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Vaginal Cancer Vaginal Cancer Rare tumor representing only 1-2% of all gynecologic malignancies 80-90% are metastatic Mean age of patients with primary vaginal cancer is 60-65 years Most primary tumors are squamous cell in origin HPV DNA identified in VAIN Vaginal Cancer precursors VAIN – avg age of VAIN 3 is 53 Ratio of VAIN to CIN is 1:23 5% progress to Vaginal Ca Hallmark of VAIN – cytologic atypia-Pleomorphisim, irreg nuclear contours and chromatin clumping – Abnormal maturation – nuclear enlargement Vaginal Cancer precursors VAIN 3 – usually occurs in upper third of vagina and is multifocal and diffuse in half the cases. – 1/3 of patients have a hx/o CIN – CIN coexists w/ VAIN in 10-20% of pts – Colposcopic findings are similar to those of CIN (aceto white epithelium with punctations and mosaic patterns) Vaginal Cancer precursors VAIN 1Proliferation of basal layer Koilocytotic atypia Enlarged pleomorphic nuclei vacuolated cytoplasm Vaginal Cancer precursors VAIN 2Proliferation of basal layer,crowding and loss of polarity Koilocytotic atypia Enlarged pleomorphic nuclei vacuolated cytoplasm Vaginal Cancer precursors VAIN 3 Increased proliferation of abnormal basal and parabasal cells replacing full thickness of epithelium Vaginal Cancer precursors Treatment Options for VAIN – Excisional Bx for small lesions – Partial Vaginectomy – Laser Vaporization – Intravaginal 5FU cream Vaginal Cancer: Predisposing Factors Low socioeconomic status History of genital warts Vaginal discharge or irritation Previously abnormal Pap smear Early hysterectomy Previous pelvic radiation (?) In-utero exposure to DES Anatomy of the Vagina Muscular dilatable tube averaging 7.5 cm in length Vaginal wall composed of three layers: mucosa, muscularis, adventitia. Epithelium normally contains no glands and changes little during reproductive cycle Lymphatic drainage of upper vagina via pelvic nodes while lower vagina drains via femoral and inguinal nodes. Natural History and Patterns of Spread Lesions usually found in the upper vagina on the posterior wall Vaginal primary tumors may spread along mucosa to cervix or vulva (changes diagnosis) Direct extension to bladder, parametria, paracolpos, rectum, cardinal ligaments, uterosacral ligaments Gross and microscopic Findings 50% of Vag Ca ulcerative 30% are exophytic 20%are annular and constricting Natural History and Patterns of Spread Any of the nodal groups may be involved regardless of the location of the tumor Inguinal nodes most often involved if lesion is in the lower 1/3 of the vagina Clinically apparent inguinal node mets seen in 5-20% of patients Incidence of pelvic nodes varies with stage and location of the tumor Lymphatic Drainage of Vagina Clinical Presentation Abnormal vaginal bleeding – 50-75% of patients with primary tumors Dysuria Pain Diagnostic Work-up Complete history and physical Speculum examination and palpation of the vagina Bimanual pelvic and rectovaginal examination Pap smear, colposcopy, directed biopsies Diagnostic Work-up Cystoscopy Proctosigmoidoscopy Chest X-ray IVP Barium enema Computed Tomography MRI (84% PPV, 97% NPV) Staging Stage I - Lesions confined to the mucosa Stage II- Subvaginal tissue involved but no extension to pelvic sidewall – IIA: Subvaginal infiltration only – IIB: Parametrial extension Stage III- Pelvic sidewall extension Stage IV- Bladder or rectal extension and/or direct extension outside of true pelvis Staging Natural History and Patterns of Failure Stage I – 10-20% pelvic recurrence, 10-20% distant Stage II – 35% pelvic recurrence, 22% distant Stage III – 25-37% pelvic recurrence, 23% distant Stage IV – 58% pelvic recurrence, 30% distant Pathology Squamous Cell CA represents 80-90% of primary tumors Vaginal SCCA may be considered primary if there is neither cervical or vulvar CA at diagnosis or for 10 years prior No correlation between grade and survival Verrucous Carcinoma Variant of well-differentiated SCCA that rarely occurs in the vagina Relatively large, well-circumscribed, soft cauliflower-like mass Cytologic features of malignancy are lacking May recur locally after surgery but rarely, if ever, metastasizes Pathology Melanoma – 2nd most common vaginal cancer – Most frequently found in the lower third – Cells may be spindle shaped, epithelioid, or small lymphocyte-like, pigmented or non-pigmented – Junctional activity helps exclude the possibility of a metastasis – Depth of invasion best predictor of survival Pathology Smooth muscle tumors Small Cell Carcinoma Endodermal Sinus Tumor Rhabdomyosarcoma (Sarcoma Boytrioides) Malignant lymphoma Clear Cell Adenocarcinoma Management Radiation therapy is the preferred treatment for most carcinomas of the vagina Surgical therapy – Irradiation failures – Non-epithelial tumors – Stage I Clear cell adenocarcinomas in young women Management Surgery – Stage I tumors of the middle or upper third of vagina treated with radical hysterovaginectomy and PLND – Stage I tumors of the lower third of vagina which may encroach on the vulva treated with radical vulvovaginectomy and bilat. groin node dissection – Pelvic exenteration possible for more invasive lesions Management Stage I – Usually managed with RT – Superficial lesions (<1cm) may be treated with vaginal cylinder covering the entire vagina (6-7 Gy mucosal dose + 2-3 Gy dose to tumor) – Thicker lesions may be treated with vaginal cylinder + single plane implant – EBRT reserved for aggressive lesions (infiltrating or poorly differentiated) Vaginal Cylinder + Single Plane Implant Management Stage I – Radical hysterectomy, partial vaginectomy, PLND may be used for lesions of the posterior and lateral vaginal fornices Stage IIA – WPRT (2000cGy) + parametrial boost for 4500cGy-5,000cGy total Management Stage IIA – WPRT (2000cGy) + parametrial boost for 4500cGy-5,000cGy total – WPRT + combination of intracavitary and interstitial implants for 5000 to 6000 cGy total Stage IIB, III, IVA – WPRT (4000 cGy) + parametrial boost (2500 cGy) Management Small Cell Carcinoma – Reasonable local control may be obtained with surgery or irradiation followed by systemic chemo – Cyclophosphamide, Adriamycin, Vincristine (CAV) X 12 cycles (some prior to initiation of RT) – Doses of RT similar to SCCA Management Rhabdomyosarcoma – Generally treated with a combination of surgery, RT, and chemotherapy – Vincristine, Dactinomycin, Cyclophosphamide (VAC) X 1-2 years effective adjuvant treatment for stage 1 dz – Local excision + interstitial/intracavitary RT + systemic chemo has replaced radical pelvic surgery as therapy of choice Sarcoma Botryoides Sarcoma Botryoides Strap cell Management Malignant Lymphoma – Vaginectomy and radical hysterectomy or pelvic exenteration has been used for localized vaginal tumors – Satisfactory results with pelvic RT (tele and brachytherapy) + systemic chemo – Cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) X 6 cycles most often used Clear Cell Adenocarcinoma and DES Exposure Incidence is between 0.14 to 1.4/1000 women exposed to DES Median age at diagnosis 19 years Lesions found mainly in the upper 1/3 of the anterior vaginal wall 90% of patients with early stage disease (I and II) at diagnosis Management Clear Cell Adenocarcinoma – Surgery for stage I lesions has advantage of ovarian preservation and better vaginal function following skin graft – Vaginectomy, radical hysterectomy PLND, paraaortic LNBx (frozen section of distal margin) – Intracavitary or transvaginal radiation can be used for small lesions – More extensive lesions: EBRT Clear cell adenocarcinoma FAVORABLE FACTORS IN SURVIVAL OF PATIENTS WITH CLEAR CELL ADENOCARCINOMA Low stage Older age Tubulocystic Pattern Small tumor diameter Reduced depth of invasion Negative nodal mets Positive ho/o DES Radiation Therapy Techniques EBRT delivered through AP:PA portals or using 4 field “box technique” 15 cm X 15 cm or 15 cm X 18 cm portals usually adequate Inguinal nodes should be electively covered (45005000cGy) for tumors of the lower 1/3 of vagina Additional 1500cGy (4-5cm depth) delivered for palpable inguinal nodes Radiation Therapy Techniques Portal for pelvic RT and elective groin coverage Portal for groin coverage with palpable inguinal nodes Radiation Therapy Techniques Intracavitary therapy utilizes vaginal cylinders (Burnett, Bleodorn, Delclos, or MIRALVA applicators) Upper 1/3 lesions can be treated with tandem and ovoids Interstitial therapy with 137Cs, 226Ra, or 192Ir needles have been used High dose rate brachytherapy (>1200cGy/hour) also used Summary Superficial stage I lesions may be treated with RT or radical hysterovaginectomy Stage IIA-IVA treated with WPRT and intracavitary RT Role of chemotherapy in advanced SCCA presently unknown Pelvic failures and distant metastases occur in 1/2 of pts with advanced dz 5 Year Survival 80 70 60 50 40 30 20 10 0 Stage I Stage II Stage III Stage IV The End