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Vaginal CancerVaginal Cancer
Vaginal CancerVaginal Cancer
Rare tumor representing only 1-2% of Rare tumor representing only 1-2% of all gynecologic malignanciesall gynecologic malignancies
80-90% are metastatic80-90% are metastatic Mean age of patients with primary Mean age of patients with primary
vaginal cancer is 60-65 yearsvaginal cancer is 60-65 years Most primary tumors are squamous cell Most primary tumors are squamous cell
in originin origin HPV DNA identified in VAINHPV DNA identified in VAIN
Vaginal Cancer precursorsVaginal Cancer precursors
VAIN – avg age of VAIN 3 is 53VAIN – avg age of VAIN 3 is 53 Ratio of VAIN to CIN is 1:23Ratio of VAIN to CIN is 1:23 5% progress to Vaginal Ca5% progress to Vaginal Ca Hallmark of VAINHallmark of VAIN
– cytologic atypia-Pleomorphisim, irreg cytologic atypia-Pleomorphisim, irreg nuclear contours and chromatin clumpingnuclear contours and chromatin clumping
– Abnormal maturation Abnormal maturation – nuclear enlargementnuclear enlargement
Vaginal Cancer precursorsVaginal Cancer precursors
VAIN 3VAIN 3– usually occurs in upper third of vagina and usually occurs in upper third of vagina and
is multifocal and diffuse in half the cases.is multifocal and diffuse in half the cases.– 1/3 of patients have a hx/o CIN1/3 of patients have a hx/o CIN– CIN coexists w/ VAIN in 10-20% of ptsCIN coexists w/ VAIN in 10-20% of pts– Colposcopic findings are similar to those of Colposcopic findings are similar to those of
CIN (aceto white epithelium with CIN (aceto white epithelium with punctations and mosaic patterns)punctations and mosaic patterns)
Vaginal Cancer precursorsVaginal Cancer precursors
VAIN 1-Proliferation of basal layerKoilocytotic atypia
Enlarged pleomorphic nucleivacuolated cytoplasm
Vaginal Cancer precursorsVaginal Cancer precursors
VAIN 2-Proliferation of basal layer,crowding and loss of polarityKoilocytotic atypia
Enlarged pleomorphic nucleivacuolated cytoplasm
Vaginal Cancer precursorsVaginal Cancer precursors
VAIN 3Increased proliferation of abnormal basal and parabasal cells replacing fullthickness of epithelium
Vaginal Cancer precursorsVaginal Cancer precursors
Treatment Options for VAINTreatment Options for VAIN– Excisional Bx for small lesionsExcisional Bx for small lesions– Partial VaginectomyPartial Vaginectomy– Laser VaporizationLaser Vaporization– Intravaginal 5FU creamIntravaginal 5FU cream
Vaginal Cancer: Predisposing Vaginal Cancer: Predisposing FactorsFactors
Low socioeconomic statusLow socioeconomic status History of genital wartsHistory of genital warts Vaginal discharge or irritationVaginal discharge or irritation Previously abnormal Pap smearPreviously abnormal Pap smear Early hysterectomyEarly hysterectomy Previous pelvic radiation (?)Previous pelvic radiation (?) In-utero exposure to DESIn-utero exposure to DES
Anatomy of the VaginaAnatomy of the Vagina
Muscular dilatable tube averaging 7.5 cm in Muscular dilatable tube averaging 7.5 cm in lengthlength
Vaginal wall composed of three layers: Vaginal wall composed of three layers: mucosa, muscularis, adventitia.mucosa, muscularis, adventitia.
Epithelium normally contains no glands and Epithelium normally contains no glands and changes little during reproductive cyclechanges little during reproductive cycle
Lymphatic drainage of upper vagina via pelvic Lymphatic drainage of upper vagina via pelvic nodes while lower vagina drains via femoral nodes while lower vagina drains via femoral and inguinal nodes.and inguinal nodes.
Natural History and Patterns Natural History and Patterns of Spreadof Spread
Lesions usually found in the upper Lesions usually found in the upper vagina on the posterior wallvagina on the posterior wall
Vaginal primary tumors may spread Vaginal primary tumors may spread along mucosa to cervix or vulva along mucosa to cervix or vulva (changes diagnosis)(changes diagnosis)
Direct extension to bladder, parametria, Direct extension to bladder, parametria, paracolpos, rectum, cardinal ligaments, paracolpos, rectum, cardinal ligaments, uterosacral ligamentsuterosacral ligaments
Gross and microscopic Gross and microscopic Findings Findings
50% of Vag Ca ulcerative50% of Vag Ca ulcerative 30% are exophytic 30% are exophytic 20%are annular and constricting20%are annular and constricting
Natural History and Patterns Natural History and Patterns of Spreadof Spread
Any of the nodal groups may be Any of the nodal groups may be involved regardless of the location of involved regardless of the location of the tumorthe tumor
Inguinal nodes most often involved if Inguinal nodes most often involved if lesion is in the lower 1/3 of the vaginalesion is in the lower 1/3 of the vagina
Clinically apparent inguinal node mets Clinically apparent inguinal node mets seen in 5-20% of patientsseen in 5-20% of patients
Incidence of pelvic nodes varies with Incidence of pelvic nodes varies with stage and location of the tumorstage and location of the tumor
Lymphatic Drainage of VaginaLymphatic Drainage of Vagina
Clinical PresentationClinical Presentation
Abnormal vaginal bleedingAbnormal vaginal bleeding– 50-75% of patients with primary tumors50-75% of patients with primary tumors
DysuriaDysuria PainPain
Diagnostic Work-upDiagnostic Work-up
Complete history and physicalComplete history and physical Speculum examination and palpation of Speculum examination and palpation of
the vaginathe vagina Bimanual pelvic and rectovaginal Bimanual pelvic and rectovaginal
examinationexamination Pap smear, colposcopy, directed Pap smear, colposcopy, directed
biopsiesbiopsies
Diagnostic Work-upDiagnostic Work-up
CystoscopyCystoscopy ProctosigmoidoscopyProctosigmoidoscopy Chest X-rayChest X-ray IVPIVP Barium enemaBarium enema Computed TomographyComputed Tomography MRI (84% PPV, 97% NPV)MRI (84% PPV, 97% NPV)
StagingStaging
Stage IStage I - Lesions confined to the mucosa - Lesions confined to the mucosa Stage IIStage II- Subvaginal tissue involved but no - Subvaginal tissue involved but no
extension to pelvic sidewallextension to pelvic sidewall– IIA: Subvaginal infiltration onlyIIA: Subvaginal infiltration only– IIB: Parametrial extensionIIB: Parametrial extension
Stage IIIStage III- Pelvic sidewall extension- Pelvic sidewall extension Stage IVStage IV- Bladder or rectal extension and/or - Bladder or rectal extension and/or
direct extension outside of true pelvisdirect extension outside of true pelvis
StagingStaging
Natural History and Patterns Natural History and Patterns of Failureof Failure
Stage IStage I– 10-20% pelvic recurrence, 10-20% distant10-20% pelvic recurrence, 10-20% distant
Stage IIStage II– 35% pelvic recurrence, 22% distant 35% pelvic recurrence, 22% distant
Stage IIIStage III– 25-37% pelvic recurrence, 23% distant25-37% pelvic recurrence, 23% distant
Stage IVStage IV– 58% pelvic recurrence, 30% distant58% pelvic recurrence, 30% distant
PathologyPathology
Squamous Cell CA represents 80-90% Squamous Cell CA represents 80-90% of primary tumorsof primary tumors
Vaginal SCCA may be considered Vaginal SCCA may be considered primary if there is neither cervical or primary if there is neither cervical or vulvar CA at diagnosis or for 10 years vulvar CA at diagnosis or for 10 years priorprior
No correlation between grade and No correlation between grade and survivalsurvival
Verrucous CarcinomaVerrucous Carcinoma
Variant of well-differentiated SCCA that Variant of well-differentiated SCCA that rarely occurs in the vaginararely occurs in the vagina
Relatively large, well-circumscribed, soft Relatively large, well-circumscribed, soft cauliflower-like masscauliflower-like mass
Cytologic features of malignancy are Cytologic features of malignancy are lackinglacking
May recur locally after surgery but May recur locally after surgery but rarely, if ever, metastasizesrarely, if ever, metastasizes
Pathology Pathology MelanomaMelanoma
– 2nd most common vaginal cancer2nd most common vaginal cancer– Most frequently found in the lower third Most frequently found in the lower third – Cells may be spindle shaped, epithelioid, or Cells may be spindle shaped, epithelioid, or
small lymphocyte-like, pigmented or non-small lymphocyte-like, pigmented or non-pigmentedpigmented
– Junctional activity helps exclude the Junctional activity helps exclude the possibility of a metastasispossibility of a metastasis
– Depth of invasion best predictor of survivalDepth of invasion best predictor of survival
PathologyPathology
Smooth muscle tumorsSmooth muscle tumors Small Cell CarcinomaSmall Cell Carcinoma Endodermal Sinus TumorEndodermal Sinus Tumor Rhabdomyosarcoma (Sarcoma Rhabdomyosarcoma (Sarcoma
Boytrioides)Boytrioides) Malignant lymphomaMalignant lymphoma Clear Cell AdenocarcinomaClear Cell Adenocarcinoma
ManagementManagement
Radiation therapy is the preferred Radiation therapy is the preferred treatment for most carcinomas of the treatment for most carcinomas of the vaginavagina
Surgical therapySurgical therapy– Irradiation failuresIrradiation failures– Non-epithelial tumorsNon-epithelial tumors– Stage I Clear cell adenocarcinomas in Stage I Clear cell adenocarcinomas in
young womenyoung women
ManagementManagement
SurgerySurgery– Stage I tumors of the middle or upper third Stage I tumors of the middle or upper third
of vagina treated with radical of vagina treated with radical hysterovaginectomy and PLNDhysterovaginectomy and PLND
– Stage I tumors of the lower third of vagina Stage I tumors of the lower third of vagina which may encroach on the vulva treated which may encroach on the vulva treated with radical vulvovaginectomy and bilat. with radical vulvovaginectomy and bilat. groin node dissectiongroin node dissection
– Pelvic exenteration possible for more Pelvic exenteration possible for more invasive lesionsinvasive lesions
ManagementManagement
Stage IStage I– Usually managed with RTUsually managed with RT– Superficial lesions (<1cm) may be treated Superficial lesions (<1cm) may be treated
with vaginal cylinder covering the entire with vaginal cylinder covering the entire vagina (6-7 Gy mucosal dose + 2-3 Gy vagina (6-7 Gy mucosal dose + 2-3 Gy dose to tumor)dose to tumor)
– Thicker lesions may be treated with vaginal Thicker lesions may be treated with vaginal cylinder + single plane implant cylinder + single plane implant
– EBRT reserved for aggressive lesions EBRT reserved for aggressive lesions (infiltrating or poorly differentiated)(infiltrating or poorly differentiated)
Vaginal Cylinder + Single Vaginal Cylinder + Single Plane ImplantPlane Implant
ManagementManagement
Stage IStage I– Radical hysterectomy, partial vaginectomy, Radical hysterectomy, partial vaginectomy,
PLND may be used for lesions of the PLND may be used for lesions of the posterior and lateral vaginal fornicesposterior and lateral vaginal fornices
Stage IIAStage IIA– WPRT (2000cGy) + parametrial boost for WPRT (2000cGy) + parametrial boost for
4500cGy-5,000cGy total4500cGy-5,000cGy total
ManagementManagement
Stage IIAStage IIA– WPRT (2000cGy) + parametrial boost for WPRT (2000cGy) + parametrial boost for
4500cGy-5,000cGy total4500cGy-5,000cGy total– WPRT + combination of intracavitary and WPRT + combination of intracavitary and
interstitial implants for 5000 to 6000 cGy interstitial implants for 5000 to 6000 cGy totaltotal
Stage IIB, III, IVAStage IIB, III, IVA– WPRT (4000 cGy) + parametrial boost (2500 WPRT (4000 cGy) + parametrial boost (2500
cGy) cGy)
ManagementManagement
Small Cell CarcinomaSmall Cell Carcinoma– Reasonable local control may be obtained Reasonable local control may be obtained
with surgery or irradiation followed by with surgery or irradiation followed by systemic chemosystemic chemo
– Cyclophosphamide, Adriamycin, Vincristine Cyclophosphamide, Adriamycin, Vincristine (CAV) X 12 cycles (some prior to initiation (CAV) X 12 cycles (some prior to initiation of RT)of RT)
– Doses of RT similar to SCCADoses of RT similar to SCCA
ManagementManagement
RhabdomyosarcomaRhabdomyosarcoma– Generally treated with a combination of Generally treated with a combination of
surgery, RT, and chemotherapysurgery, RT, and chemotherapy– Vincristine, Dactinomycin, Vincristine, Dactinomycin,
Cyclophosphamide (VAC) X 1-2 years Cyclophosphamide (VAC) X 1-2 years effective adjuvant treatment for stage 1 dzeffective adjuvant treatment for stage 1 dz
– Local excision + interstitial/intracavitary RT Local excision + interstitial/intracavitary RT + systemic chemo has replaced radical + systemic chemo has replaced radical pelvic surgery as therapy of choicepelvic surgery as therapy of choice
Sarcoma BotryoidesSarcoma Botryoides
Sarcoma BotryoidesSarcoma Botryoides
Strap cell
ManagementManagement
Malignant LymphomaMalignant Lymphoma– Vaginectomy and radical hysterectomy or Vaginectomy and radical hysterectomy or
pelvic exenteration has been used for pelvic exenteration has been used for localized vaginal tumorslocalized vaginal tumors
– Satisfactory results with pelvic RT (tele and Satisfactory results with pelvic RT (tele and brachytherapy) + systemic chemobrachytherapy) + systemic chemo
– Cyclophosphamide, adriamycin, vincristine, Cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) X 6 cycles most often prednisone (CHOP) X 6 cycles most often usedused
Clear Cell Adenocarcinoma Clear Cell Adenocarcinoma and DES Exposureand DES Exposure
Incidence is between 0.14 to 1.4/1000 Incidence is between 0.14 to 1.4/1000 women exposed to DESwomen exposed to DES
Median age at diagnosis 19 yearsMedian age at diagnosis 19 years Lesions found mainly in the upper 1/3 Lesions found mainly in the upper 1/3
of the anterior vaginal wallof the anterior vaginal wall 90% of patients with early stage 90% of patients with early stage
disease (I and II) at diagnosisdisease (I and II) at diagnosis
ManagementManagement
Clear Cell AdenocarcinomaClear Cell Adenocarcinoma– Surgery for stage I lesions has advantage of Surgery for stage I lesions has advantage of
ovarian preservation and better vaginal ovarian preservation and better vaginal function following skin graftfunction following skin graft
– Vaginectomy, radical hysterectomy PLND, Vaginectomy, radical hysterectomy PLND, paraaortic LNBx (frozen section of distal paraaortic LNBx (frozen section of distal margin)margin)
– Intracavitary or transvaginal radiation can Intracavitary or transvaginal radiation can be used for small lesionsbe used for small lesions
– More extensive lesions: EBRTMore extensive lesions: EBRT
Clear cell adenocarcinomaClear cell adenocarcinoma
FAVORABLE FACTORS IN SURVIVAL OFFAVORABLE FACTORS IN SURVIVAL OF PATIENTS WITH CLEAR CELL PATIENTS WITH CLEAR CELL
ADENOCARCINOMAADENOCARCINOMA
Low stageLow stage Older ageOlder age Tubulocystic PatternTubulocystic Pattern Small tumor diameterSmall tumor diameter Reduced depth of invasionReduced depth of invasion Negative nodal metsNegative nodal mets Positive ho/o DESPositive ho/o DES
Radiation Therapy TechniquesRadiation Therapy Techniques
EBRT delivered through AP:PA portals or EBRT delivered through AP:PA portals or using 4 field “box technique”using 4 field “box technique”
15 cm X 15 cm or 15 cm X 18 cm portals 15 cm X 15 cm or 15 cm X 18 cm portals usually adequateusually adequate
Inguinal nodes should be electively covered Inguinal nodes should be electively covered (4500-5000cGy) for tumors of the lower 1/3 (4500-5000cGy) for tumors of the lower 1/3 of vaginaof vagina
Additional 1500cGy (4-5cm depth) delivered Additional 1500cGy (4-5cm depth) delivered for palpable inguinal nodesfor palpable inguinal nodes
Radiation Therapy TechniquesRadiation Therapy Techniques
Portal for pelvic RT and elective groin coverage
Portal for groin coverage with palpable inguinal nodes
Radiation Therapy TechniquesRadiation Therapy Techniques
Intracavitary therapy utilizes vaginal Intracavitary therapy utilizes vaginal cylinders (Burnett, Bleodorn, Delclos, or cylinders (Burnett, Bleodorn, Delclos, or MIRALVA applicators)MIRALVA applicators)
Upper 1/3 lesions can be treated with tandem Upper 1/3 lesions can be treated with tandem and ovoidsand ovoids
Interstitial therapy with Interstitial therapy with 137137Cs, Cs, 226226Ra, or Ra, or 192192Ir Ir needles have been usedneedles have been used
High dose rate brachytherapy High dose rate brachytherapy (>1200cGy/hour) also used(>1200cGy/hour) also used
SummarySummary Superficial stage I lesions may be treated Superficial stage I lesions may be treated
with RT or radical hysterovaginectomywith RT or radical hysterovaginectomy Stage IIA-IVA treated with WPRT and Stage IIA-IVA treated with WPRT and
intracavitary RTintracavitary RT Role of chemotherapy in advanced SCCA Role of chemotherapy in advanced SCCA
presently unknown presently unknown Pelvic failures and distant metastases Pelvic failures and distant metastases
occur in 1/2 of pts with advanced dzoccur in 1/2 of pts with advanced dz
5 Year Survival 5 Year Survival
0
10
20
30
40
50
60
70
80
Stage I Stage I I Stage I I I Stage IV
The EndThe End