Diagnostic Algorithm for Secondary Extramammary Paget Disease from Institutional Cases and Literature Review

Area of Science:

• Oncology
• Pathology
• Immunohistochemistry

Background:

• Distinguishing primary extramammary Paget disease (EMPD) from secondary EMPD is crucial for patient management.
• While clinicopathologic correlation is standard, immunoprofiling offers a distinct diagnostic approach.
• Previous studies have explored various markers, but a comprehensive algorithm is needed.

Purpose of the Study:

• To develop a diagnostic algorithm for distinguishing primary EMPD from secondary EMPD using immunohistochemistry.
• To compare the immunoprofiles of primary and secondary EMPD cases across different origins.
• To identify key immunohistochemical markers for accurate EMPD classification.

Main Methods:

• Systematic review and meta-analysis of published EMPD cases.
• Evaluation of immunoprofiles from 480 primary and 132 secondary EMPD cases.
• Statistical comparison of marker expression (CK7, CK20, CDX2, GATA3, GCDFP15, TRPS1, SATB2, p63, uroplakin II/III, PSA, NKX3.1) between primary and secondary EMPD subtypes.

Main Results:

• Significant differences in marker expression were observed between primary EMPD and secondary EMPD of colonic, urothelial, and prostatic origins.
• CK20, GCDFP15, and TRPS1 were identified as key markers for distinguishing primary EMPD from colonic and urothelial secondary EMPD.
• Specific marker panels were found to be effective in differentiating various secondary EMPD origins.

Conclusions:

• An initial immunohistochemistry panel including TRPS1, CK7, and CK20 is proposed for EMPD diagnosis.
• TRPS1-negative cases require further specific immunostains based on suspected origin (colonic, urothelial, or prostatic).
• The proposed algorithm enhances the accuracy of distinguishing primary from secondary EMPD, guiding treatment decisions.