1. Vaginal Cancer

2. 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 years
Most primary tumors are squamous cell in origin
HPV DNA identified in VAIN

3. 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

4. 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)

5. Vaginal Cancer precursors
VAIN 1-
Proliferation of basal layer
Koilocytotic atypia
Enlarged pleomorphic nuclei
vacuolated cytoplasm

6. Vaginal Cancer precursors
VAIN 2-
Proliferation of basal layer,crowding
and loss of polarity
Koilocytotic atypia
Enlarged pleomorphic nuclei
vacuolated cytoplasm

7. Vaginal Cancer precursors
VAIN 3
Increased proliferation of abnormal basal and parabasal cells replacing full
thickness of epithelium

8. Vaginal Cancer precursors
Treatment Options for VAIN
Excisional Bx for small lesions
Partial Vaginectomy
Laser Vaporization
Intravaginal 5FU cream

9. 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

10. 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.

11. 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

12. Gross and microscopic Findings
50% of Vag Ca ulcerative
30% are exophytic
20%are annular and constricting

13. 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

14. Lymphatic Drainage of Vagina
The 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.

15. Clinical Presentation
Abnormal vaginal bleeding
50-75% of patients with primary tumors
Dysuria
Pain
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. In general, the longer the delay in diagnosis, the worse the prognosis and the more difficult the therapy.

16. Diagnostic Work-up Complete history and physical
Speculum examination and palpation of the vagina
Bimanual pelvic and rectovaginal examination
Pap smear, colposcopy, directed biopsies

17. Diagnostic Work-up Cystoscopy Proctosigmoidoscopy Chest X-ray IVP
Barium enema
Computed Tomography
MRI (84% PPV, 97% NPV)

18. 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

19. Staging

20. 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
It should be noted that these numbers are specific to squamous cell lesions. In clear cell adenoca, lung and supraclavicular nodal mets represent ~35% of recurrences in young women.

21. 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

22. 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

23. 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

24. Pathology Smooth muscle tumors Small Cell Carcinoma
Endodermal Sinus Tumor
Rhabdomyosarcoma (Sarcoma Boytrioides)
Malignant lymphoma
Clear Cell Adenocarcinoma
Endodermal sinus tumors occur in infants under age 2 years. They secrete alpha-fetoprotein and are usually treated by multiagent chemotherapy followed by operative excision.

25. 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
Rt must be individualized in the treatment of vaginal Ca. Paravaginal and/or parametrial interstitial implants must be considered in cases with gross residual tumor after teletherapy and standard brachytherapy. The direct approximation of the vagina to the bladder, urethra and rectum makes surgical treatment difficult.

26. 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

27. 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 Gy dose to tumor)
Thicker lesions may be treated with vaginal cylinder + single plane implant
EBRT reserved for aggressive lesions (infiltrating or poorly differentiated)

28. Vaginal Cylinder + Single Plane Implant

29. Management Stage I Stage IIA
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

30. Management Stage IIA Stage IIB, III, IVA
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)

31. 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

32. 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

33. Sarcoma Botryoides
Sarcoma botryoides protruding through vaginal introitus. The tumors 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).

34. Sarcoma Botryoides Strap cell
Effective control with less radical surgery has been achieved with a multimodality approach consisting of multiagent chemotherapy (VAC), usually combined with operation. Radiation therapy has also been used.

35. 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

36. 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

37. 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 adenocarcinomas seen b/c of association with
intrauterine exposure to diethylstilbestrol (DES). In general, operation is the primary treatment modality because of the young age of the patients.

38. Clear cell adenocarcinoma
Clear cell adenocarcinoma. A: Tubulocystic cell pattern. Note
hobnail cells extruding into lumina of tubular structures. (H&E stain; ×180.) B, Solid pattern.

39. Reduced depth of invasion Negative nodal mets Positive ho/o DES
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

40. 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 ( cGy) for tumors of the lower 1/3 of vagina
Additional 1500cGy (4-5cm depth) delivered for palpable inguinal nodes

41. Radiation Therapy Techniques
Portal for pelvic RT and elective groin coverage
Portal for groin coverage with palpable inguinal nodes

42. 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

43. 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

44. 5 Year Survival

45. The End