Glandular Lesions of the Uterine cervix
endocervical lesions (as many as 50%36); however, the reverse is
uncommon. In this author's experience when diagnostic archi-
tectural features of AIS are not present within the groups and
isolated squamous dysplastic cells are present, a squamous ori-
gin for the overall process is most common. These uncharacter-
istic changes in squamous dysplasias can also be appreciated in
histologic material (Fig. 9.27). Descriptions of this change were
made shortly after the widespread adoption of the endocervical
brush and were originally mistaken for microinvasive carcinoma
due to the presence of nucleoli.79 In another study, two distinct
patterns of endocervical involvement by squamous dysplasias in
brush specimens were noted—the first pattern was characterized
by 3-dimensional cell groupings with smooth external borders
and internal spindling or whorling arrangements. The second
pattern showed 2 -dimensional groups of "columnar" cells with
peripheral palisading and nuclear pseudostratification.80
This pattern is now well recognized and well studied. In most
cases, awareness of this possibility when entertaining an inter-
pretation of "atypical glandular cells" will allow discrimination
and appropriate classification. However, even with heightened
awareness, a number of squamous cases will still far more
closely resemble a glandular process and will continue to be
misclassified as such. Fortunately, management guidelines to be
discussed later should allow for proper investigation of these
cytologic abnormalities with either interpretation rendered.
Key features of high-grade squamous dysplasias involving
endocervical gland necks
• Hyperchromatic crowded groups;
• Group edges tend to be smooth or contoured but may
show some mild nuclear protrusion;
• Polarity of cells and nuclei may be retained (in distinc-
tion to loss of polarity typical of squamous lesions);
• Cigar-shaped nuclei (pseudocolumnar) may be
• Cytoplasm may be granular;
• Nucleoli can be prominent;
• Isolated dysplastic squamous cells are often present in
the background;
• Some cells can show classic glassy (keratinized)
cytoplasm; and
• Well-defined pseudostratified strips and epithelial
rosettes are lacking.
Atypical Repair
Reactive changes in epithelial cells are well described and gen-
erally well recognized as such by cytologists. The one circum-
stance in which cells reacting to some injury of the epithelium
can be problematic is in the condition of extreme reactivity, also
known as atypical epithelial repair. In this reaction, endocervical
cells involved by infection, trauma, or other disruptive effect will
take on many of the cytologic features that can also be noted in
neoplastic processes, especially in invasive adenocarcinoma. In
some cases, discrimination between these entities can be prob-
lematic, requiring histologic evaluation for definitive diagnosis.
Reparative endocervical cells have a characteristic cytologic
appearance which can be initially evaluated on low-magnification
examination. Repair presents as cohesive, flat, 2-dimensional
sheets of cells with increased amounts of dense cytoplasm with
extensions, or tails, of cytoplasm at the group margins. These
cytoplasmic extensions are often referred to as "taffy-pull"
Fig. 9.27 High-grade dysplasia extending into an endocervical gland neck
and replacing the native endocervical epithelium. When squamous lesions
of this type are sampled, the cytologic preparations often show ‘glandular”
architectural and cellular features (H&E stain, LP).
cytoplasm and are found as a result of normal cell-to-cell cohe-
sion being present at the time the cells were traumatically sam-
pled from the epithelial surface. Cytoplasmic boundaries are
well-defined and can be clearly seen in distinction to the overlap-
ping or syncytial appearance of the groups noted in many neo-
plastic processes. In addition, a brisk inflammatory response will
be noted in the background of the specimen, with neutrophils
often found intermingled with the cells in the groups. Further
examination will show enlarged nuclei, most often with smooth
nuclear outlines and uniform chromatin. Regular macronucleoli
are noted in virtually all nuclei involved by the reparative pro-
cess (Fig. 9.28). This pattern of repair is generally easy to recog-
nize; however, when repair becomes "atypical" the nuclei begin
to show variable degrees of pleomorphism of size and shape
within the groups, often taking on nuclear contour irregularities.
In addition chromatin patterns can turn from uniformly distrib-
uted to irregular and show coarse granularity. These nuclear fea-
tures can make distinction from invasive carcinoma difficult as
these are some of the classic features noted for such lesions81-83
(Fig. 9.29). Cases of invasive carcinoma should have isolated
abnormal cells, which can be found, but less commonly, in
reparative reactions. In circumstances when the differential
diagnosis is between atypical repair and invasive carcinoma, a
designation of atypical glandular cells is warranted. A complete
review of the history, along with a colposcopic examination,
and endocervical sampling procedure are required in such cases,
as will be discussed below under management options.
Key features of atypical repair
• Flat, 2-dimensional sheets of cells;
• Generally well-defined cytoplasmic boundaries;
• "Taffy pull" voluminous cytoplasm;
• Inflammation present within and around the groups;
• Enlarged nuclei with pleomorphism of size and shape;
• Irregular nuclear envelopes;
• Chromatin may be heterogeneous;
• Prominent macronucleoli;
• Mitotic activity;
• Isolated atypical cells may be present.
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