The surgical and cytopathology of viral infections: utility of immunohistochemistry, in situ hybridization, and in situ polymerase chain reaction amplification

The diagnosis of viral infections is an important part of the daily work of a surgical and cytopathologist. Some viral infections, such as human papillomavirus infection of the lower genital tract, are seen commonly, whereas others, such as fatal enteroviral infection, cannot be diagnosed on routine histological examination and need to be addressed within the clinical context. In general, viral infections are best categorized for the surgical pathologist as low copy/RNA viruses and high copy/DNA viruses. In the latter, viral DNA enters the nucleus, undergoes rapid proliferation, and causes certain cytopathologic changes characteristic of the infection. Immunohistochemistry and/or in situ hybridization yields an intense signal, reflective of the productive infection. In comparison, RNA viruses typically do not show high copy numbers and, although they can induce characteristic cytopathologic changes such as inclusions, often times they do not. In such cases, immunohistochemistry and/or in situ–based hybridization methods, particularly in situ polymerase chain reaction amplification, may be required for a definitive diagnosis. A combination of routine histopathology, clinical information, and immunohistochemistry/in situ–based nucleic acid detection methodologies will allow the surgical pathologist to correctly diagnose viral infections.