LECTURE 17.
3: MALIGNANT DISEASES OF THE VAGINA
Dr. Alvarina | April 23, 2021
OUTLINE:
I. INTRODUCTION
II. PREMALIGNANT DISEASES OF THE VAGINA
III. MALIGNANT DISEASES OF THE VAGINA
IV. TUMORS OF THE ADULT VAGINA
V. VAGINAL TUMORS OF INFANTS AND CHILDREN
VI. REFERENCES
VII. APPENDIX
INTRODUCTION
● Premalignant changes in the vagina occur less
frequently than comparable lesions in the cervix and
vulva. However, the histologic appearance of
intraepithelial neoplasia of the vagina is similar to that
described for the cervix.
● These changes are also similarly designated as
dysplasia (mild, moderate, or severe) and carcinoma
in situ.
● The term VAIN (vaginal intraepithelial neoplasia)
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
frequency of vaginal premalignancy in these patients
is approximately 1% to 3%.
● Similarly, there is an increased risk of VAIN in those
previously treated for squamous cell neoplasia of the
vulva.
● The tendency to develop premalignant changes in the
lower genital tract is known as a field defect and
denotes the increased risk of squamous cell neoplasia
arising anywhere in the lower genital tract in such
individuals.
● Most VAIN cases are related to infection with human
papillomavirus (HPV). Additional risk factors include
HIV infection, cigarette smoking, previous radiation
therapy of the genital tract, and immunosuppressive
therapy.
● In situ and invasive vaginal neoplasias have many of
the same risk factors as cervical cancer, including a
strong association with HPV infection.
● Primary cancer of the vagina is rare and constitutes
less than 2% of gynecologic malignancies.
● Most vaginal malignancies are metastatic, primarily
from the cervix and endometrium.
PREMALIGNANT DISEASES OF THE VAGINA
● VAIN usually occurs in the upper half of the vagina or
along the vaginal cuff suture line.
● Once an abnormal smear from vaginal epithelium is
identified, a biopsy is required for histologic
identification.
● Vaginal colposcopic techniques are similar to those
described for the cervix. A large speculum is used to
aid in visualizing the entire vaginal wall.
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● A useful adjunct to colposcopy for identifying an area
in which to perform a biopsy is to stain the vaginal
epithelium with Lugol’s solution and to take a biopsy
sample from the nonstaining areas.
● The more rapidly dividing dysplastic epithelium uses
up its glycogen and thus does not pick up the iodine
stain.
● Vaginal estrogen cream used for 1 to 2 weeks before
examination is helpful for evaluating postmenopausal
women and those with atrophic vaginitis who present
with cytologic atypia.
● Parabasal cells with their large nuclei, are a common
cause of false-positive Pap tests in this age group.
● A biopsy is performed with small instruments, such as
the Kevorkian or Eppendorf punch biopsy forceps.
● Occasionally, it is necessary to use a fine instrument,
such as a nerve hook, to provide traction on the
vaginal epithelium to obtain a biopsy sample.
Treatment
● The risk of progression to invasive cancer is thought
to be low, approximately 9%. Those at highest risk of
progression are women with high-risk strains of HPV,
those with VAIN-3, cigarette smokers, and
immunocompromised women.
● The principles of managing VAIN are to rule out and
prevent invasive disease and preserve vaginal
function.
● As is true for cervical dysplasia, biopsy-proved VAIN-
1, particularly those lesions associated with low-risk
strains of HPV, can be observed, provided that the
woman is compliant with follow-up. VAIN-2 and VAIN-
3 are generally treated.
● Treatment options include CO2 laser vaporization,
topical 5-fluorouracil (5-FU) cream, and wide local
excision.
● The choice of treatment depends largely upon the
number of lesions, their location, and the level of
concern for possible invasion.
● Radiation therapy, previously used to treat VAIN-2
and VAIN-3, often leads to scarring and fibrosis and is
generally not recommended for the treatment of
noninvasive disease.
● Because of the proximity of the bladder and rectum,
cryotherapy is generally not used.
● The main advantage of the CO2 laser is that it
vaporizes the abnormal tissue without shortening or
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Dr. Alvarina | April 23, 2021
narrowing the vagina, thereby preserving vaginal
function.
● Criteria for CO2 laser vaporization include a lesion
that is discrete and easily visible and proof that
invasive cancer has been ruled out.
● The beam is directed colposcopically.
● Iodine staining of the vagina can help outline those
areas requiring therapy.
● Treatment is occasionally performed on an outpatient
basis with a local anesthetic and an analgesic.
● The intensity of therapy is regulated by adjusting the
wattage of the laser, most commonly 15 to 20 W
carried to a depth of 1.5 to 2 mm. Care must be taken
not to apply the laser too deeply because of the
proximity of the bladder and bowel, particularly in
older women whose vaginal epithelium may be quite
thin.
● The success rates of laser in treating VAIN vary in the
literature but are generally in the range of 60% to
85%.
● Regular follow-up every 4 months, including a Pap
smear and colposcopy, is required during the first
year and usually 6 to 12 months thereafter.
● The primary disadvantages of laser treatment are the
lack of a pathologic specimen for evaluation of the
adequacy of margins and the fact that the procedure
can be tedious and difficult because of the many folds
and crevices at the vaginal apex.
● Topical chemotherapy, 5% 5-FU cream, can be self-
administered to cover the entire area at risk. It is most
often used for widespread multifocal lesions of HPV-
associated VAIN-1 or VAIN-2.
● The disadvantage of topical therapy with 5-FU cream
is related to the high level of motivation required to
complete therapy.
● The 5-FU cream causes exfoliation and erosion of the
vaginal mucosa and can be extremely painful.
● Wide local excision (upper vaginectomy) is the
treatment of choice for VAIN-3, especially for lesions
occurring at the cuff after hysterectomy with a high
success rate of 84%.
● Upper vaginectomy, however, 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 DISEASES OF THE VAGINA
Signs and Symptoms
● Primary vaginal cancers usually occur as squamous
cell carcinomas in women older than 60 years.
● 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.
● If this occurs, the tumor is classified as cervical or
vulvar.
● Biopsies are mandatory if the cervix is intact in order
to rule out primary carcinoma of the cervix. This is
also an important therapeutic consideration, insofar as
the same management techniques apply to small
tumors of the upper third of the vagina and cervical
carcinomas.
● Tumors of the lower third of the vagina are treated
similarly to vulvar cancers.
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● 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.
● In general, the longer the delay in diagnosis, the
poorer 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 vagina
and to rotate the speculum carefully to visualize the
entire vagina, because a small tumor may occupy the
anterior or posterior vaginal wall.
TUMORS OF THE ADULT VAGINA
A. SQUAMOUS CELL CARCINOMA
- The most common vaginal malignancy and accounts
for 90% of primary vaginal cancers
- The disease occurs primarily in women older than 60
- 20% occurs in women older than 80 years
- Most squamous cell carcinomas occur in the upper
third of the vagina
- Grossly, the tumor appears as a fungating,
polypoid, or ulcerating mass, often accompanied by
a foul smell and discharge related to 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,
vaginal tumor stage, and location of the lesion
- 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 lymphatics
spread
- Lymphatics of the vagina envelop the mucosa and
anastomose with lymphatic vessels in the muscularis
- Those of the mid 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 chain
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- Lymphatics of the distal third of the vagina drain to
the inguinal nodes and pelvic nodes, similar to the
drainage of the vulva.
- 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
Treatment
- Once vaginal malignancy is established, a thorough
bimanual and visual examination documenting the
size and location of the tumor and assessment of
spread to adjacent structures (submucosa, vaginal
sidewall, bladder, rectum) should be performed to
determine the clinical stage
- Cystoscopy or proctoscopy may be helpful to rule
out bladder or rectal invasion
- Distant spread may be evaluated by computed
tomography (CT) of the chest, abdomen, and pelvis or
positron emission tomography (PET)
- Early stage vaginal carcinoma without lymph node
involvement (stage I or II) – treated with surgery or
radiation
- Young patients with early stage disease and upper
vaginal lesions may be treated with radical upper
vaginectomy, parametrectomy, and pelvic
lymphadenectomy
- Radiation therapy – most frequently used mode of
treatment and can be used for early and advanced
disease. It is the most common therapy because
most women with vaginal carcinoma are older and
have a poorer surgical risk; radiation is highly
effective
- Pelvic exenteration – used to treat advanced
disease in the absence of lymph node metastasis, but
it is usually reserved for patients with localized
recurrence after radiation
- Cisplatin-based chemotherapy with concurrent
radiation – improved outcomes in squamous lesions
of the cervix
- Stage I vaginal carcinoma may be treated with
brachytherapy alone, without external beam therapy
- For more advanced lesions, a combination of
external beam and brachytherapy is used
Brachytherapy – a procedure that involves placing
radioactive material inside your body; sometimes
called internal radiation.
(mayoclinic.org)
- External radiation therapy with megavoltage
equipment is initially used to shrink the tumor
- The size and extent of the radiation field will be
determined by the presence or absence of nodal
disease, as determined by the pretreatment PET ot
CT scan
- The brachytherapy will bring the total dose to
between 7000 and 8500 cGy
Survival
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- Overall 5-year survival rates for patients with primary
carcinoma of the vagina have been reported to be
approximately 45%
- Stage of the tumor is the most important predictor of
prognosis
- The use of concomitant chemotherapy with radiation
can be expected to produce improved survival rates
B. CLEAR CELL ADENOCARCINOMA
- Clear cell adenocarcinomas in young women have
been seen more frequently since 1970 as a result of
the association of many if these cancers with
intrauterine exposure to DES
- Tumors are staged according to FIGO classification
- Most tumors (80%) have been diagnosed as stage I
or II
- The survival rate is related directly to the stage of
the tumor
- Surgery is the primary 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 reconstruction of the
vagina with split thickness grafts has been most
common approach
- Local excision of the tumor can be performed before
irradiation to facilitate local application
- Local vaginal excision as the sole therapy is not
usually adequate for small tumors because the tumor
frequently recurs
- Three predominant histologic patterns:
o Tubulocystic cell pattern
o Solid pattern
o Papillary pattern
- Older patients (>19 years) have been found to have
a more favourable prognosis in comparison to
younger patients (<15 years)
- There is more favourable outcome for those with the
tubulocystic pattern of adenocarcinoma, the most
frequent histologic pattern found in older patients
- Prolonged follow-up is necessary for these patients
because recurrences have been reported as long as
20 years after primary therapy
- Those with maternal history of DES use survive
longer
C. MALIGNANT MELANOMA
- Vaginal melanomas are rare and highly malignant
- 2-3% of primary vaginal cancers
- Most common presenting symptoms are vaginal
discharge, bleeding, and a palpable mass
- Lesions appear as darkly pigmented, irregular
areas and may be flat, polypoid, or nodular
- The average age of women is 57 years
- Tends to metastasize early via the bloodstream and
lymphatics, to the iliac or inguinal nodes, lungs,
liver, brain, and bones
- Poorer prognosis than those with vulvar melanoma
probably because of the delay in diagnosis
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- Treatment: surgery with wide excision of the B. SARCOMA BOTRYOIDES (EMBRYONAL

vagina and dissection of the regional lymph RHABDOMYOSARCOMA)
nodes (pelvic, inguinal – femoral, or both), depending - Uncommon vaginal sarcoma that is usually diagnosed
on the location of the lesion. in young girls
- Surgery, radiation, chemotherapy, and - Rare in a young child older than 8 years
immunotherapy have all been described, but no single - Most common symptom is abnormal vaginal
therapy or combination treatment is uniformly bleeding , with an occasional mass present at the
successful introitus
- The overall 5-year survival rate is 8.4% with and - The tumor grossly resembles a cluster of grapes
overall median survival of 20 months forming multiple polypoid masses
- Prognostic indicators include tumor size, mitotic - Believed to begin in the subepithelial layers of the
index, and Breslow tumor thickness vagina and expand rapidly to fill the vagina
- Improved survival has been noted for patients whose - Often multicentric
tumors had fewer than six mitoses/10 high-power - Histologically, they have a loose myxomatous
fields (HPF) stroma with malignant pleomorphic cells and
- Tumor thickness is important in melanoma occasional eosinophilic rhabdomyoblasts that
prognosis often contain characteristic cross-striations
- Effective control with a multimodality approach
D. VAGINAL ADENOCARCINOMAS ARISING IN consisting of multiagent chemotherapy (VAC)
ENDOMETRIOSIS combined with surgery
- Malignant transformation of extraovarian - VAC chemotherapy is effective for disease condined
endometriosis is rare but has been reported with to the vagina without nodal spread. This therapy was
increasing frequency effective without irradiation for disease that was
- The rectovaginal septum is the most common locally resected, suggesting that for these patients,
extragonadal location chemotherapy plus surgery can be effective therapy
- When these tumors occur in the vagina or
rectovaginal septum, the typical clinical C. PSEUDOSARCOMA BOTRYOIDES
presentation is pain, vaginal bleeding, or the - Rare, benign vaginal polyp that resembles sarcoma
presence of a vaginal mass in a woman who has botryoides and is found in the vagina of infants and
previously undergone prior extirpative surgery for pregnant women
endometriosis - Grossly, these polyps resemble the grapelike
- Risk factors include use of unopposed estrogen appearance of sarcoma botryoides and are therefore
and tamoxifen use called “pseudosarcoma botryoides.”
- The most common histology is endometrioid - Treatment by local excision is effective
adenocarcinoma, followed by sarcomas (25%) and
other tumors of mullerian differentiation END OF CHAPTER OUTLINE
- Treatment: surgery + radiation or chemotherapy
- Relatively favourable prognosis for women with REFERENCES
endometriosis- related malignancies, with 70% alive
at mean follow-up of 31 months ● Comprehensive Gynecology 7th Ed only
UTLINE 1
VAGINAL TUMORS OF INFANTS AND CHILDREN
A. ENDODERMAL SINUS TUMOR
(YOLK SAC TUMOR)
- A type of adenocarcinoma
- Rare germ cell tumor that usually occurs in the
ovary
- This tumor secretes α-fetoprotein, which provides a
useful tumor marker to monitor patients treated for
these neoplasms
- This tumor is aggressive and most patients have
died
- Young and Scully reported on six patients who were
free of disease 2 to 9 years after surgery, irradiation,
or both, who also received vincristine, actinomycin
D, and cyclophosphamide (VAC) therapy
- Similar good results have been reported with
combination chemotherapy and excision
- Bleomycin, etoposide, and cisplatin (BEP) has also
been used to treat the disease

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APPENDIX

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