10
Endometrial Lesions, Unusual Tumors, and Extrauterine Cancer
Fig. 10.23 Atypical glandular cells, favor endometrial origin. LBC
ThinPrep Papanicolaou x HP from a 65-year-old woman. In this case, the
nuclear features are well preserved. Note the prominent emperipolesis.
Follow-up biopsy showed complex hyperplasia with cytologic atypia
(atypical hyperplasia).
Fig. 10.24 Atypical glandular cells, favor endometrial origin. LBC
ThinPrep Papanicolaou x HP from a 65-year-old woman (same case as that of
Fig. 10.19). The degenerative features are prominent with the nuclei showing
a poor outline in the clump of atypical endometrial cells.
Consequently, the cells are often few in number and, if present,
show some degenerative changes, making detailed evaluation
difficult. The likelihood of detecting endometrial carcinoma in
these specimens is influenced by several factors. Vaginal samples
are less likely to contain these cells than endocervical samples.
Cervical stenosis or obstruction will limit cellular flow. The tech-
nique and nature of the cytologic instrument used will influence
the specimen sampling quality. Intrinsic tumor characteristics
such as large size, prolapsing tendency, and greater extent may
be associated with a greater number of detectable cells. Finally,
endometrioid adenocarcinoma of a higher grade and type II car-
cinomas are more easily detected.
If abnormal endometrial cells are present, their number is
variable, but usually they are scanty. In most cases using conven-
tional cytology there are fewer than 500 abnormal endometrial
cells in the entire slide.76 In some cases there are no more than a
few dozen cells. The paucity and inconspicuous presentation of
abnormal endometrial cells in exfoliative cytology contrasts with
the more abundant abnormal cells usually identified in cervical
adenocarcinoma. The abnormal endometrial cells are frequently
accompanied by normal-appearing endometrial cells as well.
Each group must be assessed thoroughly. It is not usually possi-
ble to diagnose cytologically any histologic type of endometrial
adenocarcinoma (see Table 10.1) due to the absence of distinc-
tive architectural features and cellular degeneration during pas-
sage downward, although occasionally the presence of distinct
papillae and/or psammoma bodies will lead to a diagnosis of
serous carcinoma.
The abnormal cells present both singly and in aggregates.
Single cells may be overlooked or obscured (Fig. 10.25). Typi-
cally, the aggregates show a peripheral rounded appearance
as a result of cell moulding, and may consist of only a few
(Fig. 10.26) to many cells (Fig. 10.27). These cellular aggregates
frequently lose their original architectural arrangement and
present as three-dimensional non-specific clusters only. Only
rarely can distinct papillae, columnar configuration, or acini be
identified. Accordingly, the nuclei show a loss of polarity and
are irregularly arranged. Nuclear crowding and overlapping is
common (Fig. 10.28). In dense groups cytoplasmic borders
become indistinct.
The cytologic appearance will be dependent upon the tumor
grade and histologic type, but in general the nuclei are larger
than both normal and hyperplastic endometrial nuclei, on
the order of 150 ^m3,76,77 (Fig. 10.29). Since many endometrial
carcinomas
are low-grade
endometrioid
adenocarcinomas,
variation in the size and shape of the abnormal cells are often
not prominent.
The cytoplasm of both the single and aggregated abnormal
endometrial cells is frequently vacuolated as a result of degen-
erative changes. These vacuoles are frequently clear and contain
neutrophils, and previously have been labeled "oxyphilic cells."
Frequently, these abnormal endometrial cells are accom-
panied by large histiocytes, and a conspicuous diathesis may
be evident in many samples, at least in conventional prepara-
tions. This diathesis consists of exudate, red blood cells, fibrin,
and cellular debris, and is frequently found even in low-grade
or early-stage endometrial adenocarcinoma.77 The tumor dia-
theses in this situation is often not classic, and may consist of
precipitated protein in a watery background only.
As similarly described for NECs the appearance of endome-
trial adenocarcinoma in liquid-based cytology varies from that
of conventional cytology. The abnormal cells present in three-
dimensional clusters, often with prominent large nuclei exhib-
iting hyperchromasia (Fig. 10.30). In some cases papillae may
be identifiable. The tumor diathesis is much less prominent
(Fig. 10.31), but subtle debris may be found clinging to the
abnormal cells. The presence of tumor diathesis in liquid-based
cytology is dependent upon the histologic type and grade of
the tumor, and the extent of the disease process.78 Detection of
diathesis in a liquid-based cytology specimen is more likely in
higher grade and stage endometrial carcinoma.
If the nuclear features warrant a diagnosis of adenocarci-
noma, then the major differential diagnosis is cervical and
upper genital tract adenocarcinoma. A number of features can be
used to distinguish cervical from endometrial adenocarcinoma
(Table 10.9). Reactive endocervical and parabasal cells also need
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