19- PREINVASIVE LESION- CANCER

Preinvasive Lesions-Cancers of Vulva and Vagina

• Preinvasive lesions and cancers of the vulva and vagina are discussed.
• The lower genital tract epithelium has a cloacogenic origin.
• A strong link exists between sexually transmitted diseases (STDs), particularly HPV, and VIN. HIV is also a factor.
• Approximately 90% of VIN lesions are HPV positive.
• Multicentric VIN is linked to high-risk HPV types (16, 18, 31).
• Vulvar condylomas and low-grade VIN relate to low-risk HPV types (6, 11).
• VIN can be classified into viral and non-viral etiologies.

Preinvasive Disease of the Vulva

• VIN is categorized into 3 grades: I, II, and III. These are based on cellular maturation and location. Grade I is immature cells in the lower third. Grade III is the complete loss of cellular maturation throughout the epithelium. Grade II lies between these.
• The most common symptom is pruritus (itching), often present in over 60% of patients with VIN.
• Diagnosis involves careful vulvar inspection and biopsy of suspicious lesions.
• The risk of malignant transformation in treated VINIII is estimated at 3.4-7%, and untreated VIN has a higher risk of progression.

Extramammary Paget's Disease

• Pruritus and vulvar soreness are common initial symptoms.
• Lesions often appear eczematoid macroscopically, often starting on hair-bearing vulvar areas, but can extend to the perirectal, buttocks, thighs, and mons.
• Most lesions are confined to the epithelial layer.
• Diagnosis is made through vulvar biopsy (a tissue sample).
• Paget's disease of the skin, an intraepithelial neoplasia (or adenocarcinoma in situ) accounts for less than 1% of vulvar malignancies.
• Less than 20% of vulvar Paget's disease is linked to underlying adenocarcinoma.
• 20-30% of patients have concurrent carcinomas elsewhere, like the breast, rectum, bladder, cervix, ovary, and urethra.
• The disease often presents as a pruritic, slowly spreading, velvety-red skin discoloration.
• The disease may persist for years with minimal evidence of an underlying adenocarcinoma.

Cancer of the Vulva

• Vulvar cancer typically occurs in postmenopausal women.
• Patients often experience a prolonged history of vulvar irritation marked by pruritus, discomfort, and possibly bloody discharge.
• Early lesions may resemble chronic vulvar dermatitis.
• Late-stage lesions can take the form of cauliflower-like growths or hard ulcerations.
• Diagnosis requires biopsy.
• Cancers arise from skin, subcutaneous tissue, or glandular elements in the vulva.
• Squamous cell carcinoma is the most common vulvar cancer type (approximately 90%).

Unusual Vulvar Malignancies

• Sarcomas, adenocarcinomas, and metastatic cancers are less common vulvar malignancies.
• Sarcomas account for 1-2% of vulvar cancers, with leiomyosarcoma being the most common.
• Adenocarcinoma of the vulva is rare, usually arising from the Bartholin's gland or urethra.
• Metastatic cancers comprise about 8% of vulvar cancers, often originating from other genital tract cancers, or in rare cases, the kidney or urethra.

Operative Mortality and Morality

• The most common complication after radical vulvectomy and bilateral inguinal dissection is wound breakdown, which occurs in over 50% of patients.
• The primary treatment for invasive vulvar cancer is surgical removal of all discernible tumors.
• If lymph node involvement is found, adjuvant radiation therapy is commonly part of the treatment.
• Chemotherapy, combining cisplatin and 5-FU, is sometimes used with radiotherapy.

Prognosis

• Stage, location, and the histological type of the lesions are factors in determining a patient's prognosis.
• The 5-year survival rate after complete surgical treatment of primary invasive squamous vulvar cancer is about 75%, and the 10-year survival rate is approximately 58%.

Preinvasive Vaginal Disease

• The majority of vaginal intraepithelial neoplasia (VAIN) cases are asymptomatic.
• HPV infection is frequently associated with VAIN.
• Abnormal Pap smears often flag the presence of vulvar or vaginal intraepithelial neoplasia.
• VAIN is diagnosed by colposcopic examination, commonly following acetic acid application, which causes affected regions to appear white.
• The location of the neoplasia is identified with a directed biopsy.
• VAIN lesions frequently appear multifocal, requiring comprehensive examination of the entire vagina.
• VAIN lesions in the upper third of the vagina are diagnosed more often.

Treatment

• Treatment of VAIN I frequently involves observation, as these lesions tend to regress.
• Surgical excision is the primary treatment for VAIN II and III.
• Laser ablation is used as an alternative for less invasive cases.

Cancer of the Vagina

• Primary vaginal cancers are relatively rare and account for approximately 0.3% of gynecologic cancers.
• 85% of these are squamous cell cancers. Other malignancies, secondary cancers, originate from the cervix, endometrium, ovary, or other structures.
• Cancer frequently originates from the cervical portion and spreads into the vagina.

Risk Factors

• Smoking, HPV infection, multiple sexual partners, past lower genital tract neoplasias, and in utero DES exposure are risk factors associated with vaginal cancer.

Unusual Vaginal Malignancies

• Rare malignancies, such as sarcomas, account for only 1-2% of vaginal cancers.
• Direct invasion of the bladder or rectum can occur.
• Lymph node metastasis is linked to tumor size.
• Tumors in the lower vagina tend to metastasize to inguinal lymph nodes. Tumors in the middle and upper portions metastasize either to the inguinal lymph nodes or directly to deep pelvic lymph nodes as well.

Adenocarcinoma

• Adenocarcinomas are a substantial component of vaginal malignancies in younger women.
• The clear cell variant is often associated with in utero DES exposure, diagnosed typically around 19 years of age.
• Melanomas primarily originate in the anterior surface and lower half of the vagina, more frequently in Caucasian women.
• Leiomyosarcoma, endometrial stromal sarcomas, and carcinosarcomas are more commonly observed in older women.

Clinical Findings

• Vaginal cancer commonly features no symptoms and is often identified via routine cytology screenings.
• Postmenopausal bleeding or bleeding after intercourse are symptoms suggesting vaginal cancer.
• Careful bimanual palpation is employed to detect submucosal nodules not visible during a colposcopic examination.

Staging System

• The staging system for vaginal cancer, as with many other cancers, is mostly clinical, relying on the results of physical examinations and scans of the tumor rather than surgical methods.

Differential Diagnoses

• Benign tumors of the vagina are less prevalent. They often appear cystic and originate from mesonephric or paramesonephric ducts.
• Endometriosis that has invaded the upper vagina is sometimes misdiagnosed for vaginal cancer unless specifically confirmed by a biopsy.

Pretreatment Evaluation

• Evaluation for metastasis typically involves chest radiography, intravenous pyelography, cystoscopy, proctosigmoidoscopy, and a CT scan of the abdomen and pelvis.

Treatment Options

• Surgical intervention, often including hysterectomy, is reserved for stage I or higher vaginal tumors that involve the upper vagina.
• Treatment for superficial cases frequently involves radiotherapy (with or without brachytherapy) and/or external beam radiotherapy.
• In the case of recurrent or advanced tumors, radical surgery is often a consideration either at the time of the initial surgery or after initial treatment with radiation.

Prognosis

• Significant prognostic factors in squamous cell vaginal cancers include tumor size, stage of the disease, and the presence or absence of regional lymph node metastasis.
• The 5-year survival rate for stage I disease is roughly 77%, decreasing to 45% for stage II, 31% for stage III, and 18% for stage IV.