Malignant Diseases of the Vagina : Intraepithelial

Neoplasia, Carcinoma, Sarcoma

Stage I: Limited to vaginal wall

Stage II: Extends to subvaginal tissue

KEY TERMS AND DEFINITIONS

A vaginal or cervical malignancy occurring
primarily after 14 years of age, often
Clear-Cell
associated
with
prenatal
exposure
to
Adenocarcinoma
diethylstilbestrol (DES).

Endodermal
Tumor

A rare adenocarcinoma of the vagina occurring

Sinus in infants younger than 2 years of age.
The propensity of squamous epithelium of the
lower genital tract (cervix, vagina, and vulva)
to undergo premalignant change due to
infection with the human papillomavirus (HPV).

Field Defect

An
extensive
pelvic
operation
usually
employed to treat a central pelvic recurrence
of cervical or vaginal carcinoma after
radiation. A total exenteration involves
Pelvic Exenteration removal of the bladder, uterus, cervix, and
rectum. An anterior exenteration spares the
rectum, whereas a posterior exenteration
spares the bladder.

Pseudosarcoma
Botryoides

A benign tumor occurring in the vagina of

infants and pregnant women that has a
polyploid shape. Microscopically it may be
confused with sarcoma botryoides.

Stage III: Reaches the pelvic sidewall

Stage IV: Extends beyond the true pelvis or
into mucosa of the bladder or rectum
VAIN of the least severe type (comparable
to mild dysplasia), occupying the lower one
Vaginal
third of the epithelium. Also termed lowIntraepithelial
Neoplasia (VAIN) 1 grade squamous intraepithelial lesion.

VAIN-2

VAIN-3

Sarcoma
Botryoides
(Embryonal
Rhabdomyosarcom
a)
Vaginal
Stage

A rare, often fatal, malignancy of the vagina

that occurs in infants and children.

Tumor A clinical classification describing the extent of

spread of vaginal carcinoma.

VAIN of intermediate severity (comparable

to moderate dysplasia), occupying the lower
two thirds of the epithelium.
VAIN of the most severe type (comparable
to severe dysplasia and carcinoma in situ),
replacing the full thickness of the
epithelium. VAIN-2 and VAIN-3 are also
combined
into
high-grade
squamous
intraepithelial lesion.

The term VAIN (vaginal, VA; 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 highgrade 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 field defect 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

Table 31-1 -- Common Primary Vaginal Cancers

Predominant
Age (years) Clinical Correlations

Tumor Type

Endodermal
sinus <2
tumor
(adenocarcinoma)

Extremely rare, -fetoprotein

secretion,
often
fatal,
multimodality therapy

Sarcoma botryoides

<8

Aggressive
malignancy,
multimodality therapy

Clear-cell
adenocarcinoma

>14

Associated with intrauterine

exposure to diethylstilbestrol

Melanoma

>50

Very rare, poor survival

Squamous
carcinoma

cell >50

Most common primary vaginal

cancer

Premalignant Disease of the Vagina

Detection and Diagnosis
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
Management
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 cuf
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.
Malignant Disease of the Vagina
Symptoms and Diagnosis
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
Table 31-2 -- International Federation of Gynecology and
Obstetrics Staging Classification for Vaginal Cancer

Sta
ge Characteristics
0

Carcinoma in situ

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)

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.
Tumors of Adult Vagina
I. Squamous Cell Carcinoma
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.

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.
II. Clear-Cell Adenocarcinoma
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
III. Malignant Melanoma
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 afected 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 highpower 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.
IV. Vaginal Adenocarcinomas Arising in Endometriosis
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 diferentiation
Treatment usually includes surgery plus radiation or
chemotherapy
Vaginal Tumors of Infants and Children
I. Endodermal Sinus Tumor (Yolk-Sac Tumor)
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
malignancy originating in the vagina of infants, predominantly
those younger than 2 years of age
II. Sarcoma Botryoides (Embryonal Rhabdomyosarcoma)
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 crossstriations (strap cells)
Management:
Virulent tumors have been treated in the past by radical
surgery, such as pelvic exenteration
Efective 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 efective for disease confined to the
vagina without nodal spread
III. Pseudosarcoma Botryoides
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
pseudosarcoma botryoides.
Treatment by local excision is efective.
KEY POINTS

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 field defect 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 difuse, 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 clearcell adenocarcinoma is approximately 80%, in part due to the
high proportion of low-stage cases.

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.

mitsiko 08.10.10