Gastrointestinal Pathology

Jocelyn Myra R. Caja, MD

Emmanuel R. de la Fuente, MD
Lorna B. Lioanag, MD
REQUIRED READINGS:
2. Tracheo-esophageal fistula
3. Diverticulum
4. Hiatal hernia
5. Mallory-Weiss syndrome
6. Reflux esophagitis
7. Barrett esophagus
8. Peptic ulcer
9. Esophageal varices
10. Achalasia
11. Tumors (squamous and adenocarcinomas)
Required Readings
2. Anatomy of the stomach
3. Acute and chronic gastritis
4. Peptic ulcer disease
5. Malignancies of the stomach and duodenum
- carcinoma
- malignant lymphoma
Required Readings
2. Anatomy of the small and large intestines
3. Infectious disease (viral infections, cholera, bacillary
dysentery, salmonella, entamoeba histolytica,
tuberculosis)
4. Hirschprung’s disease
5. Idiopathic inflammatory bowel disease
6. Acute appendicitis
7. Intestinal obstructions (intussuception, volvulus, hernias
and adhesions)
8. Diverticular disease
9. Polyps/adenomas
10. Malignancies (carcinoma, lymphoma)
11. Hemorrhoids
 PART I

PATHOLOGY OF THE
ESOPHAGUS
ESOPHAGUS
Anatomic considerations:
• from C6 - T11 / T12
• length: 10-11cm (NB)
25-27cm (adult)
3 points of luminal narrowing:
• cricoid cartilage
• left main bronchus
• diaphragm
Gastro-esophageal
junction / Z-line (arrows)
•38-41 cm from incisors

•upper & lower sphincters

defined manometrically
not morphologically
NORMAL DOUBLE CONTRAST ESOPHAGOGRAM

The barium The esophagogastric

coating gives a Z-line is seen which
smooth satin represents the
appearance to the squamo-columnar
mucosa junction (arrow)
Histologic considerations:
3 muscle layers:
– Inner circular
– Middle oblique
– Outer longitudinal - striated
muscles
in the first 6-8
cm
* no serosa (allows easy spread of
disease into mediastinum)
THE ESOPHAGEAL MUCOSA

Stratified squamous
epithelium

Lamina propria
Muscularis mucosae
Submucosa with
mucous glands

Muscularis propria
Congenital and Acquired Malformations:

• Tracheo-esophageal
fistulas
• Webs / Rings
• Heterotopic tissue
• Diverticula
• Hiatal hernia
• Mallory-Weiss tears
• Varices
Tracheo-esophageal
fistulas:
90% - Type C:
esophageal atresia;
distal esopahgus
connected to trachea

35% - premature
infants

65% - maternal
hydramnios
Hiatal hernia:
Saclike dilatation of
stomach present
above the diaphragm
* heartburns (10%);
asymptomatic(50%)
*difficult to document grossly on
autopsy
* no diagnostic microscopic findings
* ↑ incidence in peptic ulcer patients
* carcinoma is a rare complication
Sliding type (90%):
E-G junction above diaphragm
10% of population
50% of patients with
reflux esophagitis

Rolling type (10%)

(Paraesophageal)
E-G junction in normal location
Sliding type: 80-90%
• congenitally short esophagus
• esophageal scarring w/ traction on stomach
• aggravated by swallowing
• predisposes to reflux

Rolling (paraesophageal):10 -20 %

• portion of cardia protrudes thru diaphragm
into thorax alongside esophagus
• vulnerable to strangulation & infarction
 ESOPHAGEAL DIVERTICULA
• Outward protrusions of all, or portions, of
the esophageal wall
• May be acquired or congenital
• Most common location of acquired is in the
proximal portion due to uncoordinated
actions of muscles of swallowing
• May be due to traction due to pulling of
esophageal wall by scar tissue; or pulsion
due to congenital weakening of the
muscular wall
Esophageal diverticula:

Pulsion type (Zenker’s): more common

• esophago-pharyngeal junction; above cardia
• often large; collect food
• unknown etiology

Traction type:less common

• lower 1/3; near hilum
• rarely collect food
• Tuberculous lymphadenitis
 ESOPHAGEAL
DIVERTICULUM

Opened esophagus
showing opening of
diverticulum (arrow)

Histologically,
diverticula appear as
outpouching of the
esophageal wall
 ESOPHAGEAL DIVERTICULA

Mucosal view of 2 traction diverticula

 Mallory-Weiss tears:
• linear lacerations oriented longitudinally
along the long axis of the esophagus
• usually occur at the G-E junction
• occur as consequence of chornic
vomiting with severe counter peristalsis;
most commonly in alcoholics
• may involve mucosa or even full
thickness of the wall
• accounts for 5-10% of cases of massive
hematemesis; may be fatal
 Esophagus

Mallory-Weiss
Syndrome

Irregular linear
lacerations at
gastro-
esophageal
junction (arrows)
Stomach
 Esophageal varices:
• dilated coronary veins in lower esophagus
due to portal hypertension, usually in cirrhosis
• Portal hypertension causes the portal blood to
be diverted thru the gastric coronary veins
into the esophageal submucosal plexus
veins.
• complication: massive hematemesis and
rupture
• 40% fatality rate; 50% of survivors rebleed
• 40% of rebleeding cases eventually die
* varices commonly collapse postmortem
ESOPHAGEAL
VARICES

Left picture illustrates esophageal varices.

These appear are seen as dilated tortuous
submucosal veins (arrow, right picture)
ESOPHAGEAL VARICES

Submucosal
blood-filled
channels
 Esophageal dysmotility:
• Achalasia
• Idiopathic Muscular Hypertrophy
• Progressive Systemic Sclerosis
• Plummer-Vinson Syndrome
• Leiomyomatosis
 ACHALASIA
(Megaloesophagus)
3. Failure of relaxation of the smooth muscle fibers
at the gastro-esophageal junction
4. May be due to: a) aperistalsis, b) partial or
complete lower esophageal sphincter relaxation
(LES), & c) increased resting LES pressure
5. Reduction of ganglion cells due to destruction
6. Progressive dysphagia is characteristic
Achalasia
∀ ↓ peristalsis & incomplete
relaxation of LES
∀ ↑ basal LES tone;
progressive dilatation above
LES
• 2-7% develop cancer
• sporadic form: absence of
myenteric plexus in upper
esophagus
• unknown etiology
* Chaga’s disease: destruction
of plexi
ACHALASIA

Grossly, the distal end of

the esophagus is
narrowed while the
proximal end is dilated
Idiopathic Muscular Hypertrophy
• primary abnormality of neural
control of distal esophageal
musculature
• results in spasm
• predominantly affects inner circular
muscle layer
Progressive Systemic Sclerosis
• vasculitis with muscle wall
degeneration
• part of CREST syndrome
Plummer-Vinson Syndrome
• Atrophic glossitis, dysphagia
• Hypochromic, microcytic anemia
• Esophagitis in upper 1/3

* most common in middle-aged

females
* ↑ risk of CA in upper 1/3
esophagus, oropharynx & tongue
* assoc. w/ esophageal webs
Esophagitis

• Reflux esophagitis
• Infectious (bacterial, viral, fungal)
• Chemically induced (corrosives)
• Iatrogenic (irradiation, instrumentation,
Rx)
• others: Crohn’s disease
Pemphigus vulgaris
Uremia
Graft vs Host disease
Reflux esophagitis:

• recurrent or prolonged reflux

• elevated acidity & disordered motility
• basal hyperplasia > 15%;
∀ ↑ vascular pillae > 50% of mucosal height
• intraepthelial eosinophils
• assoc. w/ sliding hernia, ZE syndrome,
scleroderma
REFLUX ESOPHAGITIS

Grossly, the esophagus

is reddened and
hemorrhagic and in the
picture with linear
ulcers obliterating the
Z-line (arrows)
REFLUX ESOPHAGITIS

Histologically
characterized by:
3. Basal zone hyperplasia
4. Elongated papillae
5. Intraepithelial
neutrophils and/or
eosinophils as seen in
picture
 BARRETT’S ESOPHAGUS
• A condition in which the stratified squamous
epithelium of the esophagus is replaced by
columnar epithelium
• Usually involving the lower 3rd
• Usually acquired as a complication of reflux
esophagitis
• Complication: development of glandular
dysplasia and adenocarcinoma
BARRETT’S ESOPHAGUS

Grossly characterized by
islands of red-brown
epithelium surrounded by
gray-white squamous
mucosa (arrows)
BARRETT’S ESOPHAGUS

Histologically
characterized by the
replacement of the
stratified squamous
epithelium by gastric
epithelium; the arrow
indicates the
squamous epithelium
Barrett’s metaplasia:
• conversion of stratified
squamous epith. to
columnar epithelium in
lower esophagus
• type I: no residual
squamous islands
• type II: w/ squamous
islands
• complications: ulceration,
stricture, adenocarcinoma
(10%)
Types of Barrett’s metaplasia:

• specialized type (intestinal or colonic)

incomplete = goblet & columnar cells
complete = purely intestinal type cells
• cardiac/junctional type = entirely mucin
cells
3cm above GEJ ( 35cm from
incisors)
• atrophic fundal type = parietal & chief
cells
Dysplasia in Barrett’s metaplasia:

• Low grade - hyperchromatic crowding

nuclei
• High grade* - glandular distortion &
nuclear
hyperchromasia extends to upper
portions of eputhelium
* if high grade dysplasia is seen in biopsy,
there is 70% chance of carcinoma being
present
Infectious esophagitis:

Bacterial
Viral: CMV- submucosal cells w/ inclusions
Herpes - epith. cells w/ ground glass
nuclei
multinucleated giant cells
Fungal: Candida - white plaques
usually in middle & lower 1/3
Mucormycoses
Aspergillus
Esophageal Candidiasis:
• appear as white plaques,
linear ulcers in endoscopy
• yeasts & pseudohyphae
may be seen in biopsy
Benign Lesions:

Inflammatory polyps/fibrovascular
polyps
– submucosal proliferation of vascularized,
inflammed fibrous stroma w/ eosinophils
– 85% in upper 1/3
– usually pedunculated, solitary
– similar lesions in sstomach
• Squamous papilloma
– lower esophagus; may be multiple
– men > 40 y/o
Benign Lesions:

• Adenoma
– arises in Barrett’s esophagitis
• Gastrointestinal Stromal Tumors
(GIST)
– Leiomyoma
• Granular cell tumor
• Localized amyloidosis
 SQUAMOUS CELL DYSPLASIA

A B
Atypical cells involving the entire layer of the
surface epithelium with no maturation; A - low
power, B - high power
Esophageal Carcinoma
• > 50 y/o; male = female
• Sx: dysphagia & emaciation
• metastasizes and extends early (no
serosa)
• patients often die before widespread
metastases
• associated with cigarette smoking &
alcohol use
 SQUAMOUS CELL CARCINOMA
2. Most common type of malignancy
3. High-risk factors include tabacco use,
smoking , alcohol intake
4. Associated with epithelial dysplasia
5. Genetic predisposition
6. Prognosis poor since tumor growth and
spread to adjacent structures and lymph
nodes are rapid
Squamous Cell Carcinoma of
Esophagus:
• 80-85% of all esophageal carcinomas
• 10% of all GIT cancers
• more common in blacks and males
• 12% upper; 56 % middle; 32% lower
portion

Verrucous carcinoma:
• exophytic growth with pushing margins
• rare; slow growing, rarely metastasize
Adenocarcinoma:

• 5-10% of esophageal carcinomas;

2-8% of esophageal malignancies
• male > female (5:1), 50y/o
• middle or lower 1/3, often involve
gastroesophageal junction
• most arise from Barrett’s
esophagitis
• gross: mass or nodular elevation
Histologic types of adenocarcinoma:

• Intestinal type - same in stomach &

intestine
• Diffuse - diffuse infiltration by mucin-
producing cells
• Adenosquamous - mixture of squamous
cell & adenocarcinoma

*staging same as in SCC; most are at high

stages when diagnosed
Esophageal Carcinoma
Gross: Ulcerative/Polypoid/Diffuse infiltrative

Squamous cell Adenocarcinoma

carcinoma • lower 1/3 (90%)
• lower 1/3 > middle 1/3
> upper 1/3 * • epithelial cells
• squamous cells in in glandular
sheets w/ pattern
keratinization &
desmoplasia
* usually assoc. w/
Plummer-Vinson
syndrome
 3 PATTERNS OF SQUAMOUS CARCINOMA

FUNGATING ULCERATING INFILTRATING

WELL-DIFFERENTIATED SQUAMOUS
CARCINOMA

Marked keratinization and pearl formation

ESOPHAGEAL ADENOCARCINOMA

1. Characteristic papillary exophytic

growth of adenocarcinoma
2. Histology of adenocarcinoma
showing glands lined by malignant
cells
Other malignant tumors tumors:

• Small cell carcinoma

• Leiomyosarcoma
• Malignant lymphoma
• Plasmacytoma
• Malignant melanoma
 PART II

PATHOLOGY OF THE
STOMACH AND DUODENUM
Anatomic considerations in the Stomach:
• mucosal surface and pits lined by mucus
cells
• neck mucus cells are progenitors for
glandular epithelium
• glands of cardia and antrum similar to neck
mucus cells
• fundic glands contain parietal and chief cells
• antrum contains endocrine cells for
enteroendocrine, enterochromaffin,
Kulchitsky’s or APUD cells
SCHEMA OF DIFFERENT PORTIONS OF
STOMACH AND DUODENUM
A – gastric antrum
B – gastric corpus
CA – cardia
D1-D4 – first to fourth portions
of the duodenum respectively
E – esophagus
F – fundus
J – jejunum
PY- pylorus
TR – angle of Treitz
DOUBLE-CONTRACT APPEARANCE OF NORMAL
STOMACH

Arrow indicates
the incisura
angularis

Open arrows
indicate areae
gastricae, which
are fine irregular
undulating
pattern of
mucosal patches
1-5 mm in
diameter
 THE NORMAL GROSS STOMACH

Unopened stomach at left showing the characteristic J

shape and opened stomach showing the longitudinal
folds (rugae)
 NORMAL GASTRIC RUGAL FOLDS

The rugae appear as coarse folds of the mucosa.

 HISTOLOGY OF NORMAL GASTRIC MUCOSA

The surface is covered by tall columnar mucus-secreting

epithelium with intervening pits or foveolae (black arrows). The
surface epithelium is the same in all portions of the stomach.
However, the mucosal glands differ in the different portions of the
stomach. The block arrows indicate the surface mucus epithelium.
 THE NORMAL GASTRIC GLANDS

A B C
The glands of the stomach are tubular and consists of 3
types:1) cardiac glands (A) and 2) pyloric glands (B), both of
which consist of mucous cells, and 3) fundic glands (C), which
consists of parietal and basophilic or chief cells (C).
Acute gastritis •Acute mucosal inflammation
•hemorrhagic, erosive, stress-
related
•usually only partial erosion; not
penetrating the muscularis mucosa
•usually associated with
superficial ulcers
•severe forms have shedding of the
mucosa and extensive lamina
propria hemorrhages
•mortality can exceed 50% in
acute hemorrhagic erosive form
 Causes of Acute gastritis:
• excessive alcohol consumption, heavy smoking
• chronic aspirin or non-steroidal anti-inflammatory
drugs (NSAID) intake
• anti-cancer drugs
• hypovolemia / shock
• surgery
• severe stress
• severe burns (Curling’s ulcers)
• trauma (when associated with ↑ intracranial
pressure - Cushing’s ulcers)
 ACUTE GASTRITIS
2. Mechanism of ulcer formation may be involve:
1. back-diffusion of acid secretion
2. decreased bicarbonate buffer production
3. reduced blood flow
4. direct damage to epithelium
5. disruption of mucus secretion
• Oxygen free radicals have been implicated
 ACUTE GASTRITIS

Ulcers are characterized by multiple small punctate

hemorrhage. The necrosis and hemorrhage are
confined to the mucosa as seen in histology.
 CHRONIC GASTRITIS
• Common causes are:
a. immunologic, associated with pernicious anemia
b. infection, especially Helicobacter pylori
c. alcohol
d. cigarette smoking
e. reflux of bile
• Inflammation may be superficial involving only the
upper 3rd of the mucosa or may involve full thickness
• Mucosal inflammatory changes may progress to
atrophy, intestinal metaplasia, dysplasia, and
carcinoma
 MUCOSAL CHANGES ASSOCIATED WITH
CHRONIC GASTRITIS

A B

A illustrates superficial chronic gastritis wherein inflammation

is confined to the upper third of the mucosa (arrows). B
illustrates full thickness inflammation with atrophy of gastric
glands. Arrow shows the muscularis mucosae. Note the
reduction in mucosal thickness and loss of gastric glands.
 MUCOSAL CHANGES ASSOCIATED WITH
CHRONIC GASTRITIS

A B

A illustrates atrophy plus intestinal metaplasia. Note the almost

complete loss of gastric glands and replacement of areas of the
surface epithelium by goblet cells (arrow). B illustrates
dysplasia of the gastric epithelium.
Helicobacter pylori Gastritis

• H. pylori is a non-invasive
organism but adheres to the
surface epithelium.
• The organism contains
powerful urease and produces
large amount of extracellular
catalase.
• Inflammation that ensues
further damages the mucosa.
 PEPTIC ULCER DISEASE
• Often solitary occurring anywhere along the
gastrointestinal tract
• Common location along the antrum of stomach
and 1st portion of the duodenum
• Produced by an imbalance between the
gastroduodenal mucosal defense mechanisms and
damaging forces
• Gastric acid and pepsin are requisite for peptic
ulceration
• The role of H. pylori is important
PEPTIC ULCER DISEASE
• Two ulcers located at
the body of the stomach
(arrows).
• Peptic ulcers are
usually less than 2 cm in
diameter with smooth
borders and clean base.
• Degeneration into
malignancy usually does
not occur.
Peptic Ulcer Disease
Benign ulcers also show
mucosal folds converging
around the ulcer. In the
picture the arrow shows an
eroded artery. Hemorrhage
is the most common
complication of peptic
ulcer. Other complications
are perforation and
obstruction due to fibrosis
and subsequent stenosis.
Chronic peptic ulcer:
•solitary (80%); may occur in all levels of GIT
•male > female (3:1)
 PEPTIC ULCER DISEASE
1
2

4
A B

A is a cross section of a gastric ulcer surrounded by

dense fibrosis. B is the histologic section showing
the characteristic 4 layers:
1. Necrosis 3. granulation tissue
2. inflammatory cells 4. fibrosis.
 GASTRIC CARCINOMA
• Incidence reveals marked national variation
• Etiologic factors, probably dietary in nature, appear
to act early in the life of individuals
• Within a given country, a higher incidence is often
found in mountainous regions suggesting possible
role of soils and trace elements
• The role of H. pylori chronic gastritis has been
recognized
• Gastric atrophy, intestinal metaplasia and dysplasia
are recognized are predisposing lesions
 GROSS PATTERNS OF GASTRIC
CARCINOMA

A B

Borrmann’s Type I (A) polypoid carcinoma

showing large vegetating mass without much
hemorrhage or necrosis. Borrmann’s Type II (B)
fungating tumor with extensive surface ulceration
and hemorrhage.
 MORPHOLOGIC PATTERNS OF GASTRIC
CARCINOMA

C D

Borrmann’s Type III (C) ulcerating tumor without

significant intraluminal mass
Borrmann’s Type IV (D) infiltrating tumor
involving the entire wall
 Part III

PATHOLOGY
OF THE
SMALL AND LARGE
INTESTINES
 ANATOMY OF SMALL INTESTINE

1. Measures about 27 feet long and extends from the

gastric pylorus to the ileocecal valve
2. Divided into the 1) duodenum, 2) jejunum and 3)
ileum
3. Characterized by numerous mucosal folds and villi
4. The basic structure of all portions is similar
5. Main functions are digestion, absorption and
immunologic defense
GROSS ANATOMY OF SMALL
INTESTINE

A B

A, normal small intestine in situ.

B, surface composed of
numerous regular folds (plicae
circulares)
 HISTOLOGIC FEATURES OF
SMALL INTESTINE
• Intestinal surface is studded with innumerable villi.
• At their bases, the simple tubular invaginations
(crypts of Lieberkühn) extend to the muscularis
mucosae but do not penetrate it.
• Villi are fingerlike or leaflike mucosal evaginations
lined by epithelium with a highly cellular
connective tissue core containing lamina propria, a
capillary network and lacteals.
 HISTOLOGY OF SMALL INESTINE
4. The lining is composed of:
- absorptive cells
- goblet cells
- cup cells
- Paneth’s cells
- undifferentiated crypt cells
- tuft and M cells
- endocrine cells
 FUNCTIONS OF SMALL INTESTINAL LINING CELLS
Absorptive cells - most abundant cells on the villi; absorb
various nutrients including lipids, sugars & amino acids;
possess enzymes for terminal digestion of
carbohydrates & proteins; have conspicuous brush
border.
Goblet cells - secrete mucus, ions and water; most
abundant in the crypts; distended by mucus assuming
the shape of a brandy goblet; increase in number along
the length of the small intestine being most numerous in
the lower ileum.
Cup cells - not easily seen; may have affinity for distinctive
bacterial pathogens and thus may play a role in the
initiation of intestinal disease
M and Tuft cells: M cells play a role in protein uptake
and a route for selective antigen absorption; role of
Tuft cells is unknown.
Paneth’s cells - occur at the base of the crypts; have
secretory granules contain arginine-rich basic
protein, glycoproteins and lysozyme; lysozyme is
believed to play a major role in bacterial protection.
Endocrine cells - interspersed among the absorptive
cells; produce hormones essential for digestion and
intestinal motility.
Undifferentiated crypt cells - most abundant at the
lower crypt; responsible for the replacement of all
types of intestinal cell
 HISTOLOGY OF SMALL INTESTINE

A B C
A shows the surface of the small intestine composed of
convolutions of mucosa and submucosa, the histologic equivalent
of the valvulae conniventes. B shows several villi prominently
lined by absorptive and goblet cells, and at the base of the crypts
the Paneth’s cells (arrow). C shows prominent brush border,
absorptive and goblet cells and central empty lacteal space.
 HISTOLOGY OF SMALL INTESTINE

Higher magnifications of Paneth’s cells and surface

brush border of small intestinal mucosa (arrows)
 ANATOMY OF THE DUODENUM
• Approximately 25 cm long and has 4 parts.
• It is roughly C shaped, enclosing in its concavity the
head of the pancreas, which is adherent to it.
• Except for its 1st part, it is retroperitoneal.
• The common bile and pancreatic ducts enter the 2nd
portion at the ampula of Vater.
• The ligament of Treitz is attached to the 4th portion,
which is difficult to distinguish from the 3rd portion.
DISTINCTIVE HISTOLOGIC FEATURE OF
DUODENUM – BRUNNER’S GLANDS
The submucosa is
almost completely filled
with highly branched
tubular duodenal glands
(Brunner’s glands [black
arrow]). The muscularis
mucosae may be
disrupted as these glands
penetrate into the deep
lamina propria of the
mucosa (blue arrows)
 DISTINCTIVE HISTOLOGIC
FEATURES OF JEJUNUM AND ILEUM

Jejunum Ileum

Though essentially built along the same principles, the jejumun

and ileum differ in several respects. The lumen of the ileum is
narrower than that of the jejunum. The plicae circulares are
shorter and broader in the ileum. In the jejunum lymphatic
tissue is encountered only in the form of solitary nodules
becoming more numerous and more pronounced in the ileum.
Aggregate nodules are called Peyer’s Patches (arrow).
 ANATOMY OF THE LARGE INTESTINE
1. Consists of the cecum, vermiform appendix, ascending,
transverse, descending and sigmoid colon, and anus.
2. Begins at the ileocecal valve and end at the anus; approx.
1.5 meters in length
3. Ascending colon extends from the ileocecal valve to the
hepatic flexure and lies retroperitoneally.
4. The transverse colon is the longest; extends across the
abdomen and attached to the stomach by the gastrocolic
ligament; the omentum is attached to its anterior surface
5. Descending colon begins from the hepatic flexure and at
the pelvic brim is continuous with the sigmoid.
• The sigmoid colon passes opposite the third sacral vertebra
to become the rectum
• The rectum curves gently downward and anteriorly along
the sacrococcygeal concavity onto the pelvic diaphragm for
a distance of about 12 cm. It abuts against the prostate or
the vagina inferiorly before turning posteriorly and caudad
through the pelvic floor to become the anal canal at the
dentate line.
• Taeniae coli, a continuous coat of the longitudinal bands of
the muscularis propria, runs from the cecum to the rectum.
It is absent in the appendix and rectum.
• Divided into segments called haustra, which is essential for
colonic function.
• Plicae semilunares are cresentric folds between sacculations
that project into the lumen.
 ANATOMY OF THE LARGE INTESTINE
1. Vermiform appendix
2. Cecum
4
3. Ascending colon
9
4. Transverse colon
5
5. Descending colon
3
6. Sigmoid

8 7. Rectum
2 8. Taeniae coli
6
1
7 9. Haustrations
 ANATOMY OF LARGE INTESTINE

Double contrast barium

enema showing satin-
smooth mucosa and
prominent haustrations
2 3 (yellow arrows)

1
1. Ascending colon
2. Transverse colon
3. Descending colon
4. Sigmoid colon
4
 ANATOMY OF LARGE INTESTINE

A B

A, longitudinal band corresponding to a single taeniae coli

(arrow). B, mucosa of colon thrown into visible folds the
plicae semillunares.
 HISTOLOGY OF LARGE INTESTINE
1. Consists of smooth mucosal membrane without folds, except
distally in the rectum
2. Epithelium is columnar without villi but with abundance of
goblet cells and small number of endocrine cells.
• . The glands (crypts of Lieberkühn) are typically long,
extending from the lumen to the muscularis mucosae and
clustered into groups of five or six, separated by deep furrows.
The crypts are lined by overlapping absorptive and goblet
cells, and endocrine cells.
• No Paneth’s cells
• Like the ileum, the large intestine has large number of
lymphoid tissue
 HISTOLOGY OF LARGE INTESTINE

A B C

A, the grossly apparent flat mucosa is arranged in regular

interconnected territories (double-headed arrow) containing 10-100
parallel crypt mouths separated by deep clefts (arrow). B, en face
section of the colon demonstrating cross sections through numerous
crypts. C, higher view showing absorptive and goblet cells lining
the crypts.
 CHOLERA
• A form of enterotoxigenic diarrhea resulting from
infection with Vibrio cholerae.
• Cholera toxin binds to a specific receptor on epithelial
cells of jejunum, which leads to increased adenylate
cyclase activity, which in turn results in high cyclic-
AMP levels in the intestinal mucosa.
• Increased cyclic-AMP causes the absorptive cells to
secrete large amount of water and sodium.
• Bacteria do not invade host tissue.
• Histologic changes are very mild and intestine may
appear normal.
BACILLARY • acute infection of the large
DYSENTERY intestine characterized by painful
diarrhea, often with blood and
mucus in the stools.
• Shigella sonnei, flexneri and
dysenteriae are the causative
organisms. S. flexneri and
dysenteriae can produce necrosis,
sloughing and hemorrhage; may
resemble ulcerative colitis.
• Denuded areas are soon covered
with fibrinopurument exudate
(arrow).
 AMEBIC DYSENTERY
• Disease of large intestine resulting from infection with
the protozoan Entamoeba histolytica.
• Vegetative form in large intestine of passed out in the
stools of infected persons; when ingested, resistant to
gastric juice; cyst wall is dissolved on reaching the
intestine, thus liberating the active ameba.
• Ameba secrete a cytolytic enzyme which enable them
to pass through the intestinal epithelium.
• The disease can lead to discrete oval ulcers, which are
characteristically ‘flask-shaped’ in section, or to a
diffuse colitis
 MORPHOLOGY OF AMEBIC COLITIS

A B

A, the earliest lesions in the mucosa consist of pinhead-sized,

hyperemic and edematous areas or small yellow papulae,
which evolve to ulcers containing often actively motile
trophozoites (arrows). B, severe lesions consist of large ulcer
resulting from confluence of smaller ulcers. Ulcers have
ragged, undermined edges; intervening mucosa congested.
 HISTOLOGY OF AMEBIC COLITIS

Amebic ulcers with beginning submucous tunnel

formation imparting a flask-shaped appearance
 Amoebic colitis

Trophozoites ingest red cells (erythrophagocytosis)

 TYPHOID ENTERITIS
• Usually confined to the ileum as a consequence of typhoid fever.
• Bowel involvement involvement is only part of a widespread
symptomatic bacteremia.
• Salmonella typhi and paratyphi are the causative organisms.
• Organisms are ingested in contaminated water or in food.
• Characteristic lesions are seen in the intestinal lymphatic tissue,
especially in the terminal portion of the ileum.
• The mucosa-associated lymphoid tissue, particularly the Peyer’s
patches become enlarged and eventually ulcerated.
• Inflammatory infiltrates mostly mononuclear cells with
erythrophagocytosis
MORPHOLOGY OF TYPHOID ENTERITIS

A B C
A, Early stage: Peyer’s patches of ileum enlarged and
inflamed. B, moderately advanced stage: sloughing of
Peyer’s patch. Ulcers are parallel to long axis of intestine C,
advanced stage: slough cast off; ulcer base on muscularis
propria; perforation a common complication during this stage.
TUBERCULOSIS OF THE INTESTINES

1. Most cases in the Philippines are caused

by swallowed infected sputum from a
pulmonary cavitary lesion.
2. Usually affects the terminal ileum and
cecum causing ulceration of the mucosa
3. Accompanied by fibrous wall thickening
and enlargement of regional lymph nodes.
4. Major complications are intestinal
obstruction by strictures and adhesions,
perforation of ulcers (uncommon), and
malabsorption if involvement is
widespread.
 Tuberculosis of Intestines

5. May be divided into two distinct forms:

- ulcerative
- hypertrophic
6. Ulcerative form is most common
7. Initial lesions usually affect the Peyer’s
patches and solitary lymphoid nodules
 MORPHOLOGY OF INTESTINAL TUBERCULOSIS

Tubercles of early TB involving

the solitary lymphoid nodules

Ulcerating lesions involving the Peyer’s

patches. Ulcers are perpendicular to the
long axis of intestines.
COMPLICATIONS OF INTESTINAL TB

A B C

A, intestinal obstruction due to

kinking by TB adhesions. B,
perforation of ulcer. C,
malabsorption syndrome due to
extensive TB of S. intestine and
D mesenteric lymph nodes.
 ACUTE APPENDICITIS
1. Common cause of ‘acute abdomen’
2. Inflammation often precipitated by obstruction
due to fecalith, lymphoid hyperplasia or
tumor.
3. Superimposed ischemia due to tissue pressure
on blood vessels and thrombosis may cause
gangrene.
4. Common complication is perforation with
subsequent peritonitis
 MORPHOLOGY OF ACUTE
APPENDICITIS

A B

A, gross appendix with marked vascular congestion

and exudate on serosal surface. B, radiograph
image showing a fecalith at the proximal end
corresponding to the bulge in A.
 HIRSCHPRUNG’S DISEASE
Aganglionosis of Intestine
1. Results from a failure of migration of neuroblasts
from the vagus into the developing gut, such that the
intramural parasympathetic nerve plexuses fail to
develop, thus affecting peristaltic movement of the
affected segment.
2. Rectum and distal colon are usually involved.
3. Effects may be from life-threatening total obstruction
to mild cases causing chronic constipation.
4. Also called Congenital Megacolon.
 MORPHOLOGY OF
HIRSCHPRUNG’S DISEASE

Marked colonic dilatation

occurs due to agenesis of
the parasympathetic
ganglion cells within the
myenteric and
submucosal plexuses.
Arrow indicates the
undilated aganglionic
segment of the rectum.
 MORPHOLOGY OF
MEGACOLON

A B

A, resected portion of rectum

showing undilated aganglionic
segment with proximal dilatation of
ganglionic segment. B, microsection
of that portion showing absence of
C ganglion cells. C. normal colon
showing ganglion cells (arrow)
 INTESTINAL
OBSTRUCTION
Common causes are:
2. Intussusception, which is the invagination of a
bowel segment into the next distal segment.
3. Volvulus, which is the twisting of the bowel
occluding its lumen.
4. Hernias are intestinal protrusions through weakened
or defective portions of the peritoneal cavity;
commonly in inguinal and femoral canals.
5. Adhesions
 MORPHOLOGY OF INTUSSUSCEPTION

A B
A, external appearance of small bowel intussusception (white
arrow indicating area of invagination). B, section showing
intussuscipiens, the portion receiving (black arrow) and
intussusceptum, the portion invaginating (white arrow) both of
which show hemorrhagic infarct due to strangulation of its
blood supply.
VOLVULUS

Volvulus occurs when

any portion of the
intestine loops on
itself and
compromising is
blood supply. Most
common in the small
intestine, particularly
in children.
 IDIOPATHIC INFLAMATORY BOWEL
DISEASE
• Two conditions: Crohn’s disease and ulcerative
colitis
• Crohn’s disease most commonly affects the small
bowel, but any portion of the gut may be involved.
• Ulcerative colitis usually confined to the colon and
anus.
• Cause in not clear; many theories have been
proposed.
DIFFERENTIATION BETWEEN CROHN’S DISEASE
AND ULCERATIVE COLITIS
 A COMPARISON OF HISTOLOGIC FEATURES
OF CROHN’S AND ULCERATIVE COLITIS

Lesions of Crohn’s are focal or patchy. Ulcers are at right

angle with the long axis of the bowel producing so-called
fissure ulcers. Granulomas are more common in Crohn’s.
Acute ulcerative colitis
•seen in Idiopathic,
inflammatory bowel
disease
•rectum and left colon
are commonly affected
•presents as bloody
mucoid diarrhea
 MORPHOLOGY OF
ULCERATIVE COLITIS

A B
A, an illustration of ulcerative colitis showing
extensive ulceration and hemorrhage. B, gross
specimen showing similar features.
 Chronic ulcerative colitis

•flattened mucosa & distorted crypts

Crohn’s disease • chronic idiopathic
inflammatory bowel disease
with relapsing course; peak
incidence in the 2nd & 3rd
decades ; involves terminal
ileum (>70%); affects colon
alone in about (20%)
• thickened wall with “skip
lesions”
•linear ulcers & cobblestone
mucosa
 Crohn’s disease
• patchy mucosal
involvement (affected
mucosa has chronic
inflammatory infiltrates
&distorted crypts)
• transmural chronic
inflammatory infiltrates;
lymphoid aggregates deep in
the wall
• formation of non-caseating
granuloma
ADHESIONS
Intestinal adhesions are
due to healing of any
inflammatory process
involving the
peritoneum.
Adhesions create
fibrous bands in the
abdominal cavity or
cause loops of intestine
to adhere to one another.
 DIVERTICULAR DISEASE

1. Diverticula are herniations of mucosa into the

intestinal wall.
2. Herniations are of the pulsion type usually at sites of
weakness particularly where lymphoid aggregates
breach the muscularis mucosae.
3. Most common in the colon, particularly the sigmoid.
4. Most diverticula occur between the mesenteric and
anti-mesenteric longitudinal muscle band (taenia coli)
 DIVERTICULAR DISEASE
1. Affected segment shows thickening of the muscularis
propria, and prominence of the mucosal folds which
occludes the lumen.
2. Due to a deficiency of fiber in the diet.
3. Sigmoid motility is sensitive to the bulk of the
colonic content, and if low, due to a low fiber diet,
abnormally high intra-luminal pressure are generated.
4. Complications are diverticulitis, perforation,
peridiverticular abscess, fistula, peritonitis and
hemorrhage.
 MORPHOLOGY OF DIVERTICULA

Diverticulosis of the sigmoid colon showing ridged

mucosal surface due to hypertrophy of underlying
muscle. The opening of the diverticula can be seen
between the mucosal ridges.
 POLYPS
1. A polyp is simply a protuberant growth.
2. Wide variety of histologic types
3. Divided into epithelial (much more common) and
mesenchymal
4. 4 types of benign epithelial polyp:
- inflammatory (pseudopolyps)
- metaplastic
- hamartomatous
- adenomas (most important because of
adenoma-carcinoma sequence)
 ADENOMAS
• Can originate in any portion of the intestine, however,
mainly in large intestine.
• Benign glandular neoplasms originating from intestinal
mucosal epithelium composed of dysplastic epithelium.
• Probably the precursors of most colorectal carcinomas.
• Adenomas and carcinomas are frequently found
together in a resected segment of bowel.
• Malignant risk is associated with increasing size, villous
growth pattern, more severe degree of dysplasia.
 MOLECULAR PATHOLOGY OF
ADENOMA-CARCINOMA SEQUENCE

Genetic defects are:

2. Activation of oncogenes
3. Loss or mutations of tumor suppressor gene
4. Defective genes of the DNA repair pathway
leading to genomic instability.
 ACTIVATION OF ONCOGENES

• Overexpression of c-MYC is a feature of

most colorectal carcinoma
• c-MYC encodes a nuclear phosphoprotein
which is required for DNA synthesis.
• Increased expression of c-MYC may be
followed by increased cellular
proliferation.
 LOSS OF SUPPRESSOR GENE

• Point mutation or deletion of

chromosome 5q of suppressor gene
renders the cell more resistant.
• Damage which would normally results
in apoptosis and elimination of the cell
does not occur.
 MORPHOLOGY OF ADENOMAS

Adenomas have one of two major growth

patterns: pedunculated or sessile. The surface is
mutilobulated, reddish and friable.
Adenomas:
•tubular
adenoma
•villous
adenoma
•tubullovillous
adenoma
 HISTOLOGY OF ADENOMAS

A B C

A. tubular adenoma which maintain the original configuration of

the crypts but normal colonic epithelium is replaced by dysplastic
epithelium. B. villous adenoma consisting of finger-like processes
extending outward from the surface. C. tubulo- villous adenoma
which is a mixture of both patterns.
HISTOLOGY OF ADENOMAS
• Higher magnification of
dysplastic epithelium of
adenomas consisting of
stratified columnar
epithelium with nuclear
atypia.
• The risk of malignancy
is increased with
increasing size, villous
pattern and degree of
dysplasia.
Adenocarcinoma arising from adenoma:
 TRANSFORMATION OF
ADENOMA TO CARCINOMA

• Invasive carcinoma
arising in a villous
adenoma.
• All adenomas should
be examined well to
rule out underlying
carcinoma.
 CARCINOMA OF THE COLON
1. Most common malignancy in developed country
2. All are adenocarcinomas
3. Increased risk in patients with adenomas and
longstanding idiopathic ulcerative colitis
4. Dukes’ staging, based on local extent and
metastatic status, is the best guide to prognosis
5. Inherited genetic factors and diet play a
significant role in the pathogenesis
 MORPHOLOGY OF
COLONIC CARCINOMA

A large exophytic lesion in the cecum which

almost completely blocks the lumen.
Adenocarcinomas:
•98 % of all cancers of intestines
•50-70 % are rectosigmoid
• peak incidence: 60-70

y/o; <20% are 50yr

• annular on left side
• polypoid/fungating on
the right side
Adenocarcinomas in the colon:
• associated RAS, p53 (17p,13), DCC
(18q21) mutations
• (+) keratin & CEA (equally distributed)

Dietary factors:
• low fiber intake
• high carbohydrate intake
• high fat content
DUKES’ STAGING

A – tumor is confined to the

submucosa or muscle layer
B – tumor has spread through
the muscle layer, but does
not yet involve the lymph
nodes
C. Tumor involving lymph
nodes
 Mesenchymal tumors
• Lipoma - most common; submucosal
• Spindle cell stroma tumors:
– arise from muscularis propria; appear as
nodules or polypoid masses
– mostly leiomyomas or leiomyosarcomas
– those with neural differentiation of lacking
differentiation are called Gastrointestinal
stroma tumors (GIST)
– spindle cells in fascicles
– size & mitotic rate are predictors of poor
prognosis
 Gastrointestinal lymphoma

• GIT is the most common site of extra-

nodal lymphoma
• lymphoma accounts for 1-3% of GIT
malignancies
• increased frequency with H.pylori
associated gastritis, immunodeficiency,
post-organ transplant
immunosuppression, & celiac sprue and
in the Mediterranean region
Pathologic Lesions of the Appendix
Mucocoele - dilation of appendix by mucinous
secretions and may be caused by:
1. Mucosal hyperplasia - resembles
hyperplastic polyp; uncommon
2. Mucinous cystadenoma - common; may
rupture in about 1/5 of cases; benign such that
appendectomy is curative
3. Mucinous cystadenocarcinoma - invasive
tumor; penetrates wall of appendix; may rupture
and implant on the peritoneum or ovary
 Carcinoid tumors
• arise from GIT neuroendocrine cells
• appendix is the most common site; also
commonly seen in the small intestine,
rectum, stomach, colon
• gastric and ileal carcinoids are usually
multicentric
• immunohistochemically (+) for
chromogranin, symaptophysin and
neuron-specific enolase
 Carcinoid tumors
• often asymptomatic but may produce
symptoms depending on the substances
secreted:
– Cushing’s syndrome (ACTH)
– hyperinsulinism
– Zollinger-Ellison syndrome (gastrin)
– Carcinoid syndrome (serotonin) -
episodic attacks of vasomotor
instability, intestinal hypermotility &
bronchoconstriction
 Pseudomyxoma peritonei

• ascites composed of gelatinous material

• may result from rupture of mucinous
custadenoma, cystadenocarcinoma of
appendix or from tumors in other organs
• worse prognosis is expected if:
– arises from adenocarcinoma
– contains malignant epithelial tissue
admixed with the mucous (gelatinous)
material
– widespread involvement
ANATOMY OF THE ANUS The anus is a tubular
structure extending from the
perineal skin to the lower
end of the rectum at the
upper border of the internal
sphincter at the anorectal
ring. It is 30-40 mm long,
slightly longer in men.
A – Lower rectum
B – Anal transitional
zone (ATZ)
C – Anus
D – perianal skin
Anatomy of Anal Canal:

• The junction between the anal canal and the

perineal skin is known as the anal verge.
• The dentate or pectinate line marks the
junction between the anal canal and the rectum.
 HISTOLOGY OF ANUS

A B

Normal anal canal. A: the colorectal mucosa of

the anal canal is similar to rectal mucosa but there
is shortening and irregularity of the crypts. B: the
nonkeratinizing squamous layer below the
transition zone contains increased melanocytes.
 HEMORRHOIDS
1. Varicosities resulting from dilatation of the
submucosal venous plexuses.
2. Underlying mechanism is not clear, although
chronic constipation with straining at stool is
most commonly invoked.
3. May present with bleeding; may prolapse
through the anal verge; may undergo
inflammation, thrombosis and infarction.
MORPHOLOGY OF HEMORRHOIDS

A B

A – internal hemorrhoids
B – external hemorrhoids
The anus may have lesions that
commonly affect the skin such
as anal condyloma.