Acute Lung Injury: HRCT and Histopathologic Spectrum Obadina ET1, Kanne JP1, Torrealba JR2, Meyer CA1

1. University of Wisconsin Department of Radiology, Madison, WI; 2. University of Wisconsin Department of Pathology, Madison, WI

INTRODUCTION ACUTE FIBRINOUS AND ORGANIZING ORGANIZING PNEUMONIA

Acute lung injury (ALI) and acute respiratory distress syndrome Organizing pneumonia (OP) most often presents with a subacute Acute fibrinous and organizing pneumonia (AFOP) is Figure 3 (ARDS) are major pulmonary causes of morbidity and mortality. a recently described histologic pattern associated with clinical course without fulminant . Although it Acute pulmonary injury often results in acute hypoxemic ALI. Most patients present with severe respiratory failure AFOP is not associated with clinical ALI or ARDS, OP is discussed in respiratory failure. Patients with acute pulmonary injury typically this exhibit because it is frequently included in the pathologic similar to ARDS. However, a small subset of patients HRCT image of a patient with drug–induced AFOP present clinically with ARDS. ARDS was formally defined in 1994 may have a subacute clinical course not requiring demonstrating extensive peribronchial, subpleural, differential diagnosis of ALI. The underlying causes of OP include by the American–European Consensus Conference on ARDS as ventilatory support. AFOP can be idiopathic or related and perilobular consolidation and ground– infection, collagen vascular disease and drug reaction. It can acute hypoxemia with a ratio of partial pressure of arterial oxygen to insults such as drug reaction. glass opacity, similar to but more extensive than also be idiopathic, which is clinically referred to as cryptogenic organizing pneumonia. to the fraction of inspired oxygen (i.e., PaO2:FIO2) of 200 mm Hg organizing pneumonia (COP). or less, bilateral infiltrates with a radiographic appearance that is The dominant histopathologic finding in AFOP is consistent with pulmonary , and no evidence of cardiac fresh intra–alveolar fibrin or so–called “fibrin balls.” Histopathologic findings seen in OP include patchy accumulation failure clinically. ALI is less severe than ARDS and has similar Hyaline membranes should not be present, in contrast of loose plugs of granulation tissue (Masson bodies) in the diagnostic criteria with the exception of PaO2:FIO2 of 300 mm Hg. to DAD. Other histologic findings that can be seen with alveoli and respiratory bronchioles. Mild alveolar septal chronic AFOP include mild interstitial widening, lymphocytic Figure 4 inflammation is often present. When examined pathologically, most patients with clinical ARDS infiltrates, and organizing fibroblastic tissue. AFOP, 200X and ALI will show histologic evidence of diffuse alveolar damage HRCT findings of OP are airspace consolidation in a subpleural (DAD). However, it should be emphasized that these terms are Lung tissue demonstrates alveolar parenchyma HRCT findings of AFOP are not well described with predominantly intra–alveolar fibrin or peribronchial distribution. Ground–glass opacities may also be not synonymous. Other histologic patterns have been described but include peripheral and peribronchial foci of aggregates (“fibrin balls”) within airspaces. present, often with a bilateral asymmetric distribution. The reverse in association with ALI/ARDS. These include acute eosinophilic consolidation and ground–glass opacity, similar to Associated mild interstitial mononuclear halo sign may be present in almost 20% of cases. pneumonia (AEP), acute fibrinous and organizing pneumonia organizing pneumonia, but greater in extent with infiltrate is also noted. (AFOP), and diffuse alveolar hemorrhage (DAH). Organizing superimposed features more typical of DAD. Figure 9 pneumonia (OP) is also included in the differential diagnosis of ALI. This exhibit will illustrate the HRCT findings in the spectrum Organizing of acute lung injury with histopathologic correlation. Pneumonia HRCT image of a patient with cryptogenic organizing pneumonia ACUTE EOSINOPHILIC DIFFUSE ALVEOLAR demonstrates ground– glass attenuation PNEUMONIA HEMORRHAGE nodules with DIFFUSE ALVEOLAR DAMAGE faint peripheral AEP is characterized by fever, hypoxemia, peripheral eosinophilia Diffuse alveolar hemorrhage (DAH) is characterized by consolidation (“reverse Diffuse alveolar damage (DAD) is the most common histologic and fulminant respiratory failure. AEP may be idiopathic or hemorrhage into the alveolar spaces, and is due to injury to the halo”) in addition to nodular foci of lung manifestation of ARDS and ALI. Patients present with severe result from infection (especially parasites), toxic inhalation, drug alveolar microcirculation. Patients with DAH typically present consolidation. hypoxemia and almost always require mechanical ventilation. reaction, and recent onset of heavy smoking. At BAL, eosinophils with hypoxemia and occasionally present with fulminant Figure 10 While the precise mechanism of injury is unclear, capillary are generally greater than 25%. In contrast to other forms of respiratory failure. When there is significant alveolar hemorrhage, Organizing Pneumonia endothelial and alveolar epithelial damage result in exudation of ALI, patients with AEP usually have a dramatic response to patients will often present clinically with hemoptysis. Although fluid and products of cellular breakdown. With time, pneumocyte corticosteroids. DAH can occur with or without capillaritis, it is the cases of 10a. 40X hyperplasia and fibroblast proliferation ensue. DAH with capillaritis that may present with clinical findings of Lung section shows Histopathologic findings of AEP include intra–alveolar fibrin, ALI. Causes of DAH include immune–mediated disorders such as diffuse filling of the The histologic appearance of DAD is divided into three phases: macrophages, hyaline membranes (similar to the acute phase of collagen vascular diseases, microscopic polyangiitis, Goodpasture alveolar spaces with DAD), and numerous eosinophils. Eosinophils may be present in syndrome, Wegener granulomatosis, drug reactions, and fibroblastic plugs the acute or exudative phase, the organizing or proliferative (Masson bodies), the interstitium, may infiltrate blood vessel walls, and may form infections. phase, and the chronic or fibrotic phase. The acute phase occurs involving the during the first week after the initial insult, and findings may eosinophilic microabscesses. respiratory bronchioles, include intra–alveolar edema, interstitial widening, and hyaline Histopathologic findings seen in DAH include diffuse intra– alveolar sacs and membranes (composed of cellular and proteinaceous debris). HRCT findings of acute are nonspecific, alveolar blood admixed with hemosiderin–laden macrophages. alveoli. Thrombi may also be seen as a result of localized alterations and include consolidation and ground–glass opacities in a random Organizing fibroblastic tissue may also be present. In capillaritis, in the coagulation pathway. The organizing phase follows (2/3) or peripheral (1/3) distribution. Smooth interlobular septal are seen within alveolar septa with resultant vascular with features of interstitial fibrosis and type 2 pneumocyte thickening and small pleural effusions are frequently present and, necrosis. Hyaline membranes may also be present. hyperplasia. Squamous metaplasia, residual hyaline membranes, in the absence of cardiomegaly, are helpful clues to the diagnosis. 10b. 200X HRCT findings of DAH consist of extensive bilateral ground–glass and organizing fibroblastic tissue within air spaces may also Alveolar spaces are diffusely opacities, which may be diffuse or patchy, often in an “acinar” be present. The fibrotic phase is characterized by features of Figure 5 occupied by proliferation distribution. Subpleural sparing is often a useful diagnostic feature. interstitial lung fibrosis. of fibroblasts and myxoid Acute With subacute DAH, small poorly defined centrilobular nodules connective tissue (Masson and interlobular septal thickening can develop, presumably bodies) plugging the Initially, HRCT usually shows heterogeneous foci of consolidation Eosinophilic related to lymphatic resorption of the blood. terminal bronchioles, and ground–glass opacity with a posterior and basal Pneumonia alveolar sacs and alveoli. predominance. In the healing phase, findings of fibrosis such as HRCT image of a There is associated vascular reticulation, architectural distortion and traction young female patient Figure 7 congestion and minimal may be present. with recent onset of focal lymphocytic infiltrate. smoking shows diffuse Diffuse Alveolar septal thickening and A recent study evaluating the predictive value of CT for survival multiple peripheral foci Hemorrhage in patients with ARDS demonstrated higher mortality in those of lung consolidation. HRCT image shows patients with bilateral ground– Figure 1 greater than 80% glass acinar nodules, Figure 6 Diffuse Alveolar Damage lung involvement, predominantly affecting RA/LA ratio Eosinophilic the right lung, with CONCLUSION greater than 1, and relative sparing of Pneumonia (200X) the peripheral lung The patterns of acute lung injury and acute respiratory distress varicoid traction parenchyma. bronchiectasis. This section of lung shows syndrome have different HRCT and histopathologic features. interstitial widening Knowledge of the characteristics and features of the different accompanied by mixed patterns in the spectrum of ALI and ARDS is important and helpful infiltrates of lymphocytes, macrophages and Figure 8 for guiding appropriate diagnosis and treatment of affected eosinophils. Focal alveolar Diffuse Alveolar patients. fibroblastic proliferation is also present (arrow). Hemorrhage 8a. 100X 1a. Acute Phase Lung tissue shows HRCT image of a patient with acute DAD shows alveolar parenchyma with REFERENCES patchy consolidation and ground–glass opacities. Figure 2 patchy, intra–alveolar cell infiltrates predominantly 1. Beasley MB. The Pathologist’s Approach to Acute Lung Injury. Arch Pathol Lab Med Diffuse Alveolar Damage consisting of hemosiderin– 2010; 134: 719-727. laden macrophages. 2. Bernard GR, Artigas A, Brigham KL, et al. 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Acute Phase, 400X 2b. Organizing Phase, 200X polymorphonuclear cells HRCT of the same patient (from Figure 1a), Corresponding Author: and plasma cells are also obtained three months later, demonstrates Lung section shows alveolar lung parenchyma After the acute phase, hyaline membranes Eniola Obadina, MD seen in this case. interstitial fibrosis characterized by reticulation, with hyaline membranes (arrows), intra– become incorporated in alveolar septa with University of Wisconsin Department of Radiology traction bronchiectasis, and ground–glass alveolar red cells and interstitial mononuclear fibroblast proliferation and septal widening. E3/312 CSC opacity with a basal predominance. inflammatory infiltrates. Interstitial inflammatory infiltrates may persist Madison, WI 53792–3252 at this stage. [email protected]