Diagnostic Utility of p63 Expression in the Differential Diagnosis of Pagetoid Squamous Cell Carcinoma In Situ and Extramammary Paget Disease: A Histopathologic Study of 70 Cases

Pagetoid squamous cell carcinoma in situ (PSCCIS) is characterized by cytologically atypical cells, with abundant, pale-staining cytoplasm arranged singly and in nests within the epidermis (pagetoid distribution). The growth pattern of PSCCIS may simulate extramammary Paget disease (EMPD), and in some cases, it is difficult to differentiate the 2 entities based on histomorphology alone. In this study, biopsy samples from 30 cases of PSCCIS and 40 cases of primary EMPD were examined using immunohistochemical staining for p63. In cases where the boundaries between the pagetoid cells and surrounding keratinocytes were difficult to assess, an eosin counterstain was applied to highlight the cytoplasm of the lesional cells. The immunohistochemical results were analyzed using Fisher exact test. The results showed that all 30 cases of PSCCIS exhibited strong nuclear positivity for p63 in the neoplastic cells, when compared with 0 of 40 cases of primary EMPD (P < 0.0001). In summary, p63 is a useful marker in differentiating PSCCIS from primary EMPD. The authors propose the addition of p63 immunostain in the panel of markers when evaluating pagetoid cutaneous neoplasms.