Glandular Lesions of the Uterine Cervix
Fig. 9.31 An example of a single very high nucleus-to-cytoplasmic ratio cell
with an irregular nuclear outline and dense hyperchromasia. An indistinct
nucleolus is present. This cell was found in association with other cells
characteristic of IUD as seen in Fig. 9.30. Testing for human papillomavirus
was performed and found to be negative. No dysplasia was found on follow-
up. This presentation represents a single irritated high endocervical canal cell
(liquid-based preparation, Papanicolaou x HP).
vacuolated cells containing large numbers of neutrophils are
characteristic of endocervical polyps. Cells virtually indistin-
guishable from these can also be seen in endometrial adenocar-
cinoma and have been referred to as "bag of poly" or "oxyphil"
cells (Fig. 9.36). Close attention to clinical history, including
patient age, presenting symptoms, and clinical evidence of a
visible endocervical polyp, are important points to consider in
weighing this differential diagnosis.
Key features of endocervical polyp change
• Large hyperchromatic crowded groups of normal/reac-
tive endocervical cells;
• Bloody and necrotic diathesis can be present when
polyps are ulcerated;
• Degenerative changes can lead to coarse and hetero-
geneous chromatin pattern;
• Typical and atypical reparative changes are commonly
seen; and
• "Bag of polys" cells present—show vacuoles contain-
ing neutrophils.
Diagnostic Accuracy of Cervical Cytology
Regarding Glandular Lesions
The major difficulty in the detection of endocervical glandular
neoplasias in cervical cytology specimens appears to be sensitiv-
ity. In one large study of patients with confirmed histologic AIS,
the sensitivity of a single preceding Papanicolaou test was found
to be about 50%.93 In a follow-up study of the same popula-
tion of cases, 35% of the total were found to represent sam-
pling errors with no identifiable glandular neoplasia present on
the slides, with screening and diagnostic errors accounting for
the remainder.94 In this study, even when identifiable abnormal
glandular cells were identified, the commonly noted deficien-
cies that precluded an accurate interpretation were either poorly
preserved cells or abnormal cells being few in number. Interest-
ingly these authors also concluded that errors were found to be
diminishing over time, perhaps indicating that recognition of
the criteria and hence sensitivity may be improving with educa-
tion. A more recent study provides support for this conjecture as
100% of cases of AIS and 80% of cases of endocervical adeno-
carcinoma were found to have positive findings on the cervical
cytology specimen in the year prior to histologic diagnosis.95
Other studies have suggested that coexistence of both squamous
and glandular neoplasias may inhibit the interpretation of one
or the other lesion. The most commonly cited reasons for this
error include overwhelming numbers of one cell type obscuring
the other cell type, or lack of recognition of the specific cellu-
lar features.96 Studies specifically addressing Papanicolaou test
detection rates of invasive cervical adenocarcinoma have identi-
fied sensitivities of approximately 50%.97
Location of disease was found to be an important variable
when examining the false-negative rate for AIS. In disease found
to involve the transformation zone, one study showed that AIS
was noted to be present in all preceding cervical cytology speci-
mens, whereas for disease present higher in the endocervical
canal, only 33% showed AIS to be present on the Pap slide.98
For invasive endocervical adenocarcinomas, transformation
zone involvement conferred a higher rate of detection sensitivity
as compared to non-transformation zone involvement (55 ver-
sus 45%, respectively). Overall, any glandular neoplastic lesion
was substantially more likely to be detected if it involved the
transformation zone than if it did not (75 versus 46%, respec-
That AIS is a difficult interpretation for the average practi-
tioner is illustrated in a 2001-2002 College of American Pathol-
ogists interlaboratory peer comparison study. The ability of
participants to detect AIS in conventional specimens having this
reference interpretation was significantly less than their ability
to detect HSIL (false-negative rate of 11.7 versus 4.6%, respec-
tively).99 Comparing specific interpretations of AIS to those of
invasive adenocarcinoma and HSIL, only 46.5% of responses
in AIS cases matched the exact reference diagnosis compared to
72.2% of invasive adenocarcinomas and 73.2% of HSILs. These
data suggest that AIS is not as well and reproducibly recognized
by the average cytology practitioner. The positive predictive
value for any high-grade disease of an AIS interpretation was
shown to be substantially higher (75%) than that of either an
"AGC, favor neoplasia" (PPV = 25%) or a "minor abnormality
of glandular cells" (PPV = 10%), indicating, as expected, that
an outright positive interpretation is more predictive than an
equivocal one.100
The use of liquid-based cytology preparation has been
reported to improve the detection sensitivity of cervical glandu-
lar lesions. One study showed a statistically significant increase
in biopsy-confirmed endocervical neoplasias using ThinPrep
as compared to conventional smears.41 In other studies, non-
significant trends were also shown to favor the sensitivity
afforded by the liquid-based method.44,101
Use of ancillary techniques has been touted as a means to
improve the sensitivity and specificity of detection of endocervi-
cal adenocarcinoma and its precursors. The most widely reported
marker that may be of use is the cell cycle dysregulation protein
p16. Several studies in histologic specimens have reported high
rates of positivity with this marker in both AIS and invasive
cervical adenocarcinomas.11,102-106 Other histologic studies have
documented that p16 positivity can also be found in significant
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