Glandular Lesions of the Uterine Cervix
Fig. 9.33 Organoid configurations can be commonly noted with direct endometrial sampling. In (A, B), tubes of proliferative endometrial glands are found
intact on the slide. (C) Endometrial stromal cells streaming out from a hyperchromatic group of probable endometrial glandular epithelium. The association
of the stromal component with the glandular cells is a key differential diagnostic feature when distinguishing between direct endometrial sampling and
endocervical neoplastic glandular lesions ((A) liquid-based preparation, (B, C) conventional smears; Papanicolaou x (MP)).
Ki-67 and p16, although the staining pattern was heterogenous
rather than diffuse.107 Mini chromosome maintenance (MCM)
and CDC6 proteins, markers associated with aberrant cell cycle
proliferation, have also been shown to be overexpressed in HPV-
associated squamous and endocervical neoplasias of the cervix
(MCM5 > CDC6 ), and in addition were both found to be nega-
tive in normal tissues. Studies extended to ThinPrep Pap tests
have shown overexpression in squamous lesions, although glan-
dular lesions were not included in the study.105 Use of a marker
that is negative in endocervical neoplasia and positive under
benign conditions such as tubal metaplasia has also been touted
as a potential discriminator. Bcl-2 is a proto-oncogene that has
been consistently demonstrated to stain cases of tubal metapla-
sia, while remaining negative in endocervical neoplasia.114 In a
tissue study, 12 of 13 cases of tubal metaplasia, and 7 of 7 cases
of endometriosis showed diffuse immunoreactivity with Bcl-2.
In the same study, none of the tubal metaplasias were diffusely
immunoreactive for p16 or Ki-67, and 3 of 7 cases of endo-
metriosis showed diffuse staining for p16, with none showing
diffuse staining for Ki-67.114,115
Another marker series utilized in an attempt to differenti-
ate benign from neoplastic endocervical epithelia has been the
family of mucins (MUC). In one study, normal endocervical
epithelium, tubal metaplasia, and microglandular hyperplasia
were noted to never express MUC2, while variable percentages
of endocervical neoplasias did (AIS, 25%; invasive endocervical
adenocarcinoma, 43%), providing potential utility when this
marker is positive.116
A recent study in histologic specimens examining a malig-
nancy marker, ICM protein, in comparison to p16 showed
excellent sensitivity for AIS (93%), similar to p16, but far bet-
ter specificity with no normal endocervical or tubal metaplasia
staining.117 Use of this marker in cytologic specimens has yet to
be reported.
Overall, ancillary marker use to discriminate benign reactive
from neoplastic endocervical processes has made substantial
progress in the past decade. Studies to translate use in histologic
material to the more complicated environment of cytologic
specimens will be necessary to allow for accurate discrimination
of equivocal results.
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