P16 Expression in Primary Vulvar Extramammary Paget Disease

Area of Science:

• Gynecologic Pathology
• Dermatopathology
• Oncologic Biomarkers

Background:

• P16 immunohistochemistry aids in diagnosing human papillomavirus (HPV)-related vulvar intraepithelial neoplasia.
• Limited data exists on p16 expression in primary vulvar extramammary Paget disease (EMPD).

Purpose of the Study:

• To assess p16 expression patterns in primary vulvar EMPD.
• To correlate p16 expression with disease progression and HPV status.
• To differentiate vulvar EMPD from HPV-related vulvar intraepithelial neoplasia.

Main Methods:

• Immunohistochemistry was used to evaluate p16 expression in 40 primary vulvar EMPD cases (34 intraepithelial, 6 invasive).
• RNA in situ hybridization was employed to detect high-risk HPV in select cases.
• p16 staining patterns were correlated with disease stage and cellular localization (cytoplasmic vs. nuclear).

Main Results:

• P16 expression was observed in 90% of vulvar EMPD cases (focal in 50%, diffuse in 40%).
• Diffuse p16 staining was more frequent in invasive EMPD (100%) than intraepithelial EMPD (33.3%).
• High-risk HPV was not detected in diffuse p16-positive cases; cytoplasmic p16 was seen in intraepithelial EMPD, nuclear in invasive EMPD.

Conclusions:

• The majority of primary vulvar EMPD exhibits p16 positive immunostaining, independent of HPV infection.
• Overlapping p16 staining patterns between vulvar EMPD and vulvar intraepithelial neoplasia necessitate careful diagnostic evaluation.
• Distinguishing vulvar EMPD from HPV-related lesions based on p16 expression requires consideration of staining patterns and localization.