Endometrial Lesions, Unusual Tumors, and Extrauterine Cancer
Fig. 10.15 Lower uterine segment fragment. Conventional
cervicovaginal specimen (Papanicolaou x MP). Note tubular appearance with
peripheral epithelium and central stroma.
Fig. 10.16 Normal-appearing endometrial cells with tubal
metaplasia. (LBC ThinPrep Papanicolaou x HP). Note the ciliated border
Table 10.5 Differential diagnosis of normal endometrial cells
Endocervical cells
Parabasal cells
Naked nuclei, especially associated with atrophy
Atypical endometrial cells
High squamous intraepithelial lesion
Squamous carcinoma
Stromal cells are usually identified in association with
epithelial cells in endometrial cell balls. Distinguishing epithe-
lial and stromal cells in this setting is difficult although immuno-
cytochemistry has been used to show that most endometrial cell
balls contain a mixture of stromal and epithelial cells.46 When
seen on their own, stromal cells are often loosely clustered and
resemble histiocytes. In fact, accurate separation of stromal cells
and histiocytes by morphologic criteria alone is limited and the
two are often grouped together for reporting.14,42,43 Superficial
stromal cells have oval, eccentrically placed nuclei and ample
cytoplasm that appears wispy or degenerated. Deep stromal cells
appear as small sheets of cells with elongated, often grooved
nuclei and scant cytoplasm. Stromal cells will demonstrate
decidual changes in the second half of the cycle and appear
more widely spaced with denser cytoplasm.40 Stromal cells are
not considered to have a clinical relevance with regards to the
presence of endometrial pathology.43
The differential diagnosis of directly sampled endometrial
cells falls within the category of hyperchromatic crowded groups
or three-dimensional balls of cells with overlapping dark nuclei.41
The list is broad and contains mainly benign but some neoplas-
tic entities (Table 10.5). The distinction of NECs from endocervi-
cal cell groups is likely the most common problem (Table 10.5).
Endocervical cells are frequently seen as organized sheets with
a honeycomb pattern. The sheets may fold but overall at most a
2-dimensional configuration is maintained. The endocervical
cells are larger with abundant cytoplasm, more distinct cell bor-
ders, and larger vacuoles. The nuclei are also larger with evenly
distributed chromatin. Single cells such as lymphocytes may clus-
ter and mimics NECs (Table 10.5). These are best distinguished
based on their coarse chromatin patterns.44 Parabasal cells and
naked nuclei are often present in a background of atrophy and
have bland nuclear features. High-grade squamous intraepithe-
lial lesion (HSIL) can also enter the differential diagnosis of
NECs, especially when the dysplastic cells are present in tight
groups (i.e. endocervical crypt involvement).41,44 Careful atten-
tion should be paid to all hyperchromatic cell groups to identify
nuclear atypia and pleomorphism (Table 10.6). Searching the
background for single dysplastic cells is often helpful in distin-
guishing these groups from endometrial cells. Finally, atypical
endometrial cells must be differentiated from the degenerated
features of exfoliated endometrial cells. This is especially true
with liquid-based preparations in which NECs may appear more
pleomorphic and contain distinct nucleoli.
NECs may present in exfoliative cervicovaginal cytology sam-
ples under a variety of physiologic and pathologic conditions.
The detection of these cells varies widely but reports published
since 2001 show rates ranging from 0.8 to 7% of all smears.46-50
The significance attached to these cells depends on a variety
of factors including patient age, menstrual history, hormonal
status, and symptomatology.
NECs are shed during the menstrual period and continue to
be present in cervical samples into the proliferative phase. Stud-
ies have shown that approximately 25% of smears from the first
10-12 days of the menstrual cycle will contain NECs.6,51,52 No
clinical significance is attached to this finding.
The clinical significance of NECs in the second half of the
cycle is less certain. The above studies noted 2% of Pap tests
contained NECs after the twelfth day.52,53 This may reflect
an ongoing endometrial remodeling process that leads to
endometrial cells being shed throughout the cycle, even dur-
ing the secretory phase. However, other pathologic underlying
conditions can be associated with the presence of NECs "out
of phase." These conditions include hormonal disorders, struc-
tural abnormalities, and neoplastic conditions (Table 10.7).
Most studies have shown that in women under the age of 40
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