Reply to Sanyal et al.: Overlooked Role of Histopathology in Evaluations for Occupational/Environmental Exposures.

From the Authors:

We agree with Dr. Sanyal and colleagues that a careful histologic evaluation of biopsy specimens, when available, is a key aspect of accurately parsing the causes of interstitial fibrosis, and in cases of idiopathic pulmonary fibrosis (IPF) it may also identify environmental exposures that can contribute to progression. Such an evaluation, ideally, would entail close collaboration among pathologists and other members of the interstitial lung disease team to provide context and clinical relevance to the histologic features (1, 2). However, based on the available data, we believe that the authors’ suggestion to perform routine iron staining and polarized light microscopy in cases of typical IPF is excessive. We do agree with the authors that a research effort to characterize dust burden/particulates in the lungs of patients with IPF would be potentially informative and very welcome.

It has previously been emphasized that pathologic findings supporting occupational/environmental exposures cannot always distinguish between occupational lung diseases and other forms of pulmonary fibrosis (3). For detection of asbestos bodies, standard evaluation with hematoxylin and eosin appears to be adequate (4, 5), although iron staining can occasionally help reveal asbestos bodies that might have been missed on routine hematoxylin-and-eosin staining. It is well established that the mere finding of asbestos bodies in the lung is insufficient for a pathologic diagnosis of asbestosis. The detection of asbestos bodies only raises more vexing questions for the pathologist, including whether significant interstitial fibrosis is present, whether the fibrosis is present in the appropriate distribution for a diagnosis of asbestosis, whether usual interstitial pneumonia (UIP)-pattern fibrosis should be labeled as asbestosis, and whether UIP in an asbestos-exposed individual represents concurrent IPF or atypical asbestosis. With regard to the last question, some experts in occupational lung disease have suggested that UIP-pattern fibrosis should not be regarded as genuine asbestosis, irrespective of the status of asbestos biomarkers (6). This suggestion—based on an analysis of four asbestos-exposed cohorts in the United Kingdom—challenges the dogma that using iron stains to detect asbestos bodies is a worthwhile exercise in histologic UIP. In contrast to Sanyal and colleagues’s claim that asbestosis is underdiagnosed by pathologists, it suggests that asbestosis may have been historically overdiagnosed by pathologists, especially in patients with histologic evidence of UIP-pattern fibrosis.

Routine use of polarized light microscopy for identification of crystalline silica is appealing, but there are no data of which we are aware that demonstrate incremental diagnostic sensitivity for silicosis compared with expected findings on light microscopy (e.g., silicotic nodules, dust macules, and diffuse fibrosis without fibroblast foci). Because background dust accumulation occurs in most normal lungs, the more biologically relevant question is not whether any dust particles (including birefringent silica/silicate particles) are present but whether these particles are significantly in excess of the amount expected in normal lungs, and whether they are associated with a tissue response that would be expected in a true pneumoconiosis (nodules, inflammation, fibrosis, etc.). In this regard, at present, polarized light microscopy should be used at the discretion of the pathologist when histologic features on routine hematoxylin-and-eosin–stained slides suggest the possibility of a pneumoconiosis. Whether finding incidental silica/silicate particles in patients with IPF is of value for diagnosis or clinical care is an open question, especially considering that ongoing dust exposure is already recognized as a contributor to IPF progression. Obtaining a clinical history, as suggested by experts (2), remains the best tool for identifying ongoing significant dust exposure.

We doubt that a detailed proscriptive rubric for pathologic reports in interstitial lung disease is necessary or even advisable. Although the histopathologic criteria for calling features of UIP and other key entities in the differential diagnosis (e.g., lymphocytic bronchiolitis in hypersensitivity pneumonitis) are commonly discussed, they have not been precisely defined. Thus, there is poor agreement among lung pathologists for calling these specific histologic patterns (7). In addition, the suggestion that routine templating of reports should include an environmental assessment risks turning the pathology report into a checklist devoid of context and interpretation, which is an unfortunate trend in radiology reports. It is our opinion that descriptive pathology reports are more likely to provide useful information for clinicians. We acknowledge that some cases of pneumoconiosis are missed by pathologists (as well as clinicians and radiologists), but we are not aware of any evidence that mandatory checklists, stains, or polarizing lenses will prevent these mistakes.

In summary, we agree with the general suggestion that more careful evaluations of occupational/environmental exposures are needed (8). We think this is best accomplished in the setting of a research effort that includes the appropriate control groups rather than by adhering to a proscriptive standard that may be time consuming, unwieldy, and unevenly interpreted, and may also lead to false reassurance or even misclassification by clinicians.