RANKL expression is a useful marker for differentiation of pagetoid squamous cell carcinoma in situ from extramammary Paget disease

BACKGROUND: Pagetoid squamous cell carcinoma in situ (SCCIS) is a histopathologic variant of SCCIS composed of cells that display an abundant, pale-staining cytoplasm in a pagetoid distribution within the epidermis. As pagetoid SCCIS is sometimes difficult to differentiate from extramammary Paget disease (EMPD) histopathologically, specific markers for pagetoid SCCIS or EMPD are needed by dermatopathologists. METHODS: In this report, we employed immunohistochemical staining for receptor of activated nuclear factor kappa ligand (RANKL) and programmed death-ligand 1 (PD-L1) in six cases each of pagetoid SCCIS and EMPD. RESULTS: The Paget cells strongly expressed RANKL in EMPD, whereas the atypical keratinocytes did not express RANKL in any of the six cases of pagetoid SCCIS. In all cases of pagetoid SCCIS, atypical keratinocytes expressed PD-L1. In EMPD, Paget cells expressed PD-L1 in half of the cases at a lower level of expression than was seen in the surrounding keratinocytes. CONCLUSION: This study suggested that RANKL, but not PD-L1, could be a marker to differentiate between pagetoid SCCIS and EMPD.