Alimentary Tract (Esophagus, Stomach, Small Intestine, colon, Rectum, Anus, Biliary Tract)
nasogastric tubes has been very limited. The most common
technique involves the use of a balloon-like sampling device
that has been used predominantly in the esophagus. Briefly,
the device is swallowed in its deflated state and passed into the
stomach. Then the balloon is inflated, pulled through the gas-
troesophageal junction, and rubbed along the entire esophageal
mucosal surface. At the level of the cricoid, the balloon is deflated
and removed. The cytologic specimens are made by either direct
smearing of the balloon on glass slides or rinsing the surface with
preparation of a sediment through concentration techniques.
The balloon surface itself is covered by various types of materials
that enhance the mild abrasion of the mucosa. These blind abra-
sive techniques are used predominantly in public health or other
screening situations of high-risk populations.36-43 This balloon
sampling procedure can be effectively performed by nonphysi-
cian medical professionals quickly and with little discomfort to
patients. Obviously, the speed and relatively low expense lend
themselves well to surveillance programs. Other abrasive devices
have also been developed.44
Endoscopic retrograde cholangiopancreatography (ERCP) is
a combined radiologic and endoscopic procedure performed
under fluoroscopic control. An endoscope is passed into the
second segment of the duodenum and the papilla of Vater is
cannulated. Generally, cannulation catheters are advanced into
the area of obstruction. The brush, which is usually protected by
a sheath, is advanced into the stenotic region, which is then vig-
orously brushed. Of all the procedures discussed, this is prob-
ably the most technically complex and difficult. Unlike in the
GI tract, tissue biopsies are generally not procured. Fortunately,
complications are rare.
Overview of Gastrointestinal Epithelial
Reparative Atypia
The epithelium, both squamous and glandular, that lines the
entire GI and hepatobiliary tracts possesses only a limited array
of morphologic reaction patterns to numerous noxious stimuli.
With significant inflammation and/or a mucosal defect, i.e. ero-
sion or ulcer, the body attempts to mend the injury through
regeneration of the adjacent mucosa. The histologic appearance
of this healing process is distinctive. The reactive or regenerative
epithelial cells have nuclei larger than normal and often some-
what more ovoid in contour, have pale-staining chromatin, and
have well-developed nucleoli. In glandular elements, cytoplas-
mic mucin is often absent or inapparent. Rather, the cytoplasm
has an eosinophilic hue and cell borders are indistinct. This
creates a syncytial appearance very characteristic of regenerative
glandular GI epithelium. The cytoplasm in regenerating squa-
mous epithelial cells may appear less dense and homogeneous
than in the normal resting state. In both squamous and glan-
dular cells, cytoplasmic volume may be increased. Neutrophilic
leukocytes often infiltrate the glandular and squamous epi-
thelium. If an ulcer is present, the biopsies frequently include
fibrinopurulent exudate.
Repair is the cytomorphologic picture seen in cytologic speci-
mens of the mucosa in this healing phase. If repair did not mor-
phologically exist, GI and hepatobiliary tract cytology would
be far easier. That is, it is not usually a challenge to distinguish
normal mucosa from fully malignant cells in smears. Unfortu-
nately, from a diagnostic viewpoint, reparative atypia straddles
these two extremes. The morphologic features of reparative atypia
in cytologic smears include the presence of cohesive, generally
flat sheets of enlarged epithelial cells. These epithelial aggregates
vary from small to quite large. The preservation of intercellular
cohesion is a hallmark of this benign atypia.29,45-55 Infrequently,
one sees individually dispersed atypical cells with intact cyto-
plasm. Furthermore, relatively normal polarity is maintained
within these aggregates. That is, the cells respect the territoriality
of their neighbors. However, one may see a "streaming" effect
in which the cells and their nuclei appear to be aligned in the
same direction (Fig. 14.1). Although there may be mild aniso-
cytosis and anisonucleosis, a relative uniformity is seen from
cell to cell. Although Koss claims that the cells, for the most
part, are not enlarged compared with normal,56 most investiga-
tors believe that the cells and their nuclei are relatively increased
in size. The nuclei have smooth, round-to-oval contours with
finely granular, evenly distributed, and often rather pale-stain-
ing chromatin. The distinctive nuclear membranes are delicate
and uniform. Characteristically, these cells possess huge nucle-
oli readily apparent within the vesicular chromatin. In fact, this
nuclear-nucleolar dyssynchrony is quite characteristic of benign
repair. In other words, whereas the chromatin appears benign
and bland, the nucleoli appear quite alarming. The nucleocyto-
plasmic (N/C) ratios may also appear enhanced. As one might
expect in inflamed, regenerating epithelium, both neutrophils
and mitotic figures within the epithelial cells may be apparent
in the smears. In glandular epithelial elements, cytoplasmic
vacuolization may be much less conspicuous, although intercel-
lular borders often remain distinct. In their investigation that
compared the cytomorphologic attributes of benign repair and
carcinoma in the esophagus, Hoover and Berman claimed that
coarsely clumped chromatin, sharply angulated nuclear config-
urations, and elevated N/C ratios were the most reliable criteria
for diagnosing cancer.57 However, in many cases of esophagitis,
occasional cells with rather coarsely granular chromatin and
high N/C ratios can be found. In brushings of esophageal squa-
mous mucosa, features that appear to be more helpful in dis-
tinguishing benign from malignant cells include the presence
of hyperchromasia and irregularly thickened and contoured
nuclear membranes in the latter1
(Table 14.1).
Fig. 14.1 Reflux esophagitis. Benign reactive atypia is well developed
in these squamous epithelial cells. Intercellular cohesion is maintained;
the cells are arranged in a parallel fashion, creating a streaming repair-like
pattern. The nuclei are enlarged but they have delicate membranes, finely
granular and pale stained chromatin with small frequently multiple nucleoli
(Papanicolaou x MP).
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