Diagnostic Cytology
Large Intestine
Normal Histology and Cytology
The entire length of the large intestine is lined by a mucosa com-
posed of straight tubular crypts. Much of the surface is covered
by tall columnar absorptive cells with eosinophilic cytoplasm
and a striated luminal border less well developed than that in
the small bowel. As compared with the small intestine, goblet
cells are much more numerous in the surface epithelium and
the crypts. Paneth cells constitute a minority of the epithelial
elements, predominantly on the right side.
Cytologic brushings of normal colonic mucosa present as
large flat monolayers with sharply defined external edges. Cell
borders are distinct and nuclei are evenly distributed through-
out the sheet, creating a honeycomb arrangement. The goblet
cells appear as sharply delineated clear holes within the sheet
(Fig. 14.28A). As Paneth cells usually reside deep within the
crypt, they would not be expected in brushings.
Chronic inflammatory Bowel Disease
The large intestine may be affected by a huge variety of acute
and chronic inflammatory processes. Most of these, however,
would never be intentionally sampled for cytologic examina-
tion. Chronic inflammatory bowel disease is divided generally
into two disorders, chronic ulcerative colitis and Crohn's dis-
ease, which are clinically characterized by alternating periods of
remission and exacerbation. Although uncommon in very young
children and in the elderly, both may occur in patients of all ages.
With ulcerative colitis, the initial presentation occurs most often
in teenagers and young adults. The typical age in Crohn's disease
is only slightly older. With ulcerative colitis, bloody diarrhea
is the most frequent form of presentation. Prominent symp-
toms in most patients with Crohn's disease include abdominal
cramps often restricted to the right lower abdominal quadrant
and intermittent diarrhea that is frequently nonbloody. Consti-
tutional symptoms such as fever are much more frequent than
with ulcerative colitis.
Ulcerative colitis essentially always involves the rectum
and extends proximally without an interruption for variable
distances. If most or all of the colon is involved, patients are
said to have pancolitis. The most common endoscopic and
gross appearance is multiple ulcers with inflammation of the
surrounding mucosa. At times, the entire mucosa may appear
denuded, with only small residual mucosal tags (pseudopolyps).
Histologically, both acute and chronic alterations are evident,
even early in the clinical course. The acute changes consist
of neutrophils infiltrating the crypt epithelium and the lam-
ina propria. Basal infiltrates of plasma cells and eosinophils
and crypt architectural distortion are the major changes of
Crohn's disease, in contrast to ulcerative colitis, is a trans-
mural chronic inflammatory process characterized by diffuse
infiltrates and nodules of mononuclear inflammatory cells at all
levels of the bowel wall. Alterations within the mucosa parallel
those seen in ulcerative colitis but often are of a milder level;
ulcers are less frequent and extensive. In addition, noncaseating
granulomas are present in a proportion of patients.
A major complication of ulcerative colitis and, to a lesser
extent, Crohn's disease of the colon is the development of
adenocarcinoma. Usually these malignancies arise in patients
who have had long-standing pancolitis. As a group, this subset
of patients develops malignancies at a much younger age than
the general population. Furthermore, the neoplasms tend to
be very aggressive. Adenocarcinomas appear to evolve through
stages of glandular dysplasia.
Because of the propensity to develop adenocarcinoma,
patients with chronic inflammatory bowel disease may be sub-
jected to regular surveillance programs for dysplasia and early
carcinoma. Most of these programs entail taking numerous
endoscopic biopsies throughout the entire length of the intes-
tine. Dysplastic mucosa does not appear endoscopically differ-
ent from benign mucosa, either reactive or quiescent. Only a few
centers have incorporated brushing cytology into these surveil-
lance programs.47,51,166,167
As acute inflammation and mucosal defects characterize
the histopathology of both disorders, mucosal brushings of
benign mucosa typically show reparative atypia.47,166,167 Thus,
cohesive aggregates
of enlarged glandular
Fig. 14.28 (A) Normal colonic mucosa. Brushings of benign colonic mucosa are characterized by flat sheets maintaining a honeycomb pattern
(Papanicolaou x MP). (B) Dysplastic colonic mucosa in the setting of inflammatory bowel disease. Stratified elongate hyperchromatic nuclei dominate the
picture (Papanicolaou stain x MP).
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