Endometrial Lesions, Unusual Tumors, and Extrauterine cancer
age and discourage reporting this finding.59 Current evidence
continues to support evaluation of postmenopausal women
with NECs in Pap tests regardless of symptomatology. Evalua-
tion of premenopausal women with NECs in Pap tests, even in
the second half of their menstrual cycle, is of little value, unless
there are other clinical indication or suspicion.44
cytologic Findings during Gestation
During pregnancy, the tissues throughout the gynecologic tract
undergo changes in response to elevated hormone levels. These
changes to both the cervical and endometrial lining can be
apparent in cervicovaginal cytology. Three types of cells from the
endometrial cavity can potentially give rise to diagnostic dilem-
mas. These include decidual cells, Arias-Stella reaction, and tro-
phoblastic cells. The occurrence of both glandular and squamous
dysplasia in pregnancy mirrors that of the non-pregnant popula-
tion.65 However, the existence of these additional diagnostic pit-
falls makes the task of screening even more difficult, especially
as the clinical history of pregnancy is not always available.
Hormone stimulation in pregnancy causes morphologic
changes referred to as decidualization. This change mainly
involves the endometrial stromal cells but can extend to the
cervix and extrauterine stromal tissues as well. Whereas the
normal endometrial stromal cell has only a minimal amount
of cytoplasm, decidualized stromal cells take on a polygonal
shape with abundant cytoplasm that is baso- to eosinophilic
and finely granular.66 When encountered in cytologic prepara-
tions, decidual cells occur singly or in loose clusters. Cytoplas-
mic extensions between the cells can be seen on conventional
smears. The nucleus can be enlarged and hyperchromatic, but
the chromatin is finely distributed and sometimes glassy nucle-
oli are often present. Decidual cells are usually detected in post-
partum or postabortal cytology but can occasionally be found in
gestational samples.67 Decidual cells can be confused with para-
basal cells and squamous dysplastic cells.66-68 Parabasal cells are
uncommon in pregnancy due to the hormonal milieu. They are
usually smaller than decidual cells and have denser cytoplasm.68
More importantly the nuclear enlargement and hyperchromasia
of decidual cells can be misinterpreted as squamous dysplasia.
This is especially true if degeneration is present. Care should be
taken to look for other features of dysplasia including irregular
nuclear membranes and coarse chromatin.
Arias-Stella reaction (ASR) is an exaggerated physiologic
response to pregnancy-related hormone levels. The epithe-
lial cells of the gestational endometrium and less commonly
endocervix take on a hypersecretory appearance with promi-
nent cytoplasmic clearing and nuclear enlargement (Fig. 10.17).
In cervicovaginal cytology,
the identification of glandular
cells showing ASR is frequently thought to originate from the
endocervical glands. However, the appearance is indistinguisha-
ble from endometrium and many of these changes may involve
cells shed from the endometrial cavity.69 The features of ASR
include abundant, clear, vacuolated cytoplasm and large eccen-
tric nuclei. Cherry red nucleoli are frequently prominent.51,66-69
The cell groups are loosely cohesive and may have a hobnail
arrangement. The appearance of ASR on both cytologic and
histologic preparations is a recognized diagnostic pitfall and
a source of false-positive diagnoses due to its resemblance to
adenocarcinoma. Awareness of the overlap in the features of
ASR and clear cell adenocarcinoma is crucial to avoiding this
mistake. Lui has pointed to relative preservation of nuclear/
Fig. 10.17 Endocervical Arias-Stella reaction. Cervical biopsy,
histological section (H&E x HP). Note the large variable sized atypical nuclei
within clear cytoplasm.
cytoplasmic ratio, fine chromatin pattern, and the presence of
nuclear grooves and inclusions as aids to the recognition of
Arias-Stella reaction.51,68 Inquiries should be made regarding
the gestational status of any women of reproductive age who
present with these types of cells.
The placental trophoblastic cells can also be detected on cer-
vicovaginal cytology. Trophoblastic cells can be seen through-
out pregnancy and do not signify an increased propensity for
impending abortion.66 Syncytiotrophoblast are most commonly
seen in near term or in the immediate postpartum period. These
are large multinucleated cells with aggregated nuclei that may
show irregular nuclear borders. The cytoplasm is dense and
elongated tails of cytoplasm may be noted. These features may
lead to misinterpretation as HPV-related changes or low-grade
squamous intraepithelial lesion (LSIL). The other classic features
of koilocytosis including the distinct halo will not be present.
Immunohistochemistry for p-HCG may prove helpful in some
cases.66 The single cytotrophoblastic cells may be much harder
to delineate.70 These cells have hyperchromatic nuclei but bland
nuclear chromatin and a thick nuclear membrane. The overlap
with the features of HSIL is troublesome. A search for findings
such as inflammation, bloody background, and other elements
of pregnancy may help as clues to the correct diagnosis.66 As
with all these changes, proper clinical history is paramount.
Key features of cytologic findings during gestation
• The occurrence of both glandular and squamous
dysplasia in pregnancy is similar to that in the non-
pregnant population.
• Decidualized stromal cells take on polygonal shape
with abundant finely granular cytoplasm. The nuclei
may be enlarged but the chromatin is fine. Nucleoli
may be present.
• Arias-Stella reaction demonstrates abundant, clear
cytoplasm and large eccentric nuclei, frequently with
cherry red nucleoli.
• Syncytiotrophoblast have multiple aggregated nuclei
that may show irregular nuclear borders.
• Cytotrophoblast have hyperchromatic nuclei but bland
nuclear chromatin and a thick nuclear membrane.
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