Carcinoma of the Vulva Epidemiology

Carcinoma of the Vulva
Epidemiology
• 4% of gynecologic malignancy
• The median age of patients with invasive
vulvar cancer at diagnosis is about 65 to 70
years
• median age of women with VIN at diagnosis is
45 to 50 years
The relatively stable incidence of invasive cancer
despite a steady increase in patients
diagnosed with VIN could suggest
1. etiologic factors are different
2. Dx improved
3. effective treatment of VIN has prevented a
significant increase in the incidence of
invasive disease.
HPV
• 89 percent of VIN lesions
• 40% of invasive vulvar carcinomas
• HPV vaccination
Invasive SCC
• associated with HPV infection
• notassociated with HPV infection
HPV-positive tumors
1. Basaloid or warty carcinomas with little
keratin formation
2. often associated with VIN
3. frequently multifocal
4. in younger women (35 to 55 years)
5. more likely to have CIN
6. to have risk factors typically associated with
cervical cancer
HPV-negative tumors
1. In older women (55 to 85 years)
2. often associated with vulvar inflammation or
lichen sclerosis (but rarely with VIN)
3. Unifocal
4. well differentiated
5. Higher incidence of p53 mutations
Natural History and Pattern of
Spread
female external genitalia
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mons pubis,
labia majora, labia minora
clitoris,
vestibular bulb,
vestibular glands (including Bartholin's glands
vestibule 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 invasive
1. superficial inguinal lymph nodes(lateralized
lesions)
2. deeper femoral lymph nodes (secondarily )
3. pelvic lymph nodes (then)
4. medial femoral lymph nodes(more medial
lesions)
5. 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 vulva
• lichen sclerosis
• squamous hyperplasia
• dermatoses
About 10% of these lesions have cellular
atypia and are termed vulvar intraepithelial
neoplasia
VIN 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 HPV
• in postmenopausal women
• SCC(More than 90% )
Most squamous carcinomas are well
differentiated,
About 5% of vulvar cancers are anaplastic
carcinomas
Verrucous carcinoma
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Rare
very well-differentiated
in the fifth or sixth decade
a large, locally invasive lesion.
Even with extensive local invasion, lymph
node metastasis from verrucous carcinoma is
very rare.
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primary mammary adenocarcinoma
basal cell carcinomas
sebaceous carcinomas
Malignant melanomas
Vulvar sarcomas
Diagnosis, Clinical Evaluation, and
Staging
Patients with VIN may complain of :
• vulvar pruritus
• irritation,
• a mass
• 50% are asymptomatic
• bleeding
• tender
new vulvar lesion
• biopsy
• Once 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 examination
• wedge biopsy
• Excisional biopsy
is preferred for lesions smaller than 1 cm in
diameter.
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a careful physical examination
chest radiography
biochemical profile
Cystoscopy and proctoscopy
skeletal radiography
CT or MRI scans
PET (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 the lower urethra and/or
the vagina, or the anus (T3) and/or
Unilateral regional node metastasis (N1)
• IVA Tumor invades any of the following:
upper urethra, bladder mucosa, rectal
mucosa, pelvic bone (T4) and/or
Bilateral regional node metastasis. (N2)
• IVB Any distant metastasis including pelvic
lymph nodes. (M1)
Px
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Clinical tumor diameter
depth of invasion
tumor thickness
presence or absence of LVSI
tumor grade?
• More than 75% of patients with LVSI have
positive inguinal nodes.
Prognostic Factors
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amount of keratin
the mitotic rate
the tumor growth pattern
Aneuploid tumors (not be an independent
predictor of outcome)
• HPV DNA ( a poorer prognosis)
• age ?
LN
• presence and number of inguinal node
metastases
• bilateral node involvement
• pelvic node metastases (as stage IV)
• extracapsular extension
• surgical margins and tumor recurrence
1 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
incisions
• cure 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 possible
• Focal 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 CO2
laser.
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 often recurs
• VIN 3 can recur within the donor skin from
split-thickness grafts
T1 and T2 Tumors
• Invasive vulvar tumors can usually be treated
effectively without en 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 a 1-cm margin of 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 : modified radical or radical
vulvectomy
• separate vulvar and groin incisions.
Acute complication
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Wound seroma (15% )
urinary tract infection
wound cellulitis
temporary anterior thigh anesthesia from
femoral nerve injury
• thrombophlebitis
• pulmonary embolus.
Chronic complication
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leg edema
genital prolapse
urinary stress incontinence
temporary weakness of the quadriceps muscle
introital stenosis.
pubic osteomyelitis,
femoral hernia,
rectoperineal fistula
T3 and T4 Tumors
• T3 tumors
S +_RT
• the 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 of
concurrent chemoradiation in this setting.
Chemoradiation in Locally Advanced
Disease
• Most studies have used combinations of cisplatin
,5-FU, and mitomycin-C,
• Treatment schedules usually include a 4- to 5day infusion of 5-FU combined with one of the
other two drugs, with this course repeated every
3 to 4 weeks
CHRT
• Impressive responses
• Cisplatin
• 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 warranted
Elderly (concurrent medical problems)
Tx:
• Small T1 lesions : local resection alone
• T1 and selected T2 lesions: radical local excision
• Larger T2 lesions: modified radical or radical
vulvectomy
• Locally Advanced Disease: CHRT +S
T3 : S+_RT
T4 Tumors:RT+_S+_CHT
Treatment of Regional Disease
• patients who suffer inguinal recurrences are
rarely curable
• primary tumors 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 of
the vulva:
a survival advantage for the radiotherapy arm
• postoperative radiotherapy became standard
for most patients with inguinal node
metastases.
• Complications of lymphadenectomy
Complications
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wound disruption
infection
chronic lymphedema
perioperative mortality
‫• غدد لنفاوی اینگواینال در عمق بیش از ‪ 5‬تا ‪ 8‬سانتی متری‬
‫قرار دارد‬
• Neg inguinal nodes (by tomographic imaging)
with radiotherapy treatment planning rarely
experience a regional recurrence after
inguinal-pelvic irradiation to 40 to 50 Gy.
extent of lymph node dissections
• medial inguinal-femoral nodes may be the
primary site of drainage of some vulvar
cancers;
• now recommend removal of at least the
superficial and medial inguinofemoral 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 of stage 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.