Pathologic findings in novel influenza A (H1N1) virus ("Swine Flu") infection: contrasting clinical manifestations and lung pathology in two fatal cases

Abstract

Although novel influenza A (H1N1) virus infection has assumed pandemic proportions, there are few reports of the pathologic findings. Herein we describe the pathologic findings of novel influenza A (H1N1) infection based on findings in 2 autopsy cases. The first patient, a 36-year-old man, had flu-like symptoms; oseltamivir (Tamiflu) therapy was started 8 days after onset of symptoms, and he died on day 15 of his illness. At autopsy, the main finding was diffuse alveolar damage with extensive fresh intra-alveolar hemorrhage. The second patient, a 46-year-old woman with alcoholism, was found unresponsive in a basement and brought to the hospital intoxicated and confused. Her condition deteriorated rapidly, and she died 4 days after admission. The main autopsy finding was acute bronchopneumonia with gram-positive cocci, intermixed with diffuse alveolar damage. The pathologic findings in these contrasting cases of novel influenza A (H1N1) infection are similar to those previously described for seasonal influenza. The main pathologic abnormality in fatal cases is diffuse alveolar damage, but it may be overshadowed by an acute bacterial bronchopneumonia.

Image 1

(Case 1) Diffuse alveolar damage and intra-alveolar hemorrhage in influenza A (H1N1) virus infection. A, Gross image of congested, boggy, and consolidated lung. This macroscopic appearance is abnormal but nonspecific. B, Low magnification showing extensive diffuse alveolar damage (DAD) (H&E, ×40). C, High magnification of an alveolus lined by a hyaline membrane. Note the absence of viral inclusions (H&E, ×200). D, Extensive intra-alveolar hemorrhage (H&E, ×100). E, Low magnification of the wall of a bronchus. There is mild autolysis in the form of sloughing of the lining epithelium (arrowhead), but no evidence of necrotizing bronchitis. Note the mild chronic inflammation in bronchial submucosal glands (arrow) (H&E, ×100). F, A tiny focus of squamous metaplasia within a bronchus (H&E, ×200).

Image 1

(Case 1) Diffuse alveolar damage and intra-alveolar hemorrhage in influenza A (H1N1) virus infection. A, Gross image of congested, boggy, and consolidated lung. This macroscopic appearance is abnormal but nonspecific. B, Low magnification showing extensive diffuse alveolar damage (DAD) (H&E, ×40). C, High magnification of an alveolus lined by a hyaline membrane. Note the absence of viral inclusions (H&E, ×200). D, Extensive intra-alveolar hemorrhage (H&E, ×100). E, Low magnification of the wall of a bronchus. There is mild autolysis in the form of sloughing of the lining epithelium (arrowhead), but no evidence of necrotizing bronchitis. Note the mild chronic inflammation in bronchial submucosal glands (arrow) (H&E, ×100). F, A tiny focus of squamous metaplasia within a bronchus (H&E, ×200).

Image 2

(Case 2) Acute bacterial (pneumococcal) bronchopneumonia and influenza A (H1N1)-related diffuse alveolar damage (DAD). A, Acute bronchopneumonia, low magnification. Alveolar spaces are filled with a neutrophilic infiltrate and necrotic debris (H&E, ×100). B, Acute bronchopneumonia, high magnification. Neutrophils admixed with macrophages (H&E, ×400). C, Basophilic granular material within macrophages (H&E, ×1,000). D, Gram stain demonstrating that the tiny basophilic granular particles seen in C represent gram-positive cocci (Gram/Brown and Brenn, ×1,000). E, DAD (arrowhead) adjacent to acute bronchopneumonia (arrow) (H&E, ×200). F, DAD in lung parenchyma away from acute bronchopneumonia (H&E, ×100).

Image 2

(Case 2) Acute bacterial (pneumococcal) bronchopneumonia and influenza A (H1N1)-related diffuse alveolar damage (DAD). A, Acute bronchopneumonia, low magnification. Alveolar spaces are filled with a neutrophilic infiltrate and necrotic debris (H&E, ×100). B, Acute bronchopneumonia, high magnification. Neutrophils admixed with macrophages (H&E, ×400). C, Basophilic granular material within macrophages (H&E, ×1,000). D, Gram stain demonstrating that the tiny basophilic granular particles seen in C represent gram-positive cocci (Gram/Brown and Brenn, ×1,000). E, DAD (arrowhead) adjacent to acute bronchopneumonia (arrow) (H&E, ×200). F, DAD in lung parenchyma away from acute bronchopneumonia (H&E, ×100).