Introduction to TRPS1 as a Diagnostic Tool

Differentiating Paget disease (PD) from its morphologic mimics often presents a diagnostic challenge for pathologists. Recently, TRPS1 expression in Paget disease has emerged as a highly sensitive marker of breast origin. This GATA family transcription factor often demonstrates superior performance compared to traditional markers like GATA3. A new study has comprehensively evaluated TRPS1 across the spectrum of mammary and extramammary Paget disease, confirming its utility in routine clinical practice.

Performance Across Mammary Paget Disease Subgroups

The study examined 29 cases of mammary Paget disease involving various biomarker profiles. Regardless of ER or HER2 status, TRPS1 demonstrated strong to moderate nuclear staining in all tumor cells. Specifically, cases including ER-/HER2+, ER+/HER2+, ER+/HER2-, and ER-/HER2- all showed consistent immunoreactivity. Furthermore, Toker cells and cases of Toker cell hyperplasia also exhibited strong TRPS1 expression. This consistency makes it a reliable tool for identifying mammary PD across diverse clinical presentations.

Differentiating PD from Morphologic Mimics

A critical advantage of analyzing TRPS1 expression in Paget disease is its ability to exclude mimics. The study found that melanoma in situ and cutaneous sebaceous carcinoma were essentially negative for TRPS1. While squamous cell carcinoma (SCC) in situ showed some reactivity, the staining was predominantly weak. Moreover, TRPS1 highlighted PD tumor cells against background keratinocytes more distinctly than GATA3. Consequently, pathologists can use TRPS1 to achieve a clearer contrast and more accurate diagnosis in difficult cases.

Extramammary Paget Disease and Site-Specific Variations

The utility of TRPS1 extends to extramammary Paget disease (EMPD), though with important site-specific nuances. Perivulvar and periscrotal cases were consistently positive for TRPS1. In contrast, perianal lesions showed no or weak expression. This variation suggests that TRPS1 is particularly useful for identifying primary EMPD in most non-perianal sites. Additionally, researchers noted strong TRPS1 expression in intraepidermal metastases from breast cancer, further supporting its role in site-of-origin studies.

Clinical Implications for Pathologists

In summary, TRPS1 provides a universal and sensitive marker for mammary PD and most forms of primary EMPD. Because it maintains expression across all ER/HER2 subgroups, it is more versatile than many traditional antibodies. Practitioners should consider incorporating TRPS1 into immunohistochemical panels, especially when differentiating pagetoid neoplasms from melanoma or SCC in situ.

Frequently Asked Questions

How does TRPS1 compare to GATA3 in Paget disease?

TRPS1 typically provides a more distinct contrast between tumor cells and background keratinocytes than GATA3. It also shows higher sensitivity across different breast cancer subtypes, including triple-negative cases.

Is TRPS1 useful for perianal Paget disease?

The study indicates that perianal lesions often show weak or no TRPS1 expression. Therefore, negative TRPS1 results in the perianal region do not necessarily rule out Paget disease, and clinical correlation is required.

Can TRPS1 distinguish Paget disease from melanoma?

Yes, TRPS1 is highly effective in this regard as melanoma in situ is essentially negative for TRPS1, whereas mammary Paget disease shows strong nuclear staining.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. It is not intended to be a substitute for professional medical judgment, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

1. Rutland CD et al. TRPS1 Expression Across the Spectrum of Paget Disease and Morphologic Mimics. Appl Immunohistochem Mol Morphol. 2026 Feb 23. doi: 10.1097/PAI.0000000000001313. PMID: 41725031.

2. Cho WC et al. Immunohistochemical expression of TRPS1 in mammary Paget disease, extramammary Paget disease, and their close histopathologic mimics. J Cutan Pathol. 2023 May;50(5):434-440. doi: 10.1111/cup.14414.

3. Cook EE et al. TRPS1 is a sensitive and specific biomarker for extramammary Paget's disease (EMPD). Histopathology. 2023 Jul;83(1):104-108. doi: 10.1111/his.14908.