Fig. 9.19 Endocervical adenocarcinoma can present with many of the architectural features noted in AIS. However, as the tumors become more poorly
differentiated, these features become more difficult to discern. (A) A poorly composed strip of cells. Because these lesions are less cohesive than more
differentiated counterparts, isolated cells are more common. (B, C) Examples of flat, honeycombed sheets of malignant cells with prominent macronucleoli in
every cell. Such features can sometimes be difficult to distinguish from typical and atypical epithelial repairs (see Figs. 9.28 and 9.29). (D) An ill-defined rosette
and a "birdtail” strip of cells. A granular, ‘clinging,” diathesis pattern is present in the background (liquid-based preparations, Papanicolaou x HP).
cytology examinations when appropriate cytologic features are
present. The morphologic characteristics of these lesions are now
well-described and have been shown to be reliably predictive.
Improvements in sampling devices and techniques for analyzing
the upper regions of the endocervical canal have increased the
sensitivity for detection and interpretation, but have also pre-
sented new challenges to the specificity of interpretation.60,61 Just
as in squamous lesions, there has always been a level of mor-
phologic uncertainty in some (often a majority) of specimens
showing not completely normal endocervical cytology, but yet
not having the absolutely specific features of a diagnosable AIS
or invasive carcinoma. In the 1991 version of the Bethesda Sys-
tem (TBS), such changes were referred to as "atypical glandular
(endocervical) cells of undetermined significance (AGUS)."32
In the current 2001 Bethesda System terminology, this nomen-
clature has changed to "atypical glandular (endocervical) cells
(AGC)."9 The dropping of the "of undetermined significance"
was done as a practical consideration of the difficulties faced in
busy practitioners' offices, based on confusion with the far more
prevalent "atypical squamous cells
of undetermined significance"
(ASC-US) slide designation. In addition, the general categoriza-
tion portion of the cervical cytology report was further divided
into "Epithelial cell abnormality
—squamous or glandular"
indicate the broad designation of lesion class prior to the more
specific interpretation. As will be noted, AGC is clinically a more
significant interpretation requiring more rigorous and different
follow-up than ASC-US, and hence a nonoverlapping name was
felt to be required.
In TBS 1991, AGUS was subdivided into three categories
related to a morphologic assessment of the risk that a true
neoplastic lesion was present. These included "favor reactive,"
"not otherwise specified," and "favor neoplastic" distinctions.
Data presented at the 2001 Bethesda conference showed that
the "favor reactive" and "not otherwise specified" categories
had similar and significant (in terms of high-grade neoplastic
lesions) clinical follow-up (Table 9.2). Hence, the "favor reac-
tive" category was merged into the "not otherwise specified"
category with the proviso that changes interpreted as being