The histologic diagnosis of intraepithelial pagetoid neoplasms

Abstract

The histologic differential diagnosis of entities characterized by large, pale-staining cells scattered throughout the epidermis most commonly includes Paget's disease (mammary and extramammary), squamous cell carcinoma in-situ (Bowen's disease), and melanoma in-situ. Paget's disease is the cytologie and architectural prototype for this “pagetoid” pattern. Entities that less commonly demonstrate this histologic pagetoid pattern include sebaceous gland carcinoma, pagetoid dyskeratosis, epidermotropic metastatic carcinomas, pagetoid reticulosis, mycosis fungoides, trabecular cell carcinoma, clonal seborrheic keratosis, and hidroacanthoma simplex. In many cases these entities can be differentiated on clinical and histologic grounds using routine hematoxylin and eosin stains. Difficult cases can sometimes be differentiated using histochemical stains to demonstrate the presence or absence of cellular products such as melanin or sialomucin. However, these histochemical stains are often inconclusive or difficult to interpret in difficult cases. The advent of the immunoperoxidase technique has provided a diagnostic tool that is both more sensitive and specific than standard histochemical stains in differentiating this group of intraepithelial neoplasms. Immunohistochemistry has also resolved the nature and histogenesis of the Paget's cell, a point of controversy since its description. This review will focus on the histologie, histochemical, and immunoperoxidase evaluation of difficult intraepithelial tumors that demonstrate a pagetoid growth pattern.