Preinvasive Lesions- Cancers of Vulva and Vagina PDF

PREINVAZIVE LESIONS- CANCERS OF VULVA AND VAGINA Associate Professor Ziya Kalem M.D İSTİNYE UNIVERSITY LIV BAHÇEŞEHİR HOSPITAL PREINVASIVE DISEASE OF THE VULVA The lower genital tract epithelium is of common cloacogenic origin. A strong association exists between sexuall...

PREINVAZIVE LESIONS- CANCERS OF VULVA AND VAGINA Associate Professor Ziya Kalem M.D İSTİNYE UNIVERSITY LIV BAHÇEŞEHİR HOSPITAL PREINVASIVE DISEASE OF THE VULVA The lower genital tract epithelium is of common cloacogenic origin. A strong association exists between sexually transmitted diseases and vulvar intraepithelial neoplasia (VIN), primarily human papillomavirus (HPV), and also human immunodeficiency virus (HIV). Approximately 90% of VIN lesions are positive for HPV Multicentric VIN is primarily associated with high oncogenic risk HPV subtypes such as types 16, 18, and 31, whereas vulvar condylomata and low-grade VIN are frequently associated with low-risk HPV subtypes 6 and 11. VIN can also be classified into viral and nonviral etiologies. The long-term risk of malignant transformation of treated VINIII has been estimated at 3.4-7%, and the risk for progression of untreated VIN is thought to be higher. The most common presenting symptom is pruritus, which is seen in >60% of patients with VIN. The diagnosis is made by careful inspection of the vulvar area followed by biopsy of suspicious lesions. VIN I defined as immature cells occurring in the lower one-third of the epithelium and VIN III as complete loss of cellular maturation in the full thickness of epithelium, VIN II was designated as intermediate between VIN I and VIN III. Dysplasia of the vulva is often multicentric These lesions may be discrete or diffuse, single or multiple, and flat or raised. They even form papules and vary in color from the white appearance of hyperkeratotic tumors to a velvety red or black. The microscopic appearance of dysplastic vulvar lesions is characterized by; Cellular disorganization and loss of stratification that involves the full thiclcness of the epithelium. Cellular density is increased, and individual cells vary greatly in size, with giant and multinucleated cells, numerous mitotic figures and hyperchromatism A second type of VIN, differentiated VIN, which accounts for 50% of patients with vulvar cancer. Approximately 20% of patients have no complaints The importance of performing a biopsy of any vulvar lesion cannot be overemphasized. A biopsy should be taken from the area that appears to be the most abnormal, and multiple biopsies may be necessary in the event of multifocal disease. Differential Diagnosis The differential diagnosis includes epidermal inclusion cysts, acrochordons, seborrheic dermatoses, lichen sclerosus and other vulvar dystrophies, condyloma acuminate, granu- lomatous venereal diseases (eg, syphilis, herpes, or granuloma inguinale), pyogenic infections, or benign tumor, such as a granular cell Unusual Vulvar Malignancies Sarcomas of the vulva constitute a variety of malignant neoplasms that account for 1- 2% of vulvar cancers. The most common is leiomyosarcoma, In general, radical vulvectomy and regional lymphadenectomy are indicated, Adenocarcinoma of the vulva is exceptionally rare unless it arises from the Bartholin's gland or the urethra. Metastatic cancers of the vulva constitute 8% of all vulvar tumors. They usually originate from a genital tract tumor, and 18% arise from the kidney or urethra. Advanced cervical cancer is the most common primary tumor Operative Morbidity & Mortality The most frequently encountered complication is wound breakdown, which occurs in over 50% of patients undergoing radical vulvectomy and bilateral inguinal dissection. Treatment Staging and treatment for vulvar cancer are surgical. The primary treatment for invasive vulvar cancer is complete surgical removal of all tumor whenever possible. When disease has spread to lymph nodes, adjuvant radiation therapy is generally recommended Chemotherapeutic agents such as cisplatin and 5-FU have been combined with radiation therapy. Prognosis The principal prognostic factors in cancer of the vulva are the presence or absence of regional lymph node metastases, size and location of the lesion, and the histologic type. A 5-year survival rate of 75% and a 10-year survival rate of approximately 58% should be expected after complete surgical treatment of primary invasive squamous vulvar cancer. PREINVASIVE DISEASE OF THE VAGINA Almost all lesions of vaginal intraepithelial neoplasia are asymptomatic. Lesions often accompany HPV infection, so patients may complain of vulvar warts. An abnormal Papanicolaou (Pap) smear is usually the first sign of disease. The diagnosis is made by colposcopic examination of the vagina with a directed biopsy. After application of 3-5% acetic acid to the vagina, a lesion under the colposcope may appear as white epithelium and may have mosaicism or punctuation. Lugol's iodine may also help to identify the borders of a lesion. Because the disease process tends to be multifocal, a thorough examination of the vagina from the introitus to the apex must be conducted. Vaginal intraepithelial neoplasia (VAIN) can occur as an isolated lesion, but multifocal disease is more common. Many patients may have similar intraepithelial neoplastic lesions involving the cervix or vulva. The upper third of the vagina is where the majority of these lesions are diagnosed. As with other intraepithelial neoplasias occurring in the lower genital tract, V AIN is characterized by a loss of epithelial cell maturation. The thickness of the epithelial abnormality designates the various lesions as VAIN I, II, or III. VAIN III is synonymous with carcinoma in situ of the vagina. Treatment The primary treatment modality for VAIN is surgical excision or carbon dioxide laser ablation. VAIN I lesions usually do not require treatment, as lesions typically regress, and usually close clinical observation is sufficient. V AIN II and III can be treated by laser ablation or excision. If multifocal disease is present, a total vaginectomy may be performed with a split-thickness skin graft vaginal reconstruction. Topical 5-FU may also be used in treating multifocal VAIN. CANCER OF THE VAGINA Primary cancers of the vagina are rare, representing approximately 0.3% of gynecologic cancers. Approximately 85% are squamous cell cancers, (remainder;adenocarcinomas, sarcomas, melanomas). Secondary carcinoma of the vagina is seen more frequently than primary vaginal cancers. Secondary, or metastatic, tumors may arise from cervical, endometrial, or ovarian cancer, breast cancer, gestational trophoblastic disease, colorectal cancer, or urogenital or vulvar cancer. Extension of cervical cancer to the vagina is probably the most common malignancy involving the vagina. Riskfactors Smoking HPV infection Multiple sexual partners History of lower genital tract neoplasia In utero diethylstilbestrol (DES) exposure Squamous cell carcinoma may be ulcerative or exophytic. It usually involves the posterior wall of the upper third of the vagina but may be multicentric. Direct invasion of the bladder or rectum may occur. The incidence of lymph node metastases is directly related to the size of the tumor. Tumors in the lower third metastasize like cancer of the vulva, primarily to the inguinal lymph nodes Lesions in the middle third or upper third of the vagina may metastasize to the inguinal lymph nodes or directly to the deep pelvic lymph nodes. Adenocarcinomu account for the great majority of primary vaginal malignancies in young patients The clear cell variant has been associated with a history of exposure to DES in utero with a mean age at diagnosis of 19 years. Melanomas of the vagina are rare and most frequently arise from the anterior surface and lower half of the vagina and almost always occur in Caucasian patients. The most common primary vaginal sarcoma is embryonal rbabdomyosarcomas or sarcomabotryoides Leiomyosarcomas, endometrial stromal sarcomas, and carcinosarcomas occur in older women. Hypernepbroma of the kidney characteristically metastasizes to the lower third of the anterior wall of the vagina. Clinical Findings Vaginal cancer is often asymptomatic, discovered by routine vaginal cytologic examination, and confirmed by biopsy after delineation of the location and extent of the tumor by colposcopy. Postmenopausal vaginal bleeding and/or postcoital bleeding are the most common presenting symptoms. Careful bimanual examination with palpation of the entire length of the vagina can detect small submucosal nodules not visualized during the examination. The staging system for cancer of the vagina is clinical and not surgical Differential Diagnosis Benign tumors of the vagina are uncommon, are usually cystic, arise from the mesonephric (wolffian) or paramesonephric ducts, and are usually an incidental finding on examination of the anterolateral wall of the vagina (Gartner's duct cyst). Endometriosis that penetrates the cul-de-sac of Douglas into the upper vagina cannot be differentiated from cancer except by biopsy. Treatment Following biopsy confirmation of disease, all patients should undergo a thorough physical examination and evaluation of the extent of local and metastatic disease Pretreatment evaluation may include : Chest radiography Intravenous pyelogram Cystoscopy Proctosigmoidoscopy CT scan of the abdomen and pelvis. Surgery is reserved for patients with stage I lesions affecting the upper vagina incorporating a radical hysterectomy with an upper vaginectomy and a bilateral pelvic lymphadenectomy Otherwise the treatment consists of primary radiotherapy with brachytherapy for small superficial lesions and external beam radiotherapy with or without intracavitary radiotherapy for larger lesions. An exenterative procedure with removal of the vagina, uterus, tubes, ovaries, rectum, pelvis, and/or bladder and urethra with or without vaginal reconstruction may be considered for patients with a central recurrence after radiation therapy or select patients with stage IVA tumors. For sarcoma botryoides primary chemotherapy with vincristine, dactinomycin, and cyclophosphamide plus radiation has led to excellent results in treating patients with this disease. Prognosis The size and stage of the disease at the time of diagnosis are the most important prognostic indicators in squamous cell cancers. The 5-year survival rate is approximately 77% in patients with stage I disease, 45% in patients with stage II disease, 31% in patients with stage III disease, and 18% in patients with stage IV disease.