DNA VIRUSES
Adenovirus
Adenovirus primarily affects the immunosuppressed host but can produce outbreaks in healthy subjects living at close quarters, e.g., military recruits. Adenovirus typically produces ulcerative bronchiolitis with karyorrhexis, neutrophilic pneumonia acute intrapulmonary necrosis with hemorrhage, or DAD. Infected cells can exhibit amphophilic intranuclear inclusions with perinuclear clearing that mimic herpesvirus infection but more characteristically produce “smudge cells”, showing hyperchromatic nuclei extruding beyond the confines of their nuclear membranes.
The appearance of “smudge cells” can be mimicked by pulmonary cytotoxic drug injury or by epithelial repair in the early proliferative phase of DAD. For this reason and because of the potential overlap with herpesvirus-induced cytopathic changes, the diagnosis of adenovirus infection should always be confirmed by immunohistochemical staining, ultrastructural examination, or viral isolation.
Cytomegalovirus
Cytomegalovirus occurs at the extremes of age, or as a result of immunosuppression, and it is a common infection in HIV/acquired immunodeficiency syndrome (AIDS). The number of cells showing cytopathic changes can vary considerably and parallels the severity of infection. Cytomegalovirus (CMV) primarily targets pulmonary macrophages and endothelial cells, but virtually any cell can show cytopathic features. The most common distribution is blood-borne miliary disease but bronchiolitis and DAD also occur. The diagnostic features of infection are cytomegaly, intranuclear inclusions with characteristic Cowdry Type B inclusions, ill-defined amphophilic intracytoplasmic inclusions that are seen with hematoxylin and eosin (H&E), PAS, and GMS stains. In patients receiving prophylactic treatment with antivirals, CMV infection may fail to exhibit cytopathic changes. However, immunostains and in situ hybridization will continue to identify intracellular CMV antigens. CMV is a frequent copathogen in the immunosuppressed patient and a cause of immunosuppression in its own right. CMV infection can be seen together with other viral infections, Pneumocystis jirovecii, or opportunistic fungal infections
Herpesvirus
Herpesvirus types 1 and 2 both infect the lung. The incidence of herpesvirus infection increases with immunosuppression and when mucosal barrier defenses have been breached, herpesvirus characteristically elicits a prominent neutrophilic response that mimics pyogenic bacterial infection, and foci of necrosis, cell karyorrhexis, and piled up viral infected cells with amphophilic nuclei confirm the diagnosis. Cytopathic diagnosis includes type A or type B Cowdry nuclear inclusions showing molding of adjacent cells with multikaryon formation. Immunosuppressed patients with herpesvirus viremia develop miliary foci of hemorrhagic necrosis with prominent fibrinous exudates.
Herpesvirus pulmonary infections also develop in patients with structural abnormalities of the airways or as complications of primary infections of the oropharynx and esophagus. Intubated patients receiving chronic ventilatory support and are at increased risk due to local barotrauma from inflated endotracheal tubes. The respiratory mucosa is the primary target. At times, extensive necrosis of an ulcerated airway suggests the diagnosis but immunostaining for herpes viral antigen can demonstrate high background staining obscuring the diagnosis. When this is the case, examining paraffinembedded tissues by electron microscopy can reveal diagnostic virions.
Varicella Zoster
Varicella zoster pneumonia is a rare complication of the childhood chickenpox and it is more commonly encountered as the consequence of reactivated virus in the immunocompromised host. Following nonlethal pulmonary infections in childhood, the lung shows multiple calcified miliary lesions. Cases coming to biopsy or autopsy show miliary nodules of hemorrhagic necrosis in lung and pleura or DAD. Infected cells with primarily Cowdry type A inclusions may be seen at the edges of the lesion but they are harder to identify than in herpesvirus pneumonia.
Hantavirus
This virus produced an epidemic in the four corners region of the southwestern United States in 1993. The infection is a zoonosis transmitted by infected rodent feces. The most common radiographic presentation is diffuse pulmonary edema with pleural effusions mimicking congestive heart failure. Histologically, the lung shows pulmonary edema with scant poorly formed hyaline membranes with atypical lymphocytes circulating within the pulmonary vasculature. Confirmation of the diagnosis requires specific immunohistochemistry, serological evidence of hantavirusspecific IgM and PCR or ultrastructural identification of the causative virions.