Simultaneous vulvar intraepithelial neoplasia and Paget's disease: Report of two cases

We describe a very rare association between intraepithelial, extramammary Paget's disease and human papillomavirus- (HPV) negative, keratinized type of VIN III observed in two elderly women. In both cases, morphological and immunohistochemical investigation showed two heterogeneous but intimately admired neoplastic populations of vulvar epithelium. Atypical keratinocytes stained markedly and diffusely positive for high molecular weight cytokeratins, and moderately for p53 protein and c-erbB-2 immunostainings. Paget cells were diffusely positive for CEA, EMA, and low molecular weight cytokeratins, moderately and focally for c-erbB-2 and (in one case) for S-100. Morphological and immunohistochemical phenotypic differences between Paget cells and atypical keratinocytes suggest a simultaneous and incidental association of two distinct neoplastic disorders more than a mixed carcinoma in situ of vulvar epithelium.