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
l b
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
h
a n 2
y
e a r so
f
a g e
.
F ie
l d D
e
f
e c t
T
h
e p ro p e n s i t
y
o
f
s q
u
a mo
u
s e p i t
h
e
l
i
u
mo
f
t
h
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
p r e m a
l
i g n a n t c
h
a n g e
d
u
e to i n
f
e c t io n
w
i t
h
t
h
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
e m p
l
o
y
e
d
to t r e a t
a c e n t r a
l
p e
l
v
i c r e cu
r r e n c e o
f
c e r
v
i c a
l
o r
v
a g i n a
l
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
l
v
e s
r e mo
v
a
l
o
f
t
h
e
b l
a
d d
e r
,
u
t e r
u
s,
c e r
v
i
x
,
a n
d
r e c t
u
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
o i
d
s
h
a p e
.
M i c ro s co p i c a
l l
y
i t m ay
b
e co n
f
u
s e
d
w
i t
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.
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