiology and, as with other idiopathic interstitial pneumonias, sample size puts limitations on the diagnosis of NSIP by transbronchial biopsy. Some apparent cases of NSIP are later found to be another condition such as hypersensitivity pneumonitis. If a transbronchial biopsy shows an interstitial lymphocytic infiltrate without specific diagnostic features such as granulomas, viral inclusions, and so on, we recommend giving a descriptive diagnosis of interstitial lymphocytic infiltrates or interstitial pneumonia and providing the differential diagnosis, including NSIP, in the comment. In these situations, clinical and radiologic correlation with appropriate additional studies is often necessary to arrive at the final diagnosis.

Macrophages containing smokers pigment are often seen in transbronchial biopsies from tobacco smokers and serve as an indicator of exposure to tobacco smoke. These macrophages may be a component of defined tobacco-related diseases RBILD and DIP that are traditionally included in the idiopathic interstitial pneumonias. Diagnostic features of RBILD include a mild lymphocytic infiltrate in terminal airways, mild airway fibrosis, metaplastic bronchiolar epithelium extending from terminal airways into alveolar ducts, and associated macrophages containing finely granular brown pigment. Diagnosis of RBILD can be made on transbronchial biopsy with appropriate clinical and radiologic correlation if a diagnostic area is sampled. The features of DIP (diffuse mild thickening of alveolar walls by fibrous tissue and the uniform filling of airspaces by pigmented macrophages) may be seen on a transbronchial biopsy, but the sample size is often insufficient to rule out a less extensive process like RBILD or a so-called DIP-like reaction that may be seen in association with other lesions. The transbronchial biopsy may serve to add support to a clinical and radiologic diagnosis by demonstrating compatible features in the absence of other specific diseases.