The histopathology of pulmonary reactions to drugs

Many pathologists and pulmonologists have trained and practiced in an era during which therapeutic options for patients have increased manyfold with regard to pharmacologic agents. Toxicity to the lung may be recognized as data accumulate in the form of case reports and clinical reviews to document the clinical and pathologic manifestations. For the histopathologist, paradoxically the more we learn the more difficult problems of interpretation become. Drug reactions previously described extensively at the autopsy now can be relatively easily interpreted in living patients with tissue obtained by open lung biopsy. This latter procedure is becoming less common with diffuse infiltrative lung disease in favor of the transbronchial biopsy in which sampling error abounds. There may be no disease or minimal change. The pathologic lesions may be duly noted and described, but then defy interpretation. An accurate differential diagnosis following biopsy may not solve the clinical problems for which a tissue diagnosis was sought. A specific diagnosis may be made that does not fit the clinical picture, or the real "answer" may be revealed distressingly later in the clinical-course or, more distressingly, at autopsy. The prudent histopathologist deals with such limitation by objectively stating the observable facets of tissue injury and synthesizing an interpretation. Notwithstanding the burgeoning literature on mechanisms of injury of toxic substances, the "state of the art" in 1990 for interpretation of pulmonary drug reactions still lies with the exacting judgment of experienced clinical physicians. Proper evaluation can result in exclusion of important mimickers of interstitial lung disease, usually infection and neoplasia; accurate categorization of tissue injury and comparison with known injurious responses to the drug in question may lead to a relatively specific diagnosis of drug-induced injury. Most drug reactions in the lung are classified as an interstitial pneumonia. This article illustrates and describes several interstitial reactions to injury that have few histologic features in common. However, because the lung can only react to injury in a limited number of ways, lesions that were thought at one time to be a specific clinicopathologic entity, for example, DIP, now evoke an ever-expanding differential diagnosis. In applying diagnostic criteria emphasis must be placed on the areas of overlap among tissue reactions as well. Specific agents may cause changes that are described as common for that agent, but a given patient may react with a variation or in a distinctly uncommon manner. There is enormous potential in this field for the laboratory investigation of drug injury.(ABSTRACT TRUNCATED AT 400 WORDS)