• inclusions
• cowpox
• diagnosis
• histopathology
• orthopoxvirus

Replication of poxviruses results in the development of intracytoplasmic inclusions that may be visible by light microscopy. Kato et al (1959) classified these according to their morphology, staining properties, and rate of accumulation.¹ Type B inclusions are basophilic and occur early in the viral replication cycle. They represent the actual site of viral replication in the cytoplasm and may be seen in all productive poxvirus infections. In contrast, type A inclusions are large, well defined, eosinophilic bodies that develop late in the viral replication cycle. They are composed entirely of a single protein species that has a molecular weight of 160 kDa, but their function is not understood.² Type A inclusions are only associated with certain poxvirus infections so that their detection may be diagnostically useful.

We recently reported the clinical presentation of a veterinary surgeon working at a small animal practice who developed a black necrotic ulcer on his finger.³ Histopathology of a punch biopsy of the lesion unexpectedly revealed epidermal hyperplasia, neutrophil infiltration, and the presence of numerous large eosinophilic intracytoplasmic inclusions, consistent with poxvirus infection (fig 1). Based on this appearance, the differential diagnosis included cowpox (an orthopoxvirus infection), orf, and pseudocowpox (both parapoxvirus infections). In the context of frequent occupational exposure to cat scratches but no contact with ungulates, cowpox was the most probable diagnosis. This diagnosis was confirmed by polymerase chain reaction and partial DNA sequencing. Human cowpox is an uncommon and probably underdiagnosed infection that occurs only in Europe.⁴ Despite the name, cowpox is rare in cattle. Human infections are probably most frequently acquired from infected cats shedding virus from skin lesions, which gain entry to the human skin through abrasions or scratches.^{4, 5}

Laboratory diagnosis of cowpox may be established by electron microscopy of vesicle fluid, by polymerase chain reaction, virus isolation, or serology. However, in our case the histopathological appearances were important in establishing a probable diagnosis of human cowpox before molecular virological confirmation at a reference laboratory. Cowpox virus is recognised as causing large intracytoplasmic inclusion bodies in infected feline tissues and in in vitro cell culture.⁴ However, such inclusions were not reported among the biopsied cases included in an extensive review of this disease, in which a total of 54 published and unpublished human cases were reviewed.⁴ Indeed, an extensive search of the literature found no previous reports of such inclusions being seen in biopsied human cowpox lesions. Histopathologists should be aware that such a histological appearance in an unusual vesicular, pustular, or ulcerated skin lesion obtained from a patient with a history of contact with domestic cats probably results from cowpox infection.

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Figure 1

Histological examination of a punch biopsy of the skin ulcer stained with haematoxylin and eosin (medium power). Numerous, large, eosinophilic type A intracytoplasmic inclusions are seen (arrows).