Inverted papillomas of the skin occurred in five dogs. Lesions were 1–2 cm, circumscribed, flask-like structures below the level of the surrounding normal skin. Walls of the structures consisted of hyperplastic epidermis, forming thin papillary projections on thin fibrovascular stalks. Cells in the stratum granulosum had clear cytoplasm, numerous keratohyalin-like granules of various sizes, and poorly defined intranuclear inclusions. These cells stained positively for papillomavirus group-specific antigens by both the peroxidase-antiperoxidase and avidin-biotin methods. Virions with a mean diameter of 35.7 nm were present within nuclei in cells of the stratum granulosum when examined by electron microscopy. In situ DNA hybridization, using a canine oral papillomavirus probe, localized papillomavirus DNA in canine oral papillomas, but not in canine cutaneous squamous or inverted papillomas, suggesting that a different papillomavirus type was present in the latter lesions. Although these lesions resembled intracutaneous cornifying epitheliomas (keratoacanthomas), they appear to be a distinct lesion, probably with a different etiology.
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