TRPS1 Expression Across the Spectrum of Paget Disease and Morphologic Mimics

Paget disease (PD) is histologically characterized by malignant glandular epithelial cells singly or in clusters within the epidermis. PD most commonly involves the nipple, though it may also occur at extramammary sites. Immunohistochemistry is helpful in highlighting PD and its extent. Differentiating PD from histologic mimics with overlapping immunophenotypes can be challenging. TRPS1, a GATA family transcription factor, has emerged as a breast origin marker with greater sensitivity than GATA3. In this study, we comprehensively examined the immunohistochemical expression of TRPS1 in mammary PD (n=29) with different biomarker profiles, including ER-/HER2+ (n=12), ER+/HER2+ (n=7), ER+/HER2- (n=6), and ER-/HER2- (n=4) cases, as well as benign and malignant histologic mimics and extramammary PD (EMPD). TRPS1 demonstrated strong to moderate nuclear staining of PD tumor cells across all ER/HER2 subgroups. Toker cells/Toker cell hyperplasia (n=11) also exhibited strong TRPS1 immunoreactivity, while melanoma in situ (n=10) and cutaneous sebaceous carcinoma (n=9) were essentially negative. Squamous cell carcinoma in situ (n=13) showed predominantly weak staining for TRPS1. Two cases of presumed intraepidermal metastases in patients with breast cancer demonstrated strong TRPS1 expression. Notably, TRPS1 highlighted PD tumor cells from background keratinocytes more distinctly compared with GATA3. Among EMPD cases, perivulvar (n=10) and periscrotal (n=5) cases were consistently positive, whereas perianal lesions (n=10) showed no/weak expression. In summary, TRPS1 demonstrates universal expression in mammary PD of all ER/HER2 subgroups and in Toker cells, and corroborates recent reports regarding the utility of TRPS1 in site-of-origin studies.