Pulmonary edema, the accumulation of extravascular fluid in the lungs, often accompanies passive heart failure such as left heart failure and valvular heart disease, where it is termed cardiogenic pulmonary edema. Pulmonary edema may relate to increased capillary or venule hydrostatic pressure or to a breakdown in alveolar septal-vascular integrity due to direct injury. Pulmonary edema may result from a wide variety of potential etiologies, including infections; acute respiratory distress syndrome; inhalation of smoke, chemical agents, and other fumes and toxins; cocaine and heroin abuse; high altitude; fluid overload; and renal failure; among others. It develops as an early interstitial phase, with fluid accumulation within the alveolar interstitium, followed by a second phase with fluid accumulating within alveolar spaces. Pulmonary edema is often seen on transbronchial biopsy as part of a spectrum of changes in cases of bronchopneumonia and cases of diffuse alveolar damage of varying causes. It may occasionally be the only histologic feature present on transbronchial biopsy in these conditions. Histologically, edema fluid involves alveolar spaces and may be associated with interstitial widening, vascular congestion, and lymphatic widening. The protein that accompanies the leaked fluid stains pink with hematoxylin and eosin (H&E) stain.

Differential diagnosis includes clear fluid within alveolar spaces as occurs with near-drowning or other clear fluid aspiration; however, clinical history will help differentiate these cases. Pulmonary alveolar proteinosis may superficially resemble edema; however, it contains course granules that are periodic acid-Schiff (PAS) positive, as well as scattered cholesterol clefts. Pneumocystis pneumonia may contain eosinophilic material within alveoli, but the material surrounding the cysts has a characteristic foamy appearance. Intra-alveolar mucin associated with a mucin-secreting tumor may occasionally mimic edema on a limited biopsy, but it can be distinguished with mucin stains.