Endometrial Lesions, Unusual Tumors, and Extrauterine Cancer
the tumor, and may be supplemented by nuclear cytologic
assessment. With increasing grade of the adenocarcinoma glan-
dular or acinar development is less evident. The grade of an
endometrioid adenocarcinoma is also an important determi-
nant of management, since it is known that better differentiated
carcinomas have a better outcome. The International Federation
of Gynecology and Obstetrics (FIGO) system for evaluating and
classifying the grade of an endometrioid adenocarcinoma is the
most widely used system (Table 10.1). This grading system is not
used for type II adenocarcinomas, since all of these tumors are
high-grade neoplasms.
Although endometrioid differentiation is the most common
histologic pattern within the type I group of tumors, other routes
of differentiation, including mucinous, secretory, and ciliated
patterns, may occur. When these non-endometrioid patterns
predominate, a specific designation is used for these adenocarci-
nomas (Table 10.3). When these other patterns are present in a
smaller amount, yet still compose at least 10% of the adenocar-
cinoma, then the designation of a "mixed adenocarcinoma" is
appropriate. As noted, squamous differentiation is seen in many
endometrioid adenocarcinomas. Well-differentiated endometri-
oid adenocarcinomas exhibiting an extensive benign-appearing
squamous component have previously been labeled as "ade-
noacanthomas," whereas poorly differentiated endometrioid
adenocarcinomas exhibiting an extensive malignant squamous
Table 10.3
Criteria for the histologic grading of endometrioid
adenocarcinomas of the endometrium*
Grade 1
5% or less nonsquamous solid growth pattern
Grade 2
6 to 50% nonsquamous solid growth pattern
Grade 3
More than 50% nonsquamous solid growth pattern
Notable nuclear atypia inappropriate for the architectural grade of the
carcinoma raises the grade of otherwise grade 1
carcinomas by one level.
If mucinous adenocarcinomas are graded using these criteria most are
grade 1.
Adapted from the WHO International Classification of Tumors.
*Serous and clear cell adenocarcinomas are high-grade.
component were labeled as "adenosquamous carcinomas."
Since these labels led to some confusion in terminology and
practice, they have been discarded. Instead, the term "endome-
trioid adenocarcinoma with squamous differentiation" is pre-
ferred with an accompanying statement specifying the grade.10
As noted, both serous and clear cell adenocarcinomas com-
pose the type II group. Both of these histologic types share the
same architectural patterns and high-grade nuclear atypia. The
distinction between serous and clear cell adenocarcinomas is
based upon their cytoplasmic staining traits in an H&E sec-
tion. Serous adenocarcinomas have eosinophilic or basophilic
cytoplasm (Fig. 10.5). In contrast, clear cell adenocarcinomas
have a clear cytoplasm due to the presence of abundant gly-
cogen (Fig. 10.6). These two histologic types of adenocarci-
noma are frequently seen together; pure forms of either are
unusual. Both of these histologic patterns are associated with
an aggressive course, and it is unclear whether they have dis-
tinctive natural histories. In the future, there may be no need
to continue to recognize these two histologic appearances as
separate entities.
Sensitivity and Specificity of Sampling
Techniques for Endometrial Disease
Cells from the endometrial cavity can be retrieved and examined
using either exfoliative cervicovaginal (CV) cytology or direct
uterine sampling.
Cervicovaginal Cytology
Although the primary purpose of cervicovaginal
remains the detection of cervical carcinoma and its precursor
lesions, exfoliative cytology also reflects the physiologic state of
the cyclic endometrium and some of its abnormalities. Sponta-
neously shed endometrial cells are part of the normal cellular
sample obtained by exfoliative cytology for cervical screening.
Such shedding typically occurs during the menstrual cycle or
in the first part of the proliferative phase. Abnormally shed
endometrial cells from endometrial neoplasms can also be
sampled in this fashion and may provide an opportunity for
Table 10.4
Comparison of reporting schemes for endometrial cells from the Bethesda System,43 British,60 and Australian screening programs59
Cytologic findings
The Bethesda System, 2001
British Society for Clinical
Cytology, 2000
Australian Modified Bethesda
System, 2004
Normal endometrial cells—
women < 40 years
Optional to report
May be disregarded
Should not be reported
Normal endometrial cells—
women > 40 years
Other, endometrial cells in
a women > 40 yearsa
Negative, report presence of
endometrial cellsa
Should not be reported13
Atypical endometrial cells
Atypical endometrial cells
Borderline nuclear change,
endometrial cells
Atypical glandular cells of undetermined
Possible high-grade glandular lesion
Endometrial adenocarcinoma
Adenocarcinoma, endometrial
? Glandular neoplasia,
Adenocarcinoma, endometrial
°These categories should be accompanied by an educational note detailing the possible significance of this finding. When menstrual history is provided NECs present
in the first 12 days of the cycle may be disregarded.
Symptomatic post-menopausal women require investigation irrespective of the status of their Pap test.
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