Pathology of Small & Large Intestine

Developmental lesions
Meckel Diverticulum
Etiology and Derived from remnant of vitelline duct (yolk stalk)
Epidemiology Occurs in 2% of population
Gross: Blind pouch on antimesenteric border of ileum within 2 feet of the ileocecal
valve causing tubular outpouching of small intestine
Microscopic: True diverticulum with all 3 layers of the bowel wall (mucosa,
submucosa, muscularis propria); may contain acid-secreting gastric mucosa
and/or pancreatic tissue
Clinical Manifestations Presents in first 2 years of life. Usually asymptomatic, but
can cause peptic ulcerations leading to a GI bleed, intussusception (invagination of
a bowel segment into a more distal bowel segment), or volvulus (twisting of one
bowel portion around its own mesentery). Intussusception presents with red currant
jelly stools owing to bowel ischemia. Volvulus presents with acute abdominal pain,
constipation, gas, and sigmoid distention.
Notes Meckel diverticulum is the most common congenital abnormality.
Hirschsprung disease (also called congenital aganglionic megacolon) is due to
congenital absence of ganglion cells in the rectum and sigmoid colon, resulting in
intestinal obstruction. The condition aects males more than females, and can be
associated with Down syndrome.
Hirschsprung disease may present with delayed passage of meconium, or with
constipation, abdominal distention, and vomiting.
Grossly, the aected segment is narrowed, and there is dilation proximal to the
narrow segment (megacolon).
Microscopic: there is an absence ofganglion cells in Auerbach and Meissner plexuses,
and the diagnosis is establishedwhen rectal biopsy demonstrates the absence of
ganglion cells.
Treatment is by resection of the aected segment.

Celiac sprue (also caused gluten-sensitive enteropathy and nontropical sprue) is due
to hypersensitivity to gluten (and gliadin), (present in wheat, oat, rye, and barley).
Gross: Blunting and atrophy of small intestinal mucosal villi
Microscopic: villous atrophy & Increased lymphocytes and plasma cells in the lamina
propria; loss of brush border.
Clinical Manifestations May be symptomatic in infancy with growth retardation
and failure to thrive, but may present in young adulthood. Also may see
steatorrhea (pale, bulky, frothy, foul-smelling stool), abdominal distention, weight
loss.
Diverticular Disease (Diverticulosis and Diverticulitis)
Etiology:
* Diverticulosis: Development of diverticula is associated with increased pressure in
the bowel and bowel wall weakness; commonly seen in people > 60 years; associated
with low-fiber diet
* Diverticulitis: Caused by inflammation of diverticula, usually by impacted fecal
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material
Pathology
* Diverticula: Gross: blind pouches leading o the alimentary tract that
communicate with gut
lumen; most commonly false (pulsion) diverticula resulting from herniation of mucosa
through
defects in muscular layer; less commonly true (traction) diverticula consisting of
mucosa, muscularis, and serosa. Microscopic: atrophic mucosa with thin muscularis
propria.
* Diverticulosis: Presence of multiple diverticula most commonly in the sigmoid
colon
* Diverticulitis: Inflammation of diverticula with inflammatory infiltrate with
edema.
Acute Appendicitis
Etiology: Caused by obstruction of the appendix by a fecalith, inflammation,
foreign body, or neoplasm
Epidemiology Peak incidence is between 10 and 30 years of age
Pathology Gross: Red, swollen appendix with fibrinous exudate
Microscopic: Neutrophilic infiltrate extending through to muscularis; abscess
formation;
ulcerations; congested vasculature
Clinical Manifestations Vague periumbilical pain that later localizes to RLQ pain;
fever; anorexia; nausea; vomiting. Complications include gangrene and perforation
leading to peritonitis
Notes Appendicitis is the most common abdominal surgical emergency, aecting
10% of population.

Pseudomembranous colitis (antibiotic-associated colitis) is an acute colitis

characterized by the formation of inflammatory pseudomembranes i the intestines. It
is usually due to Clostridium diicile infection (often brought on by a course of broadspectrum antibiotics, especially clindamycin and ampicillin), but pseudomembranous
colitis can also be due to ischemic bowel disease.
i. Pathology. Gross examination shows yellow-tan mucosal membranes. Microscopic
examination shows superficial colonic necrosis with an overlying pseudomembranes;
the pseudomembranes are inflammatory exudates composed of neutrophils, mucin,
fbrin, and necrotic cellular debris.
ii. Clinically, the presentation is with diarrhea, fever, and abdominal cramps.

InfIammatory bowel disease (IBD)

The three major categories of inflammatory bowel disease are Crohns disease (CD),
also called regional enteritis, ulceratve colitis (UC), and colits of indeterminate type.
Etiology: is Idiopathic, May be related to immune system dysfunction.
Crohn's Disease

Ulcerative Colitis

Most common site

Terminal ileum

Rectum

Distribution

Mouth to anus

Rectum - colon

Gross

skip lesions (areas of

normal bowel interspersed

Extensive ulceration
(Continuous lesions of

with
diseased bowel);
Focal aphthous ulcers
with intervening normal
mucosa
Linear fssures
Cobblestone appearance
Thickened bowel wall
"Creeping fat
Microscopic

Transmural inflammation +
noncaseating granulomas
(60%)

the colon with rectal

involvement) +
pseudopolyps
(mucosal remnants of
previous ulcerations)

Cryptitis, crypt abscesses,

distortion of crypt
architecture, ulceration &
pseudopolyps

Intestinal polyps
Polyps are benign tumors or tumor-like protrusions of the intestinal mucosa. Polyps are
classified as neoplastic and nonneoplastic.
1- Non-neoplastic polyps:
hyperplastic polyps
* The most common intestinal polyps
* Small, dewlike, glistening nodules (most are <0.5 cm)
* Most often found in the rectum
* Nonneoplastic hyperplasia of colonic epithelium leads to the formation of
elongated glands
with saw-tooth appearance on cross-section.
juvenile (retention) polyps
These polyps are hamartomas typically found in the rectum of children aged
younger
than 10 years. They are pedunculated, round, and have a smooth surface.
Histologically,
they are composed of mucus-filled cystic glands and edematous, usually inflamed
stroma.
PeutzJeghers syndrome
An autosomal dominant syndrome characterized by:
* Multiple hamartomatous intestinal polyps (Polyps may be found in any part of the
intestine
but are most numerous in the small intestine.)
* Pigmented macules on the lips and the perioral skin
* Intestinal polyps composed of irregularly arranged glands surrounded by strands
of smooth
muscles (These polyps are not precancerous and only exceptionally progress to
adenocarcinoma.)

 Inflammatory polyps include benign lymphoid polyps and inflammatory

pseudopolyps consisting of granulation tissue and remnants of mucosa, caused
by chronic inflammatory bowel disease.
2- Neoplastic polyps adenomatous polyps are true neoplasms rather than
benign proliferations of tissue. They
are usually asymptomatic but can result in rectal bleeding.
a. tubular adenomas
(1) These are the most common type (75%) of adenomatous polyp.
(2) These polyps are usually small and pedunculated.
(3) They can contain malignant foci; the likelihood of malignancy is greater in
larger polyps.
b. tubulovillous adenomas
(1) These adenomas account for about 15% of adenomatous polyps.
(2) Tubulovillous adenomas resemble tubular adenomas but have a surface
covered by fingerlike villi. They are similar histologically to tubular adenomas.
(3) They are intermediate in malignant potential between tubular adenomas and
villous adenomas.
c. villous adenomas
(1) These polyps are much less common than tubular adenomas and account for
approximately 10% of adenomatous polyps.
(2) Villous adenomas are usually larger than tubular adenomas, usually sessile and
velvety, and are characterized by large numbers of fingerlike villi.
(3) They have the highest potential for malignancy of all of the
adenomatous polyps; they
become malignant in more than 30% of cases.

Colorectal Adenocarcinoma
Etiology and Epidemiology: Risk factors include adenomatous polyps, longstanding ulcerative colitis, low-fiber diet, old age, positive family history, hereditary
nonpolyposis colorectal cancer (HNPCC), and familial adenomatous polyposis (FAP)
Most commonly occurs between the ages of 60 and 80
Pathology Gross: Appearance varies from polypoid mass (proximal colon) to
lesions with ulcerated centers and irregular margins that circumscribe bowel (distal
colon)
Microscopic: Dysplastic columnar cells in glandular formation; may produce mucin,
some tumors may be anaplastic
Clinical Can be asymptomatic; if symptomatic, presents with pallor, weight loss,
intermittent diarrhea, Manifestations LLQ pain, or obstruction
Lab findings: Positive stool guaiac test; increased serum CEA; microcytic,
hypochromic anemia (iron deficiency anemia secondary to GI bleed)
Notes Colorectal cancer is the second leading cause of death owing to malignancy
in the United States.
Molecular pathogenesis
APC/-catenin pathway (also called adenoma-carcinoma sequence, Sequential
mutacions of dierent genes): Loss of tumor suppressor APC gene is followed by
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increased -catenin transcriptional activity (normal APC protein degrades catenin) leading to localized colon epithelial proliferation and formation of small
adenoma. This is followed by dysplastic change due to activating mutation in K-ras
and inhibition of tumor suppressor genes like SMAD2, SMAD4 and p53 leads
ultimately to cancer.
Right-Sided Cancer Versus Left-Sided Cancer
Gross

Polypoid mass

Circumferential growth
producing a
"napkin-ring" confguration

Clinical
Presentation

Bleeding
Occult blood in stool
Iron deficiency anemia

Change in bowel habits

Constipation or diarrhea
Obstruction