Vulva-Vaginal Carsinoma Meral Aban MD. Professor of OBS&GYN Specialist of GYN ONC..

Vulvar anatomy The vulva is comprised of the female external genitalia, which include the labia majora and minora, clitoris, vestibule, vaginal introitus, and urethral meatus.

Vulvar cancer is the fourth most common gynecologic cancer Contains 5% of all malignancies of the female genital tract (after cancer of the uterine corpus, ovary, and cervix).

Vulvar Cancer Most often found in women age 60–70. The squamous cell carcinoma of the vulva is the most common category (95%)

Epidemiology Vulvar cancer can be classified into two groups according to predisposing factors: The first type correlates with a HPV infection and occurs mostly in younger patients. The second group is not HPV associated and occurs often in elderly women without neoplastic epithelial disorders.

The second type of vulvar cancer includes vulvar non- neoplastic epithelial disorders (VNED) and advanced age that lead to cellular atypia and eventually to cancer. Diabetes mellitus, hypertension, and obesity seem to correlate with the incidence of vulvar cancer, but do not appear to be responsible. Lichen sclerosus, a subgroup of VNED, is mooted as a predisposing risk factor in the development of HPV-negative vulvar cancer.

Histology Squamous (90%).  Adenocarcinoma (Paget disease, Bartholin’s gland).  Basal cell carcinoma.  Melanoma (4–5%).  Metastasis.  Sarcoma.  Verrucous carcinoma. Vulvar melanoma is the second most common neoplasm of the vulva. The majority of lesions involve the clitoris or labia minora.

Histology Squamous cell carcinoma (SCC) accounts 95% Subtypes of vulvar SCC: warty, basaloid, and keratinizing. The warty or basaloid types of SCC are often associated with a VIN The keratinizing type usually occurs in postmenopausal women The warty/ basaloid types tend to occur more often in perimenopausal women.

Metastasis First, by direct expansion into the contiguous organs (the vagina, urethra, and anus), followed by lymphatic metastasis to regional lymph nodes (from the inguinal to the femoral to the pelvic lymph nodes), finally by hematogenous spread to distant sites (liver, lungs, and bones).

Lymphatic Drainage The majority of the vulva is drained by lymphatics that pass laterally to the superficial inguinal lymph nodes. The clitoris and anterior labia minora may also drain directly to the deep inguinal or internal iliac lymph nodes

Lymphatic drainage of the vulva

The risk of nodal metastasis increases with the stage of disease. The size of lesion, and the depth of invasion are the most important prognostic factors for vulvar cancer.

TNM and FIGO Staging

SIGNS AND SYMPTOMS Pruritus (most common). Ulceration.  Mass (often exophytic).  Bleeding.

Diagnosis The diagnosis of vulvar cancer is made by biopsy. The patient may be examined under anesthesia. Cystoscopy, proctoscopy, x-ray examination of the lungs, and IVP are used for staging purposes. Suspected bladder or rectal involvement must be confirmed by biopsy.

RISK FACTORS Postmenopausal. Smoking. Immunodeficiency syndromes.  Other risk factors: Age  HPV  VIN  HIV  Vulvar skin disease (dystrophy)  Melanoma  Atypical moles

The labia majora are the most common site of vulvar carcinoma involvement and account for about 50% of cases. The labia minora account for 15% to 20% of vulvar carcinoma cases. The clitoris and Bartholin glands are less frequently involved. Lesions are multifocal in about 5% of cases. About 90% of vulvar carcinomas are squamous cell cancers.

TREATMENT Stages I–II: Radical vulvectomy and lymphadenectomy (wide local ex- cision is sometimes possible for certain small lesions < 1 cm). Stages III–IV: As above, plus removal of affected organs and adjuvant radiation therapy.

Management of the Primary Lesion In order to avoid psychosexual morbidity, a radical wide local excision is possible in the case of localized lesions. T1 lesions with no extension to adjacent perineal structures (ie, urethra, vagina, and/or anus) might be treated by wide local excision.

Management of lymph nodes Inguinofemoral lymphadenectomy is the standard approach for evaluation of the lymph nodes in women with vulvar cancer. The groin nodes are the most important prognostic indicator in SCC of the vulva cancer. The indication for lymphadenectomy depends on the stromal invasion of tumor. If the deep of tumor stromal ınvasıon, less than 1 mm is not associated with inguinal node metastases

Sentinal Lynph Node SLN biopsy is recommended in those patients who have early stages(I or II) of vulvar cancer to avoid the operative morbidity, such as wound complications or lymphedema. The SLN can be detected using injected radio colloid 99mTc (technetium) and isosulfan or methylene blue, which are inserted around the lesion before operation.

Lymphedema

Treatment approach Depending on the results of surgical staging, women are categorized as having early or advanced stage disease Early stage disease is defined as stage I or II: These patients should undergo a surgical excision including adjuvant treatment based on the findings at the time of surgery Locally advanced stage disease is defined as stage III or IVA: Operative treatment is preferred whenever feasible. Patients who are not surgical candidates should receive primary chemoradiation. Stage IVB disease includes women with distant metastases; a primary chemotherapy is recommended, provided patients are candidates for systemic treatment. If not, palliative care is appropriate.

Prognosis Survival is dependent on the pathologic status of the inguinal nodes. In patients with operable disease without nodal involvement, the overall survival (OS) rate is 90% In the patients with nodal involvement, the 5-year OS rate is approximately 50% to 60%.

Prognosis

Non-Squamous Intraepithelial Neoplasia PAGET’S DISEASE Adenomatous Intraepithelial Hyperplasia of Ecrin and Apocrin glands Some cases have an underlying adeno-ca Apocrine sweat gland Bartholin gland, anorectum,

Histology (Paget’s Disease) The malignant cell arise from undifferentiated basal cells The “transformed cells” spread intraepithelially throughout the squamous epithelium Paget disease must be differentiated from superficial spreading melanoma PAS and musincarmine staining ( + in the Paget, - in the Melanoma) Histology (Paget’s Disease) The epidermis is permeated by abnormal cells with vacuolated cytoplasm and atypical nuclei. This heavy concentration of abnormal cells in the parabasal layers is typical of Paget’s disease. The “transformed cells” spread intraepithelially throughout the squamous epithelium and may extend into the appendages. The epidermis is permeated by abnormal cells with vacuolated cytoplasm and atypical nuclei.

Clinical Features (Paget’s Disease) Predominantly effects postmenopausal white woman Symptoms Vulvar Pruritus Vulvar Soreness The lesion has an eczematoid appearance macroscopically and usually begins on the hair-bearing portions of the vulva A second synchronous and metachronous primary neoplasm is assoc. with extramammarian Paget’s Disease in about 4% of patients. Assoc ca: Cervix, colon, bladder, gallbladder, breast Presenting Symtom is usually vulvar pruritus, and soreness.

Treatment (Paget’s Disease) wide and deep local excision should be performed Underlying dermis should be removed for adequate histologic evaluation Ifunderlying invasive ca present: Radical vulvectomy and at least ipsilateral inguinal femoral lymphadenectomy Unlike squamous cell VIN 3, in which the histologic extent of disease correlates closely with the macroscopic lesion, Paget’s disease usually extends well beyond the gross lesion

Vajinal cancer Primary cancer arises in vagina. A rare gynecologic malignancy (2% of gynecologic cancers).  Usually presents in postmenopausal women.  Increased risk in premenopausal women exposed to DES in utero.  Most common type is squamous cell carcinoma (other types are the same as vulvar cancer types).  Having CIN or VIN is a risk factor for development of vaginal cancer.

Vaginal Malignancies

DIAGNOSIS STAGING TREATMENT Biopsy of suspicious lesion. Vaginal cancer is clinically staged. The stage of tumor is the most important predictor of prognosis. TREATMENT Stages I–II: Surgical resection and radiation.  Stages III–IV: Radiation only.

Stagin of Vaginal Cancer Limited to vaginal mucosa II: Beyond mucosa but not involving pelvic wall III: Pelvic wall involvement IV: Involvement of bladder, rectum, or distant mets

VIN(Vulvar Inraepithelial Neoplasia) High-grade intra- epithelial squamous lesion and precursor of invasive squamous cell carcinoma (SCC). The International Sociaty for the Study of Vulvovaginal Disease (ISSVD) classification distinguished two diagnosis types of VIN: 1- Usual type (human papillomavirus (HPV-related type) 2- Differentiated type (not HPV-related type).

VIN The incidence of usual- type VIN is higher in younger women, while differentiated-type VIN is more common in older patients with chronic dermato- logic conditions. Differentiated-type VIN has a greater invasive potential and shorter time between diagnosis and SCC than usual- type VIN.

Dysplasia occur predominantly in the lower 1/3 of epithelium Celluler immaturity Nuclear abnormalities Maturation Disturbance Mitotic Activity VIN 1 Dysplasia occur predominantly in the lower 1/3 of epithelium VIN 2 Intermediate between VIN 1 and VIN 3 VIN 3 Dysplasia occur in the fulltichkness of epithelium

SYMPTOMS COLPOSCOPY DIAGNOSIS OF VIN Pruritus Burning Vulvar Soreness Bleeding Discharge Urination Discomfort Persistant Ulcer Skin area that has a different color Existing nevus change in symmetry or color COLPOSCOPY Asetic Asit 3%-5% Toluidin Blue 1%  Dry  Asetic Asit Rinse Normal Vulvar Epithel Vulvar epithelial changes are enhanced by applying a 3- to 5-percent acetic acid–soaked gauze pads to the vulva for 5 minutes prior to colposcopic examination. As an alternative, 1-percent toluidine blue may help define the best site for biopsy or the margins of surgical excision by staining abnormal nuclei (Joura, 1998). Procedurally, the vulva is painted with 1-percent toluidine blue, which is allowed to dry and then rinsed with 1-percent acetic acid. Toluidine blue is generally removed from normal tissue by the acetic acid rinse, whereas abnormal epithelium retains stain. Unfortunately, hyperkeratosis may give a false-negative result, and benign lesions or ulcers a false-positive test. VIN 3

TREATMENT VIN lesions are multifocal, thus requiring treatment of many areas. Treatment is according to the size of the lesion:  Small, well-circumscribed VIN: Wide local excision.  Multifocal lesions: Laser vaporization. Extensive (large) lesions: Skinning vulvectomy.