Squamous precursor lesions of the vulva: current classification and diagnostic challenges

Area of Science:

• Gynecologic Oncology
• Dermatopathology
• Molecular Pathology

Background:

• Vulvar squamous cell carcinoma (VSCC) arises from distinct oncogenic pathways.
• Two major types of vulvar intraepithelial neoplasia (VIN) are recognized: usual (uVIN) and differentiated (dVIN).
• VIN incidence is increasing, while VSCC incidence remains stable.

Purpose of the Study:

• To review the classification, epidemiology, clinical features, histomorphology, ancillary markers, and molecular genetics of uVIN and dVIN.
• To discuss the diagnostic challenges in differentiating VIN subtypes for pathologists.

Main Methods:

• Review of existing literature on VIN classification, epidemiology, clinical presentation, histopathology, and molecular genetics.
• Comparative analysis of uVIN and dVIN based on human papillomavirus (HPV) status, patient demographics, and associated conditions.
• Examination of histological and molecular differences between uVIN and dVIN, including TP53 mutation status.

Main Results:

• uVIN is HPV-driven, affects younger women, and is multicentric.
• dVIN occurs in post-menopausal women, is HPV-independent, often associated with lichen sclerosus, and has subtle morphological features.
• dVIN exhibits a higher mutation burden, particularly TP53 mutations, and carries a greater risk of malignant transformation to VSCC over a shorter interval.

Conclusions:

• Understanding the distinct characteristics of uVIN and dVIN is crucial for accurate diagnosis and patient management.
• Differentiated VIN poses a significant risk for progression to vulvar cancer, necessitating careful pathological evaluation.
• Morphological subtleties and molecular differences in dVIN present diagnostic challenges that require specialized knowledge.