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Carcinoma of the Vagina

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Carcinoma of theVulvaEpidemiology
4% of gynecologic malignancyThe median age of patients with invasivevulvarcancer at diagnosis is about65 to 70 yearsmedian age of women withVINat diagnosis is45 to 50 years
The relatively stable incidence of invasive cancer despite a steady increase in patients diagnosed with VIN could suggestetiologic factors are differentDx improvedeffective treatment of VIN has prevented a significant increase in the incidence of invasive disease.
HPV
89 percent of VIN lesions40% of invasive vulvar carcinomasHPV vaccination
Invasive SCC
associated with HPV infectionnotassociated with HPV infection
HPV-positive tumors
Basaloid or warty carcinomas with little keratin formationoften associated with VINfrequently multifocalin younger women (35 to 55 years)more likely to have CINto have risk factors typically associated with cervical cancer
HPV-negative tumors
In older women (55 to 85 years)often associated with vulvar inflammation or lichen sclerosis (but rarely with VIN)Unifocalwell differentiatedHigher incidence of p53 mutations
Natural History and Pattern of Spread
female external genitalia
mons pubis,labia majora, labia minoraclitoris,vestibular bulb,vestibular glands (including Bartholin's glandsvestibule of the vagina.
gynecologic perineum
The region between the posterior commissure of the labia and the anus is termed the gynecologic perineum.
lymphatics
Even minimally invasivesuperficial inguinal lymph nodes(lateralized lesions)deeper femoral lymph nodes (secondarily )pelvic lymph nodes (then)medial femoral lymph nodes(more medial lesions)obturator nodes(clitoris)
Despite the extensive anastomosis of lymphatics in the region, metastasis of vulvar carcinoma to contralateral lymph nodes is uncommon in patients with well-lateralized T1 lesions.
The lungs are the most common sites of hematogenous metastasis
Pathology
Nonneoplastic epithelial disorders of the vulvalichen sclerosissquamous hyperplasiadermatoses
About 10% of these lesions have cellular atypia and are termed vulvar intraepithelial neoplasiaVIN lesions are assigned a grade from 1 to 3 according to their degree of maturation
Paget's disease of the vulva
a rare intraepithelial lesion located in the epidermis and skin adnexa, accounts for 1% to 5% of vulvar neoplasms.negative for HPVin postmenopausal women
SCC(More than 90% )Most squamous carcinomas are well differentiated,About 5% of vulvar cancers are anaplastic carcinomas
Verrucous carcinoma
Rarevery well-differentiatedin the fifth or sixth decadea large, locally invasive lesion.Even with extensive local invasion, lymph node metastasis from verrucous carcinoma is very rare.
primary mammary adenocarcinomabasal cell carcinomassebaceous carcinomasMalignant melanomasVulvar sarcomas
Diagnosis, Clinical Evaluation, and Staging
Patients with VIN may complain of :vulvar pruritusirritation,a mass50% are asymptomaticbleedingtender
new vulvar lesion
biopsyOnce the diagnosis of high-grade VIN has been established, the entire vulva, cervix, and vagina should be carefully examined because patients often have multifocal or multicentric involvement.
Colposcopic examinationwedge biopsyExcisional biopsyis preferred for lesions smaller than 1 cm in diameter.
a careful physical examinationchest radiographybiochemical profileCystoscopy and proctoscopyskeletal radiographyCT or MRI scansPET (poor sensitivity but high specificity in the prediction of lymph node metastases)
(FIGO) Staging of Carcinoma of the Vulva
I Lesions 2 cm or less in size confined to the vulva or perineum. (T1) (N0)IA Lesions 2 cm or less in size confined to the vulva or perineum and with stromal invasion no greater than 1.0 mm (No)IB Lesions 2 cm or less in size confined to the vulva or perineum and with stromal invasion greater than 1.0 mm (No)
II Tumor confined to the vulva and/or perineum or more than 2 cm in the greatest dimension. (T2) (N0)III Tumor of any size with:Adjacent spread to thelower urethraand/or thevagina, or theanus(T3) and/orUnilateral regional node metastasis (N1)
IVA Tumor invades any of the following: upper urethra, bladder mucosa, rectal mucosa, pelvic bone (T4) and/orBilateral regional node metastasis. (N2)IVB Any distant metastasis including pelvic lymph nodes. (M1)
Px
Clinical tumor diameterdepth of invasiontumor thicknesspresence or absence of LVSItumor grade?More than 75% of patients with LVSI have positive inguinal nodes.
Prognostic Factors
amount of keratinthe mitotic ratethe tumor growth patternAneuploid tumors (not be an independent predictor of outcome)HPV DNA ( a poorer prognosis)age ?
LN
presence and number of inguinal node metastasesbilateral node involvementpelvic node metastases (as stage IV)extracapsular extension
surgical margins and tumor recurrence1 cm or <8mm
Treatment
Radical en bloc resection of the vulva, and inguinofemoral nodes until the early 1980s.5-year survival rates of 60% to 70%,the surgery caused significant physical and psychological complications,patients with multiple positive nodes continued to have a poor prognosis.
operating through separate vulvar and groin incisionscure rates similar to vulvectomy.role of radiotherapy in the curative management of locoregionally advanced disease.
Preinvasive Disease (VIN)-
treatment of high-grade VIN (VIN 3) should be as conservative as possibleFocal lesions can be simply excised.Multiple lesions can be excised separately or, if confluent, with a larger single excision.This approach is generally well tolerated and provides material for histologic assessment.more extensive high-grade VIN, with a CO2laser.
Extensive, diffuse VIN 3
a wider excision, particularly if the lesion involves the perianal skin.a partial vulvectomy of the superficial skin (skinning vulvectomy‌)
VIN 3 oftenrecursVIN 3 can recur within the donor skin from split-thickness grafts
T1 and T2 Tumors
Invasive vulvar tumors can usually be treated effectively withouten bloc radical vulvectomy and inguinal node dissection.Today, most gynecologic oncologists advocate an individualized approach to early invasive vulvar carcinomas.
Overall 5-year disease-specific survival rates for stage I (T1N0M0) and stage II (T2N0M0) disease are approximately 98% and 85%, respectively.
T1 and selected T2 lesions
radical local excision.A wide and deep excision of the lesion is performed, with the incision extended down to the inferior fascia of the urogenital diaphragm.An effort should be made to remove the lesion with a1-cm marginof normal tissue in all directions unless this would require compromise of the anus or urethra.
Small T1 lesions that invade 1 mm or less can be managed with local resection alone because the risk of regional spread is very small.
Larger T2 lesions:modifiedradical or radical vulvectomyseparatevulvar and groin incisions.
Acute complication
Wound seroma(15%)urinary tract infectionwound cellulitistemporary anterior thigh anesthesia from femoral nerve injurythrombophlebitispulmonary embolus.
Chronic complication
leg edemagenital prolapseurinary stress incontinencetemporary weakness of the quadriceps muscleintroital stenosis.pubic osteomyelitis,femoral hernia,rectoperineal fistula
T3 and T4 Tumors
T3 tumorsS +_RTthe vulva may be treated with opposed anterior and posterior photon fields (if the inguinal regions also require treatment) or with an appositional perineal electron beam. The vulva should receive a total dose of 50 to 65 Gy, depending on the proximity of disease to the surgical margin.
preoperative chemoradiation in some patients with T3 and T4
These reports indicated that modest doses of radiation (45 to 55 Gy) produced dramatic tumor responses in some patients with T3 and T4 disease, permitting organ-sparing surgery without sacrifice of tumor control.Investigators have emphasized the use ofconcurrent chemoradiationin this setting.
Chemoradiation in Locally Advanced Disease
Most studies have used combinations ofcisplatin,5-FU,andmitomycin-C,Treatment schedules usually include a 4- to 5-day infusion of 5-FU combined with one of the other two drugs, with this course repeated every 3 to 4 weeks
CHRT
Impressive responsesCisplatin
neoadjuvant chemotherapy in the treatment of locally advanced vulvar cancer.two to three cycles of cisplatin, bleomycin, and methotrexate followed by radical surgery.Caution is warrantedElderly (concurrentmedicalproblems)
Tx:
Small T1 lesions : local resection aloneT1 and selected T2 lesions: radical local excisionLarger T2 lesions: modified radical or radical vulvectomyLocallyAdvanced Disease: CHRT +ST3: S+_RTT4 Tumors:RT+_S+_CHT
Treatment of Regional Disease
patientswho suffer inguinal recurrences are rarelycurableprimarytumors that invade more than 1 mm must have their inguinal nodes treated
compared pelvic lymphadenectomy with inguinal and pelvic irradiation in patients with inguinal node metastases from carcinoma ofthevulva:asurvival advantage for the radiotherapy arm
postoperative radiotherapy became standard for most patients with inguinal node metastases.
Complications of lymphadenectomy
Complications
wound disruptioninfectionchronic lymphedemaperioperative mortality
غدد لنفاوی اینگواینال در عمق بیش از 5 تا 8 سانتی متری قرار دارد
Neginguinalnodes (by tomographic imaging)withradiotherapytreatment planning rarely experience a regional recurrence after inguinal-pelvic irradiation to 40 to 50 Gy.
extent of lymph node dissections
medialinguinal-femoral nodesmay be the primary site of drainage of some vulvar cancers;now recommend removal of at least thesuperficialandmedialinguinofemoral nodes.
The efficacy of sentinel lymph node evaluation in patients with T1 or T2 (less than 4 cm) vulvar cancers?whether the sentinel node procedure can effectively supplant lymphadenectomy in the management ofstage I and II vulvar cancer
Treatment of Metastatic Disease
chemotherapy ?clinicians often use single agents and combination regimens that have had some activity in the treatment of cervical cancer.

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Carcinoma of the Vagina