Peptic ulcers are most commonly located in the stomach(Ulcer is usually

located on the lesser curvature of the antrum)or duodenum, but can also
occur in the lower oesophagus, in the jejunum ,
in the ileum adjacent to a Meckel’s diverticulum.

Causes of peptic ulcer disease

RISK FACTORS

H. pylori infection (most common)

↑ gastric acid secretion, ↓ duodenal HCO3 secretion

NSAID
Particul

Cushing's ulcer (intracranial hypertension)

Curling ulcer (severe burns)

Chronic obstructive pulmonary disease (COPD)

hypersecretion of gastric juice induced by hypoxemia or hypercapnia.

Hypergastrinemia (Zollinger-Ellison syndrome)

Clinical features
recurrent abdominal pain that has three notable characteristics:
localisation to the epigastrium
relationship to food Classically, gastric ulcer pain increases while eating a meal while duodenal ulcer pain decreases
while eating a meal.

episodic occurrence

vomiting
Anemia
Haematemesis
Melena
Sources of bleeding in peptic ulcers:

greater curvature of the stomach → Left gastroepiploic artery

lesser curvature of the stomach → right gastric artery
Posterior duodenal ulcers → gastroduodenal artery

Investigations

Endoscopy

the preferred investigation (Fig. 23.39). Gastric ulcers may occasionally

be malignant and therefore must always be biopsied and followed
up to ensure healing. Patients should be tested for H. pylori
infection.

Urea breath test

patients consume a drink containing carbon isotope 13 (13C) enriched

urea
urea is broken down by H. pylori urease

after 30 mins patient exhale into a glass tube

mass spectrometry analysis calculates the amount of 13C CO2

should not be performed within 4 weeks of treatment with an
antibacterial or within 2 weeks of an antisecretory drug (e.g. a proton
pump inhibitor)

Rapid urease test (e.g. CLO test)

biopsy sample is mixed with urea and pH indicator

colour change if H pylori urease activity sensitivity 90-95%, speci city

95-98%

Serum antibody
remains positive after eradication
sensitivity 85%, speci city 80%
Stool antigen test
sensitivity 90%, speci city 95%

Management

⚫ First-line treatment

➤ eradication may be achieved with a 7 day course of

not allergic to penicillin PPI + amoxicillin + clarithromycin, or

allergic to penicillin PPI + metronidazole + clarithromycin

allergic to penicillin + previous exposure to clarithromycin PPI + bismuth

+ metronidazole + tetracycline

• Second-line treatment

If still symptomatic after rst-line give a 7-day, twice-daily course of:

PPI + amoxicillin + either clarithromycin or metronidazole (whichever was

not used rst-line)

➤ Re-testing for H. pylori before second-line treatment is considered to

con rm eradication as there are serious side effects associated with
antibiotics, e.g. Clostridium dif cile infection, and antibiotic resistance is
increasing.
798 • GASTROENTEROLOGY
21.33 Common causes of gastritis
Acute gastritis (often erosive and haemorrhagic)
• Aspirin, NSAIDs
• Helicobacter pylori (initial infection)
• Alcohol
• Other drugs, e.g. iron preparations
• Severe physiological stress, e.g. burns, multi-organ failure, central
nervous system trauma
• Bile reflux, e.g. following gastric surgery
• Viral infections, e.g. CMV, herpes simplex virus in HIV/AIDS (p. 316)
Chronic non-specific gastritis
• H. pylori infection
• Autoimmune (pernicious anaemia)
• Post-gastrectomy
Chronic ‘specific’ forms (rare)
• Infections, e.g. CMV, tuberculosis
• Gastrointestinal diseases, e.g. Crohn’s disease
• Systemic diseases, e.g. sarcoidosis, graft-versus-host disease
• Idiopathic, e.g. granulomatous gastritis
(CMV = cytomegalovirus; NSAIDs = non-steroidal anti-inflammatory drugs)
mucosal folds of the body and fundus are greatly enlarged. Most
patients are hypochlorhydric. While some patients have upper
gastrointestinal symptoms, the majority present in middle or old
age with protein-losing enteropathy (p. 811) due to exudation
from the gastric mucosa. Endoscopy shows enlarged, nodular
and coarse folds, although biopsies may not be deep enough to
show all the histological features. Treatment with antisecretory
drugs, such as PPIs with or without octreotide, may reduce
protein loss and H. pylori eradication may be effective, but
unresponsive patients require partial gastrectomy.
Peptic ulcer disease
The term ‘peptic ulcer’ refers to an ulcer in the lower oesophagus,
stomach or duodenum, in the jejunum after surgical anastomosis
to the stomach or, rarely, in the ileum adjacent to a Meckel’s
diverticulum. Ulcers in the stomach or duodenum may be acute
or chronic; both penetrate the muscularis mucosae but the acute
ulcer shows no evidence of fibrosis. Erosions do not penetrate
the muscularis mucosae.
Gastric and duodenal ulcer
The prevalence of peptic ulcer (0.1–0.2%) is decreasing in
many Western communities as a result of widespread use of
Helicobacter pylori eradication therapy but it remains high in
developing countries. The male-to-female ratio for duodenal
ulcer varies from 5 : 1 to 2 : 1, while that for gastric ulcer is 2 : 1
or less. Chronic gastric ulcer is usually single; 90% are situated
on the lesser curve within the antrum or at the junction between
body and antral mucosa. Chronic duodenal ulcer usually occurs
in the first part of the duodenum and 50% are on the anterior
wall. Gastric and duodenal ulcers coexist in 10% of patients
and more than one peptic ulcer is found in 10–15% of patients.
Pathophysiology
H. pylori
Peptic ulceration is strongly associated with H. pylori infection. The
prevalence of the infection in developed nations rises with age and
Flagella
Urea
Urease H2O
NH3 2CO2
Ammonia
'cloud'
Type IV secretion
system
Other factors
• Vacuolating cytotoxin (vacA)
• Cytotoxin-associated gene (cagA)
• Adhesins (babA)
• Outer inflammatory protein A (oipA)
Fig. 21.35 Factors that influence the virulence of Helicobacter
pylori.
in the UK approximately 50% of people over the age of 50 years
are infected. In the developing world infection is more common,
affecting up to 90% of adults. These infections are probably
acquired in childhood by person-to-person contact. The vast
majority of colonised people remain healthy and asymptomatic,
and only a minority develop clinical disease. Around 90% of
duodenal ulcer patients and 70% of gastric ulcer patients are
infected with H. pylori. The remaining 30% of gastric ulcers are
caused by NSAIDs and this proportion is increasing in Western
countries as a result of H. pylori eradication strategies.
H. pylori is Gram-negative and spiral, and has multiple flagella
at one end, which make it motile, allowing it to burrow and live
beneath the mucus layer adherent to the epithelial surface.
It uses an adhesin molecule (BabA) to bind to the Lewis b
antigen on epithelial cells. Here the surface pH is close to neutral
and any acidity is buffered by the organism’s production of
the enzyme urease. This produces ammonia from urea and
raises the pH around the bacterium and between its two cell
membrane layers. H. pylori exclusively colonises gastric-type
epithelium and is found in the duodenum only in association
with patches of gastric metaplasia. It causes chronic gastritis
by provoking a local inflammatory response in the underlying
epithelium (Fig. 21.35). This depends on numerous factors,
notably expression of bacterial cagA and vacA genes. The CagA
gene product is injected into epithelial cells, interacting with
numerous cell-signalling pathways involved in cell replication and
apoptosis. H. pylori strains expressing CagA (CagA+) are more
often associated with disease than CagA− strains. Most strains
also secrete a large pore-forming protein called VacA, which
causes increased cell permeability, efflux of micronutrients from
the epithelium, induction of apoptosis and suppression of local
immune cell activity. Several forms of VacA exist and pathology
is most strongly associated with the s1/ml form of the toxin.
The distribution and severity of H. pylori–induced gastritis
determine the clinical outcome. In most people, H. pylori causes
a mild pangastritis with little effect on acid secretion and the
majority develop no significant clinical outcomes. In a minority (up
 Diseases of the stomach and duodenum • 799

to 10% in the West), the infection causes an antral-predominant NSAIDs

pattern of gastritis characterised by hypergastrinaemia and a very Treatment with NSAIDs is associated with peptic ulcers due to
exaggerated acid production by parietal cells, which could lead impairment of mucosal defences, as discussed on page 1002.
to duodenal ulceration (Fig. 21.36). In a much smaller number of
infected people, H. pylori causes a corpus-predominant pattern Smoking
of gastritis leading to gastric atrophy and hypochlorhydria. Smoking confers an increased risk of gastric ulcer and, to a
This phenotype is much more common in Asian countries, lesser extent, duodenal ulcer. Once the ulcer has formed, it is
particularly Japan, China and Korea. The hypochlorhydria allows more likely to cause complications and less likely to heal if the
other bacteria to proliferate within the stomach; these other patient continues to smoke.
bacteria continue to drive the chronic inflammation and produce
mutagenic nitrites from dietary nitrates, predisposing to the Clinical features
development of gastric cancer (Fig. 21.37). The effects of H. Peptic ulcer disease is a chronic condition with spontaneous
pylori are more complex in gastric ulcer patients compared to relapses and remissions lasting for decades, if not for life. The
those with duodenal ulcers. The ulcer probably arises because most common presentation is with recurrent abdominal pain that
of impaired mucosal defence resulting from a combination of H. has three notable characteristics: localisation to the epigastrium,
pylori infection, NSAIDs and smoking, rather than excess acid. relationship to food and episodic occurrence. Occasional vomiting
occurs in about 40% of ulcer subjects; persistent daily vomiting
suggests gastric outlet obstruction. In one-third, the history is
less characteristic, especially in elderly people or those taking
Increased acid
load in duodenum NSAIDs. In this situation, pain may be absent or so slight that
leads to gastric it is experienced only as a vague sense of epigastric unease.
metaplasia Increased
acid Occasionally, the only symptoms are anorexia and nausea, or
4 secretion early satiety after meals. In some patients, the ulcer is completely
HCl 3 ‘silent’, presenting for the first time with anaemia from chronic
undetected blood loss, as abrupt haematemesis or as acute
perforation; in others, there is recurrent acute bleeding without
ulcer pain. The diagnostic value of individual symptoms for peptic
G ulcer disease is poor; the history is therefore a poor predictor
D
2 of the presence of an ulcer.
1 Increased
gastrin release Investigations
5 Depletion of
antral D-cell from G cells Endoscopy is the preferred investigation (Fig. 21.38). Gastric
Further
inflammation somatostatin ulcers may occasionally be malignant and therefore must always
and eventual be biopsied and followed up to ensure healing. Patients should
ulceration be tested for H. pylori infection. The current options available are
Fig. 21.36 Sequence of events in the pathophysiology of duodenal listed in Box 21.34. Some are invasive and require endoscopy;
ulceration. others are non-invasive. They vary in sensitivity and specificity.
Breath tests or faecal antigen tests are best because of accuracy,
simplicity and non-invasiveness. 21
Helicobacter Host factors
pylori factors (IL-1β
(VacA, CagA) and TNF-α
polymorphisms)

Other
environmental
factors
(NSAIDs, smoking)

Antral gastritis Pangastritis

Duodenal Gastric Gastric

ulcer ulcer cancer
Fig. 21.37 Consequences of Helicobacter pylori infection. (CagA =
cytotoxin-associated gene; IL-1β = interleukin-1 beta; NSAIDs =
non-steroidal anti-inflammatory drugs; TNF-α = tumour necrosis factor Fig. 21.38 Endoscopic identification of a duodenal ulcer. The ulcer
alpha; VacA = vacuolating cytotoxin) has a clean base and there are no stigmata of recent haemorrhage.
800 • GASTROENTEROLOGY

21.34 Methods for the diagnosis of Helicobacter

pylori infection 21.36 Indications for Helicobacter pylori eradication
Test Advantages Disadvantages Definite
Non-invasive • Peptic ulcer
Serology Rapid office kits Lacks specificity • Extranodal marginal-zone lymphomas of MALT type
available Cannot differentiate • Family history of gastric cancer
Good for population current from past • Previous resection for gastric cancer
studies infection • H. pylori-positive dyspepsia
13
C-urea breath test High sensitivity and Requires expensive • Long-term NSAID or low-dose aspirin users
specificity mass spectrometer • Chronic (> 1 year) PPI users
Faecal antigen test Cheap, specific (> 95%) Acceptability • Extragastric disorders:
Invasive (antral biopsy) Unexplained vitamin B12 deficiency*
Histology Specificity False negatives Idiopathic thrombocytopenic purpura*
Takes several days Iron deficiency anaemia* (see text)
to process Not indicated
Rapid urease test Cheap, quick, specific Sensitivity 85%
• Gastro-oesophageal reflux disease
(> 95%)
• Asymptomatic people without gastric cancer risk factors
Microbiological ‘Gold standard’ Slow and laborious
culture Defines antibiotic Lacks sensitivity *If H. pylori-positive on testing.
sensitivity (MALT = mucosa-associated lymphoid tissue; NSAID = non-steroidal
anti-inflammatory drug; PPI = proton pump inhibitor)

21.35 Common side-effects of Helicobacter pylori

eradication therapy
• Diarrhoea: 30–50% of patients; usually mild but Clostridium
difficile-associated diarrhoea can occur
• Flushing and vomiting when taken with alcohol (metronidazole)
• Nausea, vomiting
• Abdominal cramps
• Headache
• Rash
Management
The aims of management are to relieve symptoms, induce
healing and prevent recurrence. H. pylori eradication is the
cornerstone of therapy for peptic ulcers, as this will successfully
prevent relapse and eliminate the need for long-term therapy in
the majority of patients.
H. pylori eradication
All patients with proven ulcers who are H. pylori-positive should
be offered eradication as primary therapy. Treatment is based on
a PPI taken simultaneously with two antibiotics (from amoxicillin,
clarithromycin and metronidazole) for at least 7 days. High-dose,
twice-daily PPI therapy increases efficacy of treatment, as does
extending treatment to 10–14 days. Success is achieved in
80–90% of patients, although adherence, side-effects (Box
21.35) and antibiotic resistance influence this. Resistance to
amoxicillin is rare but rates of metronidazole resistance reach
more than 50% in some countries and rates of clarithromycin
resistance of 20–40% have recently become common. Where
the latter exceed 15%, a quadruple therapy regimen, consisting
of omeprazole (or another PPI), bismuth subcitrate, metronidazole
and tetracycline (OBMT) for 10–14 days, is recommended. In
areas of low clarithromycin resistance, this regimen should also
be offered as second-line therapy to those who remain infected
after initial therapy, once adherence has been checked. For
those who are still colonised after two treatments, the choice
lies between a third attempt guided by antimicrobial sensitivity
testing, rescue therapy (levofloxacin, PPI and clarithromycin) or
long-term acid suppression.
H. pylori and NSAIDs are independent risk factors for ulcer
disease and patients requiring long-term NSAID therapy should
21.37 Indications for surgery in peptic ulcer
Emergency
• Perforation
• Haemorrhage
Elective
• Gastric outflow obstruction
• Persistent ulceration despite adequate medical therapy
• Recurrent ulcer following gastric surgery
first undergo eradication therapy to reduce ulcer risk. Subsequent
co-prescription of a PPI along with the NSAID is advised but is
not always necessary for patients being given low-dose aspirin,
in whom the risk of ulcer complications is lower.
Other indications for H. pylori eradication are shown in Box
21.36. Eradication of the infection has proven benefits in several
extragastric disorders, including unexplained B12 deficiency and
iron deficiency anaemia, once sources of gastrointestinal bleeding
have been looked for and excluded. Platelet counts improve
and may normalise after eradication therapy in patients with
idiopathic thrombocytopenic purpura (p. 979); the mechanism
for this is unclear.
General measures
Cigarette smoking, aspirin and NSAIDs should be avoided.
Alcohol in moderation is not harmful and no special dietary
advice is required.
Maintenance treatment
Continuous maintenance treatment should not be necessary after
successful H. pylori eradication. For the minority who do require
it, the lowest effective dose of PPI should be used.
Surgical treatment
Surgery is now rarely required for peptic ulcer disease but it is
needed in some cases (Box 21.37).
The operation of choice for a chronic non-healing gastric ulcer
is partial gastrectomy, preferably with a Billroth I anastomosis, in
which the ulcer itself and the ulcer-bearing area of the stomach
are resected. The reason for this is to exclude an underlying
568 C H A P T E R 14 Oral Cavity and Gastrointestinal Tract

Peptic Ulcer Disease Peptic ulcers are solitary in more than 80% of patients.
Lesions less than 0.3 cm in diameter tend to be shallow,
Peptic ulcer disease (PUD) most often is associated with H.
whereas those over 0.6 cm are likely to be deeper. The
pylori infection or NSAID use. In the US, the latter is becom-
classic peptic ulcer is a round to oval, sharply punched-out
ing the most common cause of gastric ulcers as H. pylori
defect (Fig. 14–15, A). The base of peptic ulcers is smooth
infection rates fall and low-dose aspirin use in the aging
and clean as a result of peptic digestion of exudate and on
population increases. PUD may occur in any portion of the
histologic examination is composed of richly vascular granula-
gastrointestinal tract exposed to acidic gastric juices but is
tion tissue (Fig. 14–15, B). Ongoing bleeding within the
most common in the gastric antrum and first portion of the
ulcer base may cause life-threatening hemorrhage. Per-
duodenum. PUD also may occur in the esophagus as a
foration is a complication that demands emergent surgical
result of GERD or acid secretion by ectopic gastric mucosa,
intervention.
and in the small intestine secondary to gastric heteropia
within a Meckel diverticulum.

Epidemiology Clinical Features

PUD is common and is a frequent cause of physician visits Peptic ulcers are chronic, recurring lesions that occur most
worldwide. It leads to treatment of over 3 million people, often in middle-aged to older adults without obvious pre-
190,000 hospitalizations, and 5000 deaths in the United cipitating conditions, other than chronic gastritis. A major-
States each year. The lifetime risk of developing an ulcer is ity of peptic ulcers come to clinical attention after patient
approximately 10% for males and 4% for females. complaints of epigastric burning or aching pain, although a
significant fraction manifest with complications such as
iron deficiency anemia, frank hemorrhage, or perforation. The
PATH OGENE S I S pain tends to occur 1 to 3 hours after meals during the day,
is worse at night, and is relieved by alkali or food. Nausea,
H. pylori infection and NSAID use are the primary underlying
causes of PUD. The imbalances of mucosal defenses
and damaging forces that cause chronic gastritis
(Fig. 14–13) are also responsible for PUD. Thus, PUD
generally develops on a background of chronic gastritis.
Although more than 70% of PUD cases are associated with
H. pylori infection, only 5% to 10% of H. pylori–infected
persons develop ulcers. It is probable that host factors as well
as variation among H. pylori strains determine the clinical
outcomes.
Gastric hyperacidity is fundamental to the pathogenesis
of PUD. The acidity that drives PUD may be caused by H.
pylori infection, parietal cell hyperplasia, excessive secretory
responses, or impaired inhibition of stimulatory mechanisms
such as gastrin release. For example, Zollinger-Ellison syn-
drome, characterized by multiple peptic ulcerations in the
stomach, duodenum, and even jejunum, is caused by uncon-
trolled release of gastrin by a tumor and the resulting massive
acid production. Cofactors in peptic ulcerogenesis include
A
chronic NSAID use, as noted; cigarette smoking, which
impairs mucosal blood flow and healing; and high-dose cor-
ticosteroids, which suppress prostaglandin synthesis and
impair healing. Peptic ulcers are more frequent in persons
with alcoholic cirrhosis, chronic obstructive pulmonary
disease, chronic renal failure, and hyperparathyroidism. In the
latter two conditions, hypercalcemia stimulates gastrin pro-
duction and therefore increases acid secretion. Finally, psy-
chologic stress may increase gastric acid production and
exacerbate PUD.

MO R PH O LO G Y
Peptic ulcers are four times more common in the proximal
duodenum than in the stomach. Duodenal ulcers usually
occur within a few centimeters of the pyloric valve and B
involve the anterior duodenal wall. Gastric peptic ulcers are
predominantly located near the interface of the body and Figure 14–15 Acute gastric perforation in a patient presenting with free
air under the diaphragm. A, Mucosal defect with clean edges. B, The
antrum. necrotic ulcer base (arrow) is composed of granulation tissue.

vomiting, bloating, and belching may be present. Healing
may occur with or without therapy, but the tendency to
develop ulcers later remains.
A variety of surgical approaches formerly were used to
treat PUD, but current therapies are aimed at H. pylori
eradication with antibiotics and neutralization of gastric
acid, usually through use of proton pump inhibitors. These
efforts have markedly reduced the need for surgical man-
agement, which is reserved primarily for treatment of
bleeding or perforated ulcers. PUD causes much more mor-
bidity than mortality.
SUM MA RY
Acute and Chronic Gastritis
• The spectrum of acute gastritis ranges from asymptomatic
disease to mild epigastric pain, nausea, and vomiting. Caus-
ative factors include any agent or disease that interferes
with gastric mucosal protection. Acute gastritis can pro-
gress to acute gastric ulceration.
• The most common cause of chronic gastritis is H. pylori
infection; most remaining cases are caused by autoimmune
gastritis.
• H. pylori gastritis typically affects the antrum and is associ-
ated with increased gastric acid production. The induced
mucosa-associated lymphoid tissue (MALT) can transform
into lymphoma.
• Autoimmune gastritis causes atrophy of the gastric body
oxyntic glands, which results in decreased gastric acid
production, antral G cell hyperplasia, achlorhydria, and
vitamin B12 deficiency. Anti-parietal cell and anti–intrinsic
factor antibodies typically are present.
• Intestinal metaplasia develops in both forms of chronic
gastritis and is a risk factor for development of gastric
adenocarcinoma.
• Peptic ulcer disease can be caused by H. pylori chronic
gastritis and the resultant hyperchlorhydria or NSAID use.
Ulcers can develop in the stomach or duodenum and
usually heal after suppression of gastric acid production
and, if present, eradication of the H. pylori.
NEOPLASTIC DISEASE
OF THE STOMACH
Gastric Polyps
Polyps, nodules or masses that project above the level of the
surrounding mucosa, are identified in up to 5% of upper
gastrointestinal tract endoscopies. Polyps may develop as
a result of epithelial or stromal cell hyperplasia, inflamma-
tion, ectopia, or neoplasia. Although many different types
of polyps can occur in the stomach, only hyperplastic and
inflammatory polyps, fundic gland polyps, and adenomas
are considered here.
Inflammatory and Hyperplastic Polyps
Approximately 75% of all gastric polyps are inflammatory
or hyperplastic polyps. They most commonly affect persons
between 50 and 60 years of age, usually arising in a
Neoplastic Disease of the Stomach 569
background of chronic gastritis that initiates the injury and
reactive hyperplasia that cause polyp growth. If associated
with H. pylori gastritis, polyps may regress after bacterial
eradication.
M O R P HO LO G Y
In the stomach, inflammatory and hyperplastic polyps are
essentially the same entity, with the distinction based solely
on the degree of inflammation. The polyps frequently are
multiple and characteristically are ovoid in shape, less than
1 cm in diameter, and covered by a smooth surface. On
microscopic examination, polyps have irregular, cystically
dilated, and elongated foveolar glands. The lamina propria
typically is edematous with variable degrees of acute and
chronic inflammation, and surface erosions may be present.
The frequency with which dysplasia, a precancerous in
situ lesion, develops in inflammatory or hyperplastic polyps
correlates with size; there is a significant increase in risk in
polyps larger than 1.5 cm.
Fundic Gland Polyps
Fundic gland polyps occur sporadically and in persons with
familial adenomatous polyposis (FAP) but do not have
neoplastic potential. They are, however, worth mentioning
here because their incidence has increased markedly as a
result of the use of proton pump inhibitors. This likely
results from increased gastrin secretion, in response to
reduced acidity, and glandular hyperplasia driven by
gastrin. Fundic gland polyps may be asymptomatic or
associated with nausea, vomiting, or epigastric pain. These
well-circumscribed polyps occur in the gastric body and
fundus, often are multiple, and are composed of cystically
dilated, irregular glands lined by flattened parietal and
chief cells.
Gastric Adenoma
Gastric adenomas represent as many as 10% of all gastric
polyps. Their incidence increases with age and varies
among different populations in parallel with that of gastric
adenocarcinoma. Patients usually are between 50 and 60
years of age, and males are affected three times more often
than females. Similar to other forms of gastric dysplasia,
adenomas almost always occur on a background of chronic
gastritis with atrophy and intestinal metaplasia. The risk
for development of adenocarcinoma in gastric adenomas is
related to the size of the lesion and is particularly elevated
with lesions greater than 2 cm in diameter. Overall, carci-
noma may be present in up to 30% of gastric adenomas.
M O R P HO LO G Y
Gastric adenomas are most commonly located in the antrum
and typically are composed of intestinal-type columnar epi-
thelium. By definition, all gastrointestinal adenomas exhibit
epithelial dysplasia, which can be classified as low- or high-
grade. Both grades may include enlargement, elongation, and
hyperchromasia of epithelial cell nuclei, epithelial crowding,
and pseudostratification. High-grade dysplasia is character-
ized by more severe cytologic atypia and irregular architec-
ture, including glandular budding and gland-within-gland, or
cribriform, structures.