PART TWO
Diagnostic Cytology
Fig. 14.14 Benign epithelial repair
in a brushing of a
gastric peptic
ulcer. The enlarged glandular nuclei are uniform, and have vesicular
chromatin and well-developed nucleoli. Intercellular cohesion is well
maintained. A mitotic figure is present (Papanicolaou x MP).
Fig. 14.15 Gastric dysplasia. Dysplastic epithelium is characterized by
nuclear enlargement, hyperchromasia, and pseudostratification of the
nuclei. The maintenance of polarity and lack of single atypical cells favors a
dysplastic process rather than adenocarcinoma (Papanicolaou x HP).
cytopathologist is uncertain, it is prudent to undercall a speci-
men rather than yield a false-positive diagnosis129 (Table 14.1).
Gastric brushings and biopsies are diagnostically complemen-
tary. This is best witnessed in the distinction between benign and
malignant gastric ulcers. Some investigators recommend obtain-
ing six or more biopsy specimens and do not believe that gastric
brushings should be routinely employed.130-133 They would rec-
ommend restricting the use of gastric cytology to the evaluation
of huge ulcers, those occurring in the cardiac region (often more
difficult to biopsy), and in patients in whom prior biopsies were
negative for malignancy but the endoscopic appearance was sus-
picious. The majority of workers, on the other hand, believe that
brushings should be routinely incorporated into the evaluation
of any gastric mucosal abnormalities.129,134-136
Atrophic Gastritis
Chronic atrophic gastritis refers to the progressive destruction
of the secretory elements in the fundic mucosa by infiltrates
of lymphocytes and plasma cells.111
This results in a mucosa
that is thinner than normal and occupied predominantly by
mucus-secreting cells. Production of hydrochloric acid is sig-
nificantly reduced secondary to these destructive changes. Many
patients have circulating autoantibodies, and it is presumed that
in some individuals atrophic gastritis is an autoimmune disorder.
Some patients also suffer from pernicious anemia. The micro-
scopic changes of intestinal metaplasia frequently accompany
the atrophy and inflammation. The endoscopic appearance is not
characteristic unless there is marked mucosal atrophy. In this case,
the normal rugal pattern may be flat and associated with visible
submucosal blood vessels. Patients with atrophic gastritis harbor
a statistically increased risk of developing gastric adenocarcinoma.
This process appears to evolve through glandular dysplasia.137
There are no distinctive features in the cytologic brushings of
patients with uncomplicated atrophic gastritis. Smears contain
cohesive aggregates of glandular epithelial cells and variable
numbers of mixed inflammatory elements. If dysplastic glan-
dular mucosa is sampled, then the brushings yield a distinctly
different picture that closely mirrors that seen in specimens
from dysplastic Barrett's mucosa. Thus, dysplastic specimens
include small to large aggregates with somewhat irregular or
jagged edges. The constituent glandular cells have nuclei that
are larger than normal, are frequently elongated or cigar-shaped,
and possess one or more nucleoli. Their chromatin is finely to
coarsely granular and darkly stained. The nuclear contours vary
from smooth to mildly irregular. Cytoplasmic mucin is reduced
or not apparent, and the N/C ratios are increased. Within the
aggregates, the abnormal nuclei appear crowded, molded, and
overlapped (Fig. 14.15). On the basis of these features, glandular
dysplasia should generally be readily distinguished from benign
repair. On the other hand, it may be difficult to separate dys-
plasia reliably from a well-differentiated adenocarcinoma.49,50,55
The single most important feature in this separation is the pres-
ence of more than rare individually dispersed and intact abnor-
mal glandular cells. When that situation exists, adenocarcinoma
should be diagnosed.
chemotherapy-Associated Atypia
Systemically administered cytotoxic chemotherapy for the treat-
ment of cancer carries a well-recognized potential to induce
marked cytologic atypia in cells actively regenerating, including
the gastric mucosa. However, that site is usually not endoscopi-
cally sampled for histology or cytology because of the lack of
symptoms referable to the stomach. Hepatic arterial infusion
chemotherapy (HAIC) may be associated with a higher inci-
dence of gastric mucosal defects in that the hepatic artery con-
stitutes a portion of the vascular supply not only of the liver but
also of the stomach. Thus, the gastric mucosa may be exposed to
a higher concentration of cytotoxic drugs. Clinically and endo-
scopically, any associated ulcers may closely mimic both peptic
ulcers and gastric adenocarcinoma.
According to Becker and associates, the epithelial atypia in
gastric brushings from HAIC-induced ulcers far exceeds that seen
with usual peptic ulcers and could be mistaken for adenocarci-
noma.138 In their experience, the atypical epithelial cells were
present in large flat sheets, in small clusters, and individually;
three-dimensional configurations were not present (Fig. 14.16).
The most consistent characteristic was the marked increase in
cytoplasmic and nuclear volumes with a retention of a relatively
low N/C ratio. Cytoplasm was either eosinophilic or vacuolated.
Importantly, the nuclear contours typically remained smooth
388
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