Gastrointestinal

Disorders

CBIO 7170
Lyvia A. Álvarez, MD, MRO
Professor

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 Objectives

– The student will learn to recognize the different disorders that affect the gastrointestinal
tract.
– Also will recognize the benign and malignant diseases of the GI tract.

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3

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 – The digestive tract
– Begins
General – Mouth
– Oral pharynx
Aspects – Esophagus
– Lined by moist (non-keratinized)
stratified squamous epithelium.

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4
5
Atresia, and Fistulae
– Absence, or agenesis, of the esophagus is extremely rare
– In esophageal atresia a thin, noncanalized cord replaces a
segment of esophagus, causing a mechanical obstruction.
– Atresia occurs most commonly at or near the tracheal
bifurcation and is usually associated with a fistula
connecting the upper or lower esophageal pouches to a
bronchus or the trachea.
– Fistulae can lead to aspiration, suffocation, pneumonia,
and severe fluid and electrolyte imbalances
– Esophageal atresia is associated with congenital heart
defects, genitourinary malformations, and neurologic
disease.
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6
Meckel Diverticulum
– Occurs in the ileum
– Result of failed involution of the viteline duct, which connects the lumen of the
developing gut to the yolk sac.
– 2% of the population
– Common in males
– Symptomatic by age 2
– The mucosal lining of Meckel diverticulae may resemble that of normal small
intestine, but ectopic pancreatic or gastric tissue may also be present.
– The latter may result in peptic ulceration of adjacent small intestinal mucosa and
present with occult bleeding or abdominal pain resembling acute appendicitis or
intestinal obstruction.

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Pyloric Stenosis

– Congenital hypertrophic pyloric stenosis is three to four times

more common in males and occurs once in 300 to 900 live
births. • Surgical splitting of the muscularis
– Presents in the second or third week of life as new-onset (myotomy) is curative.
regurgitation and persistent, projectile, nonbilious vomiting. • Acquired pyloric stenosis occurs in
– Physical examination reveals hyperperistalsis and a firm, ovoid adults as a consequence of antral
abdominal mass. gastritis or peptic ulcers close to the
– Hyperplasia of the pyloric muscularis propria, which obstructs pylorus.
the gastric outflow tract. • Carcinomas of the distal stomach and
– Edema and inflammatory changes in the mucosa and pancreas may also narrow the pyloric
submucosa may aggravate the narrowing. channel due to fibrosis or malignant
infiltration.
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8
Hirschsprung Disease or Congenital Aganglionic
Megacolon

– 1 of 5000 live births.

– 10% of all cases occur in children with Down syndrome and serious
neurologic abnormalities are present in another 5%
– Results when the normal migration of neural crest cells from cecum
to rectum is arrested prematurely or when the ganglion cells
undergo premature death
– It results in a distal intestinal segment that lacks both the Meissner
submucosal and the Auerbach myenteric plexus (“aganglionosis”)
– Coordinated peristaltic contractions are absent and functional
obstruction occurs, resulting in dilation proximal to the affected
segment.

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Hirschsprung Disease
– Diagnosis of Hirschsprung disease requires documenting the
absence of ganglion cells within the affected segment.
– Ganglion cells can be identified using immunohistochemical
stains for acetylcholinesterase.
– The rectum is always affected, but the length of the additional
involved segments varies widely.
– Most cases are limited to the rectum and sigmoid colon, but
severe cases can involve the entire colon.
– The aganglionic region may have a grossly normal or
contracted appearance, while the normally innervated
proximal colon may undergo progressive dilation or
megacolon
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E 10
S
O
P
H
A
G
U
S

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11 The gastroesophageal junction is not an
anatomic sphincter

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Esophagogastric Junction
– Junction of esophagus and cardiac
stomach with a sudden change in
epithelium, from stratified squamous
to simple columnar.
– Mucosal glands of the cardiac portion
of the stomach are simple coiled
tubules

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Achalasia
 Criteria for definition of achalasia :
 Hypertensive Lower Esophageal Sphinter (LES)
 LES fails to relax to baseline with normal swallow
 Associated with abnormal peristalsis in the body of the
esophagus
 Contractions are feeble or non-existent, not peristaltic, or
may be biphasic or multiphasic.

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Achalasia
 Result
 Causes of Achalasia  Food accumulation
 Idiopathic or unknown  Distention
○ Esophagus becomes  Dilation
markedly dilated and thin  The esophagus empties by the Hurst phenomenon.
walled. ○ pressure of the hydrostatic column is greater
 Trypanosoma cruzii infection than the LES pressure
(Chagas' disease) ○ The LES is forced open, allowing the contents to
flow into the stomach until the LES can close
 Tumor situated in this area
again.
producing obstruction
 Complications
 Aspiration
2021  Pulmonary disease.
15
Achalasia
 Treatment
 Cut the muscles at the LES
location
 Use a dilator to try to disrupt
the muscle and force it open

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LACERATIONS
– Longitudinal tears in the esophagus near the
gastroesophageal junction are termed •These tears usually cross the
Mallory-Weiss tears, and are most often gastroesophageal junction but may also
associated with severe stretching or be located in the proximal gastric
vomiting secondary to acute alcohol mucosa.
intoxication. •Up to 10% of upper GI bleeding, is due
to superficial esophageal lacerations
– Lacerations are linear, longitudinally
•These do not generally require surgical
oriented and range in length from intervention, and healing tends to be
millimeters to several2021
centimeters. rapid and complete.
 17 Esophagitis

 ETIOLOGY:  Irritants
 Reflux of gastric contents (reflux ○ Alcohol
esophagitis) ○ Tobacco
○ Frequent/prolonged reflux due to ○ Corrosive alkalis (lye,
incompetence of LES accidental or suicide )
○ Disordered esophageal motility  Radiation
○ Elevated acid/pepsin levels and bile  Infections
reflux. ○ AIDS, Herpes simplex ,
 Gastric intubation CMV, candidiasis .
 Broad spectrum antibiotics
 Chemotherapy
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 18
A herpetic ulcer is seen microscopically to
have a sharp margin.

The ulcer base at the left shows loss of

overlying squamous epithelium with only
necrotic debris remaining.
The cells show intranuclear inclusions in
squamous epithelial cells indicative of herpes
simplex viral esophagitis.

This patient was immune compromised from

chemotherapy
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 19
Esophagitis
• STRICTURE
• Secondary to scarring in the lower esophagus
• BARRETT'S METAPLASIA
• The replacement of normal esophageal mucosa by
specialized columnar epithelium.
• Develops in 10% of adults with chronic GI reflux
COMPLICATIONS: • Results in a 30-40 fold increase in risk of esophageal
adenocarcinoma (5% lifetime risk)
• Schatzki's Ring
• Most common cause of non-progressive dysphagia.
• A thin mucosal web of tissue, which forms a
circumferential ring above a hiatus hernia.
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20

Another cause for inflammation

the Barrett's esophagus in which
there is gastric-type mucosa
above the gastroesophageal
junction.
Columnar epithelium with
intestinal metaplasia and goblet
cells in the columnar mucosa
below and squamous epithelium
above.

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 Barrett esophagus

A. Normal
gastroesophageal junction

B. Barrett esophagus.
Note the small islands of
paler squamous mucosa
within the Barrett mucosa

C. Histologic appearance of the

gastroesophageal junction in Barrett
esophagus.
Note the transition between esophageal
squamous mucosa (left) and Barrett
metaplasia, with abundant metaplastic
goblet cells (right).

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22 ESOPHAGEAL VARICES
– Venous blood from the GI tract is delivered to the liver via
the portal vein before reaching the inferior vena cava.
– Diseases that impede this flow cause portal hypertension
and can lead to the development of esophageal varices,
an important cause of esophageal bleeding.
– Portal hypertension results in the development of
collateral channels at sites where the portal and cava
systems communicate.
– These vessels, termed varices, develop in 90% of cirrhotic
patients, most commonly in association with alcoholic
liver disease.
– Worldwide, hepatic schistosomiasis is the second most
2021
common cause of varices.
23
Esophagus
 Squamous cell carcinoma
 80-85% of esophageal cancers
 More in men than women
 Non-caucasian
 Asia: women have more than men
 Clinical presentation
 Insidious onset, asymptomatic early stages
 gradual and late onset of dysphagia and obstruction
 Spread by local extension and lymphatic routes
 5% survival
2021 rate at 5 year
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Stages of Carcinoma of Esophagus

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Esophagus
•Risk Factors
•Chronic esophagitis
•Tobacco use
•Alcohol, especially hard liquor
•Nitrosamines
•Genetic factors
•Abnormal p53 in 50% of esophageal cancers
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Infiltrating
squamous
carcinoma
of
esophagus

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Esophagus
 Adenocarcinoma
 Chromosomal abnormalities and mutation or overexpression of
p53 are present at early stages of esophageal adenocarcinoma.
 Genetic changes include amplification of c-ERB-B2, cyclin D1,
and cyclin E genes;
 Tumor necrosis factor (TNF)- and nuclear factor (NF)-κB–
dependent genes suggests that inflammation may also
contribute to neoplastic progression.

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Adenocarcinoma
 15-20% of esophageal carcinomas
 More than 50% are located in the distal third of the esophagus
 Barrett’s esophagus and Barrett’s with dysplasia are recognized
precursor lesions
 Clinically it usually has invaded through the esophageal wall and into
the lymph nodes at time of diagnosis
 Overall 5-year survival is less than 25%
 5-year survival approximates 80% in the few patients with
adenocarcinoma limited to the mucosa or submucosa.
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Stomach

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Stomach
 The chief cells are paler, granular, and
basophilic at their base because of RER.
 Their zymogen granules are precursors of
pepsin.
 The rounded, pink parietal cell have a clear
acidophilic cytoplasm.
 Parietal cells secrete the precursors of HCl
and the anti-pernicious anemia factor
(also known as intrinsic factor).
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 34 Stomach
 ETIOLOGY:
 Acute Gastritis ○ ASPIRIN, ALCOHOL, AND TOBACCO
 An acute, transient  Damage the surface mucosal barrier, which
inflammatory prevents the back-diffusion of H ions.
process which may  Alcohol stimulates acid secretion and nicotine
causes vasoconstriction, which reduces blood
be hemorrhagic or
flow and allows H ions to accumulate.
erosive. ○ Chemotherapy (hepatic artery infusion)
○ Uremia
○ Staphilococcus food poisoning
○ Stress (burns)
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○ Shock
35

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ACUTE GASTRIC ULCERS
 ETIOLOGY:
 STRESS
Multiple, small (< ○ Shock,
○ burns ( Curling’s ulcers),
1cm), circular erosions ○ trauma,
○ intracranial injury( Cushing’s ulcers),
superficial ulcers ○ infection.
 Asymptomatic ○ Results from mucosal hypoxia (catecholamine or neurogenic-
induced vasoconstriction)
 Symptomatic  DRUGS
○ aspirin,
○ steroids,
○ indomethicin,
○ phenylbutazone
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ACUTE GASTRIC ULCERS
– Most critically ill patients admitted to hospital intensive care units have
histologic evidence of gastric mucosal damage.
– Bleeding from superficial gastric erosions or ulcers that may require
transfusion develops in 1% to 4% of these patients.
– Other complications, including perforation
– Prophylactic H2 histamine receptor antagonists or proton pump inhibitors may
blunt the impact of stress ulceration, but the most important determinant of
clinical outcome is the ability to correct the underlying conditions.

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Chronic Gastritis

– CHRONIC GASTRITIS – CHRONIC ATROPHIC GASTRITIS

– Unrelated to acute gastritis – Involves fundus/corpus
– Common disorder, specially in elderly primarily
– CHRONIC ANTRAL GASTRITIS – AUTOIMMUNE
– Associated with bile reflux, gastric PUD (80%), – Associated with pernicious
peptic duodenitis, aspirin, alcohol, and anemia (PA)
Helicobacter pylori. – IDIOPATHIC
– There is fibrosis of lamina propria and intestinal – Unassociated with PA
metaplasia with goblet cells and enterocytes. The
presence of neutrophils connotes activity.

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Chronic Gastritis
– CONSEQUENCES
– Hypochlorhydia/Achlorhydia
– Due to loss of parietal cell mass (fundric gastritis) with increased serum
gastrin or due to loss of gastrin-producing cells (antral gastritis) with
decreased serum gastrin.
– Pernicious Anemia
– Due to loss of intrinsic factor (IF), which is produced by parietal cells and is
required for absorption of vitamin B-12.
– Increased risk for GASTRIC CARCINOMA
– Often associated with intestinal metaplasia/dysplasia, with chronic fundic
gastritis and PA
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40
CHRONIC GASTRITIS-HELICOBACTER PYLORI
GASTRITIS
– These spiral-shaped or curved bacilli are present in gastric biopsy
specimens of almost all patients with duodenal ulcers and the majority
of individuals with gastric ulcers or chronic gastritis.
– H. pylori organisms are present in 90% of individuals with chronic
gastritis affecting the antrum.
– H. pylori infection is associated with poverty, household crowding,
limited education, African-American or Mexican-American ethnicity,
and residence in rural areas
– Colonization rates exceed 70% in some groups and vary from less than
10% to more than 80% worldwide.
– The mode of transmission is not well defined, but humans are the only
known host, making oral-oral, fecal-oral, and environmental spread the
most likely routes of infection.
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Helicobacter Pylori
– In a subset of patients the gastritis progresses to involve the gastric body
and fundus, associated with multifocal mucosal atrophy, reduced acid
secretion, intestinal metaplasia, and increased risk of gastric
adenocarcinoma.
– Four features are linked to H. pylori virulence:
– Flagella, which allow the bacteria to be motile in viscous mucus
– Urease, which generates ammonia from endogenous urea and thereby
elevates local gastric pH
– Adhesins that enhance their bacterial adherence to surface of cells
– Toxins, such as cytotoxin-associated gene A (CagA), that may be
involved in ulcer or cancer development by poorly defined mechanisms

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Chronic Gastritis
– Three antibody types: – AUTOIMMUNE GASTRITIS
– Blocking AB (75%)--blocks – Autoimmune gastritis is characterized by:
B12/IF binding – Antibodies to parietal cells and intrinsic factor that can
– Binding AB (50%)--binds to IF
be detected in serum and gastric secretions
or B12/IF
– These two ABs are in serum – Reduced serum pepsinogen I concentration
(IgG) and gastric mucosa – Antral endocrine cell hyperplasia
(IgA) and their presence is – Vitamin B12 deficiency
highly correlated with PA. – Defective gastric acid secretion (achlorhydria)
– Gastric parietal cell AB (90%)
– When associated with Pernicious Anemia, the disease is
– Less specific
autoimmune and appears to result from immunologic
destruction of parietal cells.
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Autoimmune Gastritis
– Has diffuse mucosal damage of the oxyntic (acid-
producing) mucosa within the body and fundus.
– Damage to the antrum and cardias is typically absent or
mild.
– If vitamin B12 deficiency is severe, nuclear enlargement
(megaloblastic change) occurs within epithelial cells.
– Inflammatory infiltrate is composed of lymphocytes,
macrophages, and plasma cells.
– Loss of parietal and chief cells can be extensive.
– Intestinal metaplasia, characterized by the presence of
goblet cells and columnar absorptive cells

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44
Chronic atrophic gastritis due to anti-parietal cell antibody.
The bright green immunofluorescence is seen in the paritetal cells of the gastric mucosa.

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45

Peptic Ulcer Disease

– Peptic ulcer disease (PUD) is most often associated with H.
pylori–induced hyperchlorhydric chronic gastritis, which is
present in 85% to 100% of individuals with duodenal ulcers and
in 65% with gastric ulcers.
– PUD may occur in any portion of the GI tract exposed to acidic
gastric juices, but is most common in the gastric antrum and
first portion of the duodenum.
– PUD may also occur in the esophagus as a result of GERD or acid
secretion by ectopic gastric mucosa.
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Peptic Ulcer Disease
– Locations:
– Duodenum
– 1st portion, anterior wall
– Gastric antrum, lesser curvature
– 95% within 2cm. of acid-producing border
– Esophagus (Barretts metaplasia)
– Gastroenterostomy Stoma
– Meckel’s diverticulum
– Ectopic location
– Zollinger Ellison Syndrome
– Infection with Helicobacter pylori
– 98% of peptic ulcers are duodenal and gastric
– duodenal/gastric = 4/1
2021 – 10-20% pts with gastric ulcer have concurrent duodenal ulcer
47 1. The strongest association with Helicobacter pylori is with
duodenal peptic ulceration in over 85% of duodenal ulcers.
2. Seen here is a penetrating acute ulceration in the duodenum just
beyond the pylorus.

Duodenum

Stomach

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48
MÉNÉTRIER DISEASE
– Ménétrier disease is a rare disorder caused by excessive secretion of
transforming growth factor α (TGF-α)
– The disease is characterized by diffuse hyperplasia of the epithelium of the
body and fundus and hypoproteinemia due to protein-losing enteropathy.
– Weight loss, diarrhea, and peripheral edema
– Risk of gastric adenocarcinoma is increased in adults with Ménétrier
disease.
– Ménétrier disease is characterized by irregular enlargement of the gastric
rugae
– The antrum is generally spared.
– Histologically, the most characteristic feature is hyperplasia of mucous
cells
– Diffuse or patchy glandular atrophy, evident as hypoplasia of parietal and
2021 chief cells, is typical.
 49
Gastric tumors
Polyps
– Uncommon
– 0.4% gastric polyps compared to
colon polyps in 25-50% of adults at
autopsy
– Hyperplastic-response to damage
– Fundic gland-small hamartoma
– Hyperplastic and fundic gland
Gastric polyps.
polyps are not believed to have A, Hyperplastic polyp containing corkscrew-shaped foveolar glands.
B, Hyperplastic polyp with ulceration.
malignant potential C, Fundic gland polyp composed of cystically dilated glands lined by parietal, chief,
– Adenomatous polyps and foveolar cells.
D, Gastric adenoma recognized by the presence of epithelial dysplasia.
– malignant potential
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 50
Gastric
Carcinoma
– In Japan, Chile, Costa Rica, and Eastern Europe the
incidence is up to 20-fold higher
– Mass endoscopic screening programs can be successful in
regions where the incidence is high, where 35% of newly
detected cases are early gastric cancer, tumors limited to
the mucosa and submucosa.
– In the United States, gastric cancer rates dropped by over
85%.
– Intake of green, leafy vegetables and citrus fruits, which
contain antioxidants such as vitamin C, vitamin E, and beta-
carotene, and is correlated with reduced risk of gastric
cancers.
– Gastric cancer is more common in lower socioeconomic
groups and in individuals with multifocal mucosal atrophy
2021 and intestinal metaplasia.
 51
Gastric Carcinoma
– Risk Factors • Genetic Factors – Host Factors
– Environmental • Slightly increased risk – Chronic Gastritis
– Diet with blood group A – Hypochlorhydria
• Family history of – Intestinal metaplasia
– Nitrites from water and
gastric cancer – Infection with Helicobacter
preserved food
• Hereditary pylori
– Smoked and salted nonpolyposis colon
food, pickled – Partial gastrectomy
cancer syndrome
vegetables – Gastric Adenomas
– Lack of fresh fruit and – 40% harbor cancer at
vegetable time of diagnosis
– Low socioeconomic – 30% have an adjacent
status cancer at time of
– Cigarette smoking diagnosis
2021 – Barret’s Esophagus
 Gastric Carcinoma
– Types
– Diffuse type
– Intestinal type
– Prognosis
– Invasion is most important factor
– Early
– Limited to mucosa and submucosa
– 90-95% survival at 5 years
– Late
– Beyond submucosa
2021 – Less than 10% survival at 5 years 52
53 Gastric Carcinoma

– Intestinal
– Older than 50
– Male
– Arises from metaplastic glands in chronic gastritis
– Associated with H. pylori
– Incidence decreasing in USA
– Diffuse (signet ring cell, linitis plastica)
– Younger patients, no gender preference
– Not associated with Helycobacter pylori
2021 – Incidence unchanged
54 Gastric Carcinoma

– Location
– Lesser curvature of antropyloric region is most
common
– An ulcerated lesion of the greater curvature is
more likely to be malignant
– After surgical resection, the 5-year survival rate of
early gastric cancer can exceed 90%, even if lymph
node metastases are present.
– The 5-year survival rate for advanced gastric cancer
remains below 20%.
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Duodenum
– Is composed of villi and numerous
short, darkly stained glands (crypts of
Lieberkuhn) above the thin, pink
muscularis mucosae, and pale glands
of Brunner in the submucosa below.

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 Jejunum
– Jejunum, shows long villi and short crypts.
– There are no longer any submucosal glands.
– The submucosa is thin and the muscularis
externa is relatively thicker.
– There is a serosa because the jejunum is
slung freely in mesentery.

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 57
Ileum
– Wall of ileum, with villi and short
crypts in the mucosa.
– Peyer's patches are dense
lymphatic tissue which extend
from the submucosa up into the
mucosa, interrupting the thin, pink
muscularis mucosae.

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 Colon
– Crypts of Lieberkuhn as they appear
in both the colon and appendix.
– The goblet cells are numerous
because of the need for lubrication of
the gut contents.
– Numerous lymphocytes in the lamina
propria.

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 59
Diarrhea
– Is loose, watery stools.
– A person with diarrhea typically passes stool more than three times a day.
– Acute diarrhea is a common problem that usually lasts 1 or 2 days and goes away on its
own without special treatment.
– Prolonged diarrhea persisting for more than 2 days may be a sign of a more serious
problem and poses the risk of dehydration.
– Chronic diarrhea may be a feature of a chronic disease.
– Diarrhea causes dehydration.
– People of all ages can get diarrhea and the average adult has a bout of acute diarrhea
about four times a year.
– In the United States, each child will have had seven to 15 episodes of diarrhea by age 5.
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 60 Diarrhea

– Bacterial infections – Parasites

– Contaminated food or water can cause diarrhea – Giardia lamblia, Entamoeba histolytica, and
– Campylobacter, Salmonella, Shigella, and Escherichia Cryptosporidium.
– Reaction to medicines
coli (E. coli).
– Antibiotics, blood pressure medications,
– Viral infections cancer drugs, and antacids containing
– rotavirus, Norwalk virus, cytomegalovirus, herpes magnesium can all cause diarrhea.
simplex virus, and viral hepatitis. – Intestinal diseases
– Food intolerances – Inflammatory bowel disease, colitis, Crohn’s
– Some people are unable to digest food components disease, and celiac disease often lead to
diarrhea.
such as artificial sweeteners and lactose—the sugar
– Functional bowel disorders
found in milk. – Diarrhea can be a symptom of
– irritable bowel syndrome
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 61
Diverticulosis

– Blind pouch lined by mucosa

– Acquired
– Lack or attenuated muscularis propia
– Most common left side of colon
– 50% of 60 y/o develop diverticular disease
– Focal wall weakness + increased
intraluminal pressure

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•The sigmoid colon at the right appears lighter in color than the adjacent small intestine
•Protruding from the sigmoid colon are multiple rounded bluish-gray diverticula.
• Diverticula are much more common in the colon than in small intestine, and they are more common in the left colon.

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 63
Complications
– Bleeding
– Infection
– Perforation
– Abcess
– Fistula
– Obstruction

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64
Tumors of Small & Large Bowel
– Classification is the same for small and large intestines
– Polyps; nonneoplastic
– Epithelial neoplasm
– Benign adenomatous polyps
– Adenocarcinoma
– Carcinoid
– Mesenchymal neoplasms
– Lymphoma
– Tumors of large bowel are more common

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 65
Bowel: Nonneoplastic Polyps
– Hamartomatous
– Hyperplastic
– Peutz-Jegher (Autosomal Dominant)
– asymptomatic
– multiple, throughout GI tract
– less than 5 mm
– mucocutaneous pigmentation
– single or multiple
– increased risk of GI and non-GI
– rectosigmoid cancers
– virtually no malignant – Juvenile:
potential
– children < 5
– Composed of well formed
glands and crypts – can be quite large
– rectum
2021
– no malignant potential
Hyperplastic Polyp

66

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 67
Adenomatous Polyps
– Result of epithelial proliferation and dysplasia
– Three types:
– Tubular
– Villous
– Mixed
– Risk of malignancy related to size, histologic type, and severity of dysplasia
– May be asymptomatic; commonly presents with bleeding
– Small or large, pedunculated or sessile, usually in colon
– Since they are considered premalignant, all should be removed

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Hereditary Colon Cancer Syndromes
– Familial Adenomatous Polyposis (APC)
– Autosomal dominant
– Mutation in APC gene on 5q21
– 100-2500 polyps throughout GI tract
– Virtually 100% risk of carcinoma
– Hereditary Nonpolyposis Colorectal Cancer (Lynch
Syndrome)
– Autosomal dominant
– Increased risk of GI and non-GI cancers
– Lower # of polyps than FAP
– Associated to endometrial
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69

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Colonic Neoplasia
– Adenocarcinoma
– Cumulative genetic alterations or “multi-hit” hypothesis
– Inherited or early acquired APC or HNPCC gene mutation
– Inactivation/mutation of other alleles
– Hypomethlation of DNA ( loss of methyl groups)
– Activation of K-RAS + (most frequently activated
oncogene in adenomas and colon cancers)
– Loss of DCC gene (allelic loss 18q21)
– Loss of p53 (loss of 17p)

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71

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72 Distribution of Colonic Cancer

– Ascending colon 38%

– Transverse colon 18%
– Descending colon 8%
– Sigmoid 35%
– Multiple sites 1%
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73
Adenocarcinoma of Colon
– Right colon:
– Increasing incidence, especially in elderly
– Usually polypoid
– Present with bleeding, anemia
– Left colon:
– Annular, napkin ring lesions
– Present with decreased stool caliber, obstruction
– Less than half of cancers are detectable by protoscopic
exam
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74
Adenocarcinoma of Colon
– Risk Factors:
– Increasing age (60-79 y/o)
– Inflammatory bowel disease in young persons
– Hereditary syndromes in young persons
– Dietary
– >intake for <requirements
– low fiber
– High content of refined carbohydrates
– Red meat
– Decreased intake of protective micronutrients
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75

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76

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77

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78 •Adenocarcinoma arising in the villous adenoma of Colon.
•The growth is primarily exophytic (outward into the lumen) and invasion is not seen at
this point.

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TNM Classification
Tumor

79
Tis In situ dysplasia or intramucosal carcinoma
T1 Tumor invades submucosa
T2 Tumor invades into, but not through, muscularis propria
T3 Tumor invades through muscularis propria
T3a Invasion <0.1 cm beyond muscularis propria
T3b Invasion 0.1 to 0.5 cm beyond muscularis propria
T3c Invasion >0.5 to 1.5 cm beyond muscularis propria
T3d Invasion >1.5 cm beyond muscularis propria
T4 Tumor invades adjacent organs or visceral peritoneum
T4a Invasion into other organs or structures
T4b Invasion into visceral peritoneum
Regional Lymph Nodes
NX Lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in one to three regional lymph nodes
N2 Metastasis in four or more regional lymph nodes
Distant Metastasis
MX Distant metastasis cannot be assessed
M0 2021
No distant metastasis
M1 Distant metastasis or seeding of abdomen
80 Staging of Adenocarcinoma of Colon
Most important prognostic factor Astler-Coller Classification

– A: limited to mucosa
– survival 100%
– B1: into muscularis propria; negative nodes
– Survival 67%
– B2: through muscularis propria; negative nodes
– Survival 54%
– C1: into muscularis propria; involved nodes
– Survival 43%
– C2: through muscularis propria; involved nodes
– Survival 22%
– D: distant metastatic spread low

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% Based on five year survival
81

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 82
Clinical Features

– Cecal and other right-sided colon cancers

– Fatigue and weakness due to iron deficiency anemia.
– Left-sided colorectal adenocarcinomas
– Occult bleeding, changes in bowel habits, or cramping left lower
quadrant discomfort.
– Poorly differentiated and mucinous types are associated with poor
prognosis
– Two most important prognostic factors are depth of invasion and the
presence or absence of lymph node metastases.
– Metastases may involve regional lymph nodes, lungs and bones, but as
a result of portal drainage of the colon, the liver is the most common
site of metastatic lesions
– The rectum does not drain via the portal circulation, and carcinomas of
the anal region that metastasize often circumvent the liver.
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83
Carcinoid Tumors
– Tumors of dispersed neuroendocrine system
– Present throughout GI tract, often asymptomatic
– All are potentially malignant
– Behavior correlates with size, location, and depth of penetration
– May secrete numerous bioactive hormones
– Most common sites:
– Appendix
– Small bowel
– Rectum
– Stomach
2021 – Colon
84
Carcinoid Tumors
– Solitary or multicentric firm, yellow-tan nodules
– Usually submucosal masses, sometimes with
ulceration
– Cause striking desmoplastic response
– Form islands, trabeculae, glands, or sheets
– Monotonous, speckled nuclei and abundant pink
cytoplasm
– Contain cytoplasmic secretory dense-core granules

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85

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 LYMPHOMA
– Epstein-Barr virus–positive B-cell lymphoproliferations
– Nearly 5% of all gastric malignancies are primary lymphomas
– Extra-nodal marginal zone B-cell lymphomas usually arise at
sites of chronic inflammation.
– The most common cause of “pro-lymphomatous” inflammation
in the stomach is chronic H. pylori infection, which is found in
association with most cases of gastric lymphoma.
– Three translocations are associated with gastric lymphoma
– t(11;18)(q21;q21)
– t(1;14)(p22;q32)
2021
– t(14;18)(q32;q21). 86
 GI lymphoma
87 A, Gastric MALT lymphoma replacing much
of the gastric epithelium.
Inset shows lymphoepithelial lesions with
neoplastic lymphocytes surrounding and
infiltrating gastric glands.

B, Disseminated lymphoma within the small

intestine with numerous small serosal
nodules.

C, Large B-cell lymphoma infiltrating the

small intestinal wall and producing diffuse
thickening.

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 88
Gastrointestinal Lymphoma

– Most common primary extranodal lymphoma location

– More in native of Mediterranean region
– Congenital immunodeficiency states
– HIV- infected patients
– Patients in immunosuppresive therapy
– Associated with Helycobacter Pylori infection
– T-cell lymphomas are associated with celiac sprue

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89

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 The most common lymphoma arising in a small intestine is diffuse large B-cell lymphoma,
followed by MALT lymphoma, Burkitt lymphoma, enteropathy-associated T-cell lymphoma,

90 mantle cell lymphoma, and follicular lymphoma. This follicular lymphoma shows transmural
involvement on the right side, from mucosa on the top (#1), followed by submucosa (#2),
muscularis propria (#3), and submucosa (#4).

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91 References

– Pathologic Basis of Disease; Robbins and Cotran; 9th Edition; Chapter 17

– http://library.med.utah.edu/WebPath/GIHTML/GIIDX.html#7
– Astler-Coller, Ann Surg. 139:846, 1954
– http://pathology2.jhu.edu/beweb/cancer.cfm

https://www.youtube.com/watch?v=Myv8uB4bmjw

2021