Molecular Features of Preinvasive and Invasive Vulvar Neoplasms

Area of Science:

• Oncologic Pathology
• Molecular Biology
• Gynecologic Oncology

Background:

• Vulvar neoplasms are uncommon but diverse.
• Advancements in molecular pathology impact cancer treatment strategies.
• Understanding molecular features of vulvar lesions is critical.

Purpose of the Study:

• To review recent innovations in the molecular and genetic characteristics of vulvar neoplasms.
• To highlight key molecular pathways involved in vulvar tumorigenesis.

Main Methods:

• Systematic literature search of PubMed, Google Scholar, and Scopus.
• Inclusion of peer-reviewed English literature on molecular and genetic characteristics of vulvar neoplasms.

Main Results:

• Squamous cell carcinoma (SCC) is predominant, with Human Papillomavirus (HPV) involvement in some cases.
• HPV-associated SCC involves viral proteins E6/E7; HPV-independent SCC has TP53/CDKN2A mutations.
• PI3K-Akt pathway mutations are significant in SCC pathogenesis.
• Vulvar melanoma has distinct cKIT/NRAS/BRAF mutation profiles compared to cutaneous melanoma.
• Vulvar Paget disease (VPD) shows ERBB2 amplification in <20% and rare PI3K-Akt pathway mutations.

Conclusions:

• Multiple potentially targetable molecular pathways are implicated in the tumorigenesis of SCC, melanoma, and VPD.
• These findings underscore the importance of molecular profiling for personalized vulvar cancer therapy.