1

Ma

li

g na n

t Dis ea s es o

f

t

h

e

V

a g

i

na :

I

n

tr a e p

i t

h

e

li

a

lN

e o p

l

a s

i

a,

C

a r c

i

n o ma,

S

a r c o ma

K E Y T E R M S A N D D E F I N I T I O N S

C le a r

-

C

e

l l

A de n o c a r c

i

n o m a

Av

a g i n a

lo r c e r

v

i c a

l

m a

l

i g n a n cy

o c cu

r r i n g p r i m a r i

l

y

a

ft e r 1 4

y

e a r so

f

a g e,

o

f

t e n a s so c i a t e

d

w

i t

h

p r e n a t a

l

ex

po s

u

r e to

d

i e t

h

y

l

s t i

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e s t ro

l (D E S

).

E

n

d

o

d

e r m a

l S i

n u s

T

u m o r

A r a r e a

d

e no c a r c i no m a o

f

t

h

e

v

a g i n a o c cu

r r i n g i n

i n

f

a n t s

y

o

u

n g e r t

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a n 2

y

e a r so

f

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F ie

l d D

e

f

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T

h

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y

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u

s e p i t

h

e

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t

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e

l

o

w

e r

g e n i t a

l

t r a c t

(

c e r

v

i

x

,

v

a g i n a,

a n

dv u

l

v

a

)

to

u

n

d

e r go

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h

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d

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e to i n

f

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w

i t

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t

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e

h

u

m a n

p a p i

l l

o m a

v

i r

u

s

(H P V

).

P

e

lv

i

c

Ex e n te r a t

i

o n

A n ex

t e n s i

v

e p e

l

v

i co p e r a t io n

u

s

u

a

l l

y

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l

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d

to t r e a t

a c e n t r a

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p e

l

v

i c r e cu

r r e n c e o

f

c e r

v

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l

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v

a g i n a

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c a r c i no m a a

ft e r r a

d

i a t io n

.

A to t a

l

ex

e n t e r a t io n i n

v

o

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v

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r e mo

v

a

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e

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t e r

u

s,

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m.

A n

a n t e r io r ex

e n t e r a t io n s p a r e s t

h

e r e c t

u

m

,

w

h

e r e a s a

po s t e r io r ex

e n t e r a t io n s p a r e s t

h

e

b l

a

d d

e r

.

P

se u

d

o s a r c o m a

B

o t r y o

i d

e s

A

b

e n i g n t

u

mo ro c c

u

r r i n g i n t

h

e

v

a g i n ao

f

i n

f

a n t s a n

d

p r e g n a n t

w

o m e n t

h

a t

h

a s a po

l

y

p

l

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h

a p e

.

M i c ro s co p i c a

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i t m ay

b

e co n

f

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s e

d

w

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h

s a r co m a

b

o t r

y

o i

d

e s

.

S

a r c o m a

B

o t r y o

i de s

( E

m

b

r y o n a

l

R h

a

b d

o m y o s a r c o m a

)

A r a r e,

o

ft e n

f

a t a

l

,

m a

l

i g n a n c

y

o

f

t

h

e

v

a g i n a t

h

a to c cu

r s

i n i n

f

a n t s a n

d

c

h

i

l d

r e n.

V

a g

i

n a

l T

u m o r

S

t a ge

A c

l

i n i c a

l

c

l

a s s i

f

i c a t io n

d

e s c r i

b

i n g t

h

e ex

t e n to

f

s p r e a

d

o

f

v

a g i n a

l

c a r c i no m a

.

St a g e

I:

L i m i t e

d

to

v

a g i n a

l

w

a

l l

St a g e

I I:

E

x

t e n

d

s to s

u

b

v

a g i n a

l

t i s s

u

e

St a g e

I I I:

R e a c

h

e s t

h

e p e

l

v

i c s i

d

e

w

a

l l

St a g e

I V

:

E

x

t e n

d

s

b

ey

o n

d

t

h

e t r

u

e p e

l

v

i so r i n to m

u

co s a

o

f

t

h

e

b l

a

d d

e ro r r e c t

u

m

V

a g

i

n a

l I

n t r a e p

i

t

he

l i

a

l

Ne o p

l

a s

i

a

( V A I N ) 1

V A I N o

f

t

h

e

l

e a s t s e

v

e r e t

y

p e

(

co m p a r a

b l

e to m i

l d

d

y

s p

l

a s i a

)

,

o c cu

py

i n g t

h

e

l

o

w

e r o n e t

h

i r

d

o

f

t

h

e

e p i t

h

e

l

i

u

m.

A

l

so t e r m e

d l

o

w -

g r a

d

e s q

u

a mo

u

s

i n t r a e p i t

h

e

l

i a

l l

e s io n.

V A I N

-

2

V A I No

f

i n t e r m e

d

i a t e s e

v

e r i t

y

(

co m p a r a

b l

e to mo

d

e r a t e

d

y

s p

l

a s i a

)

,

o c c

u

p

y

i n g t

h

e

l

o

w

e r t

w

o t

h

i r

d

s o

f

t

h

e

e p i t

h

e

l

i

u

m.

V A I N

-

3

V A I No

f

t

h

e mo s t s e

v

e r e t

y

p e

(

co m p a r a

b l

e to s e

v

e r e

d

y

s p

l

a s i a a n

d

c a r c i no m a i n s i t

u

)

,

r e p

l

a c i n g t

h

e

f

u

l l

t

h

i c

k

n e s so

f

t

h

e e p i t

h

e

l

i

u

m.

V A I N

-

2 a n

d

V A I N

-

3 a r e a

l

so

co m

b

i n e

d

i n to

h

i g

h

-

g r a

d

e s q

u

a mo

u

s i n t r a e p i t

h

e

l

i a

l

l

e s io n

.

The term

V A I N

(vaginal,

V A;

intraepithelial,

I

;

neoplasia,

N

) has been used

to describe these histologic changes; the comparable categories are VAIN-

1 (mild dysplasia), VAIN-2 (moderate dysplasia), and VAIN-3 (severe

dysplasia to carcinoma in situ).

VAIN-1 is classified as a low-grade squamous intraepithelial lesion,

whereas VAIN-2 and VAIN-3 are grouped as high-grade squamous

intraepithelial lesions.

VAIN occurs more commonly in patients previously treated for cervical

intraepithelial neoplasia.

The tendency to develop premalignant changes in the lower genital tract

has been termed a

f

i e

l d d

e

f

e c t

and denotes the increased risk of squamous

cell neoplasia arising anywhere in the lower genital tract in such individuals

The most common histologic type of primary vaginal cancer is squamous

cell carcinoma, which is usually seen in women older than 60.

Malignant transformation of endometriosis has been described in the

vagina and rectovaginal septum.

Clear-cell adenocarcinoma, historically associated with young women

exposed in utero to DES, may also occur in unexposed women.

Primary vaginal sarcomas are rare and are primarily a disease of children

T

a

b le

3 1

-

1

- -C

o m m o n

P

r

i

m a r y

V

a g

i

n a

l C

a n ce r s

T

u m o r

T

y pe

P

re

d

o m

i

n a n t

A

ge

(

ye a r s

) C l i

n

i

c a

l C

o r re

l

a t

i

o n s

Endodermal sinus tumor

(adenocarcinoma)

2

T

u m o r

T

y pe

P

re

d

o m

i

n a n t

A

ge

(

ye a r s

) C l i

n

i

c a

l C

o r re

l

a t

i

o n s

multimodality therapy

Clear-cell adenocarcinoma >14 Associated with intrauterine

exposure to diethylstilbestrol

Melanoma >50 Very rare, poor survival

Squamous cell carcinoma >50 Most common primary vaginal

cancer

P

re m a

l i

g n a n t

D i

se a se o

f

t

h

e

V

a g

i

n a

D

e te c t

i

o n a n

d D i

a g n o s

i

s

Detection depends primarily on cytologic screening

Continued examinations and Pap smears for women even after hysterectomy

for dysplastic conditions.

An abnormal smear from vaginal epithelium is identified, a biopsy is required

for histologic identification

colposcopic examination is usually performed to identify the areas requiring

biopsy

Lugol's solution - useful adjunct to colposcopy for identifying an area in which

to perform a biopsy

Vaginal estrogen cream used for 1 to 2 weeks before examination is helpful in

evaluating postmenopausal women and those with atrophic vaginitis who

present with cytologic atypia

biopsy is performed with small instruments, such as the Kevorkian or

Eppendorf punch biopsy forceps

M

a n a ge m e n t

Treatment options include topical 5-fluorouracil (5-FU) cream, CO2 laser

vaporization, and wide local excision

The choice of treatment depends largely on the number of lesions, their

location, and the level of concern for possible invasion.

Radiation therapy, although used in the past, often leads to scarring and

fibrosis and is generally not recommended for treatment of noninvasive

disease. Because of the proximity of the bladder and rectum, cryotherapy is

usually not used.

Main advantage of the CO2 laser is that it vaporizes the abnormal tissue

without shortening or narrowing the vagina, preserving vaginal function.

Topical chemotherapy, 5% 5-FU cream, has the advantage of self-

administration and coverage of the entire area at risk (all the vaginal

epithelium). It is most often used for widespread, multifocal lesions of

HPV-associated VAIN-1 or VAIN-2

Wide local excision (upper vaginectomy) is the treatment of choice for

VAIN-3, especially for lesions occurring at the cuff of a hysterectomy

Upper vaginectomy can result in vaginal shortening, which can be

ameliorated by the use of topical estrogen cream and a vaginal dilator (or

frequent intercourse) once healing is complete.

M

a

l i

g n a n t

D i

se a se o

f

t

he

V

a g

i

n a

S

y m p t o m s a n

d D i

a g n o s

i

s

Primary vaginal cancers usually occur as squamous cell carcinomas in

women older than age 60.

To be considered a primary vaginal tumor, the malignancy must arise in

the vagina and not involve the external os of the cervix superiorly or the

vulva inferiorly.

Tumors of the lower one third of the vagina are treated similarly to vulvar

cancers

T

a

b le

3 1

-

2

- -I

n te r n a t

i

o n a

l F

e

de r a t

i

o n o

f G

y ne c o

l

o g y a n

d O b

s te t r

i

c s

S

t a g

i

n g

C l

a s s

i f i

c a t

i

o n

f

o r

V

a g

i

n a

l C

a n ce r

S

t a ge

C h

a r a c te r

i

s t

i

c s

0 Carcinoma in situ

I Carcinoma limited to vaginal wall

II Carcinoma involves subvaginal tissue but has not extended to pelvic wall

III Carcinoma extends to pelvic wall

IV Carcinoma extends beyond true pelvis or involves mucosa of bladder or

rectum (bullous edema as such does not assign a patient to stage IV)

3

The 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.

The longer the delay in diagnosis is, the worse the prognosis and the more

difficult the therapy.

Vaginal cancer is usually diagnosed by direct biopsy of the tumor mass

Abnormal cytologic findings may prompt a thorough pelvic examination that

will lead to diagnosis of vaginal cancer.

It is important during the course of the pelvic examination to inspect and

palpate the entire vaginal tube and to rotate the speculum carefully to visualize

the entire vagina because often a small tumor may occupy the anterior or

posterior vaginal wall.

T

u m o r s o

f A d

u

l

t

V

a g

i

n a

I.

S

q u a m o u s

C

e

l l C

a r c

i

n o m a

most common of the vaginal malignancies

disease occurs primarily in those older than age 60, and 20% are older than the

age of 80.

Most squamous cell carcinomas occur in the upper third of the vagina, but

primary tumors in the middle third and lower third may occur.

Grossly, the tumor appears as a fungating, polypoid, or ulcerating mass,

often accompanied by a foul smell and discharge related to a secondary

infection

Microscopically the tumor demonstrates the classic findings of an invasive

squamous cell carcinoma infiltrating the vaginal epithelium.

Treatment of these tumors is based on the size, stage, and location.

Therapy is limited by the proximity of the bladder anteriorly and the

rectum posteriorly. It is also influenced by the location of the tumor in the

vagina, which determines the area of lymphatic spread

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.

Lymphatics of the distal third of the vagina drain to both the inguinal

nodes and the pelvic nodes, similar to the drainage of the vulva

The posterior wall lymphatics anastomose with the rectal lymphatic

system and then to the nodes that drain the rectum, such as the inferior

gluteal, sacral, and rectal nodes.

4

Management

Thorough bimanual and visual examination, documenting the size and location

of the tumor, and assessment of spread to adjacent structures (submucosa,

vaginal sidewall, bladder, and rectum) should be done to determine the clinical

stage.

Cystoscopy and/or proctoscopy may be helpful, depending on clinical concern,

to rule out bladder or rectal invasion

Distant spread may be evaluated with a computed tomography scan of the

abdomen, pelvis, and chest.

stage vaginal carcinoma, without lymph node involvement (stage I or II), may

be treated with either surgery or radiation.

Radiation therapy is the most frequently used mode of treatment and can be

used for both early and advanced disease.

Pelvic exenteration can be used primarily to treat advanced disease in the

absence of lymph node metastasis, but is usually reserved for patients with

localized recurrence after radiation

Stage I vaginal carcinoma may be treated with brachytherapy alone, without

external beam therapy

Survival.

5-year survival rates for patients with primary carcinoma of the vagina have

been report

Stage of tumor is the most important predictor of prognosis.

The use of concomitant chemotherapy with radiation can be expected to

produce improved survival rates.

I I.

C le a r

-

C

e

l l A de n o c a r c

i

n o m a

association of many of these cancers with intrauterine exposure to DES

Management:

Surgery is the primary treatment modality because of the young age of the

patients

Stage I and early stage II tumors, radical hysterectomy with partial or complete

vaginectomy, pelvic lymphadenectomy, and replacement of the vagina with

split-thickness skin grafts have been the most common approach.

Local excision of the tumor has been performed before irradiation toThree

predominant histologic patterns are found in patients with clear-cell

adenocarcinoma facilitate local application

Survival:

Older patients (older than 19 years of age) have been found to have a more

favorable prognosis in comparison to younger patients (younger than 15 years

of age).

Spread locally as well as by lymphatics and blood vessels

Spread to regional pelvic nodes becomes more frequent in higher stage tumors

I I I.

M

a

l i

g n a n t

M

e

l

a n o m a

Rare and highly malignant

Common presenting symptoms are vaginal discharge, bleeding, and a

palpable mass.

melanomas appear as darkly pigmented, irregular areas and may be flat,

polyoid, or nodular

average age of affected women is 57 years

Vaginal melanomas tend to metastasize early, via the bloodstream and

lymphatics, to the iliac and/or inguinal nodes, lungs, liver, brain, and

bones.

Survival:

Patients with vaginal melanoma have a worse prognosis than those with

vulvar melanoma, in part probably due to delay in diagnosis in comparison

with vulvar carcinomas and in part due to their mucosal location, which

seems to predispose to earlier metastasis.

Prognostic indicators include tumor size, mitotic index, and Breslow tumor

thickness. Improved survival has been noted for patients whose tumors

had fewer than six mitoses per 10 high-power fields

Management:

Surgery with wide excision of the vagina and dissection of the regional

nodes (pelvic or inguinal-femoral, or both), depending on the location of

the lesion.

Therapy is usually tailored to the extent of disease. Surgery, radiation,

chemotherapy, and immunotherapy have all been described, but no single

or combination treatment is uniformly successful.

I V

.

V

a g

i

n a

l A de n o c a r c

i

n o m a s

A

r

i

s

i

n g

i

n

E

n

d

o m e t r

i

o s

i

s

Rectovaginal septum is the most common extragonadal location.

Tumors occur in the vagina or rectovaginal septum, the typical clinical

presentation is pain, vaginal bleeding, and/or a vaginal mass in a patient

who has previously undergone extirpative surgery for endometriosis

Risk factors include unopposed estrogen and tamoxifen use

Histologic types of malignancy include endometrioid adenocarcinoma as

the most common, followed by sarcomas (25%), and other tumors of

Mllerian differentiation

Treatment usually includes surgery plus radiation or chemotherapy

V

a g

i

n a

l T

u m o r s o

f I

n

f

a n t s a n

d C h i l d

re n

I.

E

n

d

o

de r m a

l S i

n u s

T

u m o r

( Y

o

l k-

S

a c

T

u m o r

)

rare germ-cell tumor that usually occurs in the ovary.

tumor secretes -fetoprotein, which provides a useful tumor marker to

monitor patients treated for these neoplasms

tumor is aggressive, and most patients have died

5

malignancy originating in the vagina of infants, predominantly those younger

than 2 years of age

I I.

S

a r c o m a

B

o t r y o

i de s

( E

m

b

r y o n a

l R h

a

b d

o m y o s a r c o m a

)

rare sarcoma is usually diagnosed in the vagina of a young female

Rarely does it occur in a young child older than 8 years of age, although cases in

adolescents have been reported.

most common symptom is abnormal vaginal bleeding, with an occasional mass

at the introitus

The tumor grossly will resemble a cluster of grapes forming multiple polypoid

masses.

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

(

s t r a p ce

l l

s

)

Management:

Virulent tumors have been treated in the past by radical surgery, such as pelvic

exenteration

Effective control with less radical surgery has been achieved with a

multimodality approach consisting of multiagent chemotherapy (VAC), usually

combined with surgery

Radiation therapy has also been used.

They found VAC to be effective for disease confined to the vagina without

nodal spread

I I I.

P

se u

d

o s a r c o m a

B

o t r y o

i de s

Rare, benign vaginal polyp that resembles sarcoma botryoides is found in the

vagina of infants and pregnant women

Large atypical cells may be present microscopically, strap cells are absent.

Grossly, these polyps do not resemble the grapelike appearance of sarcoma

botryoides. They are called

p s e

u

d

o s a r co m a

botryoides.

Treatment by local excision is effective.

K E Y P O I N T S

Predisposing factors associated with the development of vaginal

intraepithelial neoplasia include infection with HPV, previous radiation

therapy to the vagina, immunosuppressive therapy, and HIV infection.

The tendency of intraepithelial squamous neoplasia to develop

anywhere in the lower female genital tract is termed

f

i e

l d d

e

f

e c t

and

describes the increased risk of premalignant changes occurring in the

cervix, vagina, or vulva.

Most cases of VAIN occur in the upper one third of the vagina.

VAIN can be treated by excision, laser, or 5-FU. Excision is often used for

VAIN-3, and if the apex is involved, particularly after hysterectomy, laser

treatment is generally used for discreet lesions once invasion has been

ruled out, and 5-FU cream is used to treat diffuse, multicentric, low-

grade disease.

The most common primary vaginal malignancy is squamous cell

carcinoma (90%).

Most cancers occurring in the vagina are metastatic.

Vaginal cancers constitute less than 2% of gynecologic malignancies.

Tumors of the upper vagina have a lymphatic drainage to the pelvis

similar to cervical tumors, whereas those of the lower one third of the

vagina go to the pelvic nodes and also the inguinal nodes similar to

vulvar tumors.

Radical surgery may be used to treat low-stage tumors primarily of the

upper vagina in younger patients.

Radiation therapy is the most frequently used modality for treatment of

squamous cell carcinoma of the vagina. Ideally, at least 7000 to 7500 cGy

is administered in less than 9 weeks. Concurrent chemoradiation should

strongly be considered.

The overall 5-year survival rate of patients treated for squamous cell

carcinoma of the vagina is approximately 45%.

Clear-cell adenocarcinoma is often associated with prenatal DES

exposure and has an improved prognosis if the patient is older than age

19 years and has a predominant tubulocystic tumor pattern and low-

stage disease. Those with a positive DES maternal history have a better

prognosis.

Local therapy for small, stage I clear-cell adenocarcinomas of the vagina

is best considered if the tumor is less than 2 cm in diameter, invades less

than 3 mm, and is predominantly of the tubulocystic histologic type.

Pelvic nodes should be sampled and be free of tumor.

The overall 5-year survival rate of patients treated for clear-cell

adenocarcinoma is approximately 80%, in part due to the high

proportion of low-stage cases.

6

Vaginal melanomas are usually fatal. They occur primarily in patients

older than age 50 years.

Endometrioid adenocarcinomas of the vagina may occur through the

malignant transformation of endometriosis, often associated with the

use of unopposed estrogen or tamoxifen.

Endodermal sinus tumors occur in children younger than age 2 years.

They secrete -fetoprotein and are usually treated by multiagent

chemotherapy followed by surgical excision.

Sarcoma botryoides occurs primarily in children younger than age 8

years. It is treated by a multimodality approach using multiagent

chemotherapy with surgical removal and occasionally irradiation.