Pagetoid squamous cell carcinoma in situ (Pagetoid Bowen's disease) of the external genitalia

Approximately 5% of cutaneous squamous cell carcinomas in situ (SCCIS) have a nested pattern, referred to as pagetoid SCCIS, or pagetoid Bowen's disease. This growth pattern may simulate extramammary Paget's disease (EPD) when the external genitalia are involved. We report two cases of genital pagetoid SCCIS, including the first example affecting the vulva. Using several known cases each of classic (bowenoid) SCCIS of the vulva, primary cutaneous vulvar EPD, and cutaneous melanoma in situ as controls, we performed a battery of immunohistochemical and mucin stains to study the phenotype of pagetoid SCCIS. Both cases of pagetoid SCCIS were strongly positive for cytokeratin (CK) 7, a highly sensitive and popular marker for EPD. Stains with the high molecular weight cytokeratin marker Keratin-903 (34betaE12) showed 4+ immunoreactivity, although not with the intensity seen in the juxtaposed normal keratinocytes or in the cells of classic SCCIS. Immunoreactivity scores were 2+ for CK5/6, 2+ for CK19, and 1+ to 3+ for CK 13. Unlike the Paget's cells of EPD, the nested cells of pagetoid SCCIS were devoid of mucin and were nonimmunoreactive with GCDFP-15, CEA, CAM5.2, and c-erbB2. Stains for CK20, S-100, and Melan A also were negative. Although CK7 is a sensitive marker for the Paget's cells of EPD, this study corroborates the unexpected CK7 positivity in pagetoid SCCIS, precluding its usefulness in distinguishing these two diseases. Combined with mucin stains, a limited immunohistochemical panel may be of diagnostic value in particularly difficult cases.