Malignant Diseases of the Vagina : Intraepithelial Neoplasia, Carcinoma, Sarcoma

Malignant Diseases of the Vagina : Intraepithelial Neoplasia, Carcinoma, Sarcoma

KEY TERMS AND DEFINITIONS Clear-Cell AdenocarcinomaA vaginal or cervical malignancy occurring primarily after 14 years of age, often associated with prenatal exposure to diethylstilbestrol (DES).

Endodermal Sinus TumorA rare adenocarcinoma of the vagina occurring in infants younger than 2 years of age.

Field DefectThe propensity of squamous epithelium of the lower genital tract (cervix, vagina, and vulva) to undergo premalignant change due to infection with the human papillomavirus (HPV).

Pelvic ExenterationAn extensive pelvic operation usually employed to treat a central pelvic recurrence of cervical or vaginal carcinoma after radiation. A total exenteration involves removal of the bladder, uterus, cervix, and rectum. An anterior exenteration spares the rectum, whereas a posterior exenteration spares the bladder.

Pseudosarcoma BotryoidesA benign tumor occurring in the vagina of infants and pregnant women that has a polyploid shape. Microscopically it may be confused with sarcoma botryoides.

Sarcoma Botryoides (Embryonal Rhabdomyosarcoma)A rare, often fatal, malignancy of the vagina that occurs in infants and children.

Vaginal Tumor StageA clinical classification describing the extent of spread of vaginal carcinoma.Stage I: Limited to vaginal wallStage II: Extends to subvaginal tissueStage III: Reaches the pelvic sidewallStage IV: Extends beyond the true pelvis or into mucosa of the bladder or rectum

Vaginal Intraepithelial Neoplasia (VAIN) 1VAIN of the least severe type (comparable to mild dysplasia), occupying the lower one third of the epithelium. Also termed low-grade squamous intraepithelial lesion.

VAIN-2VAIN of intermediate severity (comparable to moderate dysplasia), occupying the lower two thirds of the epithelium.

VAIN-3VAIN of the most severe type (comparable to severe dysplasia and carcinoma in situ), replacing the full thickness of the epithelium. VAIN-2 and VAIN-3 are also combined into high-grade squamous intraepithelial lesion.

The term VAIN (vaginal, VA; intraepithelial, I; neoplasia, N) has been used to describe these histologic changes; the comparable categories are VAIN-1 (mild dysplasia), VAIN-2 (moderate dysplasia), and VAIN-3 (severe dysplasia to carcinoma in situ). VAIN-1 is classified as a low-grade squamous intraepithelial lesion, whereas VAIN-2 and VAIN-3 are grouped as high-grade squamous intraepithelial lesions. VAIN occurs more commonly in patients previously treated for cervical intraepithelial neoplasia. The tendency to develop premalignant changes in the lower genital tract has been termed a field defect and denotes the increased risk of squamous cell neoplasia arising anywhere in the lower genital tract in such individuals The most common histologic type of primary vaginal cancer is squamous cell carcinoma, which is usually seen in women older than 60. Malignant transformation of endometriosis has been described in the vagina and rectovaginal septum. Clear-cell adenocarcinoma, historically associated with young women exposed in utero to DES, may also occur in unexposed women. Primary vaginal sarcomas are rare and are primarily a disease of children

Table 31-1 --Common Primary Vaginal CancersTumor TypePredominant Age (years)Clinical Correlations

Endodermal sinus tumor (adenocarcinoma)50Very rare, poor survival

Squamous cell carcinoma>50Most common primary vaginal cancer

Premalignant Disease of the Vagina

Detection and Diagnosis Detection depends primarily on cytologic screening Continued examinations and Pap smears for women even after hysterectomy for dysplastic conditions. An abnormal smear from vaginal epithelium is identified, a biopsy is required for histologic identification colposcopic examination is usually performed to identify the areas requiring biopsy Lugol's solution - useful adjunct to colposcopy for identifying an area in which to perform a biopsy Vaginal estrogen cream used for 1 to 2 weeks before examination is helpful in evaluating postmenopausal women and those with atrophic vaginitis who present with cytologic atypia biopsy is performed with small instruments, such as the Kevorkian or Eppendorf punch biopsy forceps Management Treatment options include topical 5-fluorouracil (5-FU) cream, CO2 laser vaporization, and wide local excision The choice of treatment depends largely on the number of lesions, their location, and the level of concern for possible invasion. Radiation therapy, although used in the past, often leads to scarring and fibrosis and is generally not recommended for treatment of noninvasive disease. Because of the proximity of the bladder and rectum, cryotherapy is usually not used. Main advantage of the CO2 laser is that it vaporizes the abnormal tissue without shortening or narrowing the vagina, preserving vaginal function. Topical chemotherapy, 5% 5-FU cream, has the advantage of self-administration and coverage of the entire area at risk (all the vaginal epithelium). It is most often used for widespread, multifocal lesions of HPV-associated VAIN-1 or VAIN-2 Wide local excision (upper vaginectomy) is the treatment of choice for VAIN-3, especially for lesions occurring at the cuff of a hysterectomy Upper vaginectomy can result in vaginal shortening, which can be ameliorated by the use of topical estrogen cream and a vaginal dilator (or frequent intercourse) once healing is complete.

Malignant Disease of the Vagina

Symptoms and Diagnosis Primary vaginal cancers usually occur as squamous cell carcinomas in women older than age 60. To be considered a primary vaginal tumor, the malignancy must arise in the vagina and not involve the external os of the cervix superiorly or the vulva inferiorly. Tumors of the lower one third of the vagina are treated similarly to vulvar cancersTable 31-2 --International Federation of Gynecology and Obstetrics Staging Classification for Vaginal CancerStageCharacteristics

0Carcinoma in situ

ICarcinoma limited to vaginal wall

IICarcinoma involves subvaginal tissue but has not extended to pelvic wall

IIICarcinoma extends to pelvic wall

IVCarcinoma extends beyond true pelvis or involves mucosa of bladder or rectum (bullous edema as such does not assign a patient to stage IV)

The most common symptom of vaginal cancer is abnormal bleeding or discharge. Pain is usually a symptom of an advanced tumor. Urinary frequency is also reported occasionally, particularly in the case of anterior wall tumors, whereas constipation or tenesmus may be reported when the tumors involve the posterior vaginal wall. The longer the delay in diagnosis is, the worse the prognosis and the more difficult the therapy. Vaginal cancer is usually diagnosed by direct biopsy of the tumor mass Abnormal cytologic findings may prompt a thorough pelvic examination that will lead to diagnosis of vaginal cancer. It is important during the course of the pelvic examination to inspect and palpate the entire vaginal tube and to rotate the speculum carefully to visualize the entire vagina because often a small tumor may occupy the anterior or posterior vaginal wall.Tumors of Adult Vagina

I. Squamous Cell Carcinoma most common of the vaginal malignancies disease occurs primarily in those older than age 60, and 20% are older than the age of 80. Most squamous cell carcinomas occur in the upper third of the vagina, but primary tumors in the middle third and lower third may occur. Grossly, the tumor appears as a fungating, polypoid, or ulcerating mass, often accompanied by a foul smell and discharge related to a secondary infection Microscopically the tumor demonstrates the classic findings of an invasive squamous cell carcinoma infiltrating the vaginal epithelium. Treatment of these tumors is based on the size, stage, and location. Therapy is limited by the proximity of the bladder anteriorly and the rectum posteriorly. It is also influenced by the location of the tumor in the vagina, which determines the area of lymphatic spread Lymphatics of the vagina envelop the mucosa and anastomose with lymphatic vessels in the muscularis Those of the middle to upper vagina communicate superiorly with the lymphatics of the cervix and drain into the pelvic nodes of the obturator and internal and external iliac chains. Lymphatics of the distal third of the vagina drain to both the inguinal nodes and the pelvic nodes, similar to the drainage of the vulva The posterior wall lymphatics anastomose with the rectal lymphatic system and then to the nodes that drain the rectum, such as the inferior gluteal, sacral, and rectal nodes.

Management Thorough bimanual and visual examination, documenting the size and location of the tumor, and assessment of spread to adjacent structures (submucosa, vaginal sidewall, bladder, and rectum) should be done to determine the clinical stage. Cystoscopy and/or proctoscopy may be helpful, depending on clinical concern, to rule out bladder or rectal invasion Distant spread may be evaluated with a computed tomography scan of the abdomen, pelvis, and chest. stage vaginal carcinoma, without lymph node involvement (stage I or II), may be treated with either surgery or radiation. Radiation therapy is the most frequently used mode of treatment and can be used for both early and advanced disease. Pelvic exenteration can be used primarily to treat advanced disease in the absence of lymph node metastasis, but is usually reserved for patients with localized recurrence after radiation Stage I vaginal carcinoma may be treated with brachytherapy alone, without external beam therapySurvival. 5-year survival rates for patients with primary carcinoma of the vagina have been report Stage of tumor is the most important predictor of prognosis. The use of concomitant chemotherapy with radiation can be expected to produce improved survival rates.II. Clear-Cell Adenocarcinoma association of many of these cancers with intrauterine exposure to DESManagement: Surgery is the primary treatment modality because of the young age of the patients Stage I and early stage II tumors, radical hysterectomy with partial or complete vaginectomy, pelvic lymphadenectomy, and replacement of the vagina with split-thickness skin grafts have been the most common approach. Local excision of the tumor has been performed before irradiation toThree predominant histologic patterns are found in patients with clear-cell adenocarcinoma facilitate local applicationSurvival: Older patients (older than 19 years of age) have been found to have a more favorable prognosis in comparison to younger patients (younger than 15 years of age). Spread locally as well as by lymphatics and blood vessels Spread to regional pelvic nodes becomes more frequent in higher stage tumorsIII. Malignant Melanoma Rare and highly malignant Common presenting symptoms are vaginal discharge, bleeding, and a palpable mass. melanomas appear as darkly pigmented, irregular areas and may be flat, polyoid, or nodular average age of affected women is 57 years Vaginal melanomas tend to metastasize early, via the bloodstream and lymphatics, to the iliac and/or inguinal nodes, lungs, liver, brain, and bones.Survival: Patients with vaginal melanoma have a worse prognosis than those with vulvar melanoma, in part probably due to delay in diagnosis in comparison with vulvar carcinomas and in part due to their mucosal location, which seems to predispose to earlier metastasis. Prognostic indicators include tumor size, mitotic index, and Breslow tumor thickness. Improved survival has been noted for patients whose tumors had fewer than six mitoses per 10 high-power fieldsManagement: Surgery with wide excision of the vagina and dissection of the regional nodes (pelvic or inguinal-femoral, or both), depending on the location of the lesion. Therapy is usually tailored to the extent of disease. Surgery, radiation, chemotherapy, and immunotherapy have all been described, but no single or combination treatment is uniformly successful.IV. Vaginal Adenocarcinomas Arising in Endometriosis Rectovaginal septum is the most common extragonadal location. Tumors occur in the vagina or rectovaginal septum, the typical clinical presentation is pain, vaginal bleeding, and/or a vaginal mass in a patient who has previously undergone extirpative surgery for endometriosis Risk factors include unopposed estrogen and tamoxifen use Histologic types of malignancy include endometrioid adenocarcinoma as the most common, followed by sarcomas (25%), and other tumors of Mllerian differentiation Treatment usually includes surgery plus radiation or chemotherapy

Vaginal Tumors of Infants and Children

I. Endodermal Sinus Tumor (Yolk-Sac Tumor) rare germ-cell tumor that usually occurs in the ovary. tumor secretes -fetoprotein, which provides a useful tumor marker to monitor patients treated for these neoplasms tumor is aggressive, and most patients have died malignancy originating in the vagina of infants, predominantly those younger than 2 years of ageII. Sarcoma Botryoides (Embryonal Rhabdomyosarcoma) rare sarcoma is usually diagnosed in the vagina of a young female Rarely does it occur in a young child older than 8 years of age, although cases in adolescents have been reported. most common symptom is abnormal vaginal bleeding, with an occasional mass at the introitus The tumor grossly will resemble a cluster of grapes forming multiple polypoid masses. Are believed to begin in the subepithelial layers of the vagina and expand rapidly to fill the vagina. These sarcomas often are multicentric. Histologically, they have a loose myxomatous stroma with malignant pleomorphic cells and occasional eosinophilic rhabdomyoblasts that often contain characteristic cross-striations (strap cells)Management: Virulent tumors have been treated in the past by radical surgery, such as pelvic exenteration Effective control with less radical surgery has been achieved with a multimodality approach consisting of multiagent chemotherapy (VAC), usually combined with surgery Radiation therapy has also been used. They found VAC to be effective for disease confined to the vagina without nodal spreadIII. Pseudosarcoma Botryoides Rare, benign vaginal polyp that resembles sarcoma botryoides is found in the vagina of infants and pregnant women Large atypical cells may be present microscopically, strap cells are absent. Grossly, these polyps do not resemble the grapelike appearance of sarcoma botryoides. They are called pseudosarcoma botryoides. Treatment by local excision is effective.

KEY POINTS

Predisposing factors associated with the development of vaginal intraepithelial neoplasia include infection with HPV, previous radiation therapy to the vagina, immunosuppressive therapy, and HIV infection.

The tendency of intraepithelial squamous neoplasia to develop anywhere in the lower female genital tract is termed field defect and describes the increased risk of premalignant changes occurring in the cervix, vagina, or vulva.

Most cases of VAIN occur in the upper one third of the vagina.

VAIN can be treated by excision, laser, or 5-FU. Excision is often used for VAIN-3, and if the apex is involved, particularly after hysterectomy, laser treatment is generally used for discreet lesions once invasion has been ruled out, and 5-FU cream is used to treat diffuse, multicentric, low-grade disease.

The most common primary vaginal malignancy is squamous cell carcinoma (90%).

Most cancers occurring in the vagina are metastatic.

Vaginal cancers constitute less than 2% of gynecologic malignancies.

Tumors of the upper vagina have a lymphatic drainage to the pelvis similar to cervical tumors, whereas those of the lower one third of the vagina go to the pelvic nodes and also the inguinal nodes similar to vulvar tumors.

Radical surgery may be used to treat low-stage tumors primarily of the upper vagina in younger patients.

Radiation therapy is the most frequently used modality for treatment of squamous cell carcinoma of the vagina. Ideally, at least 7000 to 7500 cGy is administered in less than 9 weeks. Concurrent chemoradiation should strongly be considered.

The overall 5-year survival rate of patients treated for squamous cell carcinoma of the vagina is approximately 45%.

Clear-cell adenocarcinoma is often associated with prenatal DES exposure and has an improved prognosis if the patient is older than age 19 years and has a predominant tubulocystic tumor pattern and low-stage disease. Those with a positive DES maternal history have a better prognosis.

Local therapy for small, stage I clear-cell adenocarcinomas of the vagina is best considered if the tumor is less than 2 cm in diameter, invades less than 3 mm, and is predominantly of the tubulocystic histologic type. Pelvic nodes should be sampled and be free of tumor.

The overall 5-year survival rate of patients treated for clear-cell adenocarcinoma is approximately 80%, in part due to the high proportion of low-stage cases.

Vaginal melanomas are usually fatal. They occur primarily in patients older than age 50 years.

Endometrioid adenocarcinomas of the vagina may occur through the malignant transformation of endometriosis, often associated with the use of unopposed estrogen or tamoxifen.

Endodermal sinus tumors occur in children younger than age 2 years. They secrete -fetoprotein and are usually treated by multiagent chemotherapy followed by surgical excision.

Sarcoma botryoides occurs primarily in children younger than age 8 years. It is treated by a multimodality approach using multiagent chemotherapy with surgical removal and occasionally irradiation.

mitsiko 08.10.10

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