Archive for the Vagina Cancer category.
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Invasive squamous cell carcinoma accounts for 90% of all invasive malignancies of the vulva, which are responsible for only 1-4% of all female cancers. Other less-common malignant lesions of the vulva are melanoma, adenocarcinoma, and sarcoma. More than three fourths of all patients diagnosed with cancer of the vulva are age 55 years or older, with at least 30% of these women older than 75 years. Approximately 500 deaths from vulvar cancer occur annually in the United States. Because of recognizable symptoms and ease of examination by biopsy, malignancies of the vulva can be detected in an early stage, when therapy can be curative. Death from vulvar cancer results from failure to control the disease after it has progressed beyond the vulva. Such instances often result from delay by the patient in obtaining care and by the physician in performing diagnostic biopsy. Regular examination of all women and increased efforts in patient education can help minimize treatment delay. Recognition of the clinical characteristics of vulvar malignancies and promotion of ready use of office biopsy could prove highly beneficial. Viagra for woman at cheap online pharmacy.
The cause of vulvar malignancies remains unknown, although the association of squamous cell carcinoma of the vulva with other neoplasms of the anogenital mucosa has long suggested a common etiology. Preliminary data on oncogenesis, however, has not been conclusive. The association of high-risk types of human papillomavirus (HPV) such as 16, 18, 31, 33, 35, and 39 with high-grade epithelial neoplasia and invasive carcinomas of the anogenital tract has been established. Vulvar cancer appears to have a multifactorial etiology, however, and HPV infection alone is probably not sufficient for malignant transformation. Primary among cofactors may be the patient’s own immune competence, including conditions of local immunodeficiency. The role of chronic vulvar dystrophy is unclear, although there is a common association. Whereas the risk of progression of vulvar dystrophy to malignancy is low, vulvar dystrophy is frequently associated with epidermoid carcinoma.
Multicentric and confluent vulvar intraepithelial neoplasia (VIN) lesions predominate among younger women, whereas the unifocal lesions, which are most likely to be associated with invasive carcinoma, are more common in older women. The lesions may appear to be white because of thick surface keratin or red if hyperemia is present within the dermal papillae. Pigmentation is common, especially with bowenoid neoplasia. Often the lesions appear as slightly raised and possibly confluent white areas resembling flat condylomata. Colposcopy with 4-5% acetic acid heightens the whitening and allows for delineation of the margins of the vulvar lesions. Subclinical HPV infections of the vulva can be distinguished with acetic acid at times. Thickened, nodular, ulcerated areas are most suspicious, as are areas of vascular prominence and atypical tissue.
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Benign Anomalies
Adenosis and vaginal epithelial changes, present in as many as 50% of women who were exposed to DES before 18 weeks of gestation, include large transformation zones extending to the vagina, cervical collars, hypoplastic cervices, pseudopolyps, and vaginal septa. As the patient grows older, these changes diminish.
The immature squamous metaplasia noted on colposcopy can lead to overzealous treatment. Among the progeny of women exposed to DES, fewer than 10% with biopsies of these areas will have significant intraepithelial neoplasia. Women with these large transformation zones should be followed with cytologic testing, iodine staining, colposcopy, and careful palpation every 6 months to 1 year. Oral contraceptive use does not increase the risk for genital tract clear-cell adenocarcinoma.
The vaginal changes and anatomic abnormalities of the uterus and fallopian tubes, occurring in some progeny, may increase the risk of early pregnancy loss, ectopic pregnancy, and preterm delivery. Careful monitoring throughout pregnancy is indicated.
Exposure to DES may place women at a small, but statistically significant, risk for developing breast cancer. The possibility of an increased risk of cancer of the uterine corpus has been raised. Because of these increased risks, women who have been exposed to DES should be followed for life with appropriate and cost-effective screening.
The rare primary adenocarcinoma of the vagina usually occurs in postmenopausal women. These lesions may arise from residual glands of müllerian origin. Metastatic lesions (from breast, bowel, cervix, endometrium, and ovary) should be ruled out.
Exposure in utero to DES has been epidemiologically associated with vaginal clear-cell adenocarcinoma since 1971. The registry for this disease now includes more than 600 cases, although millions of women were treated with DES during pregnancy, starting in the 1950s. Thus, the risk that a woman exposed to DES will develop a clear-cell lower genital tract cancer is about 1 per 1,000 women.
Registry-updated reports indicate that the age at diagnosis ranges from 7 to 42 years old. Since 1990, 35 new cases have been reported, raising concern about a second peak of occurrence. Depending on what years the registry is analyzed, 65-80% of women with clear-cell adenocar-cinoma will have a documented history of DES exposure. No history of DES exposure is noted in 20-25% of women with clear-cell adenocarcinoma. When clear-cell adeno-carcinoma is diagnosed, DES-negative patients have a worse prognosis and higher rate of distant metastases than patients who were exposed to DES. Diethylstilbestrol-associated clear-cell adenocarcinomas have a predilection for the exocervix and upper one third of the vagina.
As of 1993, 20 women under observation had developed clear-cell adenocarcinoma. Because most of the clear-cell adenocarcinomas were detected by noting submucosal nodules, careful palpation of the cervix and vagina is recommended when examining these patients. Tall, overweight adolescents may be at a relatively higher risk of developing this neoplasm.
Radical hysterectomy, upper vaginectomy, and bilateral pelvic lymphadenectomy with ovarian preservation are recommended for patients with cervical and upper-vaginal clear-cell adenocarcinoma. For tumors smaller than 2 cm in diameter and with less than 3-mm invasion, wide local excision with node dissection, supplemented by local radiation, has been used with preservation of reproductive potential. For advanced stages, irradiation is recommended.
Although 5-year survival for stage I clear-cell adenocarcinomas is higher than 93%, the 10-year survival rate is 87%. Most recurrences happen within the first 3 years, but late recurrences, 8-20 years later, have been reported. In addition to pelvic examinations during follow-up, careful attention should be directed to the supraclavicular nodes and lungs.
Treatments
Most vaginal carcinomas are best treated with radiation therapy. Patients with occult or smaller than 1-cm, stage I, superficial lesions could be considered for radical surgery. Select patients with a lesion in the upper third of the vagina may be candidates for radical hysterectomy, vaginec-tomy, and bilateral pelvic lymph node dissection. Patients with positive nodes should receive external beam irradiation through appropriately designed ports, particularly if more than three nodes are involved. Patients with mid-vaginal, early-stage cancers are probably best treated with radiation therapy. For nonsurgical candidates, when cancers are superficial, the usual treatment is a combination of interstitial implants and a vaginal cylinder. Doses range from 6,000 to 7,000 cGy to the tumor area. Patients with thick, infiltrating, stage I disease are often treated with additional external beam irradiation.
For other patients with locally advanced squamous cell cancers, individualized radiation therapy is administered. Generally used is 4,000 cGy to the whole pelvis with a 5,000- to 6,000-cGy total parametrial dose, along with a combination of interstitial and intracavitary insertions to deliver a total dose of 7,500-8,000 cGy to the vaginal lesion and 6,500 cGy to parametrial and paravaginal extensions. Use of radiation sensitizers, such as 5-fluorouracil plus cisplatin or mitomycin C, has been reported in recent series with little improvement in survival noted. Vaginal stenosis, vaginal necrosis, and proctitis are common complications. The rarely occurring fistulas to adjacent organs are usually seen in patients in whom a combination of surgery and irradiation has been tried. Ultraradical surgery is usually reserved for patients with local central recurrence.
Survival for patients with stage I vaginal cancer has been reported to range from 72% to 90%, and survival for stage II is around 55%. Approximately 45% of patients with stage III cancer will be 5-year survivors. Patients with stage IVA cancer have a 10-20% survival rate. Relatively improved survival is noted in patients younger than 60 years of age, patients with grade I tumors, and patients with nonbulky disease. Chemotherapy for distant recurrences has been largely ineffective, although cisplatin has been used.
Invasive Squamous Cell Carcinoma
Primary invasive carcinoma of the vagina accounts for 12% of all gynecologic malignancies. It is a disease of older women, with the peak incidence in the sixth and seventh decades. Only 10% of these carcinomas occur in women younger than 40 years of age. Squamous cell lesions constitute 80-90% of all invasive malignancies.
Stage 0 : Carcinoma in situ; intraepithelial carcinoma
Stage 1 : Carcinoma limited to vaginal mucosa (wall)
Stage 2 : Subvaginal infiltration into parametrium, not extending to the pelvic wall
Stage 3 : Carcinoma has extended to the pelvic wall
Stage 4 : Carcinoma has extended beyond the true pelvis or involves mucosa of bladder or rectum
Stage 4A : Carcinoma has spread to adjacent organs and/or direct extension beyond the true pelvis
Stage 4B : Carcinoma has spread to distant organs
Modified from International Federation of Gynecology and Obstetrics. Annual report on the results of treatment in gynecological cancer. 22nd edition. Stockholm: FIGO, 1994
Diagnosis
Only about 20% of patients with invasive carcinoma are asymptomatic. Most patients present with abnormal vaginal bleeding or discharge, which may be malodorous. Less frequent complaints include dysuria, urgency, constipation, and pain, all usually occurring with more advanced disease. The upper one third of the vagina is involved in 4050% of cases in reported series. Involvement of the distal third of the vagina may be noted in as many as one third of patients. Posterior wall involvement is more common than lateral or anterior locations. Tumors usually appear exo-phytic or ulcerated. Most gynecologists use FIGO clinical staging (see the box). To rule out adjacent organ primary cancers, staging pelvic examination with biopsies under anesthesia may be indicated.
Once the histologic diagnosis is made, cystoscopy and proctoscopy are indicated in patients with large tumors. Chest X-ray and intravenous pyelography or computed tomography with intravenous and oral contrast usually aid in treatment planning, particularly with clinical stage II or more advanced disease. Magnetic resonance imaging may help in differentiating between fibrotic tissue and tumor infiltration. The use of tumor markers, such as squamous cell carcinoma antigen, has been suggested to assist in surveillance, but these markers are expensive, and few data are available to support their sensitivity or specificity.
Some researchers have recommended surgical evaluation of adjacent nodes for treatment planning. Lymphatics from the upper vagina probably drain in a manner similar to that of the cervix, whereas those from the lower vagina are assumed to drain in a manner similar to that of vulvar lesions. The lymphatic drainage of the vagina is complex and consists of an extensive intercommunicating, interconnecting network. Because of the rarity of vaginal tumors, meaningful surgical studies of lymph node metastasis have not been performed. Lymphangiography may be a less costly and morbid technique for assessing lymph node involvement, particularly in obese patients.
Because patients with vaginal intraepithelial neoplasia are usually asymptomatic, an abnormal Pap test frequently leads to the diagnosis. Rarely, patients may present with postcoital spotting. Colposcopically directed biopsies usually establish the diagnosis. In the patient who has had a hysterectomy, care should be taken to evaluate the pockets sometimes present in the lateral vault areas. During inspection, the speculum blade should be withdrawn slowly and rotated in the partially open position to allow visualization of the entire vaginal tube.
Application of 4-5% acetic acid will cause affected areas to appear white and well demarcated, allowing for target biopsies. Lesions are usually located in the upper one third of the vagina, but because vaginal intraepithelial neoplasia tends to be multifocal, potential lesions in the lower vault should be identified. The lesions may be flat, slightly raised, or warty and granular. Keratinization may obscure any vascular pattern, mosaic, or punctuation. In the postmenopausal patient, lesions are sometimes not easily identified. Topical estrogen for several weeks may help mature vaginal mucosa and allow for easier detection on reexamination. Lugol’s solution may be helpful in determining the extent or location of lesions.
A mixture of 1% lidocaine and vasopressin, injected with a small-gauge spinal needle, will provide local anesthesia for the few patients who need it. The biopsy is often facilitated by grasping tissue adjacent to the lesion with a skin hook and pulling the tissue toward the surgeon. Adequate specimens can be obtained with small, alligator-jaw forceps.
Treatment
Proposed treatments for vaginal intraepithelial neoplasia include surgical excision with partial vaginectomy, laser, topical 5-fluorouracil cream, total vaginectomy with split-thickness skin graft, cryotherapy, and radiation therapy. The mainstay of treatment is wide local excision of the affected area or upper vault vaginectomy. The use of dilute vasopressin injection will facilitate surgery. Laser vaporization has been used, but a biopsy of multiple areas should be performed to rule out invasion. Vasopressin injection also facilitates laser vaporization, and the depth of destruction should be limited to 2 mm. Topical administration of 5-fluorouracil cream has yielded cure rates in selected, compliant patients and may be of particular value in immunosuppressed patients with HPV-associated vaginal intraepithelial neoplasia or in patients who have had previous irradiation. The 5% cream is applied in several regimens, such as every night for 7-10 days with a 2-week break or every week at night for 10 weeks. Caveats to ensure patient compliance and minimize morbidity include inserting one quarter to one third of the applicator high in the vagina before retiring, using a tampon, and protecting the vulva from irritation by use of petroleum jelly.
Use of cryotherapy should be discouraged. Two other, less desirable modalities include total vaginectomy with skin grafting and delivering 6,500-8,000 cGy via an intra-cavitary application. Both procedures can lead to stenosis, scarring, and the rare formation of fistulas.