PART TWO
Diagnostic Cytology
reactive processes all the way to adenocarcinoma in situ (AIS).
Therefore, lesions falling into this category should be further
subclassified, if possible, according to whether a neoplas-
tic process is favored or the changes are non-specific (NOS).
Specific comments may be added to the interpretation if perti-
nent clinical findings and/or history are available and relevant
(polyps, IUD, etc.).
Atypical Endocervical Cells, NOS
Endocervical cells can show a variety of changes associated
with benign/reactive processes in the endocervical canal.
Reactive endocervical cells can show some pleomorphism
of cell size as well as nuclear enlargement, multinucleation,
and prominent nucleoli; however, there is usually a honey-
comb or sheet-like pattern and nuclei remain round and the
chromatin bland. Such changes are usually recognized as NILM
and not included in the AGC category. Cells that show cyto-
logic changes beyond those recognized easily as reactive such
as significant nuclear enlargement/crowding, hyperchromasia,
loss of mucin, and loss of polarity should be considered for
inclusion in the atypical endocervical cells, NOS category. Such
changes may be seen in conditions such as tubal metaplasia,
radiation therapy, endocervical polyps, and microglandular
hyperplasia, and in IUD users, but also in neoplastic condi-
tions in a small percentage of cases. This category therefore
includes changes that are in excess of those attributable to a
reactive/reparative condition but which fall short of those seen
in glandular neoplasia.
Atypical Endocervical Cells, Favor Neoplastic
These cells are characterized by cellular strips and rosettes
demonstrating elongated, overlapping nuclei with moderately
coarse chromatin and hyperchromasia. The peripheral border
of the glandular clusters may be "feathered," with protruding
nuclei, in contrast to the smooth communal border typical of
glandular fragments. In LBPs cells are more rounded and three-
dimensional. Cellular changes, while suspicious for in situ or
invasive adenocarcinoma, are quantitatively or qualitatively
insufficient for an outright interpretation as such.
Atypical Endometrial Cells
These are usually small groups of cells with slightly enlarged
nuclei, and variable prominence of nucleoli and nuclear
hyperchromasia. Their distinction from cytologically benign
endometrial
cells is based primarily on the criterion of
increased nuclear size. When dealing with LBPs, it is important
to keep in mind that menstrual/shed endometrium is often
well preserved and may show nuclear size and shape pleomor-
phism and the presence of nucleoli. The differential of atypi-
cal endometrial cells is broad and may include endometrial
polyps, endometritis, IUD associated changes, hyperplasia,
and carcinoma.
Endocervical Adenocarcinoma (In Situ and Invasive)
Endocervical AIS is a high-grade endocervical neoplastic lesion
that cytologically demonstrates nuclear enlargement, hyper-
chromasia, stratification, and mitotic activity. Invasive carci-
noma overlaps cytologically with AIS, but may show features
of invasion, including prominent nucleoli and tumor diathesis.
The possibility of a coexisting squamous lesion should always
be carefully assessed when a glandular lesion is detected, due to
the high rate of coexistence of SIL in cases with AIS.66-68
Endometrial Adenocarcinoma
The cytologic features are directly related to the histologic grade
of the tumor, with well-differentiated cases yielding malignant
cells with minimal atypia and poorly differentiated tumors
being obviously malignant. Tumor diathesis is often difficult to
appreciate, particularly in LBP. In general endometrial lesions
yield fewer cells than do directly sampled endocervical lesions.
Extrauterine Adenocarcinoma
A clean background and tumors whose cytologic features are not
characteristic of uterine/cervical tumors should raise the possi-
bility of metastasis. Diathesis is usually not seen unless there
is direct extension from the rectum or bladder with associated
tissue destruction.
Diagnostic Difficulties
Criteria indicating invasion—tumor diathesis and macronucle-
oli—may be absent in the majority of well-differentiated, early
adenocarcinomas. It also can be difficult to differentiate SIL
with gland involvement from AIS. HSIL/CIS involving endocer-
vical glands may yield round cell clusters with smooth periph-
eral contours showing group polarity and "columnar" shape
of individual cells, thus mimicking a glandular abnormality.69
Additionally, SIL and AIS may coexist in up to 50% of cases, and
at conization, a high proportion of AIS specimens demonstrate
concurrent SIL.68
Benign entities such as tubal metaplasia, directly sampled
lower uterine segment (LUS) endometrial cells, and cervical
endometriosis may all morphologically mimic AIS. Fragments of
tubal metaplasia may demonstrate crowded sheets of glandular
cells with enlarged nuclei as well as cell fragments with nuclear
palisading and nuclear overlap, mimicking some of the mor-
phologic features of AIS.70 However, rosette formation is uncom-
mon in tubal metaplasia, and the nuclear chromatin tends to be
more finely granular. The most helpful findings though, when
present, are cytoplasmic terminal bars and cilia.
Directly sampled endometrial tissue may mimic AGC or glan-
dular neoplasia. Inadvertent sampling of the LUS may occur
because of closer approximation of the LUS to the cervical os
following cone biopsy71 or with aggressive use of endocervical
brushes. In contrast to spontaneously exfoliated endometrial cells,
which typically shed as tight ball-like clusters, direct brushing of
endometrial tissue yields large cellular fragments. These fragments
often recapitulate their native three-dimensional architecture
with branching tubular glands enmeshed in stroma composed of
round to spindle-shaped cells.72 Glandular cells show crowding
with overlapping round nuclei and scant cytoplasm. Peripheral
palisading may be evident. The low power recognition of branch-
ing glands and glandular-stromal complexes is an important clue
to avoid confusion with AGC or glandular neoplasia.
Conventional smears with a diagnosis of adenocarcinoma
consistently identified correctly by CAP interlaboratory glass
slide program participants were significantly more likely to
have more abnormal cells, larger abnormal cells, larger nuclei,
marked atypia, and hyperchromasia than cases that performed
poorly.73 Glandular lesions have a slightly different morphol-
ogy on LBPs; specifically the cells may be flatter, feathering less
prominent, and diathesis more difficult to appreciate.10 Details
are discussed elsewhere in this book. However, as for squamous
lesions, there have been reports showing increased detection
of glandular abnormalities on LBPs compared to conventional
smears.68,74,75
86
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