Florid Vulval Paget Disease Exhibiting p16 Immunoreactivity and Mimicking Classic VIN

The diagnosis of vulval Paget disease is generally relatively straightforward but may be difficult, especially when the Paget cells are few in number. We report 2 cases of the opposite scenario where the Paget cells were present in such large numbers and formed confluent sheets such that they effaced the residual keratinocytes. There were associated epidermal hyperplastic changes in the form of acanthosis, papillomatosis, and hyperkeratosis, and the overall morphology resulted in close mimicry of classic (undifferentiated/ human papillomavirus-related) vulval intraepithelial neoplasia. There was focal intraepidermal clefting in both cases, resulting in an acantholytic appearance. In both cases, the Paget cells were strongly positive with p16 that further heightened the mimicry of vulval intraepithelial neoplasia. The Paget cells were diffusely positive with cytokeratin 7, CAM5.2, carcinoembryonic antigen, and epithelial membrane antigen and with mucin stains, and molecular tests for human papillomavirus were negative. The p16 immunoreactivity, which has not previously been reported in vulval Paget disease, prompted us to stain a small number of additional cases of more typical vulval Paget disease with this marker. Four of 5 additional cases were positive with varying degrees and patterns of immunoreactivity. Florid vulval Paget disease may morphologically mimic vulval intraepithelial neoplasia, and this mimicry may be exacerbated by p16 immunoreactivity.