Diagnostic Cytology
along with gynecologic examination, because these women are
at a higher risk for VaIN and the examination may also provide
the only evidence of clear cell adenocarcinoma.62,66
Benign Neoplasms and Tumor-Like conditions
Fibroepithelial polyps of the vagina are uncommon benign
growths that usually develop in the lower vagina of women,
approximately 40% of whom are pregnant or receiving hormo-
nal therapy.58,68 The polyps are covered by stratified squamous
epithelium, which overlies loose to dense connective tissue
that has large pleomorphic nuclei. Cytologic scrapes reveal nor-
mal squamous cells without atypia. Other benign tumors of
the vagina include fibromas, leiomyomas, and hemangiomas,
which are rarely evaluated cytologically.
Vaginal intraepithelial neoplasia (Vain)
The risk factors for VaIN are similar to those for squamous
intraepithelial lesions (SILs) of the cervix.69,70 It is estimated that
as many as 85% of VaIN cases are associated with a previous
or concurrent history of cervical or vulvar preinvasive or inva-
sive lesions. VaIN associated with HPV infection is in a manner
more akin to that reported for the cervix than the vulva.19
An increased risk for VaIN has also been reported in patients
who have undergone hysterectomy for SIL, immunodepressed
patients, DES exposure, and patients who have undergone
radiotherapy. VaIN changes usually involve the upper vagina
or apex, less frequently the middle or lower third, and multi-
centric foci of origin are not uncommon. The histopathologic
and cellular changes in VaIN are similar to their counterparts
in the uterine cervix. The majority of patients with VaIN are
asymptomatic, and routine screening is the most effective way
of detecting these changes.71,72 Cytologically, the abnormal cells
show various degrees of cellular differentiation, mitotic activ-
ity, and nuclear atypia encompassing the spectrum of changes
observed in SILs of the cervix. Once a cytologic abnormality
is detected, the diagnostic strategy for VaIN is similar to that
for SILs of the cervix. Colposcopic examination is indicated to
identify affected areas, followed by multiple biopsies. In cases
of cervical cytology specimens showing SIL in which no lesion
is identified on the cervix, a complete evaluation of the vagina is
essential in order to rule out a morphologically identical lesion
in this site.
In women treated by radiotherapy, abnormalities have been
identified in the vaginal and cervical specimens. Early radia-
tion changes include cellular and nuclear enlargement, cyto-
plasmic polychromasia, multinucleation, and vacuolation of
the cytoplasm. With time, atrophic cells become the dominant
population. Development of VaIN after a latency period of
1 to 10 years has been termed "postirradiation dysplasia." These
legions are typically associated with HPV nucleic acid and are
morphologically identical to non-radiated VaIN.14
Malignant neoplasms
Primary malignant neoplasms of the vagina are extremely
uncommon, representing only 1-2% of all malignant tumors
of the female genital tract.73-75 Because of the close relation-
ship of the vagina to other anatomic sites, it is estimated that
80-90% of the neoplasms are secondary, originating from
adjacent sites.
Squamous Cell Carcinoma
Squamous cell carcinoma
is the most common primary malignant
neoplasm of the vagina. By definition, primary vaginal tumors
must occur in the vagina without involvement of the cervix or
vulva.73,75 Patients with prior cervical or vulvar cancer should
have a disease-free interval of five years from invasive cervical
carcinoma. Most patients with primary vaginal carcinoma are
postmenopausal. Bleeding and discharge are the most common
symptoms. Most vaginal cancers are squamous cell carcinomas
or papillary carcinoma.14 The prognosis depends on the stage of
the disease.75
Cytologic preparations reveal features analogous to those of
cervical carcinoma, and various degrees of differentiation are
observed. The cellular changes associated with primary vaginal
SCC are indistinguishable from those of secondary involvement.
Key features of VaIN and vaginal squamous cell
• Essentially similar to features of cervical SIL and cervi-
cal SCC.
Verrucous Carcinoma
Verrucous carcinomas
are well-differentiated variants of SCC,
consisting of an exophytic growth pattern that clinically is usu-
ally well demarcated.76 Verrucous carcinoma generally grows by
direct extension. Metastasis to the lymph nodes is rare. Histo-
logically, the epithelium is quite mature. Dyskeratosis and epi-
thelial pearls are often noted. Parakeratosis and hyperkeratosis
are seen at the surface.
Scrapes of verrucous carcinomas reveal abundant hyper-
keratotic or parakeratotic cells. The cells occur predominantly in
aggregates, with little pleomorphism. The nuclei show little vari-
ation or increase in size. Hyperchromasia is usually not marked.
A biopsy that includes the base of the lesion is often necessary
to establish the correct surgical diagnosis.
Primary Adenocarcinoma
Primary adenocarcinoma
of the vagina excluding clear cell carci-
nomas is rare. The diagnosis of adenocarcinoma in the vagina
should always raise the possibility of metastasis from a primary
site elsewhere. The variants of primary vaginal adenocarcinoma
include those having endometrioid, mucinous, intestinal, ade-
noid cystic, papillary serous, and mixed adenosquamous carci-
noma differentiation.77
Embryonal Rhabdomyosarcoma
Embryonal rhabdomyosarcoma
(sarcoma botryoides) is the most
frequent vaginal malignant neoplasm in infants and children.
Most occur before the age of 2 years, and 95% occur in patients
younger than 5 years. The neoplasm has a grape-like appearance,
may distend the vagina, and may protrude from the vaginal
orifice. Histopathologically, it is distinguished by the presence of
numerous spindle-shaped or round primitive rhabdomyoblastic
cells present in a band-like zone in the subepithelial area ("cam-
bium zone"). The malignant cells in the deeper layers are usu-
ally present in a myxoid background and show various degrees
of differentiation (Fig. 11.15A). The cytology features for rhab-
domyosarcoma have been mainly described in FNA smears at
other sites.67 Characteristically, they show numerous small cells
in cohesive clusters or scattered singly. The tumor cells are round
to oval or elongated and contain various amounts of cytoplasm,
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