Vulvar cancer pathophysiology

Vulvar cancer Microchapters
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]

Overview

Development of vulvar cancer is the result of multiple genetic mutations.

Pathogenesis of vulvar cancer

• Human papillomaviruses subtypes 16 and 18 (High risk) play an essential role in the pathogenesis of vulvar cancer. Once HPV enters an epithelial cell, the virus begins to make the proteins it encodes.
• Two of the proteins made by high-risk HPVs (E6 and E7) interfere with cell functions that normally prevent excessive growth, helping the cell to grow in an uncontrolled manner and to avoid cell death. Many times these infected cells are recognized by the immune system and eliminated. Sometimes, however, these infected cells are not destroyed, and a persistent infection results. As the persistently infected cells continue to grow, they may develop mutations in cellular genes that promote even more abnormal cell growth.
• HPV- related vulvar carcinoma is most commonly seen in younger women. vulvar intraepithelial neoplasia (VIN), related to HPV infection, subsequently leads to invasive vulvar cancer.

Microscopic Pathology

Histologic subtypes of vulvar Cancer include:

• Vulvar carcinomas

• Squamous cell carcinoma
• Basal cell carcinoma
• Vulvar Paget disease
• Adenocarcinoma
• Transitional cell carcinoma
• Verrucous carcinoma
• Merkel cell tumors
• Verrucous carcinoma

• Vulvar malignant melanoma
• Vulvar sarcoma

• Leiomyosarcoma
• Malignant fibrous histiocytoma
• Epithelial sarcoma

Vulvar carcinomas Subtype	Features on Gross Pathology	Features on Histopathological Microscopic Analysis
Squamous cell carcinoma of vulva	Most lesions originate in the labia, primarily the labia majora. Other areas affected are the clitoris, and fourchette, and the local glands Unifocal	Eosinophilia Extra large nuclei/bizarre nuclei Inflammation (lymphocytes, plasma cells) Long rete ridges Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges Squamous cell carcinoma of vulva
Basal cell carcinoma of vulva	Pearly nodule with telangiectasias	Basaloid cells - similar in appearance to basal cells: Moderate blue/grey cytoplasm. Dark ovoid/ellipsoid nucleus with uniform chromatin Palisading of cells at the edge of the cell nests Artefactual separation of cells (forming the nests) from the underlying stroma - key feature Surrounded by blue (myxoid) stroma - key feature Basal cell carcinoma of vulva
Vulvar melanoma	Superficial spreading is the most common type Brown/black color, but may include reddish brown or white Hyperkeratotic, diffused borders with no distinct demarcation Irregular and elevated	Presence of intraepidermal lateral spread (most characteristic feature) Dermal invasion Desmoplasia Epidermal hyperplasia Appearance of epithelioid cells with occasional spindle cells Vulvar melanoma