VAGINAL MALIGNANCY

VAGINAL MALIGNANCY - Michael P. Hopkins, MD, MEd; Ahntuan T. Huynh, DO; Eric L. Jenison, MD
BASICS
DESCRIPTION
• Vaginal intraepithelial neoplasia (carcinoma in situ): A premalignant phase with full-thickness neoplastic changes in the superficial epithelium. However, there is no invasion through the basement membrane.
• Invasive malignancies: Vaginal malignancies are squamous cell in 90% of patients; the remaining 10% are adenocarcinomas, sarcomas, and melanomas. The clear-cell carcinoma is a subtype of adenocarcinoma.
• To be classified as a vaginal malignancy, only the vagina can be involved. If the cervix or the vulva is involved, then the tumor is classified as a primary cancer arising from the cervix or the vulva.
• System(s) Affected: Reproductive
• Synonym(s): Bowen disease; Vaginal intraepithelial neoplasia (VAIN)
ALERT
Geriatric Considerations
Older patients, many with a long history of smoking, are at a higher risk for malignancies requiring surgical treatments.
Pediatric Considerations
Childhood sarcomas can be treated in a conservative fashion with multimodality therapy. This avoids the loss of the young child's bladder and/or rectum.
Pregnancy Considerations
This malignancy is not associated with pregnancy.
EPIDEMIOLOGY
Incidence
• Predominant age
- Carcinoma in situ: Mid-40s-60s
- Invasive squamous cell malignancy: Mid-60s-70s
- Adenocarcinoma: Any age range, 50s is mean age
- Mixed Mullerian sarcomas and leiomyosarcomas in the adult population: Mean age 60 years
- Sarcoma botryoides and embryonal sarcomas: Occur in the pediatric population
• Predominant sex: Female only
Prevalence
In the US: This is 1 of the rarest of all gynecologic malignancies.
RISK FACTORS
• History of squamous cell cancer of the cervix or vulva
• Smoking
• Multiple sex partners
• Age
• Vaginal adenosis
• HPV infection
• Daughters of mothers who took diethylstilbestrol (DES)
Genetics
No known genetic pattern
ETIOLOGY
• Women with a history of cervical malignancy have a higher probability of developing squamous cell malignancy in the vagina after hysterectomy.
• The human papilloma virus (HPV) has been associated with vulvovaginal, cervical, adenocarcinoma, and squamous cell carcinoma.
• Smokers have a higher incidence.
• Clear-cell adenocarcinoma of the vagina in young women has been associated with DES exposure. The incidence, however, is exceedingly rare, estimated at 1:1,000-1:10,000 DES-exposed females.
• Metastatic lesions can involve the vagina from the other gynecologic organs.
• Renal cell carcinoma and breast cancer can metastasize to the vagina (rarely).
ASSOCIATED CONDITIONS
Due to the field effect, patients with vaginal cancer are more likely to develop malignancy in the cervix or vulva and should be followed closely.

DIAGNOSIS
SIGNS AND SYMPTOMS
• Abnormal bleeding is the most common symptom. This results from a fungating tumor present in the vagina.
• Dyspareunia
• Postcoital bleeding can result from direct trauma to the tumor.
• Pain along with symptoms and signs of hydroureter are late findings when the tumor has spread into the paravaginal tissues and extends to the pelvic side wall.
• In the pediatric population, sarcomas can present either as a mass protruding from the vagina or as abnormal genital bleeding.
TESTS
Lab
Cytology will usually be positive when an obvious lesion is present.
Imaging
• Chest x-ray: Lung metastases are a late finding.
• Intravenous pyelogram (IVP): To evaluate for ureteral obstruction
• CAT scan to evaluate the retroperitoneum and especially the lymph nodes in the pelvic and periaortic area
• Lymphangiography is also useful for evaluation of the lymph node status.
• Barium enema to rule out rectal invasion
Diagnostic Procedures/Surgery
• Colposcopy with directed biopsies for small lesions
• Wide excision under anesthesia of superficial disease may be necessary to ensure that invasive cancer is not present.
• Cystoscopy to rule out bladder invasion
• Sigmoidoscopy to rule out rectal invasion
Pathological Findings
• Stage 0: Carcinoma in situ
• Stage I: Infiltrative tumor not involving the paravaginal tissues
• Stage II: Paravaginal extension but not to the side wall
• Stage III: Paravaginal extension to the side wall
• Stage IVA: Tumor involving the bladder or the rectum
• Stage IVB: Distant metastatic disease
DIFFERENTIAL DIAGNOSIS
• VAIN involves premalignant changes that do not infiltrate beyond the basement membrane.
• Adequate biopsies ensure that invasive lesions are not overlooked. Invasive lesions penetrate the basement membrane and cannot be treated conservatively. Other malignancies such as endometrial, cervix, bladder, or colon cancer can invade directly into the vagina or metastasize to the vagina.
• In the childbearing ages, trophoblastic disease should be considered. The vagina is a common site of metastases. Biopsy will usually provide a clue to the primary site.
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient or inpatient, depending on treatment
• Carcinoma in situ can be treated by a variety of methods: Laser vaporization under microscopic guidance; fluorouracil (Efudex) intravaginal cream; partial vaginectomy
• In all tumor types, metastatic disease from the vagina to other sites is only minimally responsive to chemotherapy.
Diet
Unrestricted unless undergoing radiation
Activity
• Patients are usually ambulatory and able to resume full activity by 6 weeks after surgery.
• Most patients are fully active while receiving radiation therapy.
SPECIAL THERAPY
Radiotherapy
• Treatment with radiotherapy is dependent on the stage of disease. This treatment option should be discussed with physicians experienced with this malignancy. (1,2)[C]
MEDICATION (DRUGS)
First Line
• With 1 exception, there are no chemotherapeutic agents to which this tumor is responsive. The exception is the childhood sarcomas, which have been treated with combinations of
- Vincristine
- Dactinomycin (actinomycin-D)
- Cyclophosphamide (Cytoxan)
- Cisplatin
- Etoposide (VP-16)
• Patients with advanced cervical cancer receive concurrent irradiation and cisplatin-based chemotherapy. This may become a treatment option for advanced carcinoma of the vagina. (2)[C]
• Adjuvant chemotherapy has no proven benefit in squamous cell or adenocarcinoma of the vagina.
• Intraepithelial neoplasia of the vagina can be treated with topical chemotherapy (5-fluorouracil cream). (1,3)[C]
• Contraindications
- The diagnosis must be established with certainty prior to treatment.
- If there is any doubt that a process beyond in situ disease exists, vaginectomy must be performed. Because these patients are often elderly, aggressive therapy is limited by the patient's performance status and ability to tolerate radical surgery, chemotherapy, or radiation.
• Precautions: Refer to the manufacturer's literature.
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
Ondansetron (Zofran), dronabinol (Marinol), metoclopramide (Reglan), and others for nausea control
SURGERY
• Whenever there is a doubt as to the presence or absence of invasive disease, vaginectomy must be performed.
• Invasive lesions are usually treated by radiation therapy, but stage I lesions can be treated with radical hysterectomy, radical vaginectomy with pelvic lymph node dissection. (1)[C]
• If the lesion involves the lower vagina, inguinal node dissection must also be done, as cancer involving the lower vagina can metastasize to the groin region.
• Premenopausal women, who desire to retain ovarian function, are better candidates for radical surgery for early-stage disease.
• Younger patients, who have not completed their family, can occasionally be treated with limited resection and localized radiation to the area.
• Sarcomas are treated by radiation therapy followed by pelvic exenteration if persistent disease is present.
• Childhood sarcomas are treated with chemotherapy followed by local resection. Childhood sarcomas are responsive to multiagent combination chemotherapies.
FOLLOW-UP
PROGNOSIS
Stage and 5-year survival
• I: 60%
• II: 40%
• III: 20%
• IVA: 5%
• IVB: 0%
COMPLICATIONS
Those associated with major abdominal surgery or radiation therapy
PATIENT MONITORING
• Pelvic examination and Pap smear every 3 months for 2 years and then every 6 months for subsequent 3 years
• Chest x-ray once a year
REFERENCES
1. Creasman WT. Vaginal cancers. Curr Opin Obstet Gynecol. 2005;17:71-76.
2. Grigsby PW. Vaginal cancer. Curr Treat Options Oncol. 2002;3:125-130.
3. Cardosi RJ, Bomalaski JJ, Hoffman MS. Diagnosis and management of vulvar and vaginal intraepithelial neoplasia. Obstet Gynecol Clin North Am. 2001;28:685-702.
4. Yalcin OT, et al. Vaginal intraepithelial neoplasia: Treatment by carbon dioxide laser and risk factors for failure. Eur J Obstet Gynecol Reprod Biol. 2003;106:64-68.
MISCELLANEOUS
This is an uncommon malignancy, and patients should be treated by a physician familiar and experienced with this malignancy.