‫بسم اهلل الرحمن الرحيم‬

GASTROINTESTINAL TRACT
ESOPHAGUS
Anatomy, physiology & histology
• Esophagus: food moving through laryngopharynx is routed into the esophagus as the
epiglottis closes off the larynx
• esophagus extends about 25 cm from pharynx to stomach; route is through thoracic
cavity posterior to trachea & then piercing diaphragm at esophageal hiatus to extend
into abdominal cavity
• esophagus joins stomach at cardiac orifice
• cardiac (gastroesophageal) sphincter: smooth muscle valve preventing backflow of
food from stomach into esophagus
• heartburn: symptom of gastroesophageal reflux disease (GERD); backflow of acidic
gastric juice from stomach into esophagus
• histology:
– mucosa: nonkeratinized stratified squamous epithelium
– submucosa: contains mucus-secreting esophageal glands
– muscularis externa: shifts from skeletal muscle in superior region to mixed skeletal & smooth
muscle to all smooth muscle in inferior region
– adventitia: fibrous connective tissue replaces serosa of stomach & intestines
Gastro-oesophageal junction
 Congenital oesophageal diseases
• Agenesis: complete absence of oesophagus
• Atresia: non-canalized segment of oesophagus
• Fistula: communication between oesophagus
with trachea or main stem bronchus
• Stenosis: abnormal narrowing of a small
segment of oesophagus
Fistulas
 Motor dysfunctioning lesions
• Achalais: defect in relaxation of oesophageal muscles after propulsive wave of
peristalsis.
• Oesophageal webs: narrowing of upper oesophageal segment (above aortic
arch) due to presence of circumferential mucosal folds. May be associated
with iron deficiency anaemia and hypochlorohydra to form the triad of
Plummer-Vinson syndrome.
• Oesophageal rings: narrowing of lower oesophageal segment (close to
oesophago-gastric junction)due to presence of circumferential mucosal folds.
• Hiatal hernia: gastro-oesophageal junction disorder resulting in herniation of
a part of stomach above diaphragm.
• Mallory- Wiess syndrome: bleeding from tears (a Mallory-Weiss tear) in the
mucosa at the junction of the stomach and oesophagus, usually caused by
severe retching, coughing, or vomiting.
Achalasia
Rings
 INFLAMMATIONS
Causes of oesophagitis:
• The most common cause is gastro-oesophageal reflux disease (reflux
oesophagitis).
• Infections (most commonly candida, herpes simplex and
cytomegalovirus). These infections are typically seen in
immunocomprimized people, such as those with HIV.
• Chemical injury by alkaline or acid solutions may also cause oesophagitis,
and is usually seen in children or in adults who attempt sucide.
• Physical injury resulting from radiation therapy or by nasogasrtric tubes.
• Eosinophilic oesophagitis which is thought to be related to food allergies.
• hyper acidity
 Reflux oesophagitis
Mucosal inflammation
caused by reflux of
gastric acid into the
esophagus. With
increasing severity, may
be associated with
erosions, ulceration and
stricture formation
 Acute oesophagitis
• Acute esophagitis is
manifested here by
increased neutrophils in
the submucosa as well
as neutrophils
infiltrating into the
squamous mucosa at
the right.
• Marked neutrophil
infiltrate can be
found in reflux, as
well as esophagitis of
other etiologies
Candida oesophagitis
 Herpetic oesophagitis
• Rounded, erythematous
ulcerations of the lower
esophagus. Biopsies of
these lesions reveals
intranuclear inclusions
in squamous epithelial
cells indicative of
herpes simplex virus
esophagitis.
 Herpetic oesophagitis
A herpetic ulcer is seen microscopically At high magnification, the squamous
to have a sharp margin. The ulcer base at mucosa at the margin of the herpetic ulcer
the left shows loss of overlying shows pale pink "ground glass" inclusions
squamous epithelium with only necrotic within squamous epithelial cells. Some of
debris remaining the inclusions are clustered together--
multinucleation is another common viral
cytopathic effect
Eosinophilic oesophagitis
 Barrett’s oesophagitis
• Another cause for inflammation is
a so-called "Barrett's esophagus"
in which there is gastric-type
mucosa above the
gastroesophageal junction.

• The columnar epithelium to the

left and the squamous epithelium
at the right. This is "typical"
Barrett's mucosa, because there is
intestinal metaplasia as well (note
the goblet cells in the columnar
mucosa).
 Oesophageal varices
• Oesophageal varices are extremely dilated sub-mucosal veins in the lower
oesophagus. They are most often a consequence of portal hypertension,
commonly due to cirrhosis.
• Patients with oesophageal varices have a strong tendency to develop bleeding.
• Pathogenesis:
The majority of blood from the oesophagus is drained away via the
oesophageal veins, which drain deoxygenated blood from the oesophagus to
the azygus vein which in turn, directly drains into the superior vena cava. These
veins have no part in the development of oesophageal varices. The remaining
blood from the oesophagus is drained away via the superficial veins lining the
oesophageal mucosa, which drain into the left gastric vein which in turn, drains
directly into the portal vein. These superficial veins (normally only
approximately 1mm in diameter) become distended up to 1-2 cm in diameter
in association with portal hypertension
Oesophageal varices
 Tumors of the oesophagus
• Benign oesophageal tumors:
1) mostly C.T. tumors as leiomyoma, fibroma,
lipoma, lymphangiomas -------etc
2) Squamous cell papilloma is rarely seen in
the oesophagus.
Oesophageal squamous cell papilloma
 Malignant oesophageal tumors
Carcinomas: (squamous cell carcinoma or adenocarcinoma)
• About 10% of GIT cancers
• Asymptomatic till late stages
• In adults above 50 years
Causative and risk factors:
A) Squamous cell carcinoma:
1) smoking
2) alcohol
3) Dietary and environmental factors that cause chronic irritation and inflammation of the esophageal
mucosa
4) Predisposing underlying conditions, such as achalasia, esophageal diverticula and webs, Plummer-
Vinson syndrome, and human papillomavirus (HPV) infection
B) Adenocarcinoma:
1) Barrett's esophagus
2) Gastroesophageal reflux disease (GERD)
3) Obesity (by increasing the risk of GERD)
 Stages of oesophageal carcinomas:
The TNM system is based on several key pieces of information:
• T refers to how far the primary tumor has grown into the wall of the esophagus
and into nearby organs.
• N refers to cancer spread to nearby lymph nodes.
• M indicates whether the cancer has metastasized (spread to distant organs).
• G describes the grade of the cancer, which is based on how the patterns of cancer
cells look under a microscope.
 T categories:
• TX: The primary tumor can’t be assessed.
• T0: There is no evidence of a primary tumor.
• Tis: The cancer is only in the epithelium (the top layer of cells lining the
inside of the esophagus). It has not started growing into the deeper layers.
This stage is also known as high-grade dysplasia. In the past it was
called carcinoma in situ.
• T1: The cancer is growing into the tissue under the epithelium, such as the
lamina propria, muscularis mucosa, or submucosa.
T1a: The cancer is growing into the lamina propria or muscularis mucosa
T1b: The cancer has grown through the other layers and into the submucosa
• T2: The cancer is growing into the thick muscle layer (muscularis propria).
• T3: The cancer is growing into the outer layer of the esophagus (the
adventitia).
• T4: The cancer is growing into nearby structures.
T4a: The cancer is growing into the pleura, the pericardium, or the diaphragm.
The cancer can be removed with surgery.
T4b: The cancer cannot be removed with surgery because it has grown into the
trachea, the aorta, the spine, or other crucial structures.
N categories:

• NX: Nearby lymph nodes can’t be assessed.

• N0: The cancer has not spread to nearby lymph nodes.
• N1: The cancer has spread to 1 or 2 nearby lymph nodes.
• N2: The cancer has spread to 3 to 6 nearby lymph nodes.
• N3: The cancer has spread to 7 or more nearby lymph nodes.

M categories:

• M0: The cancer has not spread (metastasized) to distant organs or

lymph nodes.
• M1: The cancer has spread to distant lymph nodes and/or other
organs. (Common sites of spread include the liver and lungs.)
Grade:
The grade of a cancer is based on how normal (or differentiated) the
cells look under the microscope. The higher the grade, the more
abnormal the cells look. Higher grade tumors tend to grow and spread
faster than lower grade tumors.

• GX: The grade cannot be assessed (treated in stage grouping as G1).

• G1: The cells are well-differentiated.
• G2: The cells are moderately differentiated
• G3: The cells are poorly differentiated
• G4: The cells are undifferentiated (these cells are so abnormal that
doctors can’t tell if they are adenocarcinoma or squamous cell
carcinoma).

Location
Some stages of early squamous cell carcinoma also take into account where
the tumor is in the esophagus. The location is assigned as either upper,
middle or lower based on where the upper edge of the tumor is.
Squamous cell carcinoma stages:

• Stage 0: Tis, N0, M0, GX or G1; any location: This is the earliest stage
of esophageal cancer. It is also called high-grade dysplasia.

• Stage IA: T1, N0, M0, GX or G1; any location.

• Stage IB: Either of the following:

 T1, N0, M0, G2 or G3; any location.
 T2 or T3, N0, M0, GX or G1; location lower.

• Stage IIA: Either of the following:

 T2 or T3, N0, M0, GX or G1; location upper or middle.
 T2 or T3, N0, M0, G2 or G3; location lower.

• Stage IIB: Either of the following:

 T2 or T3, N0, M0, G2 or G3; location upper or middle.
 T1 or T2, N1, M0, any G; any location.
• Stage IIIA: Any of the following:
 T1 or T2, N2, M0, any G; any location.
  T3, N1, M0, any G; any location.
 T4a, N0, M0, any G; any location.

• Stage IIIB: T3, N2, M0, any G; any location.

• Stage IIIC: Any of the following:

 T4a, N1 or N2, M0, any G; any location.
 T4b, any N, M0, any G; any location.
 Any T, N3, M0, any G; any location.

• Stage IV: Any T, any N, M1, any G; any location: 

Adenocarcinoma stages
The location of the cancer along the esophagus does not affect the stage of adenocarcinomas.
• Stage 0: Tis, N0, M0, GX or G1.
• Stage IA: T1, N0, M0, GX, G1, or G2.
• Stage IB: Either of the following:
 T1, N0, M0, G3.
 T2, N0, M0, GX, G1, or G2.
• Stage IIA: T2, N0, M0, G3.
• Stage IIB: Either of the following:
 T3, N0, M0, any G.
 T1 or T2, N1, M0, any G.
• Stage IIIA: Any of the following:
 T1 or T2, N2, M0, any G.
 T3, N1, M0, any G.
 T4a, N0, M0, any G.
• Stage IIIB: T3, N2, M0, any G.
• Stage IIIC: Any of the following:
 T4a, N1 or N2, M0, any G.
 T4b, any N, M0, any G.
 Any T, N3, M0, any G.
• Stage IV: Any T, any N, M1, any G.
Fungating oesophageal carcinoma
• Fungating mid-oesophageal sq.C.C. • Ulcerated lower oesophageal
adenocarcinoma
• Invasive oesophageal sq.c.c. • H.P. of high grade oesophageal sq.c.c.
 STOMACH
Anatomy and histology:
Cardia: The gastric pits (GP) are lined with
a simple columnar epithelium devoid of
goblet cells. Cardiac glands (CG) make a
mucous secretion for protection of the
epithelium from erosion. They're located
in the lamina propria, above the
muscularis mucosae (MM).

Fundus: Gastric fundal mucosa, with

short pits lined by pale columnar mucus
cells leading into long glands which
contain bright pink parietal cells that
secrete hydrochloric acid.
pylorus

Gastro-duodenal junction
 Gastric diseases
1) Congenital:
a- diaphragmatic hernia
b- pyloric stenosis
2) Inflammation (gastritis):
a- acute gastritis
b- chronic gastritis
c- hypertrophic gastritis
d- granulomatous gastritis
e- eosinophilic gastritis
3) Peptic ulcers
4) Tumors:
a- bengin as leiomyomas and polyps
b- malignant; carcinomas, lymphomas or sarcomas
 GASTRITIS
• Acute or chronic inflammation of the mucosal layers of the stomach.

• Acute gastritis may be caused by excessive intake of alcohol, ingestion

of irritating drugs, food poisoning, and infectious diseases.
• The ingestion of corrosives (acids, alkalies) causes a severe chemical
gastritis, necessitating immediate emptying and thorough washing of
the stomach.
• The chief symptoms are severe upper-abdominal pain, nausea,
vomiting, loss of appetite, thirst, and diarrhoea; the illness develops
suddenly and subsides rapidly. The only treatment necessary is
temporary avoidance of food, followed by a non-irritating diet,
sedatives, and antispasmodics; rarely, fluids by intravenous injection
may be required.
 Classification of gastritis
• Endoscopic criteria of gastritis: • Classification according to etiology
1. erythematous/exudative gastritis 1. Type A : Autoimmune gastritis - Associated with
pernicious anaemia. Body of the stomach is usually
2. superficially erosive gastritis affected.
3. polypoid gastritis with erosions
4. atrophic gastritis 2. Type B : Environmental gastritis- Result from
dietary or intraluminal factors, specially Helicobacter
5. hemorrhagic gastritis
pylori.  Usually localized in the antrum. In severe
6. bile gastritis cases, the inflammation spreads to the proximal part
7. giant folds gastritis of the stomach.

3. Type C :  Chemical gastritis- Associated with

• Classification according to localisation :
ingestion of non-steroidal  anti-inflammatory drugs or
1. Pangastritis bile influx
2. gastritis of the body
3. antral gastritis 4. distinct forms of gastritis

• Grading: normal, low-, middle-, high- grade

 Histologic variants of gastritis
• atrophic gastritis  chronic gastritis with infiltration of the lamina propria, involving the
entire mucosal thickness, by inflammatory cells.
• catarrhal gastritis  inflammation and hypertrophy of the gastric mucosa, with excessive
secretion of mucus.
• eosinophilic gastritis  that in which there is considerable edema and infiltration of all coats
of the wall of the pyloric antrum by eosinophils.
• erosive gastritis , exfoliative gastritis that in which the gastric surface epithelium is eroded.
• giant hypertrophic gastritis  excessive proliferation of the gastric mucosa, producing diffuse
thickening of the stomach wall.
• hypertrophic gastritis  gastritis with infiltration and enlargement of the glands.
• polypous gastritis  hypertrophic gastritis with polypoid projections of the mucosa.
• pseudomembranous gastritis  that in which a false membrane occurs in patches within the
stomach.
• superficial gastritis  chronic inflammation of the lamina propria, limited to the outer third
of the mucosa in the foveolar area.
 Acute gastritis
• Histopathological features in acute gastritis:
Mild form:
Edema in lamina propria; Slight hyperemia in the interfoveolar area ; Surface epithelium is intact ; Scattered
neutrophils within mucosal epithelial cells (active inflammation).

Acute erosive/hemorrhagic gastritis:

-With more severe mucosal damage, erosion and hemorrhage develops.
-Erosive gastritis are mucosal lesions , which do not penetrate the muscular layer of the mucosa. The erosions present as
lacerations,
-Lesion is acccompanied  by a dense acute inflammatory infiltrate and extrusion of fibrin, containing purulent
exudate into the lumen.
-Deep mucosa (glandular zone) is usually unaffected unless stress ulcer results due to local necrosis.
-Crypts may be dilated & filled with acute inflammatory cells in erosive gastritis.

Healing phase:
Epithelial regeneration ; Elongation of pit ; Pseudostratified appearance of superficial epithelium; Residual
cluster of neurtrophils in the pit .

Regenerative changes include:

Regular glands arranged parallel to one another ; Lamina propria separating the glands ;
Basally located nucleii ; Basophilic cytoplasm ; Increased nuclear cytoplasmic ratio ; Increased mitotic activity.
(be careful not to diagnose malignancy)
Hypertrophic gastritis
• This is a typical gross
picture of acute gastritis
with a diffusely
hyperemic gastric
mucosa.

• Microscopically; gastric
mucosa demonstrates
infiltration by
neutrophils.
Acute erosive gastritissome:
large areas of gastric hemorrhages
because the superficial mucosa is
eroded away

Acute gastric ulcer: A 1 cm acute gastric

ulcer. The ulcer is shallow and sharply
demarcated, with surrounding
hyperemia.
• Acute gastric ulcer
here is sharply
demarcated from
normal gastric
mucosa. Ulcer base
contains abudant
polymorphs and
necrotic debris.
 Autoimmune gastritis
• Also known as Type A gastritis is limited to corpus-fundus mucosa.
-  Patient usually presents with pernicious anaemia.
- Associated with other autoimmune diseases (Hashimoto’s
thyroiditis, Addison’s disease)
-  Diffuse atrophy of parietal and chief cell mass.
-  Hypo or achlorhydria , hypergastrinemia, decreased pepsinogen
levels.
-  Associated with  antibodies to parietal cells, intrinsic factor and
gastrin receptor.
- Cobalamin deficiency  eventually leads  to pernicious anaemia.
- May develop gastric polyps.
- Increased risk of developing gastric carcinoma.
 
• Gross appearance : Pathology located in the gastric corpus.
  Microscopic features: 
   Early stage:  Mononuclear cells consisting of lymphocytes and plasma cells in the
lamina propria.  Usually located around fundic glands and infiltration of the glands by
lymphocytes. Glandular destruction is present. Focal mucous neck cell hyperplasia
   Florid stage:  Parietal and chief cell atrophy. Increased lymphocytic infiltration.
Focal intestinal metaplasia.
   End stage:  Fundic mucosa is completely replaced by pyloric or intestinal glands.
-Other features:
  In patients with pernicious anaemia the superficial gastric epithelium may appear
megaloblastic.
  Focal pancreatic metaplasia is sometimes present.
  G-cell hyperplasia in the antrum
  Hypergastrinaemia leads to hyperplasia of corpus enterochromaffin cells, causing
first linear, then nodular lesions and eventually  multiple microcarcinoids and
carcinoid tumours.
In cases of co-existing helicobacter pylori infection, histological features of both Type
A and Type B gastritis are present.
Mucosa thinned out with
pebbled appearance.
• Autoimmune gastritis. Diffuse
mononuclear infiltrates within the
lamina propria that are heavier in
the deeper, glandular portions (A).
• Patchy lymphocytic infiltrates and
damage to oxyntic glands (B).
• Parietal cell pseudohypertrophy
with "snouting" resulting from
luminal cytoplasmic projections
(C).
• Metaplastic epithelium of the
intestinal (D), pyloric (E), and
pancreatic acinar types (F).
• Linear enterochromaffin cell-like
cell hyperplasia on hematoxylin
and eosin stain (G) and with
chromogranin stain (H).
 Helicobacter-associated gastritis
• H.pylori are Small curved  gram negative bacillus that colonizes the mucus layer of the
stomach.
• Pathogenesis:
1) The organisms adheres to the foveolar epithelium ——→ identify cell surface proteins,
glycoconjugates and helps in colonization.
2) Corkscrew-like  movement along  the lateral border of the foveolar cells ——→ weaken
the mucosal barrier.
3) Production of bacterial enzymes ——→ digest  gastric mucin and further damage the
epithelium.
4) The intracellular space is widened and there is invasion by neutrophil polymorphs.

• Helicobacter associated patterns of gastritis include:

(i) Antral-predominant  gastritis (principal cause of peptic ulcer)
(ii) Multifocal atrophic gastritis involving corpus, fundus and antrum (may develop gastric
ulcer and gastric carcinoma).
H pylori are  also associated with the  development of gastric lymphoma.
Methyline blue stain Steiner stain
• Eosinophilic gastroenteritis
• diffuse eosinophilic gastroenteritis
• Involves distal stomach, proximal
duodenum; may cause pyloric
obstruction;
• Usually idiopathic; associated with
allergies (cow’s milk or soy protein in
infants),
• peripheral eosinophilia in 75%,
• Micro: diffuse, sheet like,
monomorphic infiltration of
eosinophils, may be transmural; also
variable edema,
• DD:  inflammatory fibroid polyp,
lymphoma, carcinoma
• Granulomatous gastritis
• Causes: common variable
immunodeficiency, Crohn’s disease,
foreign body, histoplasmosis,
idiopathic, post-barium studies,
sarcoidosis, tuberculosis, tumors,
vasculitis; rarely Langerhans cell
histiocytosis
• Chronic granulomatous disease:
may present with distinct or poorly
formed granulomas in children
with pigment-laded macrophages;
associated with outlet obstruction,
Lymphocytic gastritis
• Associated with celiac disease, rarely with Helicobacter pylori (HP), with Crohn’s
disease, HIV, lymphoma, esophageal carcinoma, inflammatory polyp
• Endoscopy: normal (low grade) or nodules, erosions and large folds (more severe
disease, aka varioliform gastritis); most severe form may resemble Menetrier’s disease
• Gross: antral (celiac disease) or corpus (H. pylori infection) involvement
• Micro: increased lymphocytes in surface and foveolar epithelium, as well as lamina
propria; 25+ lymphocytes per 100 epithelial cells is minimum; most cases have 30-65
lymphocytes/100 epithelial cells; lymphocytes are small and round without atypia, most
are T cells; may have clear halo (artifact); lymphoepithelial lesions are rare, no active
gland destruction
• Lymphocytes most numerous in varioliform gastritis (large folds due to foveolar
hyperplasia, not considered Menetrier’s disease)
• DD: MALT lymphoma (expanded lamina propria, dense collection of monocytoid cells 
larger than small lymphocytes, may be plasmacytoid, have Dutcher bodies; also
intraepithelial lymphocytes, infiltration of muscularis mucosa; lymphoepithelial lesions
usually contain 3+ cells; often active gland destruction; B cell origin vs. T cell for
lymphocytic gastritis)
PEPTIC ULCER
Benign peptic ulcer
• The arrow marks a small benign
prepyloric ulcer
•The edges are smooth, round and
the sides of the ulcer straight
•The nicely punched out appearance
is typical of benign ulcers
TUMOURS OF THE
STOMACH
Benign Gastric Tumours
• Hyperplastic polyps
There is marked elongation of the pits with
branching, resulting in a corkscrew appearance or
in cystic dilatation of foveolae. Also, there is an
infiltration of lamina propria with plasma cells,
lymphocytes, eosinophils, mast cells, macrophages,
and neutrophils. The gastric glands do not normally
participate in the formation of the polyps. The
surface may be ulcerated and inflamed with
regenerative atypia. There may also be invagination
of the surface mucosa with budding
An example of gastric
hyperplastic polyp showing
a polypoid configuration
with tortuous and
hyperplastic foveolar
epithelium in low
magnification (a). Higher
magnification shows
hyperplastic and tortuous
foveolar epithelium of the
gastric hyperplastic polyp
(b). The lamina propria
shows edematous stroma
and scarce inflammation (c)
and there is focal intestinal
metaplasia without
dysplasia (d).
• Inflammatory fibroid polyps
These polyps are centered on the
submucosa. Small, thin walled
vessels surrounded by spindle cells
are arranged in an "onion-skin"
pattern. CD 34 positive and c-kit
negative
Thick and thin walled blood vessels,
stellate fibroblasts, scattered
lymphocytes and eosinophils. Shown
clearly in the inset view H&E 100.
• Hamartomatous polyps of
the Peutz-Jeghers type:
Gastric mucosa is less
frequently involved than the
small bowel and the colon.
They are composed by
hyperplastic glands
separated by branching cores
of smooth muscle with
atrophy of deep glandular
components. Dysplasia is
very uncommon
• Juvenile polyps
These polyps are very rare and are usually
associated with juvenile polyposis. They are
composed of edematous and inflamed
mucosa with tortuosity of the foveolar zones
and are easily confused with hyperplastic
polyps. There is an association with an
increased risk of cancer.
• Gastric polyps in Cowden Disease
The foveolar glands are enlarged and
elongated. Smooth muscle fibers are
intermingled within the mucosal
components and the cystic structures
extend into the submucosa.
• Gastric polyps in Cronkhite-Canada
syndrome
These polyps are usually associated with
lesions in other parts of the GI tract. They
are indistinguishable from juvenile polyps
and hyperplastic polyps, and they are
diagnosed if in the presence of alopecia,
nail atrophy, or hyperpigmentation
• Fundic gland polyps
These are dilated glands lined by fundic
epithelium mixed with normal glands.
There is usually no inflammation or
atypia, but some disordered muscle
fibers may be seen.
• Adenomatous polyps
• They are composed of tubules or villi of dysplastic
epithelium with some degree of intestinal-type
differentiation. They can be low grade or high grade, based
on the degree of dysplasia. The risk of malignancy is related
to the size, the degree of dysplasia, and the villosity of the
growth pattern. Forty percent to 50% of lesions greater
than 2 cm contain carcinomatous transformation.
gastric adenomatous polyps are usually exophytic lesions composed of
interlacing sheets of irregular tubular epithelium that may form complex
structures with a cribriform architecture (arrows). Cells are crowded in a
disorderly arrangement (inset high-power histological view), often
elongated, with hyperchromatic nuclei and occasional mitoses. Paneth
cells, and rarely oxyntic cells, may be found in various proportions.
• Gastric carcinoids
Gastric carcinoids are very rare, representing less than 0.5%
of gastric neoplasms, and are seen in 3 different settings:
1) autoimmune atrophic gastritis,
2) Zollinger Ellison syndrome, and
3) MEN-1 syndrome,
or they may be seen sporadically.
They are usually broad-based, yellowish polypoid lesions
overlined by normal mucosa.
Chromogranin A is positive, but chromogranin B is usually
negative. Synaptophysin is positive in 50% of cases.
 • Histopathology
• Gross Pathology • Well-differentiated
• Generally: • Cells of diffuse (neuro)endocrine system
– small – several types in normal stomach
– sharply outlined – Predominant growth pattern:
– covered by flattened mucosa1 microglandular
– trabecular
• Occasionally:
– rarely insular
– appearance of gastric polyps
– Nuclei: regular
• ECL-cell Tumor – normochromatic
• Usually multiple – scanty mitoses
• Often polypoid – Vascularization florid Exceptionally, clear
• Throughout fundus cytoplasm.
• G-cell Tumor – Usually no necrosis
– Ultrastructurally: dense-core secretory
• Usually: granules: in cytoplasm, usually abundant
– solitary
– ECL-cell Tumor
– in antrum
– Various types of smooth muscle
proliferation:
– possibly due to production of basic
fibroblastic growth factor
• Special Stains and Immunohistochemistry
• Consistent positivity for:
– neuron-specific enolase
– chromogranin
– synaptophysin
– keratin
• May be focal mucin positivity
• ECL-cell Tumor
• Non-argentaffin
• Strongly argyrophilic
• Diffuse hyperplasia of similar argyrophilic cells in surrounding mucosa
• Nonreactive for standard gastroduodenopancreatic hormones No peptide secretory product
yet identified, but cells store histamine
• G-cell Tumor
• Non-argentaffin
• Non-argyrophilic
• Immunoreactive for gastrin
 Stomach cancer
What causes stomach cancer?  
 
The major risk factors for stomach cancer are listed below:
• Bacteria infection: Helicobacter pylori may be a major cause of stomach cancer. Long-term infection can lead to
inflammation and damage to the inner layer of the stomach, a possible pre-cancerous change. This bacterium is also
linked to some types of lymphoma of the stomach.
• Diet: smoked foods, salted fish and meats, and pickled vegetables. On the other hand, eating whole grain products
and fresh fruits and vegetables that contain vitamins A and C appears to lower the risk of stomach cancer.
• Tobacco and alcohol abuse.
• Obesity.
• Earlier stomach surgery.
• Pernicious anemia.
• Menetrier disease.
• Gender: Stomach cancer is more common in men than it is in women.
• Age: There is a sharp increase in stomach cancer after the age of 50.
• Type A blood: For unknown reasons, people with type A blood have a higher risk of getting stomach cancer.
• Family history.
• Stomach polyps: mainly adenomatous polyps
• Epstein-Barr virus: This virus causes “mono” (infectious mononucleosis). It has been found in the stomach cancers of
some people.
 These are the stages of stomach cancer: (TNM)

• TX: The main (primary) tumor cannot be assessed.

• T0: No signs of a main tumor can be found.
• Tis: Cancer cells are only in the top layer of cells of the mucosa (innermost layer of the stomach) and have
not grown into deeper layers of tissue such as the lamina propria or muscularis mucosa. This stage is also
known as carcinoma in situ.
• T1: The tumor has grown from the top layer of cells of the mucosa into the next layers below such as the
lamina propria, the muscularis mucosa, or submucosa:
 T1a: The tumor is growing into the lamina propria or muscularis mucosa.
 T1b: The tumor has grown through the lamina propria and muscularis mucosa and into the
submucosa.
• T2: The tumor is growing into the muscularis propria layer.
• T3: The tumor is growing into the subserosa layer.
• T4: The tumor has grown into the serosa and may be growing into a nearby organ (spleen, intestines,
pancreas, kidney, etc.) or other structures such as major blood vessels.
 T4a: The tumor has grown through the stomach wall into the serosa, but the cancer hasn’t grown
into any of the nearby organs or structures.
 T4b: The tumor has grown through the stomach wall and into nearby organs or structures.
N categories of stomach cancer
NX: Nearby (regional) lymph nodes cannot be assessed.
N0: No spread to nearby lymph nodes.
N1: The cancer has spread to 1 to 2 nearby lymph nodes.
N2: The cancer has spread to 3 to 6 nearby lymph nodes.
N3: The cancer has spread 7 or more nearby lymph nodes.
N3a: The cancer has spread to 7 to 15 nearby lymph nodes.
N3b: The cancer has spread to 16 or more nearby lymph nodes.

M categories of stomach cancer

M0: No distant metastasis (the cancer has not spread to distant organs or
sites, such as the liver, lungs, or brain).
M1: Distant metastasis (the cancer has spread to organs or lymph nodes
far away from the stomach).
TNM stage grouping
Stage 0: Tis, N0, M0
This is stomach cancer in its earliest stage. It has not grown beyond the inner layer of cells that
line the stomach (Tis). The cancer has not spread to any lymph nodes (N0) or anywhere else
(M0). This stage is also known ascarcinoma in situ.
Stage IA: T1, N0, M0
The cancer has grown beneath the top layer of cells in the mucosa into tissue below, such as the
connective tissue (lamina propria), the thin muscle layer (muscularis mucosa), or the submucosa
(T1). The cancer has not spread to any lymph nodes (N0) or anywhere else (M0).
Stage IB: Any of the following:
T1, N1, M0: The cancer has grown into the layer of connective tissue (lamina propria), and
may have grown into the thin layer of muscle beneath it (muscularis mucosa) or deeper into the
submucosa (T1). Cancer has also spread to 1 or 2 lymph nodes near the stomach (N1), but not to
any distant tissues or organs (M0).
OR
T2, N0, M0: The cancer has grown into the main muscle layer of the stomach wall, called
the muscularis propria (T2). It has not spread to nearby lymph nodes (N0) or to any distant
tissues or organs (M0).
Stage IIA: Any of the following:

T1, N2, M0: The cancer has grown beneath the top layer of cells of the mucosa into the
layer of connective tissue (lamina propria), thin muscle layer (muscularis mucosa), or the
submucosa (T1). It has spread to 3 to 6 nearby lymph nodes (N2). It has not spread to distant
sites (M0).

OR
T2, N1, M0: The cancer has grown into the main muscle layer of the stomach called the
muscularis propria (T2). It has spread to 1 or 2 nearby lymph nodes (N1), but has not spread to
distant sites (M0).

OR
T3, N0, M0: The cancer has grown through the main muscle layer into the subserosa, but
has not grown through all the layers to the outside the stomach (T3). It has not spread to any
nearby lymph nodes (N0) or to distant tissues or organs (M0).
Stage IIB: Any of the following:

T1, N3, M0: The cancer has grown beneath the top layer of cells of the mucosa into the
layer of connective tissue (lamina propria), the thin muscle layer, or the submucosa (T1). It
has spread to 7 or more nearby lymph nodes (N3). It has not spread to distant tissues or
organs (M0).
OR
T2, N2, M0: The cancer has grown into the main muscle layer, called the muscularis
propria (T2). It has spread to 3 to 6 nearby lymph nodes (N2), but it has not spread to distant
tissues or organs (M0).
OR
T3, N1, M0: The cancer has grown into the subserosa layer, but not through all the layers
to the outside of the stomach (T3). It has spread to 1 or 2 nearby lymph nodes (N1), but has
not spread to distant tissues or organs (M0).
OR
T4a, N0, M0: The cancer has grown completely through all the layers of stomach wall
into the outer covering of the stomach (the serosa), but it has not grown into nearby organs
or tissues, such as the spleen, intestines, kidneys, or pancreas (T4a). It has not spread to any
nearby lymph nodes (N0) or distant sites (M0).
Stage IIIA: Any of the following:

T2, N3, M0: The cancer has grown into the main muscle layer, called the muscularis
propria (T2). It has spread to 7 or more nearby lymph nodes (N3), but has not spread to
distant tissues or organs (M0).

OR
T3, N2, M0: The cancer has grown into the subserosa layer, but not through all the layers
to the outside of the stomach (T3). It has spread to 3 to 6 nearby lymph nodes (N2), but it
has not spread to distant tissues or organs (M0).

OR
T4a, N1, M0: The cancer has grown completely through all the layers of the stomach
wall into the outer covering of the stomach (the serosa), but it has not grown into nearby
organs or tissues (T4a). It has spread to 1 or 2 nearby lymph nodes (N1), but it has not
spread to distant sites (M0).
Stage IIIB: Any of the following:

T3, N3, M0: The cancer has grown into the subserosa layer, but not through all the layers
to the outside of the stomach (T3). It has spread to 7 or more nearby lymph nodes (N2), but
it has not spread to distant sites (M0).

OR
T4a, N2, M0: The cancer has grown completely through all the layers of the stomach wall
into the serosa (the outer covering of the stomach), but it has not grown into nearby organs
or tissues (T4a). It has spread to 3 to 6 nearby lymph nodes (N2), but it has not spread to
distant sites (M0).

OR
T4b, N0 or N1, M0: The cancer has grown through the stomach wall and into nearby
organs or structures such as the spleen, intestines, liver, pancreas, or major blood vessels
(T4b). It may also have spread to up to 2 nearby lymph nodes (N0 or N1). It has not spread to
distant sites (M0).
Stage IIIC: Any of the following:

T4a, N3, M0: The cancer has grown completely through all the layers of the stomach wall
into the serosa, but it has not grown into nearby organs or tissues (T4a). It has spread to 7 or
more nearby lymph nodes (N3), but it has not spread to distant sites (M0).

OR
T4b, N2 or N3, M0: The cancer has grown through the stomach wall and into nearby
organs or structures such as the spleen, intestines, liver, pancreas, or major blood vessels
(T4b). It has spread to 3 or more nearby lymph nodes (N2 or N3). It has not spread to distant
sites (M0).

Stage IV: Any T, any N, M1

The cancer has spread to distant organs such as the liver, lungs, brain, or
bones (M1).
• Gross appearances:
1) ulcerated lesion
2) exophyytic or polypoid lesion
3) diffuse infilterative lesion (linitis plastica)
4) submucosal lesion
 Histopathology
• Gastric adenocarcinoma: is a malignant epithelial tumor, originating from
glandular epithelium of the gastric mucosa.
• Histologically, there are two major types of gastric adenocarcinoma (Lauren
classification): intestinal type or diffuse type.
a) Intestinal type adenocarcinoma tumor cells describe irregular tubular
structures, harboring pluristratification, multiple lumens, reduced stroma ("back
to back" aspect). Often, it associates intestinal metaplasia in neighboring
mucosa. Depending on glandular architecture, cellular pleomorphism and
mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well,
moderate and poorly differentiate.
b) Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica, leather-bottle
stomach) Tumor cells are discohesive and secrete mucus which is delivered in
the interstitium producing large pools. It is poorly differentiated. If the mucus
remains inside the tumor cell, it pushes the nucleus at the periphery. “signet-ring
cells".
• Around 5% of gastric carcinomas are lymphomas (MALT lymphoma)
• Carcinoid and stromal tumors may also occur.
• A suspicious gastric ulcer that was diagnosed as cancer on
biopsy and resected.
• Endoscopic image of linitis
plastica, the entire stomach
is invaded, leading to a
leather bottle-like
appearance with blood
coming out of it.
Poor to moderately differentiated
adenocarcinoma of the stomach

Adenocarcinoma of the stomach and

intestinal metaplasia
 Metastatic signet cell carcinoma

Gastric signet cell carcinoma

 Mucosal associated lymphomatous tissue
(MALT) tumours
• H. pylori infection stimulates the production of lymphoid
infiltrates, which leads to the formation of acquired mucosa-
associated lymphoid tissue (MALT) in the gastric mucosa. As a
result of both direct and indirect immunological stimulation
(by auto-antigens and Helicobacter-pylori-specific T cells,
respectively), infiltrating B-cells actively proliferate and
occasionally undergo malignant transformation because of
the acquisition of genetic abnormalities.
• A low power view of a
gastric maltoma. A clue
to the malignant nature
of this lymphoid infiltrate
is its density and extent.
Focally the glands are invaded and
destroyed by the lymphoid cells to
produce a lymphoepithelial lesion, as
seen here in the center. These lesions
are particularly common in gastric
maltomas.

A higher power, note that most of the

cells are about the size of benign small
lymphocytes. Nuclear contour varies from
oval to irregular to occasionally cleaved.
Some cells in some cases may have
modest amounts of cytoplasm keeping
the nuclei are arm's length from each
other. Such cells may be called
"monocytoid".
 Gastrointestinal stromal tumour
(GIST)
Gastrointestinal stromal tumors (GISTs) are mesenchymal
neoplasms of the gastrointestinal (GI) tract and are thought to
develop from the interstitial cells of Cajal, innervated cells
associated with the Auerbach plexus.
GISTs are typically defined by the expression of c-KIT (CD117)
in the tumor cells, as these activating KIT mutations are seen
in 85-95% of GISTs. About 3-5% of the remainder of KIT -
negative GISTs contain PDGFR alpha mutations.
This is an endoscopic picture of gastric GITS.
Note the submucosal tumor mass with the
classic features of central umbilication and
ulceration.

Endoscopic picture of GITS in small intestine

with secondary haemorrage
• Photograph of the representative
findings of gastrointestinal stromal
tumors. (A) Epithelioid type GIST. (B)
Spindle cell type GIST. (C) Mixed
epithelioid and spindle cell type
GIST. (D) hyaline changes observed
in GIST. (E) Myxoid changed observes
in GIST. (F) Ischemic tumor necrosis
observed in GIST. (G) Mucosal
invasion observed in the small
intestinal mucosa. (H) Skeinoid fibers
observed in the small intestinal GIST.
(I) Paraganglioma-like patterns
observed in the small intestinal GIST.
GOOD LUCK

Dr. Ashgan El-Sarha