Surgical Pathology and Current Molecular Aspects of Dysplasia in the GI Tract
Section 6 -
Small Intestinal Metaplasia and Dysplasia
Robert D. Odze, M.D.
Jonathan Glickman, M.D., Ph.D.
Mark Redston, M.D.
Mucous cell metaplasia and pylori or "pseudopyloric" metaplasia are the two most common forms of
metaplastic reaction in the small intestine. Mucous cell metaplasia of the intestinal villous epithelium
commonly occurs in association with chronic peptic duodenitis, and is most pronounced in the bulb and
first portion of the duodenum .
In many (if not most) cases of duodenal ulcer and duodenitis in the
proximal duodenum, H. pylori infection of the stomach is also present . However, other etiologies,
such as Crohn's disease or NSAID-related injury, may also give rise to duodenal ulcers. In mucous cell
metaplasia, the villous epithelium, which is normally comprised of absorptive and goblet cells, is
replaced by gastric-type mucous cells. In contrast to the acid mucin-positive goblet cells of the normal
intestinal epithelium, these cells contain neutral mucin and, therefore, stain positively with PAS and
negatively with Alcian Blue. Biopsies of chronic duodenitis also show villous shortening and Brunner's
gland hyperplasia, and a variable amount of chronic active inflammation. Overall, these changes can
easily be distinguished from gastric heterotopia, the latter of which contains architecturally intact
gastric oxyntic-type mucosa (chief cells and parietal cells)
in addition to surface mucous cells . H.
pylori organisms may colonize metaplastic epithelium and can cause further mucosal damage 
Pyloric metaplasia, a condition in which small intestinal crypts are replaced by gastric type mucous
glands, is present in up to 22% of biopsies with chronic ileitis, often secondary to Crohn's disease ,
but it can occur secondary to drug-induced (e.g. NSAID) injury as well. It is usually an incidental
finding which helps confirm the presence of chronic mucosal injury, but may occasionally form an
endoscopically visible nodule. Some investigators have hypothesized that these glands represent an
"ulcer-associated cell lineage" that secrete a variety of growth regulatory peptides that help in the
mucosal healing process
Some of these peptides include TGF alpha, EGFR, TFF-1 as well as other
A. Dysplasia in Crohn's Disease
Crohn's disease (CD) may involve any portion of the gastrointestinal tract, but affects
the ileum in approximately 80% of individuals. Approximately 5% of CD patients will develop cancer over
their lifetime, usually after at least 15 years of disease
Although patients with CD have a
20-100 fold greater relative risk of small intestinal adenocarcinoma compared to the general population,
the absolute risk of malignancy in this location is actually quite low . Approximately 70% of
CD-associated carcinomas occur in the colon and rectum
It is widely believed that carcinoma in CD evolves through progressive stages of dysplasia, similar to
ulcerative colitis (UC). However, relatively few studies have examined CD-associated dysplasia of the
small intestine. Low or high-grade dysplasia is present adjacent to adenocarcinoma in up to 80% of cases
, and is morphologically similar to that seen in the colon of patients with CD or UC. Thus, the
classification and morphologic criteria of CD-associated dysplasia are similar to ulcerative
colitis-associated colonic dysplasia (see section on colitis).
B. Dysplasia in Sporadic and Polyposis-Associated Adenomas
Adenomas are far less common in the small intestine compared to the colon. They account for less than
1% of all intestinal adenomas . The majority of adenomas arise in the ampullary and/or periampullary
region, and may be pedunculated or sessile, single or multiple. Small intestinal adenomas closely
resemble colonic adenomas morphologically. Most contain low grade dysplastic epithelium and commonly
contain abundant Paneth cells. In fact, in diagnostically difficult cases, the presence of Paneth cells
in the upper crypt and surface villi may help differentiate true adenomatous epithelium from reactive
epithelium, where Paneth cells are limited to the crypt bases. Approximately 45-60% of small intestinal
adenomas contain adenocarcinoma
Similar to the colon, larger adenomas (>1-2 cm), or those
with a villous architecture, more frequently contain carcinoma.
Adenomatous epithelium is present in the duodenum in up to 92% of patients with familial
adenomatous polyposis, and is usually located in the ampullary or periampullary region. These patients
have a 4% lifetime risk of developing carcinoma in this location, which is 100 times greater than that of
the general population. In fact, periampullary adenomas represent a major cause of morbidity and
mortality in FAP patients who have had a total colectomy. In one follow-up study, approximately 15% of
ampullary adenomas progressed to carcinoma over a mean interval of 3.5 years .
C. Dysplasia in Peutz-Jeghers Syndrome
Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant
inherited cancer syndrome characterized by the presence of hamartomatous polyps and mucocutaneous melanin
Polyps associated with PJS may occur anywhere in the GI tract, from the stomach to
the colon, but most occur in the jejunum and ileum, where they are multiple in number. The histologic
appearance of PJS polyps is distinctive. They show a central core of branching smooth muscle bundles
that supports nondysplastic intestinal mucosa. These polyps may show epithelial misplacement into the
polyp stalk in up to 10% of cases. This feature may cause confusion with invasive well-differentiated
Patients with PJS have up to 80% lifetime risk of developing cancer. Approximately 75% of
malignancies originate in the GI tract
Gastrointestinal carcinomas often arise in polyps, with
low and high grade dysplasia, but can also develop in non-polypoid areas of mucosa as well . The
precise risk of dysplasia, or malignant degeneration, in PJS polyps is controversial, since several large
retrospective series failed to show any appreciable risk of dysplasia or carcinoma in these lesions
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