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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5511_Библиотеки_им_академика_М_И_Перельмана.pdf
and with less or no association with HPV. It is also described as VIN,
simplex (or differentiated) type — usually unifocal, seen as ulcer,
warty papule or hyperkeratotic plaque. It may become invasive cancer
in 9% of cases if untreated or 3.3% if treated. It may have a higher risk
for cancer.
29,32
The treatment of VIN is surgical resection of the lesion. Other
destructive treatments do not have a pathology specimen to check for
invasive cancer. There should be a 3 mm or greater depth to remove
the hair follicles and a 1 cm margin around the VIN in the surgical
specimen. Long-term follow-up is important, especially for immunosuppressed patients. The incidence of HPV related VIN is increasing
together with invasive cancer in young women throughout the world.
About 2.5%–7.0% of women no matter how treated for vulvar intraepithelial neoplasia (VIN) will develop invasive cancer.
26(b),33,34
In 2004, it
was decided to avoid the diagnosis of VIN 1 and combine VIN 2 and 3.
VIN 1 has histologic variability and may be an indication of acute
HPV infection. VIN 2 and 3 have a high risk of invasive cancer and
require excision. At present general population screening for VIN or
invasive cancer “… is not recommended.” (Nevertheless the vulva
should always routinely be inspected.)
32
For patients with VIN or
cancer careful periodic evaluation is recommended. It should be
kept in mind that colposcopy may be difficult because of a large
area and great variability of the vulvar lesions and that in hyperkeratinized lesions maybe topical acetic acid may take a long time to reveal
abnormalities.
VULVAR CANCER
Vulvar cancer represents 5% of female genital cancers, much less than
endometrial, ovary and cervix. About 90% of vulvar cancer is squamous cell carcinoma, originating from the keratinized skin. More
than 20% of vulvar intraepithelial neoplasia (VIN) is associated with
human papilloma virus (HPV) (usually younger women). Vulvar cancer usually occurs in postmenopausal women with a mean age of 65;
however, the age of the patients may be going down to 55.
138 A Altchek
The risk factors include smoking, vulvar dystrophy (lichen sclerosus) and vulvar or cervical intraepithelial neoplasia, HPV infection,
immunodeficiency and previous cervical cancer. Although the incidence of vulvar intraepithelial neoplasia (VIN) is increasing in young
women, earlier detection and treatment keeps the incidence of vulvar
cancer stable. The usual clinical picture is a unifocal vulvar plaque,
ulcer or fleshy, nodular, warty mass on the labia majora. About 5% are
multifocal. There may be a synchronous secondary CIN in 20% of
cases.
33
The symptoms include (1) pruritus, especially with lichen sclerosus or squamous cell hyperplasia and (2) vulvar bleeding or discharge. Some are asymptomatic.
29
Biospy is essential and best done from the center of the lesion. It
should include some surrounding skin, underlying dermis and underlying connective tissue to determine the depth of stromal invasion. If
there is no gross lesion, a suspicious colposcopy (done with 5% acetic
acid which shows acetowhite areas with abnormal blood vessels) must
be biopsied. The differential diagnosis includes seborrheic keratosis,
lichen sclerosus, other dermatoses, condyloma acuminata, epidermal
inclusion cysts, lentigo, hidradenoma, acrochordons and Bartholinitis.
If these apparent conditions do not respond to treatment biopsy
should be considered.
Over 90% of vulvar cancer is squamous cell carcinoma which is
usually located on the labia or vestibule. There are two types:
1. The more common type is the differentiated, keratinizing, sim-
plex type, occurring in older women, not associated with HPV
but rather with chronic dystrophies.
2. Less commonly, the warty Bowenoid type is associated with HPV
16, 18 and 33, and occurs in younger women. The risk factors
are those of HPV infection (early age at first sexual activity, multiple sex partners, HIV and smoking). These cancers usually are
found in early stages.
32,33
Some high grade VIN and VAIN may be monoclonal from CIN 3 or
cervical cancer.
Early Diagnosis of Cervical, Vaginal and Vulvar Cancer 139
Other vulvar cancers are:
1. Malignant melanoma, the second most common, causing 5% of
primary vulvar neoplasms and 3%–7% of all melanomas. It usually present in postmenopausal white women with a median age
of 68 (range 10–99). Other skin melanomas usually develop
before age 45. It is usually pigmented, arising de novo on the clitoris
or labia minora. It can also develop from junctional or compound
nevi.
2. Verrucous carcinoma is a variant of squamous cell cancer.
3. Basal cell carcinoma represents 2% of vulvar malignancies and
usually presents in white women, is locally invasive and often
associated with previous or simultaneous malignancy elsewhere.
4. Soft tissue sarcoma causes 1%–2% of vulvar malignancy.
5. Extramammary Paget’s disease represents less than 1% of vulvar
malignancies and is usually found in white women in their 60th
and 70th decades. It usually causes pruritus, is multifocal, well
demarcated and eczematoid. Invasive adenocarcinoma may be
found in or underneath the lesion in 4%–17% of cases. There may
also be a synchronous neoplasia in another site in 20%–30% of
cases.
6. Bartholin gland adenocarcinoma is rare, involving patients with a
median age of 57 (when inflammatory disease does not usually
occur). It presents as a solid mass with deep infiltration and
metastasizes readily. In women over 40, any mass in the
Bartholin area should be biopsied.
26(b)
Practical Clinical Evaluation
A basic evaluation of the vulva was published in “Vulvar Diseases” in
1983.
35
Heading the list of diagnostic equipment is well-trained eyes!
Inspect the intertriginous area between the vulva and the thighs,
the skin of the hairy areas, of the mons and labia majora, the interlabial sulci, lateral and medial surface of the labia minora, the prepuce
and glans, and the vestibule up to the hymenal ring. The colposcope
is of relatively little value in the initial examination because it would
140 A Altchek
take too much time. A simple 2x or 4x magnifying glass at least
three inches in diameter is excellent together with good lighting.
A circular fluorescent light surrounding a large round magnifying lens
is recommended.
A color photographic record of serial observation is very helpful
especially when following an untreated patient with carcinoma in situ,
vulvar dystrophies over a long time and to evaluate the effect of therapy on a lesion. The toluidine blue test is recommended. It is a
nuclear stain. Diluted acetic acid bleaches any dye not bound to the
nucleus. With normal skin keratin layer there are no surface nuclei and
the dye is washed away. Nuclei are present on the surface in ulcers and
parakeratosis representing an abnormality of squamous cell maturation when nucleated squames are present in the top epithelial layer.
Parakeratosis may also be present in benign conditions with rapid cell
turnover such as condylomata acuminata. Acetic acid by itself dehydrates cells so that area of increased density and atypia becomes white
and opaque.
The skin must be clean when doing the test. One percent aqueous toluidine blue is applied with a large cotton swab and allowed
to dry for 1 to 2 minutes. Then it is rinsed with 1% aqueous acetic
acid. The skin is then examined with magnification and good light.
Most early squamous neoplasms have a surface layer of hyperkeratosis or parakeratosis. The latter is detected by the stain. The
vagina and the vestibule have non-keratinizing squamous epithelium; the outer layer containing nucleated squamous cells will stain
positively with Lugol solution. Pap smear cytology of the vulva is
not feasible.
35
Gynecologists and most physicians are somewhat reluctant to
managing vulvar problems. We were sparingly taught about it in medical school and during training as house doctors we were only briefly
lectured on sexually transmitted diseases and the vulva. (We never
learned about doing biopsies.) Even dermatologists are not well
versed in vulvar problems. They rarely inspect the vulva and are
taught that local factors (heat, humidity, friction) change the appearance of dermatoses such as psoriasis. Assuming that the gynecologist
knows how to do it, in general one never regrets doing a biopsy but
Early Diagnosis of Cervical, Vaginal and Vulvar Cancer 141
may often regret not doing it. Visual clinical diagnosis is often difficult. Failure of therapy is an appropriate reason to perform a biopsy.
Vulvar biopsies should be done liberally. Gynecologists should do
more but have limited experience. It should be done for difficult
diagnoses of benign conditions as well as to rule out malignancy,
especially with hyperpigmented or exophytic lesions, changes in
blood vessels appearance, or lesions which persist despite therapy.
Before injecting local anesthesia with a 1 ml tuberculin syringe and
fine #25 gauge needle, topical EMLA cream is used to numb the
area.
32
Another topical is 4% liposomal cream or lidocaine-prilocaine
which, however, take longer to act.
34
The standard vulvar “punch”
biopsy is the Keyes 3 mm–5 mm instrument (Fig. 3) which resembles a “cork borer” and operates by twisting at a right angle to the
skin surface. The entire thickness of the skin is bored out to check
for invasion. The base is cut with fine scissors, the specimen is lifted
with a fine forceps and placed on dry blotting paper for a moment to
become adherent and orient the sectioning and then placed in a preservative — fixing solution and send to a dermato-pathologist or
gynecologic pathologist.
32
142 A Altchek
Fig. 3 The standard Keyes punch biopsy. It is a “cork borer” device which is
rotated or twisted to the appropriate depth. The 3 mm–5 mm width is usually used.
Biopsies of ulcers are done at the edge, and for hyperpigmented
areas in the widest part of the lesion. If there is suspicion of early vulvar squamous cell carcinoma, multiple biopsies are indicated because
different areas may have different depths of invasion. If there is a palpable tumor, biopsies should include the center and surrounding
area.
36
Ethyl chloride or other refrigerant spray is used for momentary local skin anesthesia but it is not used on the vestibule because
its mucocutaneous surface is very sensitive. The biopsy site is
cleansed with an alcohol wipe. The usual local anesthesia is 2% lidocaine (Xylocaine) injected with a 30-gauge needle, with or without
epinephrine. With the latter it takes longer for the anesthetic to act
but it lasts longer and improves hemostasis. The tissue to be biopsied
is compressed between the thumb and index finger of the surgeon’s
hand while the other dominant hand rotates the Keyes punch into
the subcutaneous fat. Monsel’s solution or silver nitrate stick is used
for hemostasis.
VIN lesions have usually a raised surface. About 2/3 retain 1%
toluidine blue vital stain after being decolorized with 1% acetic acid.
About 1/3 are pigmented and dark, but some are pink, white-gray or
red. They may be macular, popular, single or multiple or confluent.
There may be pruritus. They may also develop in the perianal skin and
anal canal. Vulvar invasive cancer usually occurs on the labia majora or
minora, is usually single with a papillomatous appearance or endophytic and ulcerated. Lichen sclerosus is a chronic inflammatory dermatosis with lymphocytic infiltration and fibrosis of the stroma and
probably related to autoimmunity.
37
It may occur in one out of 30
women over 65 years old.
About 20% of lichen sclerosus (LS) occurs in prepubertal children. There is no association with malignancy in the child. The risk of
vulvar and perianal cancer developing in elderly women with lichen
sclerosus increases with age, from 2.0 to 25 per 100,000 at age 75. It
is thought that squamous cell carcinoma of the vulva (SCCV) may
present ten years after the onset of lichen sclerosus. Recurrent or metachronous SCCV in lichen sclerosus is suggestive of a “field effect”.
Most vulvar cancers in older women develop from differentiated VIN
and are not related to HPV. The young women with HPV-associated
Early Diagnosis of Cervical, Vaginal and Vulvar Cancer 143
VIN have an undifferentiated VIN which may resolve without treatment or infrequently progresses to SCCV.
The older women with long-term chronic inflammation from
lichen sclerosus or lichen simplex chronicus are at risk to develop
SCCV.
Recommendations for following women with lichen sclerosus of
the vulva:
1. Careful observation if there is difficulty in controlling symptoms
or there is localized thickening of the skin.
2. Careful observation of women with previously treated vulvar
squamous cell carcinoma associated with lichen sclerosus or vulvar intraepithelial neoplasia (VIN).
3. Careful observation if the biopsy is not positively diagnostic for
differentiated VIN.
Vulvar biopsy or excision should be done liberally of any suspicious area.
There is a small risk that years after surgical construction of a
vagina from split-thickness skin graft or a segment of ileum or colon,
the neovagina may develop carcinoma in situ or squamous cell inva-
sive carcinoma in the former and adenocarcinoma in the latter. The
risk for neoplasia is increased after X-ray treatment or chronic treatment with podophyllin or with cauterization.
38
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