14
Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
Paneth cells may also be evident. It must be emphasized that
Barrett's metaplasia can only be diagnosed by the intestinal-type
mucosa, and thus recognition of goblet cells is paramount.
The importance of Barrett's metaplasia lies in the fact that it
is a premalignant change, as the majority of adenocarcinomas
occurring in the esophagus arise on a background of this pre-
existing change, usually the intestinal type.77,79 It is recognized
that there is an intermediate morphologic stage between benign
metaplasia and frank carcinoma, namely glandular dysplasia.
In brushings from patients with benign Barrett's esophagus,
the smears generally contain abundant glandular epithelium
punctuated by goblet cells.4,6,53,55,80 The specimens are domi-
nated by large flat sheets of cohesive uniform-appearing glandu-
lar epithelial cells. The sheets and aggregates have sharp smooth
borders. That is, they do not appear frayed and irregular. This
reflects the retention of a normal level of intercellular cohesion.
Normal polarity is also maintained. Thus, within the sheets, the
nuclei appear equidistant from one another, and intercellular
borders are distinct. This creates the classic honeycomb appear-
ance. In the presence of reparative atypia in benign Barrett's
epithelium, there may be a streaming effect in which the cells
and their nuclei all appear to flow in the same direction. The
metaplastic nuclei are uniform from cell to cell, having round
or slightly ovoid contours, delicate smooth nuclear membranes,
and very finely granular vesicular chromatin. In general, nucle-
oli are inconspicuous, but in some cases of atypia, they may be
quite enlarged. When viewed on end, the cardiac-type mucus
cells have a hexagonal configuration, whereas the goblet cells
have a more rounded contour (Fig. 14.7). The latter appear as
sharply punched-out clear areas. The smear background typi-
cally is clean, although a few inflammatory elements may be
scattered about. A discussion of dysplasia on Barrett's esophagus
and adenocarcinoma in Barrett's is presented in the following
section.
Barrett's Dysplasia and Adenocarcinom a
The incidence of adenocarcinoma of the esophagus is rising in
epidemic proportions in the United States and other portions of
the Western world. Two decades ago, adenocarcinoma constituted
only 5-10% of all primary malignancies of this organ. Today,
it accounts for about half.77-79,81-83 Almost all adenocarcinomas
arise on a background of preexisting Barrett's metaplasia and
are thus related to chronic reflux disease.77,84 In contrast to squa-
mous cell carcinoma, adenocarcinoma affects whites three times
more often than blacks. Men are affected much more frequently
than women. In whites, the male-to-female ratio is 7:1, in blacks
the difference is even greater. Although the overall prognosis
remains rather dismal, the use of neoadjuvant radiation and
chemotherapy has improved clinical outcomes.85
These neoplasms almost always present in the distal third of
the esophagus and often appear to straddle the gastroesopha-
geal junction. The most common clinical presentation relates to
the progressive development of dysphagia. Endoscopically, they
appear as either large ulcers or fungating polypoid masses; the
diameter of the lumen is often greatly reduced.
Histologically, most esophageal adenocarcinomas are well
to moderately differentiated.77 That is, most consist of lumen-
containing glands or tubules. In contrast to gastric adenocarci-
nomas, signet ring cell carcinoma is quite uncommon. As with
squamous cell carcinoma, the single most important histologic
prognostic factor is the depth of invasion into the esophageal wall.
Adenocarcinomas
in the setting of Barrett's
esophagus
arise through a sequence of mucosal alterations that include
premalignant or dysplastic glandular changes. Dysplastic Bar-
rett's epithelium is the precursor to invasive adenocarcinoma
and the dysplastic cells have some but not all the features of
malignant cells. Dysplastic glandular epithelium in Barrett's is
characterized by columnar-shaped cells having enlarged, oval
to somewhat elongated hyperchromatic nuclei that are typically
pseudostratified. The nuclei may have processed large nucleoli
and increased N/C ratios. In low-grade dysplasia the nuclei
remain concentrated in the basal portion of the cells with mild
nuclear atypia and pleomorphism often in crowded groups with
nuclear stratification (Fig. 14.8A). In high-grade dysplasia many
nuclei are oriented toward the glandular lumina with the higher
degree of nuclear atypia and pleomorphism often found in
crowded groups or occasionally with isolated cells (Fig. 14.8B).
Dystrophic goblet cells with abnormally positioned and/or
sized nuclei may be present.
The cytologic diagnosis of adenocarcinoma of the esophagus
can be readily made. However, it is less widely recognized that
one can render a diagnosis of glandular dysplasia in esophageal
Fig. 14.7 Barrett's esophagus. Smears from Barrett's esophagus honeycomb and picket-fence-like arrangements of glandular cells with interspersed
manifest goblet cells (Papanicolaou x MP, HP).
381
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