9
Glandular Lesions of the Uterine cervix
Fig. 9.24 In this large group of tubal metaplasia (one border showed
cilia not present here), a number of mitotic figures were identified (arrows).
Attention to the lack of chromatin coarseness and the lack of apoptotic
fragments is a useful feature indicating that this group is not likely to
represent a neoplastic process (conventional smear, Papanicolaou x MP).
of these cells can also present as pseudostratified strips, in a
similar fashion to the configurations commonly noted in AIS.
In addition, the nuclei may be enlarged, although not as large
or as consistently so as in AIS. There may be micronucleoli, and
mitoses can occasionally be present (Fig. 9.24). The presence
of cilia or terminal bars is a good indicator that any such group
is of benign origin; however, in many cases cilia may not be
preserved in the cytologic sample. The key to distinguishing
difficult presentations of tubal metaplasia where cilia are absent
is a careful review of nuclear chromatin. Most often cells of
tubal metaplasia will have normal "endocervical" chromatin
that is finely granular and evenly distributed. The typical chro-
matin pattern of AIS or invasive endocervical adenocarcinoma is
coarse, and evenly or heterogeneously distributed, respectively.
In addition, apoptotic nuclear fragments are not generally found
in cases of benign tubal metaplasia, but may be commonly noted
in neoplasias. Although many of the architectural features noted
in AIS, such as epithelial rosette formation, marginal feathering
in groups, and pseudostratified strips of cells, can be found in
some cases of tubal metaplasia, these features are not generally
as well developed and a composite of all such features is rare in
tubal metaplasia. Because tubal metaplasia is a common find-
ing in samples obtained from high in the endocervical canal,
it is only reasonable to assume that ciliated columnar cells
would be commonly noted in cases containing real neoplastic
endocervical processes. Therefore it is extremely important to
remember that a finding of tubal metaplasia in a case should
not militate against an appropriate interpretation for the cells of
a true endocervical glandular neoplasia elsewhere on the slide.
In one report, the authors noted 40% of squamous dysplasias
had evidence of tubal metaplasia in association.74 The issue of
whether cilia is a certain predictor of a benign process (100%
NPV) has often been raised. There are known ciliated malignant
entities that may present in the cervix, such as well-differentiated
serous carcinomas. In addition a report of tubal metaplasia as
representing a potential dysplastic process has been put forth.49
In rare cases of ciliated malignancy, obvious malignant features
in the nuclei should be present, such as enlargement, pleomor-
phism, and abnormal chromatin patterns. As to the issue of tubal
metaplasia representing a dysplastic process, there has been no
compelling evidence forthcoming that such is the case. Tubal
metaplasia is extremely common and unlikely to represent any-
thing other than a benign metaplastic process. Therefore, with
a significant degree of confidence, it can be stated that in the
absence of overt features of malignancy within the cells in ques-
tion, the presence of cilia on columnar cells is a feature indica-
tive of a benign process.
Key features of tubal metaplasia
• Incomplete features of AIS;
• Pseudostratified strips of cells;
• Nuclear feathering;
• Rosettes;
• Finely granular, evenly distributed chromatin;
• "Washed-out" appearance to nuclei;
• Enlarged nuclei with pleomorphism;
• Nucleus-to-cytoplasmic ratio increased;
• Occasional mitoses and rare apoptotic bodies; and
• Cilia/terminal bars.
High-Grade Squamous Dysplasias Presenting
as Atypical Glandular cells
As noted in the introduction to this section, high-grade squa-
mous dysplastic lesions are the most common positive follow-
up to an atypical glandular cell interpretation. This occurs on
average in about 50-60% of cases. The appearance of high-grade
squamous dysplasia involving areas above the transformation
zone are well known to involve the surface epithelium, and also
to replace the endocervical lining extending into the endocer-
vical gland crypts. In this circumstance, the dysplastic cells in
the cytologic preparation tend to show many morphologic
features suggestive of glandular differentiation. New sampling
devices have contributed to this pattern by sampling more cells
from higher in the canal than was done with older devices. This
phenomenon was originally noted during the early adoption
of endocervical brush technology.78
The features that may be noted in this setting include hyper-
chromatic crowded groups of cells with palisading of nuclei
showing maintenance of polarity, granularity and amphophilia
of cytoplasm, the presence of nucleoli, and some accentuation
of nuclear protrusion at group margins in a manner akin to the
feathering noted in cases of endocervical neoplasia. Chromatin
patterns are coarsely granular and hyperchromatic in similar
fashion to more conventional presentations of high-grade squa-
mous dysplasia (Fig. 9.25). Hyperchromatic crowded groups of
"AGC-like" high-grade squamous intraepithelial lesions (HSIL)
differ from the classically described appearance of syncytial
groups of HSIL in which polarity is not maintained, nuclei are
round to oval, and no nucleoli are noted. Once the cytologist is
familiar with this pattern as a variant of squamous dysplasia, key
differential features may be utilized to distinguish these proc-
esses from true endocervical neoplasia. These features include the
lack of characteristic architectural features of AIS—pseudostrati-
fied strips of cells, rosette formation, and lack of well-developed
feathered borders. In addition, the presence of isolated diag-
nostic cells of squamous dysplasia is virtually always noted in
the background of such cases and should be diligently sought
when this differential diagnosis is being considered (Fig. 9.26).
Squamous dysplasias are often present with true glandular
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