- Premalignant and Malignant Neoplasms.
After completing this tutorial the student
will be able to:
- classify the premalignant conditions and
malignant neoplasms of the vulva
- describe their epidemiologic features
- describe their clinical features
- describe/recognize histologic features
and grade various lesions
- determine clinical behavior and outcome
- Vulvar Intraepithelial Neoplasia VIN ("Dysplasia")
VIN represents a spectrum of neoplastic changes in the vulvar
epithelium that range from mild cellular dysplasia to the most
severe cellular changes that fall short of invasive carcinoma.
It is a precursor lesion of vulvar squamous cell carcinoma.
The lesion occurs in elderly women, but is becoming increasingly
common in young women between 20 and 35 years old. Most cases
(about 90%) are associated with HPV, especially types 16, 18
and other high-risk types.
- Clinical presentation.
VIN presents as a white, red, or hyperpigmented indistinct macular
lesion or well-defined raised plaque, which may be single or multiple.
It is frequently multifocal with associated lesions in the cervix
(more often) or the vagina.
Note white flat patches and plaques.
Question: What benign lesions of the vulva may be clinically
confused with VIN?
Both architectural and cytologic abnormalities are present. The
normal progression of cell maturation within the vulvar squamous
epithelium from basal layer to surface is lost (loss of polarity).
Cytologic abnormalities are in the form of dysplastic cells with
nuclear hyperchromasia and showing variation in shape and size
(cellular pleomorphism). Some may have appearances of undifferentiated,
basaloid cells, while others may show evidence of single cell
keratinization (dyskeratosis). There is increase in the number
of mitotic figures with mitosis present above the basal layer.
Abnormal mitoses may also be seen.
NOTE: Although the lesion is associated with HPV infection
koilocytes are rarely present.
There is hyperkeratosis, and dysplastic cells with nuclear hyperchromasia
and pleomorphism are present. Mitoses (in circles) are seen above
the basal layer.
The number and distribution of dysplastic cells vary considerably
within the thickness of the squamous epithelium reflecting the
varying severity of the condition. A convention to grade the severity
of VIN has therefore been developed This is based on the proportion
of the total thickness of the epithelium replaced by dysplastic
cells and is done in thirds of the total thickness of the epithelium
- VIN 1: Mild; dysplastic cells are confined to the lower
third of the epithelium.
- VIN 2; Moderate; dysplastic cells occupy up to the
lower two thirds of the epithelium
- VIN 3; Severe, carcinoma-in-situ; dysplastic cells
extend into the upper third of the epithelium. Carcinoma-in-situ
may be used when dysplastic cells occupy the full thickness
of the epithelium and the underlying stroma has not been invaded.
The lesion may regress spontaneously, recur after local excision,
or progress to invasive squamous cell carcinoma if untreated (10%
of cases). The risk of progression to invasive carcinoma increases
with age and in immunosuppressed women.
- Invasive squamous cell carcinoma
Squamous cell carcinoma is the commonest malignant tumor of the
vulva, representing about 95% of all vulvar malignancies. Risk
factors include cigarette smoking, number of sexual partners,
and chronic granulomatous disease. Vulvar squamous cell carcinomas
may be divided into two general "types":
The first type affects older women and not related to HPV
The second type affects younger women and related to HPV
The lesion begins as an area of induration but progresses to
form an exophytic mass or an endophytic ulcer with raised, everted
edges. The labia are the most common location (90% - labia majora
more than minora; clitoris 10%).
Ulcerated endophytic tumor with raised everted edges.
Microscopically, most squamous cell carcinomas of the vulva are
well differentiated with keratinization. Poorly differentiated
tumors are uncommon. Associated VIN may be present at the margins.
Well differentiated squamous cell carcinoma. Nests of tumor cells,
some with keratin pearls, are present.
The tumors grow slowly and extend to the contiguous skin, invade
deeply to involve the vagina and rectum and metastasize to regional
lymph nodes. The outcome depends on stage, especially regional
node status. Overall 5-year survival of treated patients is 50%
for positive nodes and 75% for negative nodes.
Question: Which clinical features determine the risk of
metastatic spread of vulvar squamous cell carcinoma?
- Superficial invasive squamous cell carcinoma
This is defined as squamous cell carcinoma that measures less
than 2 cm in diameter, invades to a depth less than 1 mm and shows
no lymphovascular invasion.
The importance of these tumors is that they show a decreased
risk of spread to regional lymph nodes and therefore have better
prognosis than more deeply invasive tumors. The overall 5-year
survival is greater than 90%.
- Extramammary Pagets disease
This is a rare disease of the vulva, which affects predominantly
post-menopausal women. The lesion usually occurs on the labia
majora and presents as an erythematous (red), sharply demarcated
area. It is itchy or may give rise to a burning sensation. It
may be single or multicentric and may involve the perianal region.
The microscopic extent of the disease is often greater than is
Vulvar Pagets disease. Note erythematous lesion on left
Microscopically, the lesion is identified by the presence of
large, pale, mucin-containing epithelial cells scattered singly
or in small nests within the epidermis. It is associated with
an underlying invasive adenocarcinoma in 20% of cases.
Vulvar Pagets disease. Tumor cells with abundant pale cytoplasm
infiltrate the epidermis individually and in nests.
Untreated, vulvar Pagets disease runs a slowly progressive,
indolent course. Recurrence after treatment is not uncommon due
to inadequate excision (note that microscopic extent often exceeds
clinically visible margins) or multicentricity. Metastases do
not occur if the disease remains in situ (i.e. within the epidermis).
Prognosis depends on whether there is an associated invasive tumor.
Question: Which other parts of the body may similar lesions