Over 90% of vulvar malignancies are squamous cell carcinoma.
Most cases occur in older women (over 60).
Aetiology and Pathogenesis
There are two primary pathways through which vulval SCC is thought to arise:
- The HPV-associated pathway, which is due to infection with HPV. Disease is more commonly bulky or verrocous; it occurs in a younger population and is associated with a higher number of sexual partners
- The lichen sclerosis pathway, which is related to the development of lichen sclerosis. This is the more common variant, and occurs in older women without evidence of HPV infection.
Lichen sclerosis is a disorder of unknown incidence and aetiology that most commonly affects the vulva. It may occur at any age but is more prevalent in older women. About 1/3rd of patients have extragenital skin disease. The most common symptom is itch. Early stages are characterised by thinning of the epithelium with a white 'cigarette paper' appearance; progressive disease leads to anatomical destruction of the labia minora and clitoral hood. Treatment is with high dose corticosteroids. Women with lichen sclerosis have a 5% lifetime risk of developing vulval SCC.
The classical histopathological appearances of lichen sclerosis are:
- Replacement of the dermis with dense collagen (sclerosis)
- Either atrophy of the overlying epidermis or alternatively thickening of the epidermis due to hyperplasia
For a good demonstration of LS see this YouTube video, where I have obtained the information on histopathology.
Both HPV associated and LS associated disease leads to development of vulvar intraepithelial neoplasia (VIN). The type of VIN that develops varies according to cause; HPV associated VIN is typically warty or basaloid whereas the VIN related to LS is 'differentiated VIN'. Differentiated VIN is limited to the deep layers of the epithelium and may have an overlying 'normal' epithelium. See the Vulval Intraepithelial Neoplasia section.
The other important risk factor in the development of vulval malignancy is smoking.
Most (80%) lesions are found when they are locally invasive only. The remaining 20% of patients will have regional involvement. Most commonly the inguinal nodes are involved. Bilateral involvement usually only occurs with lesions < 1 cm from midline. Pelvic nodes are rarely involved without inguinal node involvement, although some case reports suggest that ciltoral lesions may spread to pelvic nodes alone in some cases. Distant metastases are rare but may occur in neglected disease.
Symptoms usually include itch, pain or bleeding. On examination a lesion is usually visible but may have a variety of appearances (from flat to nodular with or without verrocous surface). Most lesions are on the labia majora; the clitoris and labia minora are involved less frequently. There are no special bloods or imaging that need to be performed although advanced cases warrant full CT staging of the chest and abdomen.
Macroscopically squamous cell carcinoma can possess a number of appearances. Lesions may be flat, raised, often with an irregular surface.
Microscopically, there is usually evidence of squamous differentiation with keratin deposits and intercellular bridging. Immunohistochemistry is unhelpful.
Genetics differ between the two aetiologies of SCC. HPV related malignancies contain evidence of viral oncogenes E5 and/or E6. Lichen sclerosis related disease often has loss or non-functioning mutations of TP53.
Staging / Classification
The FIGO and 7th edition TNM staging now match for vulval malignancy.
|Tis||Vulval carcinoma in situ (VIN)|
|T1a||Tumour confined to vulva and/or perineum, no greater than 2 cm in size, less than 1 mm depth of invasion|
|T1b||As for T1a but with greater than 1 mm depth invasion|
|T2||Tumour > 2 cm in size, no invasion of adjacent structures|
|T3||Tumour involves lower urethra, vagina or anus|
|T4||Tumour involves upper urethra, bladder, rectum or is fixed to the pubic bone|
|N1||Unilateral regional nodes involved|
|N2||Bilateral regional nodes involved|
Final TNM/FIGO Stage