The pathologist should be aware of the artifacts and nonspecific changes that may be seen in a transbronchial biopsy in order to avoid misinterpretation of these as pathologic changes.

Tissue compression by transbronchial biopsy forceps causes collapse of lung parenchyma and, to a lesser extent, the bronchial wall. Lung parenchymal compression may appear on examination as rounded spaces or holes mimicking fungal organisms or lipid vacuolization. Collapsed lung parenchyma may be misinterpreted as fibrosis or increased cellularity within the interstitium. Bronchial wall compression, with collapse of blood vessels and loss of normal architecture, might mimic scarring within the bronchial wall. Bleeding is a normal result of the biopsy procedure and may occasionally mimic pathologic hemorrhage. When bleeding is associated with a pathologic condition, the biopsy generally contains associated fibrin and hemosiderin-laden macrophages. The adherence to strict criteria for the diagnosis of various conditions characterized by hemorrhage will help the pathologist avoid overdiagnosis of these conditions. Biopsy fixation in 10% formalin minimizes artifactual changes, whereas the use of alcohol-based nonaldehyde fixatives may increase the incidence of artifact, as may the use of saline to transport the biopsy to the laboratory.

Lymphocytes and other inflammatory cells may exhibit crush artifact. That crush artifact may occasionally be substantial enough to mimic small cell carcinoma. The diagnosis of small cell carcinoma must be made based only on the examination of intact (not crushed) small cell lung cancer cells.

Deep transbronchial biopsies may include pleura. Reactive mesothelial cells from the pleural surface should be recognized as such and not misinterpreted as a neoplasm.

A variety of endogenous structures may be found on transbronchial biopsy. Blue bodies may be present, occasionally in increased numbers that incorrectly suggest inorganic dust exposure. Blue bodies are intra-alveolar basophilic, laminated, calcified, frequently multiple concretions that range from 15 to 40 μm. Alcian blue and periodic acid-Schiff (PAS) stains highlight blue bodies. They are formed within macrophages and giant cells.

Calcium oxalate crystals occur within giant cells and may be seen along with blue bodies. They are found in association with granulomatous inflammation and are birefringent, identifiable with polarized light. The crystals are irregular, glassy sheets with sharply angled edges, ranging from 1 to 20 μm. Calcium oxalate crystals may mimic foreign material. Charcot-Leyden crystals, needle-shaped crystals seen within macrophages, form due to the collection of eosinophilic debris within macrophages and may be found in biopsies from patients with asthma, hypersensitivity pneumonitis, and eosinophilic pneumonia, among other diseases. Other endogenous structures, such as cholesterol clefts, psammoma bodies (calcospherites), dystrophic ossification, and Schaumann bodies may occasionally be found on transbronchial biopsy.

Exogenous structures such as ferruginous bodies, including asbestos bodies, may be found in transbronchial biopsies and are apparent both on hematoxylin and eosin (H&E) stain and iron stain. Although ferruginous bodies, including asbestos bodies, are not diagnostic of any disease state, it is important to differentiate them from other foreign material.