Vulvar Malignancy – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

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 (90% of patients) (1). The malignancy can be well, moderately, or poorly differentiated.
  • Other invasive cell types include melanoma, Paget disease, adenocarcinoma, adenoid cystic carcinoma, small cell carcinoma, verrucous carcinoma, and sarcomas. Sarcomas are usually leiomyosarcoma and probably arise at the insertion of the round ligament in the labium major.
  • System(s) affected: Reproductive

Geriatric Considerations

  • Older patients with associated medical problems are at high risk from radical surgery. The surgery, however, is external, usually well tolerated, and is the treatment of choice. Patients who are not surgical candidates can be treated with primary radiotherapy.
  • In the very elderly, palliative vulvectomy provides relief of symptoms for ulcerating symptomatic advanced disease.

Epidemiology

Incidence

  • In the US, invasive vulvar malignancy is the 4th most common gynecologic malignancy, accounting for 3,580 new cases in 2009.
  • Predominant age:
    • In situ disease: Mean age 40s
    • Invasive malignancy: Mean age 60s, with a range of 20s–90s

Risk Factors

  • Smoking
  • Vulvar dystrophy
  • HPV infection
  • Autoimmune processes

Genetics

No known genetic pattern

General Prevention

  • Human papillomavirus (HPV) vaccination has the potential to decrease vulvar cancer by 1/3 (1).
  • Abstinence from smoking/smoking cessation counseling

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. 40% of vulvar cancers are attributable to oncogenic HPV.
  • 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.

Commonly 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

History

Complaints of pruritus or raised lesion in the vaginal area

Physical Exam

  • 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.

Diagnostic Tests & Interpretation

Lab

Initial lab tests

  • Hypercalcemia can occur when metastatic disease is present.
  • Squamous cell antigen can be elevated with invasive disease.

Follow-Up & Special Considerations

  • Any woman complaining of symptoms related to the vulva should have a close examination and biopsies 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 biopsies 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 exam and biopsy.
  • When symptoms persist, reexamination 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.

Imaging

Initial approach

  • CXR to evaluate for metastatic disease
  • CT scan to evaluate pelvic and periaortic lymph node status

Diagnostic Procedures/Surgery

Office vulvar biopsy is done to establish the diagnosis.

Pathological Findings

A surgical staging system is used for vulvar cancer (International Federation of Obstetrics and Gynecology Classification):

  • Stage I: Tumor confined to the vulva:
    • Stage IA: Lesions ≤2 cm in size, confined to the vulva or perineum, and with stromal invasion ≤1.0 mm, no node metastasis
    • Stage IB: Lesions >2 cm in size or with stromal invasion >1.0 mm, confined to the vulva or perineum, with negative nodes
  • Stage II: Tumor of any size with extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with negative nodes
  • Stage III: Tumor of any size with or without extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with positive inguino-femoral lymph nodes:
    • Stage IIIA:
      • (i) With 1 lymph node metastasis (≥5 mm), or
      • (ii) 1–2 lymph node metastasis(es) (<5 mm)
    • Stage IIIB:
      • (i) With 2 or more lymph node metastases (≥5 mm), or
      • (ii) 3 or more lymph node metastases (<5 mm)
    • Stage IIIC: With positive nodes with extracapsular spread
  • Stage IV: Tumor invades other regional (2/3 upper urethra, 2/3 upper vagina), or distant structures
    • Stage IVA: Tumor invades any of the following:
      • (i) Upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to pelvic bone or
      • (ii) Fixed or ulcerated inguino-femoral lymph nodes
    • Stage IVB: Any distant metastasis including pelvic lymph nodes

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

There are no curative drugs.

Medication

  • As an adjuvant therapy, fluorouracil (Efudex) cream for in situ disease can produce occasional results but is not well tolerated because of irritation of the vulva. Adjuvant chemotherapy has not proven to be effective in this disease.
  • Chemoradiotherapy with cisplatin and 5-fluorouracil has been successful in advanced or recurrent disease, although local morbidity is increased (2)[B].
  • Metastatic disease, especially in the subcutaneous tissues of the leg or abdomen, will produce 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 manufacturer’s literature for each drug.

Additional Treatment

General Measures

  • 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.

Issues for Referral

Patients may need care from a gynecologic oncologist and/or a radiation oncologist.

Additional Therapies

  • Radiation therapy is used as adjuvant therapy for patients with positive inguinal lymph nodes.
  • Preoperative radiation/chemotherapy may allow for a less radical surgical procedure in patients with advanced disease (3,4)[B].
  • Postoperative radiation as an adjuvant treatment decreases recurrence frequency and may improve survival (3)[B].
  • Radiation is contraindicated with verrucous carcinoma because it induces anaplastic transformation and increases metastases.

Surgery/Other Procedures

  • In situ disease can be treated with wide excision or laser vaporization of the affected area. Laser vaporization is preferable in the younger patient, whereas 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 (2)[C].
  • Stage IA is treated with radical local excision without lymph node dissection because lymph node metastases are <1% (2)[C].
  • Stage IB is treated with radical local excision with lymph node dissection because the risk of metastases increases to 8% (2)[C].
  • Modified radical vulvectomy and groin node dissection are recommended for stage II (2)[C].
  • Radical vulvectomy and bilateral inguinal lymph node dissection are recommended for stage III and stage IVA lesions (2)[C].
  • Bulky advanced-staged lesions are often treated initially with chemoradiation followed by less radical surgery (4)[B].
  • Adjuvant radiation therapy is recommended with microscopically positive lymph nodes (2)[C].
  • Pelvic exenteration after radiation provides effective therapy for advanced or recurrent malignancies involving the bladder or rectum.
  • More limited surgery:
    • Has been undertaken for early invasive lesions, especially in young patients, to preserve the clitoris and sexual function
    • Sentinel lymph node (SLN) biopsy also has been advocated in early invasive lesion, however, data show lower accuracy compared to complete dissection (5)[C].
    • 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 also can be used for smaller unilateral lesions.

In-Patient Considerations

Typically inpatient for treatment

Initial Stabilization

In advanced malignancy involving the urethra and rectum, concomitant cisplatin/5-fluorouracil (5-FU) chemotherapy with radiation produces a significant decrease in size of the primary tumor, usually obviating the need for pelvic exenteration.

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

  • Clinical exam of the groin nodes and vulvar area every 3 months for 2 years; then every 6 months for 3 years
  • Annual CXR

Diet

Unrestricted, unless undergoing radiation

Patient Education

  • American College of Obstetricians and Gynecologists (ACOG), 409 12th St., SW, Washington, DC 20024-2188; (800) 762-ACOG; http://www.acog.org
  • American Cancer Society: http://www.cancer.org
  • Medline Plus: http://www.nlm.nih.gov/medlineplus/vulvarcancer.html

Prognosis

The 5-year survival is based on stage:

  • Stage I: 78.5%
  • Stage II: 58.8%
  • Stage III: 43.2%
  • Stage IV: 13.0%

Complications

  • The major complications from radical vulvectomy and groin node dissection are:
    • Wound breakdown
    • Lymphocysts
    • Lymphedema
    • Urinary stress incontinence
    • Psychosexual consequences
  • 2 common complications with radical vulvectomy and bilateral groin node dissection:
    • In the immediate postoperative period, ∼50% of patients experience breakdown of the wound. This requires aggressive wound care by visiting nurses as often as twice a day. The wounds usually granulate and heal over a period of 6–10 weeks.
    • ∼15–20% of patients experience some form of mild-to-moderate lymphedema after the groin node dissection. These patients should be instructed in the use of leg elevation and support hose. <1% of patients experience severe, debilitating lymphedema.

References

1. Smith JS, Backes DM, Hoots BE, et al. Human Papillomavirus Type-Distribution in Vulvar and Vaginal Cancers and Their Associated Precursors. Obstet Gynecol. 2009;113:917–24.

2. de Hullu JA, van der Zee AG. Surgery and radiotherapy in vulvar cancer. Crit Rev Oncol Hematol.2006;60:38–58.

3. Montana GS. Carcinoma of the vulva: combined modality treatment. Curr Treat Options Oncol. 2004;5:85–95.

4. de Hullu JA, van der Avoort IA, Oonk MH, et al. Management of vulvar cancers. Eur J Surg Oncol. 2006.

5. Radziszewski J, Kowalewska M, Jedrzejczak T, et al. The accuracy of the sentinel lymph node concept in early stage squamous cell vulvar carcinoma. Gynecol Oncol. 2010;116:473–7.

Additional Reading

CDC. Quadrivalent human papillomavirus vaccine: Recommendations of the advisory committee on immunization practices. MMWR. 2007;569(No. RR02).

Crosbie EJ, Slade RJ, Ahmed AS, et al. The management of vulval cancer. Cancer Treat Rev. 2009;35:533–9.

Codes

ICD9

184.4 Malignant neoplasm of vulva, unspecified

Snomed

94143002 primary malignant neoplasm of vulva (disorder)

Clinical Pearls

  • 40% of vulvar cancers are attributable to oncogenic HPV. Therefore, HPV vaccination has the potential to decrease vulvar cancer by 1/3.
  • Biopsy all suspicious or nonhealing vulvar lesions.

Jean-Paul Marat

Many tips are based on recent research, while others were known in ancient times. But they have all been proven to be effective. So keep this website close at hand and make the advice it offers a part of your daily life.