Diagnostic Cytology
Fig. 9.23 An example of a large hyperchromaticcrowded group of normal endocervical cells obtained using sampling devices designed to gather
many cells and to sample the upper areas of the endocervical canal. (A) The entire group while a higher magnification of one edge is shown in (B). Close
attention to nuclear detail and organization of the group, particularly at the visible group margins, should allow a correct "negativeā€ interpretation (liquid-based
preparation, Papanicolaou x (A) MP, (B) HP).
the identification of a "significant" lesion (defined variably, but
generally a high-grade preneoplasia or neoplastic lesion) fol-
lowing an AGC is considerably more than that expected from an
ASC-US.62 This follow-up data varied widely, but the mean "sig-
nificant" follow-up (of either squamous or glandular type) was
41%, with those having "significant" glandular lesions being
11%. Of note, the follow-up of AGC with squamous intraepi-
thelial lesions or squamous carcinoma was the predominant
finding in virtually all studies, with true glandular lesions rep-
resenting a minority of cases, and occasionally representing
0% of cases in follow-up of AGC.71,72 Based on these compiled
data, a good "rule of thumb" regarding what can be expected in
follow-up of AGC interpretations would be benign or reactive
findings in approximately 30-40% of cases, squamous lesion in
approximately 50-60% of cases, and true glandular lesions in
approximately 10% of cases.
In the benign/reactive category, a variety of patterns may
fall within the above-noted criteria that define a case as AGC.
These include large numbers of benign endocervical cells when
arranged in densely packed hyperchromatic crowded groups,
the presence of tubal metaplasia, atypical repair, changes associ-
ated with endocervical polyps and intrauterine devices (IUD),
and directly sampled endometrium.
New sampling devices (brooms and brushes) gather more
cells from
areas within the endocervical
endocervical cell collection combined with the use of LBP
methods that fix these larger groups together prior to placing
them onto the glass slide can yield large densely packed groups
of endocervical cells (Fig. 9.23). These groups may show sig-
nificant nuclear overlap and individual nuclei may appear more
hyperchromatic. In addition, any reactivity of the endocervical
cells can yield substantial pleomorphism of size of endocervical
cell nuclei and can yield the presence of nucleoli, and occasion-
ally mitotic figures. Such changes have been reported to increase
the percentages of AGC interpretations in laboratories during
initial use of these techniques.60 Careful attention to the more
easily identified normal cells generally present at the margins of
the groups will allow the observer to infer that these are also rep-
resentative of the non- or poorly visualized cells present in the
more central areas. Cells and nuclei at the margins should be of
normal size, show evenly distributed, finely granular chromatin,
and have smooth nuclear contours. Generally, experience will
mitigate this initial "over-reaction" to a new pattern found as a
result of new technology. One recommendation that this author
has found to be of use in the continued evaluation of equivocal
results as detailed earlier is to ask the clinician to obtain a con-
ventionally prepared cervical specimen at the follow-up visit.
Often, the flattening of cells and cell groupings on the conven-
tionally prepared slide can improve the ability to discriminate
between reactive and neoplastic processes.
Benign and Non-Glandular Neoplastic
Processes that Mimic Endocervical
and Endometrial Neoplasia
Tubal Metaplasia
Tubal metaplasia is a normal variant type of endocervical epi-
thelium that is very common, although most prominently so
in women of mid-childbearing ages (>30) and older, where
the upper endocervical canal (as well as the endometrial lin-
ing epithelium) is virtually always involved.10 Tubal metaplastic
epithelium consists of the mingling of three cell types, mimick-
ing the normal lining of the fallopian tubes. These consist of
ciliated columnar cells, non-ciliated secretory cells, and tall slen-
der, closely packed cells, referred to as intercalated or "peg" cells
(see Figs 9.5 and 9.6). In one study of cytology specimens
obtained from the upper endocervical canals of hysterectomy
patients, the finding of groups having resemblance to AIS was
highly correlated to the paired histologic finding of tubal meta-
plasia.10 A number of reports have detailed the cytologic features
of tubal metaplasia and have detailed clues to assist in proper
benign interpretations.73-77 In commonality to the cells of AIS,
tubal metaplastic epithelium may present as hyperchromatic
crowded groups. Because nuclei in tubal metaplasia are not
generally as consistently placed at the base of the cell, groups
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