VULVAR MALIGNANCY

VULVAR MALIGNANCY - Michael P. Hopkins, MD, MEd; Noridelle Gilo, MD; Eric L. Jenison, MD
BASICS
DESCRIPTION
• Carcinoma in situ (Bowen disease): Premalignant changes involving the squamous epithelium of the vulva
• Squamous cell carcinoma: Invasive squamous cell carcinoma is the most common malignancy involving the vulva (85% of the patients). The malignancy can be well, moderately, or poorly differentiated.
• Other invasive cell types include melanoma, Paget disease, adenocarcinoma, adenocystic carcinoma, small cell carcinoma, and sarcomas. Sarcomas are usually leiomyosarcoma and probably arise at the insertion of the round ligament in the labium majus.
• System(s) Affected: Reproductive
• Synonym(s): Bowen disease; Vulvar cancer
ALERT
Geriatric Considerations
• Older patients with associated medical problems are at high risk for radical surgery. The surgery, however, is external, usually well tolerated, and is the treatment of choice.
• In the very elderly, palliative vulvectomy provides relief of symptoms for ulcerating symptomatic advanced disease.
Pregnancy Considerations
This malignancy is not associated with pregnancy.
GENERAL PREVENTION
• Any woman complaining of symptoms related to the vulva should have a close examination and biopsies made of appropriate areas.
• The vulva can be washed with 3% acetic acid to highlight areas. Areas of white raised epithelium should be biopsied.
• Patients with new onset of pruritus should be biopsied in the area of pruritus.
• Liberal biopsy must be used to diagnose in situ disease prior to invasion and to diagnose early invasive disease.
• The patient should not be treated for presumed benign conditions of the vulva without full examination and biopsy.
• When symptoms persist, re-examination and rebiopsy should be undertaken.
• The treatment of benign condyloma of the vulva has not been shown to decrease the eventual incidence of in situ or invasive disease of the vulva.
EPIDEMIOLOGY
• Predominant age
- In situ disease: Mean age, 40s
- Invasive malignancy: Mean age, 60s, with a range of 20s-90s
• Predominant sex: Female only
Incidence
In the US: Invasive vulvar malignancy is a rare gynecologic malignancy, accounting for ~2,000 new cases per year.
RISK FACTORS
• Old age: Invasive disease is rarely seen before age 40 years, and the majority of patients are elderly.
• In situ disease can occur at any age but is rarely seen before the age of 25 years.
• Human papilloma virus (HPV)
• Immunosuppression
Genetics
No known genetic pattern
ETIOLOGY
• Patients with cervical cancer are more likely to develop vulvar cancer at a later date. This is due to the so-called field effect with a carcinogen involving the lower genital tract.
• HPV has been associated with squamous cell abnormalities of the cervix, vagina, and vulva but has not been proven to be the causative agent.
• Smoking is associated with squamous cell disease of the vulva, possibly from direct irritation of the vulva by the transfer of tars and nicotine on the patient's hands or from systemic absorption of carcinogen.
ASSOCIATED CONDITIONS
• Patients with invasive vulvar cancer are often elderly and have associated medical conditions.
• High rate of other gynecologic malignancies. Patients should be evaluated for these.


DIAGNOSIS
SIGNS AND SYMPTOMS
• In situ disease: A small raised area associated with pruritus
• Invasive malignancy: An ulcerated, nonhealing area; as lesions become large, bleeding occurs with associated pain and foul-smelling discharge
• In far advanced disease: The patients can develop rectal bleeding or urethral obstruction.
• Large involved inguinal lymph nodes are also associated with advanced disease.
TESTS
Lab
• Squamous cell antigen can be elevated with invasive disease.
• Hypercalcemia can occur when metastatic disease is present.
Imaging
• Chest x-ray to evaluate for metastatic disease to lungs
• CAT scan to evaluate pelvic lymph node status and periaortic lymph node status
Diagnostic Procedures/Surgery
• Office vulvar biopsy. Vulvar punch biopsy should be done to establish the diagnosis.
• Wide excision can be performed for carcinoma in situ, and any lesion about which there is doubt should be further excised for definitive diagnosis to ensure that invasive disease is not coexistent with the carcinoma in situ.
• Cystoscopy and sigmoidoscopy should be performed if there is a question of invasion into the urethra, bladder, or rectum.
Pathological Findings
• A surgical staging system is used for vulvar cancer: TNM classification = tumor, node, and metastases
- T1: Tumor 2.0 cm
- T2: Tumor >2.0 cm
- T3: Lower urethra or vagina involved
- T4: Upper urethra, bladder, or rectum involved
- N0: Nodes negative
- N1: Unilateral positive lymph nodes
- N2: Bilateral positive lymph nodes
- M0: No metastatic disease
- M1: Distant metastatic disease, positive pelvic lymph node
• International Federation of Obstetrics and Gynecology Classification using TNM
- Stage I: T1, N0, M0
 Stage IA: T1a:  1 mm stromal invasion
 Stage IB: T1b: > 1 mm stromal invasion
- Stage II: T2, N0, M0
- Stage III: T1-3, N1, M0; T3, N0-l, M0
- Stage IVA: T1-3, N2, M0
- Stage IVB: Any T, any N, any M
DIFFERENTIAL DIAGNOSIS
• The definitive diagnosis for vulvar lesions is made by biopsy. Infectious processes can present as ulcerative lesions and include syphilis, lymphogranuloma venereum, and granuloma inguinale.
• Crohn disease can present as an ulcerative area on the vulva.
• Rarely, lesions can metastasize to the vulva.
TREATMENT
GENERAL MEASURES
• Appropriate health care: Inpatient for treatment
• In advanced malignancy involving the urethra and rectum, concomitant cisplatin/5-fluorouracil (5-FU) chemotherapy with radiation produces significant decrease in size of the primary tumor, usually obviating the need for pelvic exenteration.
Diet
Unrestricted, unless undergoing radiation
Activity
Patients are usually ambulatory and able to resume full activities by 6 weeks after surgery unless wound breakdown occurs.
SPECIAL THERAPY
Radiotherapy
• Radiation therapy is used as adjuvant therapy for patients with positive inguinal lymph nodes.
• Pre-operative radiation may allow for a less radical surgical procedure in patients with advanced disease. [B]
• Postoperative radiation as an adjuvant treatment in early/intermediate stage disease decreases recurrence frequency and may improve survival. [B]
MEDICATION (DRUGS)
• There are no curative drugs.
• As an adjuvant therapy, fluorouracil (Efudex) cream for in situ disease can produce occasional results, but the regimen is not well tolerated because of the excoriation and irritation of the vulva. Adjuvant chemotherapy has not proven to be effective in this disease.
• Chemoradiotherapy has been successful in limiting spread of locally advanced or recurrent disease, though local morbidity is increased.
• Metastatic disease, especially in the subcutaneous tissues of the leg or abdomen, will produce hypercalcemia, which is treated in the usual medical fashion for hypercalcemia.
• Contraindications
- Elderly patients: If chemotherapeutic agents are used, pay close attention to the patient's performance status and ability to tolerate aggressive chemotherapy.
• Precautions: The usual precautions for chemotherapy agents. Refer to the manufacturer's literature for each drug.
• Significant possible interactions: Refer to the manufacturer's literature for each drug.
Second Line
• Surgery: In situ disease can be treated with wide excision or laser vaporization of the affected area. Laser vaporization is preferable in the younger patient, where as wide excision is preferable in the elderly patient, in whom the risk of invasive disease is also higher.
• 0.5 mm of negative margin is adequate for in situ disease.
• Invasive disease is treated primarily by radical vulvectomy and bilateral groin node dissection.
• Pelvic exenteration after radiation provides effective therapy for advanced or recurrent malignancies involving the bladder or rectum.
• More limited surgery
- Has been undertaken for invasive lesions, especially in young patients, to preserve the clitoris and sexual function
- Radical vulvectomy with bilateral groin node dissection through separate incisions provides better cosmetic results than the en bloc technique.
- Radical hemivulvectomy and unilateral groin node dissection can also be utilized for smaller lesions.
FOLLOW-UP
PROGNOSIS
The 5-year survival is based on stages
• Stage I: 90%
• Stage II: 85%
• Stage III: 70%
• Stage IVA: 25%
• Stage IVB: 5%
COMPLICATIONS
The major complications from radical vulvectomy and groin node dissection are wound breakdown, lymphedema, and urinary stress incontinence.
PATIENT MONITORING
• Clinical examination of the groin nodes and vulvar area every 3 months for 2 years, then every 6 months for 3 years.
• Chest x-ray should be obtained once a year.
REFERENCES
1. Cardosi RJ, Bomalaski JJ, Hoffman MS. Diagnosis and management of vulvar and vaginal intraepithelial neoplasia. Obstet Gynecol Clin North Am. 2001;28:685-702.
2. Montana GS. Carcinoma of the vulva: Combined modality treatment. Curr Treat Options Oncol. 2004;5:85-95.
3. Tyring SK. Vulvar squamous cell carcinoma: Guidelines for early diagnosis and treatment. Am J Obstet Gynecol. 2003;189(3 Suppl):S17-S23.
4. Hoffman MS. Squamous-cell carcinoma of the vulva: Locally advanced disease. Best Pract Res Clin Obstet Gynaecol. 2003;17:635-647.
5. Hopkins MP, Reid GC, Vettrano I, Morley GW. Squamous cell carcinoma of the vulva: Prognostic factors influencing survival. Gynecol Oncol. 1991;43:113-117.