Stomach Pathology

Lisa Stevens, D.O.

 Gastropathy Versus Gastritis
Gastritis: mucosal inflammatory process
Neutrophils = acute gastritis
Gastropathy: Absent/rare inflammatory cells
NSAIDs, alcohol, bile, and stress induced injury
Acute mucosal erosion or hemorrhage (Curling
ulcers)
Hypertrophic gastropathy
Mntrier disease
Zollinger-Ellison Syndrome
 Morphology of Gastropathy
Moderate edema of the lamina propria
Slight vascular congestion
Intact surface epithelium is intact
Foveolar cell hyperplasia
Corkscrew glands
Epithelial proliferation
 Morphology of Gastritis
Neutrophils above the basement membrane
Direct contact with epithelial cells
Active inflammation (instead of acute)
Erosion
Loss of the epithelium
Superficial mucosal defect
Pronounced mucosal neutrophilic infiltrate
Fibrin-containing purulent exudate in the lumen
Hemorrhage
Acute erosive hemorrhagic gastritis
Concurrent erosion and hemorrhage
 Stress-Related Mucosal Disease
Severe trauma
Extensive burns
Intracranial disease
Major surgery
More than 75% of critically ill patients
Endoscopically visible gastric lesions during the first 3 days of
their illness
Stress ulcers: Shock, sepsis, or severe trauma
Curling ulcers: Proximal duodenum; severe burns or trauma
Cushing ulcers: Gastric, duodenal, and esophageal ulcers;
intracranial disease
 Stress-Related Mucosal Disease
Pathogenesis
Related to local ischemia
Systemic hypotension
Reduced blood flow
Intracranial injury lesions
Direct stimulation of vagal nuclei
Hypersecretion of gastric acid
Systemic acidosis
 Stress-Related Mucosal Disease
Morphology
Shallow erosions
Acute ulcers
Rounded and less than 1 cm in diameter
Ulcer base
Stained brown to black by acid digestion of
extravasated blood
May be associated with transmural inflammation and local
serositis
Found anywhere in the stomach
Multiple
 Stress-Related Mucosal Disease
Morphology
Microscopic findings
Sharply demarcated
Normal adjacent mucosa
Suffusion of blood
Mucosa and submucosa
Inflammatory reaction
 Gastric Bleeding
Non-stress related
Dieulafoy lesion
Submucosal artery that does not branch properly within the wall of
the stomach
Most commonly found along the lesser curvature near GEJ
Erosion of the overlying epithelium---gastric bleeding
Associated with NSAID use
GAVE (gastric antral vascular ectasia)
Longitudinal stripes of edematous erythematous mucosa
Ectatic mucosal vessels
Paler mucosa
Watermelon stomach
Reactive gastropathy with dilated capillaries containing fibrin thrombi
Idiopathic
Cirrhosis and systemic sclerosis
 Chronic Gastritis
Most common cause
Infection with the bacillus H. pylori
Most common cause without infection:
Autoimmune gastritis (will see lymphocytes)
Longstanding H. pylori infection
Atrophic gastritis
Symptoms less severe but more persistent
Nausea and upper abdominal pain
 Chronic Gastritis
Helicobacter pylori Gastritis
Spiral-shaped or curved bacilli
Gastric biopsy specimens
Patients with duodenal or gastric ulcers
Chronic gastritis
H. pylori organisms
Present in 90% of individuals with chronic gastritis
of antrum
 Chronic Gastritis
Helicobacter pylori Gastritis
Associated with:
Poverty, household crowding, limited education
African American or Mexican American ethnicity
Residence in rural areas
Birth outside of the United States
Humans are the primary carriers
Fecal-oral route
 Chronic Gastritis
Helicobacter pylori Gastritis
Gastric biopsy specimens
H. pylori in infected individuals
Concentrated within the superficial mucus
Organisms demonstrated with special stains
Antral biopsy is preferred
 Chronic Gastritis
Helicobacter pylori Gastritis
Inflammatory infiltrate
Neutrophils within the lamina propria
Intraepithelial location
Accumulation in lumen of gastric pits--pit abscesses
Superficial lamina propria
Large numbers of plasma cells
Increased numbers of lymphocytes and macrophages
Intraepithelial neutrophils and subepithelial plasma cells
Mucosa-associated lymphoid tissue (MALT)
Potential to transform into lymphoma
Dog saliva treat dog and person
Can do a silver stain
or a thiazine stain

Normal

Lymphoid follicle
(has a germinal center)
 Chronic Gastritis
Helicobacter pylori Gastritis
Long-standing H. pylori gastritis
Involves the body and fundus
Mucosa can become atrophic---loss of parietal and
chief cells
Development of atrophy of the stomach
Associated with intestinal metaplasia and increased risk
of gastric adenocarcinoma
 Autoimmune Gastritis
Spares the antrum
Associated with hypergastrinemia
Characterized by:
Antibodies to parietal cells and intrinsic factor
Serum and gastric secretions
Reduced serum pepsinogen I concentration
Endocrine cell hyperplasia
Vitamin B12 deficiency
Defective gastric acid secretion (achlorhydria)
 Autoimmune Gastritis
Pathogenesis
Loss of parietal cells
Secretion of gastric acid and intrinsic factor
Absence of acid production stimulates gastrin release
Hypergastrinemia and hyperplasia of antral gastrin-
producing G cells
Lack of intrinsic factor disables ileal vitamin
B12 absorption
Vitamin B12 deficiency and slow-onset megaloblastic
anemia (pernicious anemia)
Chief cell destruction
Reduced serum pepsinogen I concentration
CD4+ T cells (against parietal cell components)
Principal agents of injury
 Autoimmune Gastritis
Morphology
Diffuse mucosal damage of the oxyntic mucosa
Body and fundus
Severe Vitamin B12 deficiency
Nuclear enlargement (megaloblastic change) in epithelial
cells
Inflammatory infiltrate
Lymphocytes, macrophages, and plasma cells
Lymphoid aggregates and follicles
Extensive loss of parietal and chief cells
 Autoimmune Gastritis
Clinical Features
Median age at diagnosis: 60 years old
Slightly more women than men affected
Associated with other autoimmune diseases
Hashimoto thyroiditis
Insulin-dependent (type I) diabetes mellitus
Addison disease
Primary ovarian failure
Primary hypoparathyroidism
Graves disease
Vitiligo
Myasthenia gravis
Lambert-Eaton syndrome
Lymphocytes
 Complications of Chronic Gastritis
Peptic Ulcer Disease
Chronic mucosal ulceration : duodenum or
stomach
Nearly all peptic ulcers are associated with:
H. pylori infection
NSAIDs
Cigarette smoking
 Peptic Ulcer Disease
Clinical Findings
Epigastric burning or aching pain
Iron deficiency anemia, hemorrhage,
or perforation
Pain:
1-3 hours after meals during the day
Worse at night (between 11 PM and 2 AM)
Relieved by alkali or food (so they eating something
else and it goes away)
Nausea, vomiting, bloating, belching, and significant
weight loss
 Peptic Ulcer Disease
Morphology
Most common in the proximal duodenum
Within a few centimeters of the pyloric valve
Involve the anterior duodenal wall
Solitary in more than 80% of patients
Classic peptic ulcer
Round to oval sharply punched-out defect
Hemorrhage and fibrin deposition
Perforation into the peritoneal cavity
Surgical emergency
 Peptic Ulcer Disease
Morphology
Active ulcers
Lined by a thin layer of fibrinoid debris
Neutrophilic inflammatory infiltrate
Granulation tissue
Fibrous or collagenous scarulcer base
Punched out

Pus
 Hypertrophic Gastropathies
Uncommon diseases
Giant cerebriform enlargement of rugal folds
Epithelial hyperplasia without inflammation
Linked to excessive growth factor release
Two well-defined examples
Mntrier disease Looks like a brain in the
stomach
Zollinger-Ellison syndrome
 Mntrier Disease
Rare disorder
Excessive secretion of transforming growth
factor
Diffuse hyperplasia of the foveolar epithelium
Body and fundus
Hypoproteinemia
Protein-losing enteropathy
Increased risk of gastric adenocarcinoma
Inflammatory and Hyperplastic Polyps
Most common in individuals between 50 and 60
years of age
Association with chronic gastritis
Ovoid in shape
Smooth surface
Microscopic findings:
Irregular, cystically dilated, and elongated foveolar
glands
Edema and acute/chronic inflammation of lamina
propria
 Fundic Gland Polyps
Sporadic
Familial adenomatous polyposis
Increased markedly--increasing use of proton
pump inhibitor therapy
Asymptomatic
Associated with nausea, vomiting, or
epigastric pain
 Fundic Gland Polyps
Gastric body and fundus
Well-circumscribed lesions
Smooth surface
Single or multiple
Composed of cystically dilated, irregular glands
FAP-associated fundic gland polyps
Dysplasia/cancer
Sporadic fundic gland polyps carry no cancer risk
Inflammatory and Hyperplastic Polyps

Gastric gland dilation

(indication of a polyp)
 Gastric Adenoma
50 and 60 years of age
Males are 3x more often than females
Increased in individuals with FAP
Adenocarcinoma
Related to the size of the lesion
Increased in lesions greater than 2 cm in diameter

Assume LOW GRADE DYSPLASIA

 Gastric Adenoma
Morphology
Solitary lesions less than 2 cm in diameter
Located in the antrum
Intestinal-type columnar epithelium
Varying degrees of dysplasia
Dysplastic changes
Low grade
Enlargement, elongation, pseudostratification, and hyper-
chromasia of nuclei
Epithelial crowding
High-grade
Severe cytologic atypia
Irregular architecture
Glandular budding and gland-within-gland (cribriform) structures
 Gastric Adenocarcinoma
Most common malignancy of the stomach
Early symptoms
Dyspepsia, dysphagia, and nausea
Discovered at advanced stages
Weight loss, anorexia, early satiety, anemia, and
hemorrhage
 Gastric Adenocarcinoma
Metastatic sites
Supraclavicular sentinel lymph node (Virchow
node)
Periumbilical lymph nodes (Sister Mary Joseph
nodule)
Left axillary lymph node (Irish node)
Ovary (Krukenberg tumor)
Pouch of Douglas (Blumer shelf)
 Gastric Adenocarcinoma
Gastric dysplasia and adenoma
Precursor lesions
Partial gastrectomies for PUD
Residual gastric stump
Hypochlorhydria, bile reflux, and chronic gastritis
 Gastric Adenocarcinoma
Classified according to:
Location
Gross and histologic morphology
Gastric antrum
Lesser curvature is involved more often than the greater curvature
Intestinal morphology tumors
Bulky tumors
Glandular structures
Exophytic mass/ulcerated tumor
Apical mucin vacuoles and abundance of mucin in the lumina
Diffuse infiltrative growth pattern tumors
Signet-ring cells: Large mucin vacuoles that expand the cytoplasm
Discohesive cells
Permeate the mucosa and stomach wall individually or in small
clusters
 Gastric Adenocarcinoma
Desmoplastic reaction
Stiffens the gastric wall
Large areas of infiltration
Diffuse rugal flattening
Rigid, thickened wall
Leather bottle appearance
Linitis plastica
 Lymphoma
Extranodal lymphomas
GI tract---particularly the stomach
Allogeneic hematopoietic stem cell and organ transplant
recipients
Bowel : Epstein-Barr virus-positive B-cell lymphoproliferations
Lymphomas of mucosa-associated lymphoid tissue (MALT)
Arise at sites of chronic inflammation
Gastric MALT
Result of chronic gastritis
H. pylori infection
t(11;18)(q21;q21)
t(1;14)(p22;q32)
t(14;18)(q32;q21)
 Lymphoma
Gastric MALToma
Dense lymphocytic infiltrate in the lamina propria
Diagnostic lymphoepithelial lesions
Reactive-appearing B-cell follicles
 Carcinoid Tumor
Well-differentiated neuroendocrine tumors
Associated with:
Endocrine cell hyperplasia
Autoimmune chronic atrophic gastritis
MEN-I
Zollinger-Ellison syndrome
 Carcinoid Tumor
Gross findings:
Intramural or submucosal masses
Small polypoid lesions
Overlying mucosa
Intact or ulcerated
Yellow or tan
Very firm
Intense desmoplastic reaction
 Carcinoid Tumor
Histologic findings:
Islands, trabeculae, strands, glands, or sheets
Uniform cells
Scant, pink granular cytoplasm
Round to oval stippled nucleus
Minimal pleomorphism
Immunohistochemical stains
Endocrine granule markers
Synaptophysin and chromogranin A
Salt and pepper
 Carcinoid Tumor
Sixth decade
Symptoms are determined by the hormones
produced
Gastrin producing tumors
Zollinger-Ellison syndrome
Ileal tumors
Carcinoid syndrome
Cutaneous flushing, sweating, bronchospasm, colicky abdominal
pain, diarrhea, and right-sided cardiac valvular fibrosis
Vasoactive substances secreted by the tumor into the systemic
circulation
 Carcinoid Tumor
The most important prognostic factor for GI carcinoid tumors is
location
Foregut carcinoid tumors
Stomach, duodenum proximal to the ligament of Treitz, and esophagus
Rarely metastasize
Cured by resection
Midgut carcinoid tumors
Jejunum and ileum
Multiple
Aggressive
Greater depth of local invasion, increased size, and presence of necrosis and
mitoses
Worse outcome
Hindgut carcinoids
Appendix and colorectum
Incidentaloma
Appendix--any age; located at the tip; almost always benign
 Gastrointestinal Stromal Tumor (GIST)
Most common mesenchymal tumor of the abdomen
Arises from the interstitial cells of Cajal
Pacemaker cells of the gastrointestinal muscularis propria
Mean age: 60 years old
GISTs in children
Carney triad
Young females
Gastric GIST
Paraganglioma
Pulmonary chondroma
Increased incidence of GIST--neurofibromatosis type 1
Approximately 75% to 80% of all GISTs
Oncogenic, gain-of-function mutations in the receptor tyrosine
kinase KIT
 GIST
Primary gastric GISTs
Large--30 cm in diameter
Solitary, well-circumscribed, fleshy mass
Cut surface shows a whorled appearance
Spindle cells
Epithelioid cells
 GIST
Symptoms related to mass effect
Mucosal ulceration can cause blood loss
Prognosis correlates with tumor size, mitotic
index, and location