PART TWO
Diagnostic Cytology
Fig. 11.11 Malacoplakia. (A) Histopathological view of vaginal malacoplakia (H&E x HP); (B) cytology (Papanicolaou xHP),
Fig. 11.12 Vaginorectal fistula. Benign-appearing mucinous columnar
glandular cells present in a vaginal smear (Papanicolaou xMP).
vagina is uncommon.60 It is usually thought to be secondary to
implantation at the time of surgery, but even this is believed to
be a rare event.
Diethylstilbestrol-Related Abnormalities
One of the most common changes observed in women exposed
to diethylstilbestrol (DES) in utero is vaginal adenosis. It has
been reported to occur in 35% to more than 90% of the female
offspring of DES-exposed women.61,62 Vaginal
adenosis
is
defined as the presence of glandular epithelium or its mucinous
products in the vagina. The incidence of adenosis in women not
exposed to DES varies markedly, ranging from 0 to 40.8%.63 The
change is most frequently observed in the upper one-third of
the vagina; the anterior vaginal wall is more commonly involved
than the posterior or lateral walls. The gross appearance of the
lesion depends on the age of the patient. Early lesions appear as
grape-like clusters or as white areas. With the passage of time,
squamous metaplasia occurs on the surface and ultimately
replaces the glandular epithelium in the lamina propria, result-
ing in involution of the process. Microglandular hyperplasia of
vaginal adenosis has been observed.
Histologically, the columnar epithelium may resemble that
of the endocervix, the endometrium, or the uterine tube. The
majority of adenosis is of endocervical type (Fig. 11.13A). In
cellular samples of adenosis obtained by scraping the vagina,
columnar epithelial cells resembling endocervical cells can be
identified. These may be seen alone or in combination with
immature or mature squamous metaplastic cells (Fig. 11.13B).
With involution, only squamous metaplastic cells may be
noted. Anucleated squamous cells indicative of hyperkeratosis
are occasionally seen.
Various other changes in women exposed to DES in utero
have been reported. Changes attributed to DES have included
malignant neoplasms (clear cell carcinoma), cervical erosions,
genital ridges, cervical hoods, adenosis, and various abnormali-
ties of the uterus.64 Third-generation carryover effects of in utero
DES exposure are unlikely.65
The least common change is the development of clear cell
carcinoma.62,66 The risk of developing clear cell carcinoma in
DES-exposed women from birth to age 34 years is estimated at
0.1%. The risk of development increases from age 15, plateau-
ing from 17 to 22 years of age and declining thereafter. The neo-
plasm most frequently originates from the anterior vaginal wall,
usually in the upper third, and less frequently from the posterior
or lateral aspects. Although the majority (55%) of clear cell car-
cinomas are of vaginal origin, 42% are of cervical origin. Adeno-
sis has been noted to coexist with clear cell carcinoma in 95% of
the cases studied. However, at present, no definitive proof exists
that significant epithelial abnormalities are more common in
DES-exposed women than in unexposed women. Atypical vari-
ants of adenosis have been described as having nuclear and
cytoplasmic abnormalities.
Three histopathologic patterns of clear cell carcinoma, includ-
ing tubulocystic, solid, and papillary, have been noted. The cells
have abundant clear cytoplasm with demonstrable glycogen on
periodic acid-Schiff stains. Bulging of the nuclei toward the glan-
dular lumen occurs, prompting their designation as "hobnail"
cells. Cytologically, the cells derived from clear cell carcinoma
may be isolated or in aggregates.67 The cells are usually uniform
in size. Their cytoplasm is often poorly stained and finely vacu-
olated. The nuclei are enlarged and hyperchromatic and may
range from finely granular to coarsely clumped. Macronucleoli
are frequently observed (Figs. 11.14A, 11.14B). Regular cytologic
examination of at-risk women should continue after menopause
280
previous page 279 ComprehensiveCytopathology 1104p 2008 read online next page 281 ComprehensiveCytopathology 1104p 2008 read online Home Toggle text on/off