Pathology DHB 2

Grades 35

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GIT 1, Liver 1, microscopic colitis, 2 tumors of salivary

Midterm
glands

Created
A Abdelrhman Mohamed
by

GIT 1

Reflux esophagitis
Incontinence of the esophagogastric valve causes the regurgitation of
gastric acid into the lower part of esophagus (GERD).

A genetic predisposition has been detected.

It is usually associated with sliding hernia.

Symptoms: Food regurgitation, heart burn, pain, and dysphagia.

Barrett’s Metaplasia
Definition: the stratified squamous epithelium of lower
esophagus is changed to columnar intestinal epithelium (A
type of Intestinal metaplasia)

Gross by endoscopic examination:

Single or multiple finer-like projections of columnar mucosa

Above the squamocolumnar junction (Z-line)

Pathology DHB 2 1
 Salmon- pink coloration.

Complications:
1. Peptic ulceration

2. Bleeding: hematemesis or melena

3. Esophageal stricture: Fibrosis- Dysphagia

4. Malignancy: Adenocarcinoma. The process of malignant transformation:

Reflux esophagitis- columnar metaplasia, dysplasia, carcinoma in situ
and invasive cancer

Peptic ulcer
Definition: Ulcer that develop in the lining of stomach, Lower
esophagus or duodenum.

Rare sites:
1. Jejunum after gastro-jejunostomy (A surgical procedure that connects
part of the stomach to the jejunum).

2. Meckel's diverticulum due to presence of heterotopic gastric mucosa.

Jejunum after gastro-

jejunostomy

Meckel's diverticulum

Pathology DHB 2 2
 Predisposing Factors:
1. Sex - Age: Male - Adult

2. Diet: Hot - Spicy food - Alcohol - Smoking

3. H-pylori bacteria

4. Drugs: High dose of NSAID - Corticosteroids

5. Stress- Major operations

6. Genetic susceptibility: Blood group O

7. Gastrin producing tumor of pancreas ZES

Pathogenesis:
1. Hyperacidity: increase acid secretion (especially during night)

2. Infective theory: H-pylori

3. Neurogenic theory: Abnormal vagal nerve stimulation

Gross and Microscopic:

Gross Microscopic

Base: is formed of fibrous tissue with

Usually single. complete destruction of muscle layers

Contents: granulation tissue, necrotic tissue

Duodenal ulcers are smaller in size. and inflammatory cell exudate.

Blood vessels in the base show endarteritis,

Round or oval. In lesser curvature
obliterans and venous thrombi
they are saddle-shaped.

Size: 0.5-3 cm.

The edge is clear cut.

Surrounding mucosa is flat and

atrophic.

Serosa is thick and opaque due to

adhesions.

Pathology DHB 2 3
 Gross Microscopic
Regional lymph nodes are enlarged

Complications:
1. Hemorrhage: hematemesis or melena (occult blood in stool)

2. Perforation: sub-diaphragmatic abscess or generalized peritonitis.

3. Scar contraction: pyloric stenosis with marked dilatation of stomach.

Ulcers on lesser curvature cause hour-glass deformity.

4. Penetration: Adhesions between stomach and adjacent organs e.g.

pancreas

5. Malignant transformation: in less than 1% of cases in untreated ulcers

larger than 3 cm.

Hour-Glass deformity

Gastric carcinoma
Pre-cancerous conditions and risk factors:

1- H. Pylori infection:
They cause chronic gastritis, followed by atrophic gastritis and intestinal
metaplasia, The carcinogenic effects through:

Excessive cell proliferation

Production of Nitrous oxide (strong gastric carcinogen)

Pathology DHB 2 4
 Decrease Vit. C production

DNA damage

2- Chronic atrophic gastritis and intestinal metaplasia.

3- Dysplasia (intraepithelial neoplasia).

low grade high grade

irregular crowded tubular glands with no

Atypical glands with little or no mucin
mucin

low mitosis marked hyperchromasia and mitosis

occupies less than half of mucosa occupies the whole depth of mucosa

4- Adenomas: the following conditions are more prone to

malignant change:
Non pedunculated sessile adenomas

tubular adenomas

large adenomas more than 2cm in diameter

adenomas with high intraepithelial neoplasia

5- Chronic peptic ulcer

6- Inheritance: Gastric carcinoma is more common in

individuals with blood group A.

7- Diet: Alcohol, tobacco and excess processed meat.

8- Age and sex: It occurs above the age of 50 years, more in

males.

Sites:
Common sites are: pre-pyloric region, pyloric antrum, and lesser curvature. It
is less common in cardia or body and rare in fundus.

Grossly:

Pathology DHB 2 5
 Malignant ulcer (More than Infiltrating mass (Linitis
Polypoid or fungating mass
2.5 cm in diameter) plastica)

It invades the wall of

stomach with marked
thickness and reactive
fibrosis. The stomach is
large irregular mass, Large with raised everted transformed into a rigid
ulceration, hemorrhage edge, necrotic floor and short narrow tube. No
and infection. indurated base. gross masses or ulcers are
seen. This tumor is highly
invasive with poor
prognosis.

Polypoid or fungating mass

Malignant ulcer Linitis plastica

Microscopic:

Tubular It is formed of branching tubular structures lined by

adenocarcinoma: malignant columnar mucin secreting cells.

It is formed of well differentiated exophytic elongated

Papillary
finger-like processes lined by malignant cuboidal cells
adenocarcinoma:
along a fibrovascular core.

Mucinous Glands lined by malignant columnar cells are seen amidst

adenocarcinoma: wide pools of extracellular mucin.

Tumor is formed of groups of small cells with intracellular

Signet ring mucin, compressing the nucleus peripherally, simulating a
adenocarcinoma: signet ring. It is a highly invasive tumor of high grade
malignancy and poor prognosis.

Pathology DHB 2 6
 Tumor is formed of sheets of large or small undifferentiated
Undifferentiated
cells with no attempt at gland or mucin production. It is of
carcinoma:
high grade malignancy.

Adenosquamous and squamous carcinoma occur on top of

Rare types:
squamous metaplasia.

Complications: Pain, weight loss, nausea, vomiting and

bleeding.

Spread:
local spread, lymphatic spread and blood spread to liver leads to jaundice
and ascites. Spread by peritoneal cavity to both ovaries leads to Krukenberg
tumor

GIST
Most common mesenchymal tumor of the GIT

Arises from the interstitial cells of Cajal within the myenteric plexus of
the muscularis propria

GIST arising outside of the gastrointestinal tract (omentum, mesentery,

retroperitoneum or pleura)

3 histologic types: spindle, epithelioid and mixed

Prognosis: depends on tumor size, mitotic rate and site of origin

IHC: DOG1- CD117(c-Kit)- CD34

Inflammatory bowel diseases

Ulcerative Colitis Crohn’s disease

Def. chronic non specific chronic granulomatous

inflammatory affecting the inflammation affecting any part
rectum and colon at any age

Pathology DHB 2 7
 Ulcerative Colitis Crohn’s disease
of GIT, ileum is the commonest
site

- Affects females more than

males
- Peak incidence 20-25 y
- Genetic background
Etiology and
- A possible microbial invader Similar to ulcerative colitis
Pathogenesis
- Abnormal host immune-
reactivity to an exogenous or
endogenous Antigen.
- A psychosomatic disorder.

- Autoimmune disease - Autoimmune disease

- infection - infection
Causes
- Psychogenic - Psychogenic
- Genetic predisposition - Genetic predisposition

Mucosa is elevated to form

Grossly Wall thickened Typical cobble-stone
appearance

Mucosa in-between ulcers is

Granular serosa with adherent
swollen and hyperemic forming
creeping mesenteric fat.
Pseudo-polyps.

mucosa congestion and show Regional mesenteric nodes are

shallow ulcers enlarged

Multiple ulcers: Linear mucosal ulcers:

-Superficial -Congested margin
-Large sized -Sharp edges
-Irregular -Fibrotic floor.
-Sharp edges -Indurated b
-Necrotic floor ase.
-Soft base.

Lesion is segmental with

intervening normal areas (Skip
lesions).

Microscopically Ulcerated mucosa Ulceration

Chronic mucosal damage with

Crypt abscesses
villous blunting and atrophy.

Trasnmural inflammation with

Goblet cell depletion
lymphoid aggregates.

Pathology DHB 2 8
 Ulcerative Colitis Crohn’s disease

Lamina propria shows

Non caseating granuloma leads
neutrophils and mononuclear
to cobble stone appearance.
leucocytes.

Pseudo-polyps (swollen Fibrosis, mucosal and neural

congested edematous inflamed hypertrophy, vasculitis and
mucosa). dysplasia.

Intestinal hemorrhage, Colonic

stricture, Malabsorption.
Colonic perforation, fistula.

Intestinal hemorrhage, Intestinal

Complications Extra colonic manifestations: stenosis, Malabsorption, Fistula,
hepatic steatosis, biliary Amyloidosis.
cirrhosis and amyloidosis.

Colorectal Carcinoma.

Pathology DHB 2 9
 Ulcerative colitis

Ulcerative colitis

Crohn’s disease
Cobble stone appearance.

Salivary tumors
Pleomorphic adenoma Warthin tumor

Microscopic: Benign triphasic salivary Microscope: Common tumor of parotid

gland neoplasm composed of epithelial gland with double layer of epithelial cells
(ductal) cells, myoepithelial cells and (palisading oncocytic columnar cells
chondromyxoid stroma. with underlying discontinuous basal
cells) resting on dense lymphoid stroma.
No myoepithelial component

Pathology DHB 2 10
 Pleomorphic adenoma Warthin tumor
The stroma has
mature lymphoid tissue with germinal
centers

Also called papillary cystadenoma

Most common salivary gland neoplasm
lymphomatosum - adenolymphoma

The second most common benign

Most commonly affected site is the
salivary gland tumor (males smoker
parotid gland.
above 40 years)

Gross:

1-Primary tumor: well demarcated, gray-

white myxoid mass Gross: capsulated - lobulated -
multicystic
2- Recurrent tumor: numerous myxoid to
fibrotic nodules of various size, giving a
shotgun bullet appearance

Benign metastasizing mixed tumors: late

Arises from infitration of lymphoid tissue
metastasis after tumor excision. Benign
in parotid glands or induction of cystic
morphology in original and metastatic
and oncocytic changes by inflammation
tumor. Associated with incomplete
infiltrate
surgery or local recurrence

Risk factors for malignant transformation:

multiple recurrences, submandibular
location, older age, larger size, increased
mitotic rate and radiation exposure

IHC:

- Ductal (epithelial) cells are positive for

cytokeratins.
- Myoepithelial cells are positive for GFAP,
S100 and Actin

Liver 1

Acute viral hepatitis

Pathological features of acute viral hepatitis:

Pathology DHB 2 11
 1. The liver is slightly enlarged and bile stained.

2. Hydropic (ballooning) degeneration of hepatocytes.

3. Necrosis of the hepatocytes, centrilobular and focal. Few necrotic cells

appear shrunken with eosinophilic cytoplasm and pyknotic nuclei and are
called acidophilic or Counciloman bodies.

4. The necrotic areas and the portal tracts are infiltrated by lymphocytes,
macrophages, eosinophils, and plasma cells.

5. Cholestasis: Bile retention in hepatocytes and bile canaliculi. The

canaliculi are dilated and filled with thick bile plugs.

6. Kupffer cells show hyperplasia and hypertrophy. They engulf cellular

debris and bile pigment.

Fate of acute viral hepatitis:

1. Complete recovery in most cases specially HAV infection. The reticular
framework of the liver lobules is usually intact, so it provides a matrix for
the regenerating liver cells.

2. Failure of recovery with progress of the disease to fulminating viral

hepatitis which is a fatal condition due to:

a. few days, called massive liver cell necrosis (acute yellow atrophy)

b. few weeks, called subacute massive necrosis. Rarely post necrotic

cirrhosis develops.

Chronic hepatitis
Definition: It is a primary liver inflammation continuing without
improvement for at least 6 months.

Etiological classification of chronic hepatitis:

Chronic hepatitis B-C-D

Alcoholic hepatitis

Autoimmune hepatitis

Pathology DHB 2 12
 Drug induced

Primary biliary cirrhosis

Secondary biliary cirrhosis

Wilson’s disease

Hemochromatosis

α1antitrypsin deficiency

Types of chronic hepatitis:

Chronic persistent hepatitis Chronic active hepatitis Chronic lobular hepatitis

Presence of piecemeal
necrosis and spotty or patchy
inflammation within the
In which there is restriction Mild: inflammatory lobule with minimal portal
of inflammatory infiltrate infiltrates erode minimally tract inflammation. It can
to the portal tract without into the parenchyma plus mimic acute viral hepatitis,
piecemeal necrosis. It is necrosis of periportal so the duration must
the most common long hepatocytes. exceed 6 months. It is
term sequela more common with virus
Sever: bridging necrosis C.
plus confluent or
multilobular necrosis

Types of liver necrosis:

1- Apoptosis of hepatocytes: It is death of individual cells.
2- Spotty necrosis: It is necrosis of minute clusters of hepatocytes

3- Focal necrosis: it is necrosis involving larger groups of hepatocytes within

a lobule.
4- Zonal necrosis: It refers to necrosis involving a particular zone of the
acinus, such as centrilobular: acinar zone 3
5- Piecemeal necrosis (interface hepatitis): It is a common type of necrosis
seen in hepatitis. It is characterized by inflammation extending from the
portal tract into the periportal zone, with necrosis of periportal hepatocytes
and disruption of the limiting plate.
6- Bridging necrosis (stage 3 fibrosis): It is defined as bridging fibrosis that
extends across lobules.

Pathology DHB 2 13
 7- Confluent or Multilobular: It is necrosis involving multiple lobules

Microscopic changes in different types of chronic hepatitis:

Chronic hepatitis Autoimmune Primary biliary
Alcoholic hepatitis
B, C and D: hepatitis cholangitis (PBC)

Steatosis, Portal tract plasma

ballooning cell rich previously known
degeneration and inflammation and as primary biliary
- Lymphocyte
hepatitis. piecemeal cirrhosis, is an
aggregates in the
necrosis. autoimmune
portal tract
Emperipolesis: disease of the liver.
- degenerative
Mallory body: is a apparent It results from a
changes in the
deeply eosinophilic engulfment of slow, progressive
bile duct
intracytoplasmic lymphocytes by destruction of the
- steatosis
inclusion that hepatocytes. small bile ducts of
- Kupffer cells or
represents Hepatocyte the liver, causing
lymphocyte
aggregates of rosette formation bile to build up in
aggregates within
misfolded and variable the liver, a condition
the lobules.
intermediate fibrosis. called cholestasis.
filaments.

Secondary Alpha-1 antitrypsin

Wilson disease Hemochromatosis
biliary cirrhosis deficiency

It develops due It is a rare genetic - It is a disorder - Is a hereditary

to long-term disorder characterized where too much genetic disorder
partial or total by excess copper iron builds up in which may lead to
obstruction of stored in various body your body (iron the development of
the large bile tissues, particularly overload). lung
ducts outside the liver, brain, and Normally, your and/or liver disease.
of the liver. corneas of the eyes intestines absorb
When the ducts (Kayser Fleisher ring). just the right - lung conditions
are damaged, The disease is amount of iron. such as:
bile builds up in progressive and, if left emphysema (Alpha-
the liver and untreated, it may -But in 1 is a protease
damages cause liver disease, hemochromatosis, inhibitor)
the liver tissue. central nervous your body absorbs
system dysfunction, too much iron - Liver diseases
and death. which is deposited such as:
mainly in liver, hepatitis, cirrhosis

Pathology DHB 2 14
 Secondary Alpha-1 antitrypsin
Wilson disease Hemochromatosis
biliary cirrhosis deficiency
pancreas and skin and hepatocellular
(Bronze diabetes) carcinoma
hyperglycemia and
dark skin color.

Liver cirrhosis
METAVIR scoring system: Liver fibrosis is classified to stages 0
to 4
1. F0—no fibrosis

2. F1—portal fibrosis

3. F3—bridging fibrosis

4. F4—cirrhosis

Definition: It is a chronic diffuse liver disease characterized by

degeneration and necrosis of the liver cells followed by
regeneration causing nodules which lack the normal lobular
pattern and then diffuse fibrosis.

Gross picture:
1- The liver is reduced in size.
2- It is firm in consistency due to diffuse fibrosis.
3- The outer surface is diffusely nodular and the capsule is thickened.
4- The cut surface shows complete replacement of the normal lobular
architecture by rounded regenerating nodules of variable sizes separated by
grayish white fibrous septa.
According to the size of the regenerating nodules, cirrhosis is classified into:

Micro-nodular cirrhosis: the cirrhotic nodules are under 3mm.

Macro-nodular cirrhosis: the nodules are larger than 3mm.

Mixed micro and macro-nodular cirrhosis.

Pathology DHB 2 15
 Microscopic picture:
the liver shows complete loss of normal lobular pattern. The liver shows
variable size regeneration nodules separated by fibrous tissue. The nodules
show absent or eccentric central vein. The liver cells are hyperplastic,
degenerated, or necrotic. The fibrous septa are infiltrated by lymphocytes
and show proliferated bile ducts and capillaries.

Pathophysiology: It includes combination of:

Fibrosis: excessive production of collagen type I / III by hepatic stellate
cells (Ito cells) and portal fibroblasts through stimulation by different
inflammatory cytokines.

Regeneration of hepatocytes: through proliferation of progenitor cells.

Effects of liver cirrhosis:

1. Portal hypertension caused by:

a. Pressure of the regeneration nodules on the hepatic veins.

b. Development of anastomosis between the branches of the hepatic

artery and portal vein. The higher arterial pressure is transmitted to
the portal vein.

Portal hypertension leads to the following manifestations:

1.Chronic venous congestion of the portal draining area with

gastrointestinal symptoms.

2.Splenomegaly.

3.Ascites

4.Varices of the anastomotic veins between the portal and systemic

circulation:

At the lower end of the esophagus leads to esophageal varices.

At the lower end of the rectum leads to hemorrhoids (piles).

Around the umbilicus leads to caput medusa.

2. Ascites: it is due to

Pathology DHB 2 16
 A. Portal hypertension.
B. Hypo-proteinemia.
C. Sodium and water retention due to hyperaldosteronism.

3. Hypersplenism: It causes anemia, leucopenia and thrombocytopenia.

4. Impaired liver functions:

Hypo-proteinemia.

Decrease estrogen inactivation by the liver results in: gynecomastia,

atrophy of the testis and decrease pubic and axillary hair. Palmer
erythema and arterial spider (dilated vessels on the face, neck and
arms) are also noticed.

Decrease vitamin A formation.

5. Malignancy particularly in macro-nodular cirrhosis.

Hepatocellular Carcinoma
Definition: It is a malignant tumor of hepatocytes.

Clinical Presentation: abdominal mass, ascites, jaundice,

hypoglycemia, hypercholesterolemia, erythrocytosis,
hypercalcemia and elevated A.F.P.
Hypoglycemia: is due to impaired gluconeogenesis: glucose under
production of high level of Insulin growth factor II produced by the tumor

Hypercalcemia: a paraneoplastic syndrome due to release of parathyroid

hormone related protein

Hypercholesterolemia: a paraneoplastic syndrome with associated

genetic mutation in LDL receptors. The abnormal receptor is unable to
bind LDL leading to decrease LDL clearance

Erythrocytosis: a paraneoplastic syndrome with secretion of

erythropoietin

AFP: is a plasma protein produced by yolk sac and fetal liver. Its
measurement in maternal blood screen for Down syndrome and neural

Pathology DHB 2 17
 tube defects. In HCC, AFP is produced by regenerating hepatocytes.

Predisposing factors:
1. Male gender above 50 years

2. Liver cirrhosis specially macro-nodular associated with

hemochromatosis, biliary cirrhosis and α1antitrypsin deficiency

3. Liver cell dysplasia

4. Atypical adenomatous hyperplasia

5. Hepatitis virus B and C.

6. Thorium dioxide (Thorotrast) radioactive exposure.

7. Androgenic anabolic steroid.

8. Heavy alcohol, tobacco use and obesity.

9. Tyrosinemia

10. Ataxia telangiectasia.

11. Aflatoxin: metabolic product of aspergillus flavus.

12. Bilharziasis

Gross picture: It presents as single mass or multiple nodules or

diffuse liver

Microscopic picture:
Classic type Sclerosing type: Sarcomatoid type Fibrolamellar type

Trabecular, solid Like classic type Tumor cells are polygonal cells with
sheets, or tubular but with dense spindle like fibrous stroma and
(pseudo glandular) fibrotic stroma sarcoma cells. oncocytic features.
patterns. Network between tumor It is seen in young
of sinusoidal cells. without cirrhosis
vessels surround and it has a good
the tumor cells. prognosis.
The stroma is Ultrastructure
scanty. examination
reveals numerous
mitochondria and

Pathology DHB 2 18
 Classic type Sclerosing type: Sarcomatoid type Fibrolamellar type
neurosecretory
granules.

Immunohistochemical markers: Tumor cells are positive for

Alpha-fetoprotein (AFP), Keratin and Epithelial membrane
antigen (EMA).

Spread: Early blood spread through sinusoids.

Prognosis:
Better prognosis Poor prognosis

Small size Portal vein invasion

capsulated tumor elevated AFP positivity

single mass multiple masses.

fibrolamellar type and less mitotic count after cirrhosis

Microscopic colitis
Definition: An inflammation of the colon that causes persistent
watery diarrhea. The disorder gets its name because
microscopic examination is necessary for diagnosis, since the
tissue may appear normal with a colonoscopy

Subtypes:
1. Collagenous colitis: in which a thick layer of protein (collagen) develops
in colon tissue

2. Lymphocytic colitis: in which lymphocytes increase in colon tissue

Symptoms:
Chronic watery diarrhea

Abdominal pain

Weight loss

Nausea

Fecal incontinence

Pathology DHB 2 19
 Dehydration

Causes:
Is not clear: dysregulated immune reaction to an unknown luminal
antigen

The causes may include:

Medications: NSAIDs, aspirin and beta blockers

bacteria toxins

viruses that trigger inflammation

autoimmune disease

poorly absorbed bile acid

Risk factors:
Age: 50 to 70 years

Sex: more common in women. an association between post-menopausal

hormone therapy and microscopic colitis

Autoimmune disease: such as celiac disease, thyroid disease,

rheumatoid arthritis, type 1 diabetes or psoriasis

Genetic link: family history of irritable bowel syndrome

Smoking

Lymphocytic colitis Collagenous colitis

- normal colonoscopy or mild

Biopsies from the ascending,
nonspecific erythema or
transverse, descending and
edema
Diagnosis sigmoid colon are recommended
- biopsies from all segments
due to patchy involvement of the
of the colon, proximal to
colon
rectosigmoid

Colonic intraepithelial Colonic sub-epithelial collagen

lymphocytosis (>20 per 100 band ± intraepithelial
Microscopic
enterocytes) with diffuse lymphocytosis, surface mucosal
description
increase in lamina propria damage and lamina propria
inflammatory cells inflammation

Pathology DHB 2 20
Pathology DHB 2 21