Glandular Lesions of the Uterine Cervix
Fig. 9.36 (A, B) "Bag of polyps" cells are commonly associated with endocervical polyps. They can be indistinguishable from similar cells associated with
endometrial adenocarcinoma. Close attention to clinical history and communication with the clinician is imperative to arrive at a proper clinical triage of a
patient presenting with such cells (liquid-based preparations, Papanicolaou x (A) HP, (B) MP).
Management of Glandular Neoplastic Lesions
and Atypical Glandular Cells
In the 2006 management guidelines from the American Soci-
ety of Colposcopy and Cervical Pathology (ASCCP),118 defini-
tive neoplastic lesions (AIS, invasive carcinoma) identified on
cytologic examination will require colposcopic examination
with endocervical sampling. In women over the age of 35 years,
the addition of endometrial sampling is recommended. In the
event that no lesion is identified on the initial evaluation, re-
review of cytology slides is recommended. For cases in which
the original interpretation is confirmed, an excisional procedure
is recommended. For AIS, conization or hysterectomy would be
determined by consultation between clinician and patient with
regard to maintenance of childbearing considerations.
For cases of atypical endocervical or glandular cells, the ini-
tial management recommendations are the same as for iden-
tified definitive neoplastic lesions, and include colposcopic
examination and endocervical sampling, with endometrial sam-
pling added in the 35 and older population. For lesions identi-
fied on histologic examination (AIS, invasive carcinoma, CIN),
treatment would proceed as is appropriate for those lesions. For
initially negative results, re-review and confirmation of cytologic
findings is recommended. In cases of AEC/AGC that are not
further specified (NOS category), follow-up cervical cytology
examinations at repeated 6-month intervals if the HPV status
is unknown or positive, and at 12-month intervals if the HPV
status is negative, is recommended. After four NILM specimens,
the patients can be returned to the routine screening pool. Man-
agement as recommended by the guidelines would be required
for any cytologic abnormality identified during this period. For
cases of AEC/AGC where a neoplastic process is favored, and in
which the initial findings fail to reveal a lesion, an excisional
procedure is recommended, with a cold knife conization being
the preferred method.
The use of tests for high-risk human papillomavirus (hrHPV)
as a triage to colposcopy for equivocal glandular specimens
(AEC/AGC) has been theorized to be of potential use. The
premise for this triage is that virtually all endocervical neoplastic
lesions are associated with hrHPV. As noted earlier, sensi-
tive assays have shown that 100% of AIS and 94% of invasive
adenocarcinomas are hrHPV positive.11 A number of studies
have tested the utility of this method.119,120 One study showed
100% sensitivity for high-grade squamous neoplasias and AIS
following equivocal cervical cytology specimens.119 Another
study showed 83% sensitivity for significant lesions with a nega-
tive predictive value of 91-95%. The authors noted that the PPV
for a significant lesion (57-61%) was substantially higher than
for the currently utilized triage of equivocal squamous cervical
cytology specimens.67 The 2006 ASCCP consensus guidelines118
have taken note of the hrHPV triage studies to date but have
declined to make a recommendation for the use of hrHPV test-
ing as a triage method to determine which patients should have
a colposcopy and endocervical sampling, and which can be fol-
lowed by more conservative measures. The data from studies to
date were not felt to be to the level of confirmation that would
allow hrHPV-negative patients to be reliably predictive of non-
disease. However, it was recognized that a hrHPV result can be
very useful in developing the overall management process, espe-
cially when a woman has an initially negative colposcopic exam-
ination. Patients whose hrHPV test is negative might be more
conservatively managed than those having positive tests in this
circumstance. In addition, data from the ALTS trial indicated that
colposcopic examinations appeared to be more accurate when
the HPV result was known by the clinician—meaning that espe-
cially with a positive result, clinicians might be prone to look
more carefully or biopsy more equivocal areas than with nega-
tive or unknown results.121 Incorporation of the hrHPV result
into overall management decisions for endocervical or glandular
atypias was therefore recommended in the 2006 guidelines.
Finally a number of important caveats should be mentioned
about the cytology laboratory management of equivocal glan-
dular cytologic presentations. First, communication between
cytologist and clinician is important for optimal specimen
interpretation. Communication can provide important addi-
tional information to both parties which may guide specimen
interpretation and patient management. Obtaining prior and
current history is important, such as knowledge of a prior cone
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