Pathology of

the Stomach
Aiman Zaher, MD

Objectives
At the end of this segment, when given a
clinical presentation, gross specimen and/or
photomicrograph, students will be able to:
Compare and contrast the clinical presentations,
etiologies, pathogenesis, gross and microscopic
changes found in developmental, inflammatory,
circulatory, mechanical, and neoplastic disorders
of the stomach.

Objectives
At the end of this segment, when given a
clinical presentation, gross specimen and/or
photomicrograph, students will be able to:
Predict the clinical complications associated with
diseases of the stomach.
Define the words in the glossary.

Glossary

Acute gastric ulceration

Excavated
Exophytic
Helicobacter pylori
Hypertrophic gastropathy
Linitis plastica

Peptic ulcers
Phytobezoars
Pyloric stenosis
Rugae
Trichobezoars
Ulcers in cancer

Normal Anatomy

Robbins
7th Edition,
Fig. 17-12a

Rugae = longitudinal
infoldings of both mucosa
and submucosa on the
inner surface of the
stomach
Gastric wall comprised of a
mucosa, submucosa,
muscularis propria, and
serosa

Congenital
Anomalies

Congenital Anomalies
Heterotopic rests
Pancreatic rests located in the pylorus become
inflamed leading to obstruction
Gastric rests in duodenum or more distal sites
undergo peptic ulceration, leading to bleeding
Gastric rests in upper esophagus lead to
inflammation and discomfort

Diaphragmatic hernia
Results from defective closure of the diaphragm,
usually on the left
May be asymptomatic or cause respiratory
problems for newborns

Congenital Anomalies
Pyloric Stenosis (Congenital Hypertrophic Pyloric Stenosis)
Incidence 1/300-900 live births
M:F = 3-4:1
May be associated with Turner Syndrome, Trisomy 18
and esophageal atresia
Presents as regurgitation and persistent projectile
vomiting at 2-3 weeks of age
Results from hypertrophy and possibly hyperplasia of
muscularis propria of pylorus
(Pyloric stenosis can also be acquired in adults as a
complication of antral gastritis, peptic ulcer, carcinoma,
or prolonged pyloric spasm.)

Pyloric Stenosis
-Morphology

PJ Goldblatt, MD

Hypertrophy of
Muscularis Propria

Inflammatory
Diseases

Gastritis
Definition
Inflammation of the gastric mucosa
Histologic diagnosis!

Often clinically overused term and, at the

same time, under diagnosed
Most patients with chronic gastritis are
asymptomatic.

Acute Gastritis
Definition
An acute mucosal inflammatory process, with
neutrophilic infiltrate, that is usually transient.
There may be hemorrhage into the mucosa or
sloughing of the mucosa.
Severe erosive form is an important cause of
severe GI bleeding

Acute Gastritis
Etiology
Frequently associated with, among others:

heavy use of NSAIDS, especially aspirin

excessive alcohol consumption
heavy smoking
severe stress e.g. trauma, burns, surgery
Ischemia
Systemic infection

Often, idiopathic

Acute Gastritis Pathogenesis

In concert or
individually

Acid secretion +
+ back diffusion

Bicarbonate
buffer
+

Direct
Mucosal
Injury

Disruption
of
Mucus layer

Acute Gastritis

Blood flow

Acute Gastritis - Morphology

Ranges from edema with neutrophil infiltration, vascular congestion, and an
intact epithelium, to erosion (mucosal defect that does not cross the muscularis
mucosa) and hemorrhage.

PJ Goldblatt, MD

Acute Gastritis - Morphology

PJ Goldblatt, MD

PJ Goldblatt,
MD

Acute Gastritis
Clinical Features
broad range of signs and symptoms that depend on the
severity of the the condition
Asymptomatic
Epigastric pain, nausea & vomiting
Hemorrhage, massive hematemesis, melena, or fatal blood loss

One of the major causes of massive hematemesis,

particularly in alcoholics.
~25% patients taking aspirin for rheumatoid arthritis will
develop acute gastritis, and some will bleed

Chronic Gastritis
Definition
Chronic mucosal inflammatory changes leading to
atrophy and metaplasia (usually without erosions)

Dysplasia and ultimate neoplasia are

complications.

Chronic Gastritis
Etiology
Many causes but two important types:
90% of patients with antral chronic gastritis:
Helicobacter pylori infected
Motile, gram negative curvilinear rods that elaborate
urease (buffers gastric acid) & toxins and have adhesins
to bind to the epithelium
Colonization rate increases with age: 50% of adults over
50 in the US

Autoimmune - antibodies to parietal cells, gastrin

receptor, intrinsic factor, and H+,K+ ATPase
<10% of cases of chronic gastritis
Possible autosomal dominant inheritance

Chronic Gastritis
Pathogenesis
H. pylori (urease NH4+ + toxins) + Host (acid + peptic
enzymes) Chronic Inflammation
Antibodies Gland destruction + Mucosal atrophy
acid intrinsic factor (which can lead to pernicious
anemia)

Chronic Gastritis
Morphology

Varying degrees of mucosal damage possible

Mucosal lesions are reddened, with thickened rugae
Atrophied rugae in long-standing cases
Lymphocytes and plasma cell infiltrate; neutrophils
indicate active inflammation (may or may not be present)
Regeneration - constant feature
Metaplasia - mucosa of antral and body-fundic regions
converts to columnar absorptive cells and goblet cells
(intestinal metaplasia)
Atrophy - marked loss of glands
Dysplasia precursor lesion to gastric cancer in atrophic
gastritis

H. pylori Gastritis - Morphology

H. pylori organisms along

superficial mucus layer of
antral biopsy
Web Path

Autoimmune Gastritis -Morphology

Diffuse mucosal damage of the body and fundic
mucosa. Antrum less involved.

PJ Goldblatt, MD

Chronic Gastritis
Clinical Features
Usually only a few symptoms: nausea, vomiting,
upper abdominal discomfort
H. pylori
Most infected person have gastritis, but are
asymptomatic
Hypochlorhydria, but NOT achlorhydria and pernicious
anemia (parietal cells never completely destroyed)
Gastrin normal to slightly elevated
Antibiotics are treatment of choice

Autoimmune Form
Hypo to achlorhydria (severe loss of parietal glands)
Hypergastrinemia
10% have pernicious anemia

Chronic Gastritis
Clinical Complications
H. pylori
H. pylori predisposes to peptic ulcers in duodenum and
stomachMost patients with a peptic ulcer are infected.
Risk of gastric carcinoma and lymphoma

Autoimmune Form
Often seen in association with other autoimmune
disorders (Hashimoto thyroiditis, Addison disease, and
type I diabetes)
Significant risk for the development of gastric
carcinoma (2-4%) and endocrine tumors (carcinoid
tumor)

Peptic Ulcers
Definition
A breach in the mucosa that extends into the
submucosa or deeper.
Chronic relapsing and solitary lesions, <4 cm
diameter (except in Zollinger-Ellison Syndrome)

Location
Can occur anywhere in the GI tract where there is
exposure to acid/peptic juices, but most common
in the duodenum and stomach

Peptic Ulcers
About 10% of American men and 4%
American women will develop them.
Diagnosed middle-aged to older adults.
M:F; gastric 1.5-2:1; Duodenal 3:1; women
after menopause.
Recently, decreased incidence of duodenal
ulcers for unknown reasons, but not gastric
ulcers

Peptic Ulcers
Etiology and Pathogenesis
Appear to be produced by imbalances between
the gastroduodenal mucosal defense mechanisms
and the damaging forces of gastric acid and
pepsin.
Hyperacidity is not a pre-requisite since only a
minority have it with duodenal ulcers, and even
fewer with gastric ulcers
Ulceration occurs when
mucosal blood flow decreased
gastric emptying is delayed
epithelial restitution is impaired

Peptic Ulcers - Pathogenesis

H. pylori
Only 10-20% of infected individuals develop ulcers
Present in virtually all duodenal and 70% of
gastric ulcers
Even without invading the tissue, this organism
causes intense inflammatory and immune
responses

Peptic Ulcers - Pathogenesis

Robbins
7th Edition,
Fig 17-7

Peptic Ulcers - Morphology

Vast majority located in proximal duodenum or the
lesser curvature of the stomach
10-20% of people with a gastric ulcer also have a
duodenal ulcer
If < 0.3cm, they are most often erosions, > 0.6cm
usually ulcers
Chronic gastritis & H. pylori infection almost universal
Classic appearance is a round to oval, sharply
punched-out defect with straight walls and a smooth
base
Active ulcers histologically have:

thin layer of necrotic debris with fibrin

neutrophils below
monocytes and granulation tissue below that
solid fibrous scar

Peptic Ulcers - Morphology

Chronic
Gastritis

GRIPE

Peptic Ulcers - Morphology

GRIPE

Peptic Ulcers - Morphology

GRIPE

Peptic Ulcers

Clinical Features

Epigastric gnawing, burning or aching pain

Can present with iron-deficiency anemia, frank hemorrhage,
or perforation
Worse at night and 1-3 hours after eating
Relieved by food or antacids most of time
Other signs include belching, nausea, vomiting, chest pain
boring to the back (with perforation)
Chronic, recurring lesions that impair quality of life
Untreated can take an average of 15 years to heal versus a
few weeks w/ treatment
Malignant transformation does NOT occur with duodenal
ulcers and rare with gastric ulcers
Complications include bleeding, perforation, and obstruction
from edema and scarring

Zollinger-Ellison Syndrome
Multiple peptic ulcerations in the stomach,
duodenum, and jejunum
Due to excess gastrin secretion by a tumor
(gastrinoma), leading to excess gastric acid
production

Acute Gastric Ulceration

Definition
Multiple lesions in stomach and occasionally the
duodenum that range from erosions to ulcerations
The erosions are extensions of acute gastritis
The deeper lesions are well-defined ulcers, but are
NOT precursors to chronic peptic ulcers

Acute Gastric Ulceration

Etiology
NSAIDS or severe physiologic stress (stress
ulcers; shock, burns, sepsis, and severe trauma)
Curling ulcers = asstd w/ severe burns or trauma;
occur in proximal duodenum
Cushing ulcers = asstd w/ intracranial injury,
operations or tumors; occur in stomach,
duodenum, and esophagus; high incidence of
perforation

Pathogenesis - similar to acute gastritis

NSAIDS inhibit cyclooxygenase and
prostaglandins
Intracranial injury directly stimulate vagus nuclei,
leading to increased acid production

Acute Gastric Ulceration Morphology

Usually <1 cm, multiple circular lesions found anywhere in the stomach and duodenum

Acute Gastric Ulceration

Complications
Must remove underlying condition for healing to occur
Mucosa can recover completely in this case

Most critically ill patients admitted to ICU acutely develop

histologic evidence of gastric mucosal damage
1-4% will bleed and require transfusion

Mechanical

Gastric Dilation
Etiology and Pathogenesis
Outlet obstruction
pyloric stenosis
paralytic ileus
intralumenal concretions e.g. bezoars

Stomach may hold up to 10-15 liters of fluid, leading to

rupture
Stomach is the primary site for development of luminal
concretions of indigestible ingested material
Phytobezoars = concretions of plant matter
Trichobezoars = AKA hairballs
Bizarre bezoars associated with illicit drug takers, glue
swallowers, and neuropsychiatric patients (pins, nails, razor
blades, etc.)

Trichobezoar

Other bezoars
PJ Goldblatt, MD

Hypertrophic Gastropathy
Definition
Characterized by cerebriform enlargement of the
gastric rugal folds
Caused by mucosal epithelial hyperplasia, without
inflammation

These conditions may mimic infiltrative

carcinoma or lymphoma on examination
Excess acid secretion associated with these
disorders predisposes to peptic ulcers

Hypertrophic Gastropathy
Types
Mntriers disease:
occurs in males in the 4th-6th decades
hyperplasia of mucous cells, with atrophy of glands
gastric secretions contain excessive mucus and little acid
protein loss hypoproteinemia (protein-losing
gastropathy)

Hypertrophic-hypersecretory gastropathy:
hyperplasia of parietal and chief cells in gastric glands

Gastric Gland Hyperplasia:

secondary to excessive gastrin secretion from
gastrinoma (Zollinger-Ellison Syndrome)

Parietal cell hypertrophy without excess acid seen

in chronic use of acid secretion inhibitors

Morphology

PJ Goldblatt, MD

Neoplasms

Benign Processes
Hyperplasic Polyps
Mucosal masses that project above the level of
the surrounding mucosa, single or multiple
Majority in patients with achlorhydria, atrophic
gastritis and pernicious anemia
Most often seen with chronic gastritis
No malignant potential

Benign Processes
Adenomas
True neoplasms with proliferative dysplastic
epithelium
Have malignant potential
Usually single and in the antrum
Sessile or pedunculated
Incidence goes up with age, especially the 70s
M:F 2:1
40% have malignant foci when removed and risk of
malignancy in adjacent mucosa as high as 30%
Associated with chronic gastritis with intestinal
metaplasia and autoimmune gastritis

Hyperplastic and adenomatous polyps

cannot be differentiated endoscopically
they must be biopsed!

Gastric Carcinoma
Epidemiology
90-95% of malignant tumors of the stomach are
carcinoma
Second most common tumor in the world
Incidence particularly high in Japan, parts of South
America, China, Portugal, Russia, and Bulgaria; but 4-6X
less common in the US, UK, Canada, Australia

Lower socioeconomic groups

M:F = 2:1
Incidence has declined in most countries
2.5% of all cancer deaths in U.S. and leading
cause of cancer death worldwide
5 year survival = < 20% in the US

Gastric Carcinoma
Risk Factors
Environmental: Nitrites (from food preservatives),
smoked and salted foods, pickled vegetables,
deficiency of fresh fruits and vegetables, cigarette
smoking
Host Factors: chronic atrophic gastritis,
adenomatous polyps, partial gastrectomy and H.
pylori infection (risk increased 5-6X)
Genetic Factors: more common in persons with
blood group A, family history of gastric cancer

Gastric Carcinoma
Classification
Depth of Invasion
Greatest impact on clinical outcome
Early form confined to mucosa and submucosa. Good
prognosis (90-95% 5-year survival rate with surgical
treatment)
Advanced form has extended into muscular wall.
Spread is by local invasion, lymphatics, blood (to liver
and lungs) and trans-celomic. Bad Prognosis (<15% 5year survival)

Gastric Carcinoma
Classification
According to Macroscopic Growth Pattern:
Present in both early and advanced forms

Exophytic = mass protrudes into lumen

Flat/depressed = no obvious tumor mass
Excavated (Ulcerative) = shallow or deeply erosive crater
Linitus Plastica = broad portion of gastric wall or entire
stomach is extensively infiltrated with malignancy, creating
a rigid, thickened appearance like a leather bottle

According to Histologic Pattern

Intestinal type: glandular, expansile growth pattern
Predominates in high-risk areas and develops from
precursor lesions

Gastric type: infiltrating pattern of poorly differentiated

cells; signet ring conformation = mucin expansion in
cells puts nuclei at the periphery
Incidence the same everywhere and no known precursor
lesion

Gastric Carcinoma
Location
Curvatures
40% - Lesser Curvature
12% - Greater Curvature

Other
50-60% - Pylorus and Antrum
25% - Cardia
Remander Body and Fundus

Early Gastric Carcinoma

Defined as being confined to the mucosa and submucosa
regardless of lymph node metastasis

Early Gastric Carcinoma

Advanced Gastric Carcinoma

Late Gastric Carcinoma

Defined as extending below the submucosa into muscle
regardless of lymph node metastasis
Robbins 6

th

Edition

Gastric Carcinoma - Morphology

Exophytic Growth Pattern

GRIPE

Gastric Carcinoma - Morphology

GRIPE

Gastric Carcinoma - Morphology

Excavated Growth Pattern:

Heaped-up, beaded margins
and necrotic base
differentiate this cancer from
chronic peptic ulcer

GRIPE

Intestinal Variant - Morphology

Composed of glands
resembling colonic
adenocarcinoma

Web Path

Intestinal Variant - Morphology

Web Path

Diffuse Variant - Morphology

Gastric-type mucus cells
that dont form glands,
but rather permeate the
wall as individual cells or
clusters

Web Path

Diffuse Variant - Morphology

Web Path

Signet Ring Cells - Morphology

Web Path

Gastric Carcinoma
Clinical Features
Insidious disease
Asymptomatic until late in the course
Weight loss, abdominal pain, anorexia, vomiting, altered
bowel habits
Sometimes dysphagia, anemia, and hemorrhage
Early detection important
Japan uses endoscopic screening programs, resulting in 35% of
newly diagnosed gastric carcinoma being found in an early stage
US & Europe only catch 10-15% in the early stage

Gastric Carcinoma
Clinical Complications
Local invasion of pancreas, duodenum, and
retroperitoneum
At death, peritoneum seeded and mets to liver and lungs
common.
Metastasis to regional and distant nodes
Frequently mets to Virchows node (supraclavicular node) as
the first clinical manifestation

Mets to Ovaries = Krukenberg Tumors

Prognosis
Determined by depth of penetration and extent of nodal
involvement, not histology
Surgical resection w/ or w/out adjuvant chemotherapy
and radiation

Other Gastric Neoplasms

Less common gastric tumors
Lymphomas (5%); but the stomach is the most common
site for extranodal lymphoma (20%)
GI stromal tumors
Neuroendocrine cell tumorsCarcinoids (rare)
Lipomas
Metastatic cancers (unusual)

References
Kumar, Abbas, & Fausto: ROBBINS & COTRAN
PATHOLOGIC BASIS OF DISEASE, 7th Edition,
pp. 810-827.