Vulval Dystrophies
The vulva is the part of the female genital tract located between the genitocrural folds laterally, the mons pubis anteriorly, and the anus posteriorly.The vulva comprises the: Labia minora, Labia majora, Clitoris, Vaginal orifice, Vestibule, Skene ducts, Hymen, Urinary meatus.
Embryologically: it is the result of the junction of the cloacal endoderm, urogenital ectoderm, and paramesonephric mesodermal layers.
Different epithelia, from keratinized squamous epithelium to squamous mucosa, cover the vulva. The labia minora are rich with sebaceous glands but have few sweat glands and no hair follicles.
The word dystrophy is derived from the Greek words for 'poor nutrition'. Is a degeneration of the vulvar tissue. It occurs in women who are past menopause.
Types:
Atrophic Dystrophy: In young women this is termed lichen sclerosus et atrophicus and this is intensely itchy.
In older women it is termed senile vulvitis and it should not be itchy.
Characteristically the vulva looks pale red and shiny but as elastic tissue replaced by collagen it becomes flat, white and shiny.
Hypertrophic Dystrophy = Squamous cell hyperplasia
Red thickened skin with exaggerated skin folds. There are white patches of macerated horny skin in moist areas.
Mixed Dystrophy
Contains areas of both atrophic and hypertrophic dystrophy.
Dysplasia - Vulval Intra-epithelial Dysplasia = Cellular Atypia
Atypia is associated with HYPERLINK "http://www.mcevoy.demon.co.uk/Medicine/Pathology/Microbiology/Viruses/HPV.html" HPV infection. Up to 10% of these progresses to HYPERLINK "http://www.mcevoy.demon.co.uk/Medicine/Pathology/Oncology/Gynae/Vulval.html" vulval carcinoma.Degrees of dysplasia categorized, including VIN (vulval intra-epithelial neoplasia).
This histological diagnosis depends on
degree of disorder of basal cells of epithelium
atypical activity
lack of maturation
nuclear pleomorphism, bizarre mitotic figures
thickened Malpighian layer (rete peg layer) with elongation of rete pegs
abnormal shape of rete pegs with denticulate processes
hyalinised sub-epithelial layer
loss of elastic fibres (absent)
Areas of atypia need local excision or laser vaporization.
Other classification:
Thick lesions, Thin skin.
The thickened type of vulval dystrophy is usually caused by irritation. It can develop at any age. itching or burning in the vulvar area. white, thickened surface with some cracking. Bleeding may also occur.
Thin skin vulval dystrophy is mostly found in menopausal women. Itching and pain during sex are often the first symptoms.
Benign vulval diseases:
Include infectious disorders
Non-neoplastic epithelial disorders
Benign tumors, hamartomas and cysts
Congenital malformations and vulval atrophy.
Vulval dystrophies were originally referred to as non neoplastic epithelial disorders. According to the classification adopted by the International Society for the Study of Vulval Disease in 1987.
-non-neoplastic epithelial disorders:
Classification:
a-non-neoplastic disorders: Lichen sclerosis, squamous cell hyperplasia, other dermatoses
b-vulval intraepithelial neoplasia (VIN): Squamous VIN, non-squamous VIN, pagets disease.
The most common symptoms are:
dry, reddened areas in the vulva
itchy vulva
white or thickened areas of the vulva
shiny skin around the vulva
pain during sex
Shrinkage of the labia and vaginal opening.
Diagnosis: biopsy of the vulvar tissue to rule out cancer. Check for signs of infection.
Treatment:
Depends on the cause
Do not use perfumed laundry detergent or fabric softener
Do not use tampons or scented toilet paper
Creams will relieve the symptoms.
Keep the area dry
Wear lose clothing and
Stop using vaginal sprays
Dont use perfumed soap
Lichen sclerosus:
The etiology unknown.
It appears as a white, usually symmetric, lesion with a wrinkled, parchmentlike surface and causes atrophy of the labia minora pudendi.
Pathologic examination shows thinning of squamous epithelium, loss of rete pegs, and deep dermal inflammatory cells. Because of loss of elastic fibers in layers beneath the epithelium, the lesion can actually appear thickened. Over time, the introitus becomes narrowed and appears fibrotic.
Diagnosis is based on the histologic finding of thinning of the epithelium
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treatment of lichen sclerosus:
application of 2% testosterone to the vulva twice daily for 6 to 12 weeks.
Some patients have complete remission with this method.
Side effects of testosterone include clitoral hypertrophy, hirsutism, and increased libido, and in patients who cannot tolerate these, progesterone may be used. Another treatment option is topical corticosteroid, which has the additional benefit in patients with intense pruritus of providing immediate relief.
Oral retinoids have been used. However, because of side effects these agents should be used cautiously and only when other methods have failed
Squamous cell hyperplasia:
Like lichen sclerosus, squamous cell hyperplasia is a white lesion.
histologic findings are the opposite of those of lichen sclerosus, consisting of thickening of the squamous epithelium, elongation of rete pegs (acanthosis), and hyperkeratosis. Inflammatory cells are present throughout the dermis. Squamous cell hyperplasia is believed to be a reaction to chronic pruritus from a variety of stimuli (e.g., recurrent candidiasis, eczema, chemical irritation from soaps).
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Pruritus may be relieved by removing all possible irritants
applying the scabicide crotamiton (Eurax) cream
topical steroid suitable for long-term use, traditionally.
However, if 1% hydrocortisone effectively relieves pruritus, it may be a better choice for long-term treatment because it is less potent.
Surgical intervention for squamous cell hyperplasia (as well as for lichen sclerosus) should be considered cautiously, because the recurrence rate is about 40% to 50%. Squamous cell hyperplasia may also be a later stage in progression of lichen sclerosus. The combination of squamous cell hyperplasia and lichen sclerosus (formerly called mixed dystrophy) is found in 15% of biopsy samples from white lesions.
Malignant potential of lichen sclerosus and squamous cell hyperplasia. Vulvar carcinoma develops in about 1% to 5% of patients with these disorders and in a higher percentage if cellular atypia is present.
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Therefore, it is important to monitor patients with lichen sclerosus and squamous cell hyperplasia at regular intervals and to take biopsy samples of any changes in lesions.
colposcopic examination should be considered for biopsy.
Other non-neoplastic dermatoses:
--Psoriasis is a multifocal disease that may affect vulvar tissue as well as skin of the joints, knees, and scalp.
--Seborrheic dermatitis, another multifocal disease of the sebaceous glands commonly affecting the scalp, may affect the labia majora pudendi only.
--Tinea cruris begins as raised, sharply demarcated, red lesions on the thighs and can spread to the labia.
These lesions are best diagnosed by biopsy, which is easily accomplished by punch biopsy with local anesthetic.
Paget's disease A patient with Paget's disease of the vulva (adenocarcinoma in situ) may present with pruritus and weeping or bleeding of the lesion. The lesion appears to have an eczematous or velvet like surface. Typical histologic appearances of Paget's disease.
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Wide local excision is recommended because the margins of Paget's disease often extend beyond what is seen on gross examination, which explains the high incidence of recurrence. Because of the 20% incidence of underlying adenocarcinoma, the dermis should be removed for accurate diagnosis. Thorough evaluation of the cervix, colon, bladder, gallbladder, and breasts is necessary when Paget's disease of the vulva is found; there is a 30% incidence of concomitant primary carcinoma in these locations
Vulval intraepithelial neoplasia (VIN)
The term VIN refers to particular changes that can occur in the skin that covers the vulva. VIN is not cancer and in some women it disappears without treatment. it is referred to as a pre-malignant condition. Although VIN used to be quite uncommon, it is now being recognised and diagnosed more frequently. It can affect women of any age from the 20s onwards, but is more common in women over 50. VIN is often divided into three stages VIN 1, 2 and 3 which describe how deeply the abnormal cells have gone into the surface layer of the vulva. Most women are diagnosed with VIN 3.
VIN 1 Only one-third of the thickness of the surface layer of the vulva is affected.
VIN 2 Two thirds of the thickness of the surface layer of the vulva is affected.
VIN 3 The full thickness of the surface layer of the vulva is affected.
Causes:
is associated with an infection in the skin of the vulva by HYPERLINK "http://www.cancerbacup.org.uk/Cancertype/Cervix/Pre-cancerousconditions/HumanpapillomavirusHPV" \t "_top" human papilloma virus (HPV). There are over 100 types of the virus and the most common types can cause warts on the skin of the hands or verrucas on the feet. Some types can affect the genital area including the cervix, vulva and anus.
HPV is so common that most sexually active women will be exposed to it at some time in their life. In most women, their bodies' own immune system will get rid of the HPV naturally.
Infection with HPV on its own will not cause VIN. Other factors that depress the bodys immune system may also need to be present.
The signs and symptoms of VIN vary and may include some or all of the following:
itching and soreness in the vulval area
burning sensation.
one or more areas of reddened or discoloured skin in the vulval area
raised areas of skin that can vary in size
A warty appearance of the skin.
Rarely, no symptoms.
examine the vulval area and may use a colposcope which magnifies the area so that any changes can be clearly seen.
biopsy. A local anaesthetic cream is usually used. to numb the vulval area before the biopsy is taken, and it takes 20 minutes to work.
The doctor may also examine the cervix and vaginal walls to look for any abnormalities in the cells.
Treatment:
Mild cases, treatment may not be needed, but you will need to have the area checked regularly by your doctor. Treatment may be needed for VIN 2 or 3. The type of treatment that is most appropriate for you will depend on:
how abnormal the cells are
the size of the affected area
The estimated risk of the area developing into cancer.
Surgery
local surgical excision.
Rarely, if the affected areas are large or there are several areas, a vulvectomy may be done, in which the whole vulva is removed. Sometimes the vulval tissue can be replaced with skin taken from another part of the body (a procedure known as a skin graft).
Laser excision treatment may be used for areas in which it is difficult to remove the VIN, such as around the clitoris.
Diathermy: A tiny electrical current is passed through a probe, which is used to cut out the affected areas. colposcope is used to identify the abnormal areas.
Medical treatments
Steroid cream. It reduces inflammation and can control symptoms, but does not cure the condition.
Follow-up: follow up is mandatory.
CANCER OF THE VAGINA:
Cancer of the vagina is rare, representing about 1-2% of gynecological cancers. It is almost always a HYPERLINK "http://www.gyncancer.com/glossary.html" \l "squamous" squamous cell cancer. The exception is an HYPERLINK "http://www.gyncancer.com/glossary.html" \l "adeno" adenocarcinoma that occurs in women who were exposed to DES (diethylstilbestrol) in-utero. One of the reasons that it is rare is that cancers of the vagina that also involve the vulva are considered to be vulvar cancers; if it involves the cervix it is considered to be a cervical cancer.
There is a premalignant phase for squamous cell cancer of the vagina similar to the squamous cell cancers of the vulva and cervix.
The premalignant phase is vaginal HYPERLINK "http://www.gyncancer.com/glossary.html" \l "intra" intraepithelial neoplasia grade III (VaIN III). This is also sometimes called carcinoma-in-situ. The premalignant phase is usually asymptomatic but can be detected by routine Pap test. It can be treated by excision, laser evaporation or occasionally by a chemotherapy type of vaginal cream. There is no recognized cause for vaginal HYPERLINK "http://www.gyncancer.com/glossary.html" \l "squamous" squamous dysplasias or cancer, although it is similar to the squamous dysplasias of the cervix.
Pathology:
Squamous cell carcinoma may be ulcerative or exophytic, It usually involves the posterior wall of the upper third of the vagina, but may be multicentric.
Lymphatic drainage of the vagina consists of meshwork in the mucosa and sub mucosa, the upper third drainage is as cervical cancer, the lower third as vulvar cancer, the middle third may metastasise to inguinal lymph nodes or to the deep pelvic lymph nodes.
Melanoma rarely occurs in the anterior surface and lower half of the vagina.
Sarcoma of the vagina occurs in children under 5 years of age, rabdomyosarcoma in the upper anterior vaginal wall called sarcoma botryoides.
Clear cell adenocarcinoma arise in conjunction with vaginal adenosis in women who were exposed to DES (diethylstilbestrol) in-utero. Adenocarcinomas of the vagina associated with DES exposure were more frequent in the 1970's and 1980's. DES, diethylstilbestrol, is a synthetic estrogen hormone that was given to pregnant women in the 1950's to try to prevent miscarriages. The female infants of these women, who took the DES, had some developmental abnormalities of their vaginas and cervices that put them at risk for developing a particular type of adenocarcinoma called a clear cell carcinoma.
Metastatic adenocarcinoma to the vagina from adjacent or distant organs
Clinical findings:
Vaginal cancer is often asymptomatic. May cause symptoms of abnormal bleeding, postmenopausal bleeding and foul discharge. Bleeding after intercourse is a symptom of cancer of the vagina as well as cancer of the cervix.
Diagnosis of primary vaginal cancer is established after eliminating other sources of malignancies. History, examination, cytological examination of the cervix, endometrial biopsy, colposcopy and biopsy
Staging:
It is clinical not surgical
FIGO staging:
Stage 0 carcinoma in situ, intra epithelial carcinoma
I vaginal mucosa
II to sub vaginal tissue but not to pelvic wall
III to pelvic wall
IV beyond the true pelvis or to rectum or bladder or distant metastasis
Treatment:
Pre treatment evaluation, include chest x-ray, IVU, cystoscopy, sigmoidoscopy, CT-scan.
Invasive squamous cell cancer of the vagina is usually treated by radiation. Although it can be removed surgically, the bladder or rectum or both would have to be removed with it in order to get a good margin around the cancer. As a general rule squamous cell cancers of the vagina do not spread early, so they are usually localized to the pelvic area on diagnosis. This is a good situation for radiation since that area can easily be irradiated and radioactive material can easily be placed into the vagina next to the cancer. The prognosis for localized disease is good.
The type of surgery and radiotherapy depend on the site of the tumor:
In the upper vagina treat as ca cervix.
In lower vagina as cancer of the vulva.
Radiation used is external pelvic irradiation followed by intracavitary.
A very small tumor may be treated by vaginectomy.
Sarcoma botryoides is treated by chemotherapy plus radiotherapy.
Melanomas treated with radiation and or surgery.
Women who have had a hysterectomy for non cancer problems should still have a Pap test every several years. They can still develop malignant and pre-malignant vaginal changes.
Prognosis:
5 year survival rate is 77% in stage I
Melanomas are very malignant
Sarcomas associated with recurrence
Vulval Neoplasia
Incidence: representing about 5% of all gynecologic cancers, and only about 1% of all female cancers in general. There are about 3,000 new cases in reported annually in the US, but the incidence has been rising over the past several years. The cause for the growing number of cases is not well-understood.
Epidemiology: Predominantly a disease of older women, but occasional cases in teenagers and not infrequent in 20-40 yr old age group.
Vulvar cancer is most common in women over 50 years of age, with a median age of 65 75 years old at diagnosis.
Types
85% are squamous cell carcinoma
10% are melanoma
5% are various rarities:
HYPERLINK "http://www.cancerhelp.org.uk/help/default.asp?page=4958" \l "adeno" Adenocarcinoma: Adenocarcinomas of the vulva are also rare, but can develop from glands such as the Bartholin's glands at the vaginal opening.
HYPERLINK "http://www.cancerhelp.org.uk/help/default.asp?page=4958" \l "ver" Verrucous carcinoma
HYPERLINK "http://www.cancerhelp.org.uk/help/default.asp?page=4958" \l "sarc" Sarcomas
Site:
About 70% of vulvar cancers involve the labia (mainly the labia majora).
15% - 20% involve the clitoris, and another 15% - 20% involve the perineum, which is the area of sensitive skin located between the vagina and the anus.
In about 5% of cases, the cancer is present at more than one site.
Etiology
Risk factors
In addition to older age, vulvar cancer has been associated with a history of:
infection with high-risk HPV types, (i.e.: HPV 16,18,31)
multiple sexual partners/ sexually transmitted diseases
cervical cancer
immunodeficiency
presence of chronic vaginal and vulvar irritation
smoking
Cancer predominantly arises in areas of vulval intra-epithelial neoplasia.
HPV is thought to be the precursor.
Clinical Features & Presentation
Pre-malignant lesion = Leukoplakia
characterized by white patches around vulva due to skin thickening & hypertrophy
it is itchy
biopsy
Malignancies usually present with
lump (hard nodule)
ulcer with sloughing base & raised edges (indurated ulcer with everted edge strongly suggests carcinoma)
pain and bleeding from vulva
The size of the lesion often correlates with its progression; 50% present with lymph node involvement already present. 50% arise on one labium majus, 25% arise on a labium minus. Some cases have multiple affected areas. Young women often present with malignant change in a vulval condyloma. May have had persistent vulval itching for months or years.
The classic symptom is vulvar itching (pruritus), reported in almost 90% of the women with vulvar cancer. There can also be associated pain, bleeding, vaginal discharge, and/or painful urination (dysuria). Also, women often develop a visible vulvar mass: the squamous cell subtype can look like elevated white, pink or red bumps, while vulvar melanoma characteristically presents as a colored, ulcerated growth. There can be portions of the tumor that look sore and scaly or cauliflower-like (similar to HPV-related warts)
Diagnoses
thorough gynecological examination should be performed using a colposcope (special magnifying instrument) for better visualization. Any suspicious areas should be tested by applying a dilute solution of acetic acid to the region; abnormal areas typically turn white, making them easier to identify. Also, any abnormal-appearing area should be sampled along with surrounding normal tissue using a thick wedge-shaped biopsy (usually under local anesthesia). If the area is small, it should be entirely removed in the process of the biopsy (so-called excisional biopsy). Chest x-ray and CT scan of the abdomen/pelvis can be done to look for disease spread to lymph nodes and/or distant organs. If spread to bladder or rectum is suspected, endoscopy (cystoscopy and proctoscopy, respectively) should be performed
Pathology
Progression of vulval intra-epithelial neoplasia (VIN) is a pre-invasive phase very like CIN and similarly associated with HPV infection - types 16, 18, 33.
Even very early stages of invasion through basement membrane are associated with metastasis. This tumour spreads rapidly to inguinal lymph nodes by embolisation within lymphatic (rather than permeation). From there it passes to the femoral and pelvic nodes.
Staging
Unlike vaginal cancer, which is typically clinically staged, the International Federation of Gynecology and Obstetrics (FIGO) uses a surgical staging system for vulvar cancer. This means that the stage of the cancer is not actually determined until after surgery is performed and the specimen is examined by the pathologist. Like vaginal cancer, vulvar cancer has five main FIGO stages (0, I, II, III, and IV). They are:
Stage 0 - Vulvar intraepithelial neoplasia
Stage I - cancer is limited to the vulva and perineum, and measures < 2 cm in size
Stage II - cancer is limited to the vulva and perineum, but tumor is > 2 cm in size
Stage III - cancer spread to vagina, urethra, anus, and/or the lymph nodes in the groin
Stage IV - cancer spread to bladder, bowel, pelvic bone, pelvic lymph nodes, and/or other parts of the body
T N M STAGING OF VULVAR CANCERS
T-0 pre-malignant change
T-1A a cancer less than 2.0cm in diameter and less than 1.0mm in depth of invasion T-1B a cancer less than 2.0cm in diameter but greater than 1.0mm in invasion
T-2 greater than 2.0 centimeters in diameter
T-3 involves vagina, urethra or anus
T-4 involves bladder, rectum or pelvic bone
N-0 no lymph nodes involved N-1 lymph node metastases to one groin N-2 lymph node metastases to both groins
M-0 no distant metastases M-1 any distant metastases
Vulvar cancer treatment:
Treatment
Basis of treatment is excision
small non-invasive VIN may be treated with laser (esp. good for small multiple lesions) or modified vulvectomy NB large lesions cannot be treated with the laser as it is too painful
simple vulvectomy + prophylactic post-op radiotherapy to inguinal lymph nodes for small vulval carcinomas of < 2cm
radical vulvectomy if carcinoma > 2cm + lymphadenectomy (of either just inguinal or in more advanced disease inguinal, femoral and pelvic lymph nodes
Wherever possible vulvectomy is avoided because it is so traumatic and psychologically distressing and a local excision operation with 5mm borders is performed.
Topical 5-fluorouracil cream is useful in 50% cases but patient tolerance is low as the cream causes ulceration. In frail elderly patients palliative care and even palliative surgery is very important as the late stages of vulval carcinoma have serious morbidity.
Surgery, radiation therapy and chemotherapy are the main treatment options, and are typically used in various combinations. As with many cancers, the optimal treatment depends on the disease stage and patient factors such as age and other medical conditions.
Treatment options by stage are as follows:
Stage 0
Wide local excision, laser surgery, or a combination of both
Skinning vulvectomy
Chemotherapy ointment
Stage I
Wide local excision
Radical local excision with removal of all nearby groin/ upper thigh lymph nodes
Radical vulvectomy and removal of nearby groin lymph nodes (and sometimes lymph nodes on opposite side of the body)
Radiation therapy alone (in selected patients)
Stage II
Radical vulvectomy and removal of groin lymph nodes on both sides of the body, plus postoperative radiation therapy to the pelvis if lymph nodes are positive for cancer
Radiation therapy alone (in selected patients)
Stage III
Radical vulvectomy and removal of groin/ upper thigh lymph nodes on both sides of the body, plus postoperative radiation therapy to the pelvis and groin if lymph nodes are positive for cancer or if the primary vulvar tumor is very large
Radiation therapy and chemotherapy, followed by radical vulvectomy and removal of lymph node removal of lymph nodes on both sides of the body.
Radiation therapy (in selected patients) with or without chemotherapy.
Stage IV
Pelvic exenteration, which entails radical vulvectomy and removal of the lower colon, rectum, or bladder (depending on where the cancer has spread), as well as the uterus, cervix, and vagina
Radical vulvectomy followed by radiation therapy
Radiation therapy followed by radical vulvectomy
Radiation therapy (in selected patients) with or without chemotherapy, and possibly following surgery
Complications
Wound breakdown (necrosis) and infection are common problems.
Chronic lymphoedema of lower limbs occurs due to node dissection in ~ 20%.
Prognosis
In early stage disease, when lymph nodes are not involved, the overall 5-year survival rate is 90%.
Once cancer has spread to the lymph nodes, the overall 5-year survival rate drops to 50% - 70%.