The Bethesda System for Reporting cervical cytology
Atypical glandular cells are estimated to be reported in only 0.2%
of cervical cytology tests in the United States.31 While AGC may be
associated with benign and reactive conditions such as endocervi-
cal/endometrial polyps, it is clear from several studies that AGC is
a "high-risk" interpretation compared to ASC; the reported rate of
neoplasia in follow-up of AGC ranges from 9 to 38%.67,68,76,77
Due to the high risk of a significant lesion associated with
a cytologic interpretation of AGC, colposcopy with endocervi-
cal sampling is recommended for women with all subcatego-
ries of AGC and AIS. In women over 35 years of age, additional
endometrial sampling is recommended. Endometrial sampling
is also recommended for women under the age of 35 with clini-
cal indications suggesting that they may be at risk for neoplas-
tic endometrial lesions, such as unexplained vaginal bleeding
or conditions suggesting chronic anovulation. In women with
atypical endometrial cells, both endometrial and endocervical
sampling should be done initially. In 2006 ASCCP suggested
that while HPV testing alone is not appropriate for initial triage
of any subcategory of AGC or AIS, HPV DNA testing at the time
of colposcopy is preferred in women with atypical endocervical,
endometrial, or glandular cells NOS, and the results should be
utilized in overall patient management.9
Educational Notes/Suggestions
The use of educational notes/comments is optional. If these are
used by the pathologist/laboratory, it is suggested that they be
concise, be phrased in the form of a suggestion, not a directive,
and be substantiated by published guidelines from professional
organizations.7 Examples can be found in the second edition of
the Bethesda atlas.10
Ancillary Testing
If ancillary testing, such as high-risk HPV, has been performed,
whether the report is issued concurrently with the cervical cytol-
ogy result or as an addendum/separate report will depend on
the laboratory's information system, turnaround time for such
testing, and clinical expectations. The methodology utilized for
the ancillary test should be specified. Suggestions for reporting
of molecular tests are provided in the Bethesda atlas.10
Automated Review
For cervical cytology preparations that undergo computer-only
or computer-assisted review, the type of instrument used and
any result should be included in the report. In addition, if there
was no "human" review of the slide, this should be made clear
in the report.
Interobserver Reproducibility
in Cervical Cytology
In an effort to improve standardization, clarity, and reproduc-
ibility of cervical cytology reporting, the second edition of the
Bethesda atlas10 emphasized more detailed morphologic criteria
and had many more images, which were complimented by addi-
tional images on the Bethesda website.11
In addition, as part of
the ASC-NCI Bethesda Project, a web based interobserver repro-
ducibility study was designed to gauge cervical cytology repro-
ducibility prior to publication of the atlas and website. A range
of classic and borderline images (77) were included for inter-
pretation; approximately 651 cytotechnologists and pathologists
worldwide participated in the study. It was apparent from the
results that the morphology presented was more important in
classifying images correctly than were professional or academic
degrees, or other variables assessed. In this study, exact agree-
ment with the TBS panel was relatively low (57%), although
agreement was 84.1% at the threshold of distinguishing NILM
from non-negative. Participants achieved a higher sensitivity for
correctly classifying high-grade squamous lesions than that for
high-grade glandular lesions. The details of this study have been
published12 and all the images and associated histograms of
participants' responses are available for review on the Bethesda
The Bethesda System and Reporting
Anal-Rectal Cytology
Anal cancer is considered an appropriate target for cytologic
screening in selected high-risk populations. The anatomic com-
monality of the anal-rectal canal and the cervical mucosa is
reflected in that both have a transformation zone. HPV is a com-
mon risk/etiologic factor for cancers of the anus and cervix and
subsequently the morphology of cytology samples from both
sites is comparable. It follows that sampling devices, preparation
techniques, and morphologic interpretation using the Bethesda
system terminology utilized for cervical cytology can readily be
applied for anal-rectal cytology screening.
Adequacy criteria for anal-rectal cytology are based, at
present, on limited personal experiences. As a guide, minimum
adequacy cellularity should be in the range of 2000-3000 nucle-
ated squamous cells for conventional smears and for LBP sam-
ples 1-2 nucleated cells/high-power field for ThinPrep (20 mm
diameter) preparations and 3-6 nucleated squamous cells/high-
power field for SurePath (13 mm diameter) preparations.10
Normal elements seen in anal-rectal specimens include
nucleated, anucleate, and metaplastic squamous cells, rectal
columnar cells, fecal matter, and mucus. A comment should
be included in the report about the presence of a transformation
zone component. Cytomorphologic criteria are quite similar
to those utilized for cervical cytologic interpretation; how-
ever, there is a higher incidence of poor preservation, cellular
cytoplasmic keratinization/parakeratosis,
and classic koilocytes are less frequently identified.10,78
When targeting high-risk groups, the rate of epithelial abnor-
malities noted is far higher than that reported for cervical cytol-
ogy.78,79 Reports from the United States suggest that anal-rectal
cytology screening is sensitive but has low specificity for predict-
ing the grade of the lesion, with a tendency to under-represent
the grade of squamous abnormality. While it has been shown
that screening high-risk patients by cytology is effective, the
present impediments to the success of early detection of anal
cancer by this method include limited clinical expertise and
means for the subsequent treatment/follow-up of these patients,
and the high risk of complications associated with excisional
procedures at this site.
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