Vulvar cancer is a malignant, invasive growth in the vulva, or the outer portion of the female genitals. The disease accounts for only 0.6% of cancer diagnoses but 5% of gynecologic cancers in the United States. The labia majora are the most common site involved representing about 50% of all cases, followed by the labia minora. The clitoris and Bartholin glands may rarely be involved. Vulvar cancer is separate from vulvar intraepithelial neoplasia (VIN), a superficial lesion of the epithelium that has not invaded the basement membrane—or a pre-cancer. VIN may progress to carcinoma-in-situ and, eventually, squamous cell cancer.
According to the American Cancer Society, in 2014, there were about 4,850 new cases of vulvar cancer and 1,030 deaths from the disease. In the United States, five-year survival rates for vulvar cancer are around 70%.
Squamous cell carcinoma
Most vulvar cancer (approximately 90%) is squamous cell carcinoma, which originates from epidermal squamous cells, the most common type of skin cell. Carcinoma-in-situ is a precursor lesion of squamous cell cancer that does not invade through the basement membrane. While this type of lesion is more common with older age, young women with risk factors may also be affected. In the elderly, complications may occur due to the presence of other medical conditions.
Squamous lesions tend to arise in a single site and occur most commonly in the vestibule. They grow by local extension and spread via the local lymph system. The lymphatics of the labia drain to the upper vulva and mons, then to both superficial and deep inguinal and femoral lymph nodes. The last deep femoral node is called the Cloquet’s node. Spread beyond this node reaches the lymph nodes of the pelvis. The tumor may also invade nearby organs such as the vagina, urethra, and rectum and spread via their lymphatics.
A verrucous carcinoma of the vulva is a rare subtype of squamous cell cancer and tends to appear as a slowly growing wart. Verrucous vulvar cancers tend to have good overall prognoses.
Melanoma is the second most common type of vulvar cancer and causes 8–10% of vulvar cancer cases. These lesions arise from melanocytes, the cells that give skin color and are most common in Caucasian women 50–80 years old. Melanoma of the vulva behaves like melanoma in any other location and may affect a much younger population.
There are three distinct types of vulvar melanoma: superficial spreading, nodular, and acral lentigous melanoma. Vulvar melanomas are unique in that they are microstaged with the Chung, Clark and/or Breslow systems, which specify stage and tumor depth of invasion. In general, they come with a high risk of metastasis and carry a poor overall prognosis.
Basal cell carcinoma
Basal cell carcinoma makes up about 1–2% of vulvar cancer. These tend to be slow-growing lesions on the labia majora but can occur anywhere on the vulva. Their behavior is similar to basal cell cancers in other locations. They often grow locally and have low risk for deep invasion or metastasis.
Treatment involves excision, but these lesions have a tendency to recur if not completely removed.
Bartholin gland carcinoma
Main article: Bartholin gland carcinoma
The Bartholin gland is a rare malignancy and usually occurs in women in their mid-sixties.
Other lesions, such as adenocarcinoma (of the Bartholin glands, for example) or sarcoma, may cause vulvar cancer as well. Erythroplasia of Queyrat, typically found on the penis may affect the vulvae in females.
Although the exact cause of vulvar cancer isn't known, certain factors appear to increase your risk of the disease.
- Increasing age
- Exposure to human papillomavirus
- Being infected with the human immunodeficiency virus (HIV)
- Having a history of precancerous conditions of the vulva
- Having a skin condition involving the vulva
Signs and symptoms
Many malignancies can develop in vulvar structures. The signs and symptoms can include:
- Itching, burn, or bleeding on the vulva that does not go away.
- Changes in the color of the skin of the vulva, so that it looks redder or whiter than is normal.
- Skin changes in the vulva, including what looks like a rash or warts.
- Sores, lumps, or ulcers on the vulva that do not go away.
- Pain in the pelvis, especially during urination or sex.
Typically, a lesion presents in the form of a lump or ulcer on the labia majora and may be associated with itching, irritation, local bleeding or discharge, in addition to pain with urination or pain during sexual intercourse. The labia minora, clitoris, perineum and mons are less commonly involved. Due to modesty or embarrassment, patients may put off seeing a doctor.
Melanomas tend to display the typical asymmetry, uneven borders and dark discoloration as do melanomas in other parts of the body.
Adenocarcinoma can arise from the Bartholin gland and present with a painful lump.
Some conditions such as lichen sclerosus, squamous dysplasia or chronic vulvar itching may precede cancer. In younger women affected with vulvar cancer, risk factors include low socioeconomic status, multiple sexual partners, cigarette use and cervical cancer. Patients that are infected with HIV tend to be more susceptible to vulvar cancer as well. Human papillomavirus (HPV) infection is associated with vulvar cancer.
Examination of the vulva is part of the gynecologic evaluation and should include a thorough inspection of the perineum, including areas around the clitoris and urethra, and palpation of the Bartholin's glands. The exam may reveal an ulceration, lump or mass in the vulvar region. Any suspicious lesions need to be sampled, or biopsied. This can generally be done in an office setting under local anesthesia. Small lesions can be removed under local anesthesia as well. Additional evaluation may include a chest X-ray, an intravenous pyelogram, cystoscopy or proctoscopy, as well as blood counts and metabolic assessment.
Other cancerous lesions in the differential diagnosis include Paget's disease of the vulva and vulvar intraepithelial neoplasia (VIN). Non-cancerous vulvar diseases include lichen sclerosus, squamous cell hyperplasia, and vulvar vestibulitis. A number of diseases cause infectious lesions including herpes genitalis, human papillomavirus, syphilis, chancroid, granuloma inguinale, and lymphogranuloma venereum.
Anatomical staging supplemented preclinical staging starting in 1988. FIGO’s revised TNM classification system uses tumor size (T), lymph node involvement (N) and presence or absence of metastasis (M) as criteria for staging. Stages I and II describe the early stages of vulvar cancer that still appear to be confined to the site of origin. Stage III cancers include greater disease extension to neighboring tissues and inguinal lymph nodes on one side. Stage IV indicates metastatic disease to inguinal nodes on both sides or distant metastases.
- Illustrations showing stages of vulvar cancer'"`UNIQ--ref-0000001B-QINU`"'
Stage 1A and 1B vulvar cancer
Staging and treatment are generally handled by an oncologist familiar with gynecologic cancer. Surgery is a mainstay of therapy depending on anatomical staging and is usually reserved for cancers that have not spread beyond the vulva. Surgery may involve a wide local excision, radical partial vulvectomy, or radical complete vulvectomy with removal of vulvar tissue, inguinal and femoral lymph nodes. In cases of early vulvar cancer, the surgery may be less extensive and consist of wide excision or a simple vulvectomy. Surgery is significantly more extensive when the cancer has spread to nearby organs such as the urethra, vagina, or rectum. Complications of surgery include wound infection, sexual dysfunction, edema and thrombosis, as well as lymphedema secondary to dissected lymph nodes.
Sentinel lymph node (SLN) dissection is the identification of the main lymph node(s) draining the tumor, with the aim of removing as few nodes as possible, decreasing the risk of adverse effects. Location of the sentinel node(s) may require the use of technetium(99m)-labeled nano-colloid, or a combination of technetium and 1% isosulfan blue dye, wherein the combination may reduce the number of women with "'missed"' groin node metastases compared with technetium only.
Radiation therapy may be used in more advanced vulvar cancer cases when disease has spread to the lymph nodes and/or pelvis. It may be performed before or after surgery. Chemotherapy is not usually used as primary treatment but may be used in advanced cases with spread to the bones, liver or lungs. It may also be given at a lower dose together with radiation therapy.
Women with vulvar cancer should have routine follow-up and exams with their oncologist, often every 3 months for the first 2–3 years after treatment. They should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival and is associated with its own side effects and financial costs.
Overall, five-year survival rates for vulvar cancer are around 78% but may be affected by individual factors including cancer stage, cancer type, patient age and general medical health. Five-year survival is greater than 90% for patients with stage I lesions but decreases to 20% when pelvic lymph nodes are involved. Lymph node involvement is the most important predictor of prognosis. Thus, early diagnosis is important.
Vulvar cancer causes less than 1% of all cancer cases and deaths but around 6% of all gynecologic cancers diagnosed in the UK. Around 1,200 women were diagnosed with the disease in 2011, and 400 women died in 2012. Vulvar cancer causes about 0. 6% of all cancer cases but 5% of gynecologic cancers in the United States. About 4900 cases are diagnosed each year in the United States.
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Although the vulva only comprises a small amount of the body's surface area, it is host to a surprisingly large number of diseases and ailments. Although many vulvar conditions cause symptoms such as burning, pruritus, other discomfort, or discharge, many do not. Thus, our patients may not seek the services of a health care provider until their condition is in a relatively advanced stage. Furthermore, many vulvar cancers are ignored by health care providers until they have reached an advanced stage, which often leads to radical and extremely disfiguring surgery. An understanding of the common nonneoplastic vulvar disorders that may mimic cancer, potentially precancerous lesions, and vulvar cancer itself will arm the primary care health care provider with the information needed to manage many of these conditions and to identify those needing biopsy or referral.
The participant should be able to:
- Identify common vulvar conditions, particularly those mimicking vulvar neoplasia.
- Understand the steps in evaluating vulvar conditions.
- Identify those lesions requiring biopsy.
- Identify vulvar conditions that require potential surgical management or referral.
- Candida (yeast)
- Bacterial vaginosis (Gardnerella)
- Tinea cruris (i.e. Trichophyton rubrum)
- Sexually transmitted infections (i.e. IAPV, herpes, syphilis, LGV, chancroid)
- Parasites and Insect bites
Epithelial Disorders (Nonneoplastic)
- Lichen sclerosus
- Squamous hyperplasia
- Vulvar vestibulitis
- Lichen simplex chronicus
- Lichen planus
Raised Lesions or Masses
- Bartholin gland cysts or abscesses
- Inclusion cysts
- Other various cysts
Potentially Premalignant or Malignant
- Vulvar intraepithelial neoplasia (VIN)
- Paget's Disease
- Squamous cell carcinoma
Miscellaneous Vulvar Disorders
- Factitial dermatitis
- Genital atrophy
- Trauma (i.e. hematoma, sexual assault)
It is evident the list of possible vulvar abnormalities is exhausting. When confronted with a vulvar lesion, it is helpful to "categorize" these using a system that helps jog the memory and decreases the chance of missing a diagnosis. Therefore, this paper will focus on visible lesions of the vulva that may mimic cancer. Tips on office evaluation and biopsy techniques are discussed, as well as basic treatment strategies.
- White Lesions
- Lichen sclerosus
- Squamous cell hyperplasia
- Squamous cell carcinoma of the vulva
- Lichen sclerosus
- Red or Dark Lesions
Lichen sclerosus is a benign disorder of the vulvar epithelium that can affect women of any age group. It causes thinning of the vulvar tissue with edema and fibrosis. If untreated, the labia may fuse together, the clitoris may shrink, and the introitus may become stenotic. The skin has a white, thin, shiny, "parchment paper" appearance. Fissures may be present. Bilateral symmetry is common. Some patients are asymptomatic, while others report pruritus, painful intercourse, and anorgasmia from clitoral shrinkage. There is a familial tendency. The diagnosis is by biopsy (see description of biopsy techniques below). Pathologists identify lichen sclerosus by hyperkeratosis, edema, loss of vascularity, and loss of rete ridges. Treatment has changed somewhat over the years. Formerly, testosterone cream was used, but most experts currently use high-potency steroid creams such as clobetasol propionate 0.05% twice daily for 3 weeks, then before bed each night for a few months. This disorder may require a lifetime of treatment, including either high-potency steroids once or twice weekly, or over the counter steroids every night. Long term use of high-potency steroids is associated with erosion, fissuring, and contractures, therefore lower-potency medications should be substituted if possible for chronic therapy. Patients need annual exams and biopsy of any worsening or new lesions, as progression to cancer can occur in about 3% of these cases.
Squamous cell hyperplasia
Squamous cell hyperplasia is a common and benign vulvar condition that can look similar to other white vulvar lesions, including condyloma, VIN and carcinoma. The skin is typically white or off-white, with focal lesions. The cause is unknown, but may be due to a vulvar irritant callusing thickening of the skin. Pruritus is commonly found and may bring the patient to her health care provider. Diagnosis is by biopsy. Colposcopy with acetic acid application may reveal a thickened epithelium, with possible inflammation. Biopsy yield hyperkeratosis. Treatment consists of twice daily steroids for 3 weeks, then once daily thereafter until symptoms disappear. Chronic treatment with OTC steroids is sometimes necessary. Patients should also decrease exposure to vulvar irritants, for example perfumes, dyed toilet paper, etc. Biopsy of any new or persistent lesions is advocated as 4% of these patients may develop squamous cell carcinoma of the vulva.
Vulvar leukoplakia is caused by vulvar irritation. It produces hyperkeratosis (excessive surface keratin) and creates a white, plaque-like area that is often strikingly white even without acetic acid application. While leukoplakia itself is a benign process, it may cover or be associated with an underlying VIN or carcinoma, therefore biopsy is prudent to rule out a more ominous disorder.
A complete discussion of HPV is beyond the scope of this presentation. However, from the viewpoint of a health care provider examining a patient's vulva, HPV can mimic a number of other disorders, including VIN and even vulvar cancer. Some advocate biopsy of HPV lesions before starting treatment, while others suggest simply treating the warts with standard measures. Some studies have shown that 80% or more of VIN in younger women is associated with HPV. HPV lesions on older patients, or those with associated leukoplakia or other atypical appearances, should be evaluated by biopsy and histology to rule out VIN.
Vulvar intraepithelial neoplasia is a potentially precancerous condition that can be either white, dark, or red. Excess keratin production leads to a white appearance, whereas excess melanin production leads to dark lesions. Formerly, many confusing terms existed to describe VIN, including Bowen's disease. Currently, VIN I refers to mild dysplasia, VIN II equals moderate dysplasia, and VIN III denotes severe dysplasia (also called carcinoma in situ). VIN may be focal or affect multiple sites on the vulva. Colposcopy with acetic acid may help delineate areas of VIN and make biopsy easier. As discussed previously, VIN in younger women is strongly associated with HPV (particularly types 16 and 18), and the epidemic of HPV infections has led to VIN in young women.
VIN may be asymptomatic and can come to the attention of a patient's health care provider during an annual examination. Pruritus, however, may be present, as well as a burning sensation of the vulva. Biopsy of any white, red, or dark lesion is prudent, particularly in the older patient. Progression from VIN to cancer is uncommon in younger women, but more likely in older patients. Diagnosis is by biopsy, with colposcopy and acetic acid application. Multiple areas may need biopsy. The risk for progression to cancer is actually low for VIN, particularly in younger patients, but treatment is still necessary prevent patients from disease progression. Many treatment options exist, including topical 5-fluorouracil, laser vaporization (particularly useful for with low risk of subsequent cancer), wide local excision (the usual treatment of choice), and "skinning" vulvectomy for more advanced disease. Wide local excision is often adequate, as long as margins are free of dysplasia and vulvar colposcopy with acetic acid rules out other areas of VIN.
See discussion later in this presentation.
This vulvar disorder causes generalized erythema of the vulvar skin with red or yellow-brown plaques. These lesions may be covered by a nonadherent, oily scale. Pruritus and the finding of similar extraovular lesions increases suspicion, and biopsy make the diagnosis. Seborrheic dermatitis may mimic chronic candida, psoriasis, contact dermatitis, and, if focal, VIN, although this is usually a generalized disorder of the vulva. Treatment consists of topical steroids.
About 3% of adult women have psoriasis, with approximately 20% of these women having vulvar involvement. There is a familial tendency. Vulvar disease is manifested by red or red-yellow papules in intertriginous areas, with scales that produce pinpoint bleeding when removed. These lesions may enlarge to form focal, red plaques. This condition may mimic candidiasis. Diagnosis is clinical or preferably by biopsy, and treatment consists of topical 1% hydrocortisone cream, with referral to a gynecologist or dermatologist if treatment is unsuccessful.
Lichen planus can by an intensely pruritic and painful condition that may be an autoimmune phenomenon. Small, flat, violaceous papules develop on mucous membranes, including the vulva. If untreated, intense inflammation, ulceration and vulvar damage may occur. Biopsy will confirm the diagnosis, and treatment instituted with topical steroid creams. Oral steroids may be necessary for intense pruritus.
Lentigo produces freckle-like, pigmented lesions that may be solitary or, more frequently, multifocal. This is a benign condition, but may be confused with melanoma (i.e. lentigo melanoma), therefore biopsy or excisional biopsy is necessary.
Nevi are not uncommon on the vulva, and can have a variety of color schemes, ranging from brown, brown-black, black, flesh-colored, or red. Since about 30% of melanomas arise from preexisting nevi, biopsy is mandatory for any nevus that has changed appearance, size, or color. Some advocate biopsy of all vulvar nevi, since patients are often reluctant to self-examine this area.
Paget's disease of the vulva can produce lesions that are white or red. However, an eczematoid, erythematous lesion is most common. Paget's disease produces pruritus. This condition is associated with malignancy of the vulva and other extraovular locations, such as the breasts and colon. Biopsy is mandatory, and treatment is wide local excision, although, unfortunately, local recurrence is not uncommon.
Vulvar carcinoma and melanoma:
Vulvar carcinoma is an uncommon gynecologic malignancy, representing 4-5% of all gyn tumors. Most vulvar carcinomas are squamous cell (90%) while about 5% are melanomas. Squamous carcinomas usually appear as vulvar masses of irregular and polypoid shape. Sometimes leukoplakia is present, and these lesions can be white, red, or pigmented. Vulvar cancer may appear as benign diseases such as nevi, dermatoses, or nonneoplastic conditions like squamous hyperplasia. Later-stage or advanced disease can produce a large, exophytic vulvar mass, but less advanced disease may arise as a smaller lesion. Sadly, many patients report a "sore" that has not healed for over a year before seeking medical attention. Any health care provider evaluating a vulvar lesion in a patient with a history of a non-healing sore or chronic pruritis should strongly consider biopsy, with colpgscony if necessary, or referral for biopsy. The vulva is rich in lymphatics so these cancers tend to spread to the groin (inguinal) nodes. Prognosis depends on the lesion size and extent of spread. Treatment depends on the extent of disease and anatomic location. Some lateral tumors are treated with radical wide excision, and possible ipsilateral inguinal-femoral lymphadenectomy. More extensive disease may require bilateral lymphadenectomy, and some cases require a modified radical vulvectomy, a disfiguring procedure. Thus, prevention of this disease by treating VIN, or diagnosis at an early stage, may allow the gynecologic-oncologist to treat this disease by less radical methods.
Melanoma typically appear like melanoma in other areas. It occurs mainly on the labia minora and clitoris, in white women between ages 50-80. Biopsy proves the diagnosis, and surgical excision via radical wide local excision with large margins is acceptable treatment.
Vulvar biopsy is a surprisingly easy office-based technique. Colposcopy of the vulva with acetic acid application, which can be challenging, will often help locate the optimum biopsy site. One should consider performing a biopsy for any of the following vulvar lesions:
- Any enlarging vulva lesion or one that has changed color or appearance.
- Lesions that are raised or pigmented.
- Presumed BPV unresponsive to office treatments.
- Vulvar dermatoses where the diagnosis is in doubt or there is no response to treatment.
- Any lesion that appears malignant.
- Any lesion that has associated white or thickened areas.
Vulvar biopsy can be performed by shaving the lesion, excising with scissors or scalpel, or using a Keyes punch. I prefer the scissors or 4mm Keyes punch. After informed consent is given, the patient undergoes colposcopy if indicated. The vulva is cleansed with betadine or a similar agent, and local anesthesia is always applied, usually using a 25-gauge needle with lidocaine or a similar agent. Usually 1-3 cc is necessary to produce an adequate wheal, which will raise the lesion slightly, making biopsy easier.
A representative area or the actual lesion is removed with the scissors, scalpel, or Keyes punch, and sent for permanent pathologic section. If a defect larger than a pencil eraser is produced there may be difficulty with hemostasis, requiring placement of an interrupted 4-0 or 3-0 delayed absorbable suture (for example vicryl). However, most of these excision sites respond well to silver nitrate application or direct pressure. The patient should use hydrogen peroxide and perhaps Neosporin or Polysporin ointment for about a week to facilitate healing. Infection and subsequent bleeding are rare, but if the patient reports increasing pain, she should be evaluated immediately. The results of her biopsy can be discussed at a 2-week follow up appointment.
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