Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore

Abstract

Severe acute respiratory syndrome (SARS) is an infectious condition caused by the SARS-associated coronavirus (SARS-CoV), a new member in the family Coronaviridae. To evaluate the lung pathology in this life-threatening respiratory illness, we studied postmortem lung sections from 8 patients who died from SARS during the spring 2003 Singapore outbreak. The predominant pattern of lung injury in all 8 cases was diffuse alveolar damage. The histology varied according to the duration of illness. Cases of 10 or fewer days' duration demonstrated acute-phase diffuse alveolar damage (DAD), airspace edema, and bronchiolar fibrin. Cases of more than 10 days' duration exhibited organizing-phase DAD, type II pneumocyte hyperplasia, squamous metaplasia, multinucleated giant cells, and acute bronchopneumonia. In acute-phase DAD, pancytokeratin staining was positive in hyaline membranes along alveolar walls and highlighted the absence of pneumocytes. Multinucleated cells were shown to be both type II pneumocytes and macrophages by pancytokeratin, thyroid transcription factor-1, and CD68 staining. SARS-CoV RNA was identified by reverse transcriptase-polymerase chain reaction in 7 of 8 cases in fresh autopsy tissue and in 8 of 8 cases in formalin-fixed, paraffin-embedded lung tissue, including the 1 negative case in fresh tissue. Understanding the pathology of DAD in SARS patients may provide the basis for therapeutic strategies. Further studies of the pathogenesis of SARS may reveal new insight into the mechanisms of DAD.

FIGURE 1

Hyaline membranes lining alveolar walls, interstitial and airspace edema, interstitial infiltrates of inflammatory cells, and vascular congestion characterize acute-phase DAD.

FIGURE 2

Loss of cilia, bronchiole epithelial denudation, and deposition of fibrin within the lumen and on exposed basement membranes signaled injury to small airways.

FIGURE 3

(A) Pancytokeratin is strongly positive in hyaline membranes, which cover most, but not all of the edematous alveolar walls. No epithelial lining cells are seen. (B) As repair occurs, hyperplastic type II pneumocytes (arrow) grow over bare alveolar walls (arrowheads).

FIGURE 4

In organizing-phase DAD, fibroblast proliferation is seen in the interstitium (arrow) and also in air spaces (arrowheads).

FIGURE 5

(A) Hyperplastic type II pneumocytes display striking cytological atypia including cytomegaly, nucleomegaly, clearing of nuclear chromatin, and prominent nucleoli. (B) Pancytokeratin staining the same multinucleated giant cell is shown. The surrounding cells are a combination of macrophages and neutrophils.

FIGURE 6

(A) Numerous neutrophils and macrophages fill alveoli in acute bronchopneumonia. (B) In addition to acute bronchopneumonia, case 2, a diabetic patient, also demonstrated pseudomembranous and superficially invasive Aspergillus tracheitis.