Definition/General
Introduction:
Gastric peptic ulcer is a mucosal defect that extends through the muscularis mucosae into the submucosa
Most commonly caused by Helicobacter pylori infection (60-70%) and NSAIDs (20-30%)
Represents imbalance between aggressive factors and mucosal defense mechanisms.
Origin:
Results from disruption of mucosal barrier
H
pylori causes chronic gastritis leading to ulceration
NSAIDs inhibit COX-1, reducing protective prostaglandins
Acid hypersecretion in some cases
Mucosal ischemia contributes to ulcer formation.
Classification:
Acute ulcers (superficial, multiple)
Chronic ulcers (deep, single, well-demarcated)
H
pylori-associated vs NSAID-induced
Stress ulcers (ICU patients)
Zollinger-Ellison syndrome (hypergastrinemia)
Size: <1 cm vs >1 cm.
Epidemiology:
Incidence declining in developed countries due to H
pylori eradication
Peak age 40-60 years for H
pylori ulcers
Male predominance (2:1)
NSAID ulcers increasing in elderly
Duodenal ulcers 4x more common than gastric ulcers.
Clinical Features
Presentation:
Epigastric pain (85-90% cases)
Postprandial pain (worse with food)
Nausea and vomiting (40-50%)
Early satiety (30-40%)
Weight loss (20-30%)
GI bleeding (hematemesis, melena)
Asymptomatic in 15-20%.
Symptoms:
Burning epigastric pain
Pain 1-2 hours after meals
Nighttime awakening
Antacid relief
Iron deficiency anemia (chronic bleeding)
Hematemesis (active bleeding)
Melena (upper GI bleeding).
Risk Factors:
H
pylori infection (strongest risk factor)
NSAIDs use (especially COX-1 selective)
Smoking (delays healing)
Alcohol consumption
Psychological stress
Corticosteroids
Advanced age
Zollinger-Ellison syndrome.
Screening:
H
pylori testing (serology, stool antigen, breath test)
Upper endoscopy (gold standard)
Upper GI series (barium study)
Serum gastrin levels (if ZES suspected)
Complete blood count (anemia)
Stool occult blood.
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Gross Description
Appearance:
Round to oval mucosal defect with sharply demarcated edges
Clean base in chronic ulcers
Punched-out appearance
Surrounding mucosal edema and erythema
Radiating mucosal folds toward ulcer base
Fibrin exudate in acute phase.
Characteristics:
Well-demarcated margins in chronic ulcers
Smooth, indurated base
White-gray fibrinous exudate
Hyperemic rim around edges
Puckering of surrounding mucosa
No obvious mass lesion (vs carcinoma).
Size Location:
Size typically 1-3 cm (range 0.5-5 cm)
Antrum most common location (60-70%)
Lesser curvature predilection
Incisura angularis common site
Multiple ulcers in 10-15% cases
Giant ulcers >3 cm (5% cases).
Multifocality:
Usually solitary (80-85% cases)
Multiple ulcers suggest ZES or NSAID etiology
Kissing ulcers on opposite walls
Associated duodenal ulcers in 10-15%
Concurrent gastritis common.
Microscopic Description
Histological Features:
Four-layer histology in chronic ulcers
Surface fibrinopurulent exudate
Zone of necrosis beneath surface
Granulation tissue with capillary proliferation
Fibrous scar tissue at base
Chronic inflammatory infiltrate
Arterial thickening (endarteritis obliterans).
Cellular Characteristics:
Neutrophilic infiltrate in acute phase
Lymphocytes and plasma cells in chronic phase
Macrophages with hemosiderin
Fibroblast proliferation
Endothelial proliferation in granulation tissue
Smooth muscle proliferation in vessels.
Architectural Patterns:
Mucosal discontinuity extending into submucosa
Loss of normal mucosal architecture
Reactive epithelial changes at margins
Glandular regeneration at edges
Vascular proliferation
Fibrosis in chronic cases.
Grading Criteria:
Acute ulcers: Superficial, neutrophilic infiltrate, minimal fibrosis
Chronic ulcers: Deep, chronic inflammation, significant fibrosis, endarteritis obliterans
Healing ulcers: Re-epithelialization, granulation tissue, reduced inflammation.
Immunohistochemistry
Positive Markers:
H
pylori immunostain (identifies organisms)
Ki-67 (increased proliferation at margins)
Cytokeratin (epithelial regeneration)
SMA (smooth muscle in vessels)
CD31 (endothelial proliferation).
Negative Markers:
Generally not required for diagnosis
p53 (should be negative, excludes malignancy)
Chromogranin (excludes neuroendocrine tumors).
Diagnostic Utility:
H
pylori immunostain increases organism detection
Ki-67 shows regenerative activity
p53 negativity supports benign nature
Cytokeratin demonstrates epithelial repair.
Molecular Subtypes:
H
pylori-associated: CagA+ strains more virulent
NSAID-induced: COX-1 selectivity important
Hypersecretory states: Gastrinoma, hypercalcemia
Genetic factors: IL-1β polymorphisms.
Molecular/Genetic
Genetic Mutations:
Generally no specific mutations in benign ulcers
TP53 mutations absent (vs malignancy)
Host genetic factors: IL-1β, TNF-α polymorphisms
H
pylori virulence factors: CagA, VacA, BabA.
Molecular Markers:
COX-1 inhibition in NSAID ulcers
Prostaglandin E2 reduction
Inflammatory cytokines (IL-1β, TNF-α, IL-8)
Growth factors (EGF, TGF-α) in healing
Apoptosis markers in acute phase.
Prognostic Significance:
H
pylori eradication leads to healing in 85-90%
NSAID cessation promotes healing
Giant ulcers (>3 cm) heal slower
Elderly patients heal more slowly
Smoking delays healing
Recurrence rare after H
pylori eradication.
Therapeutic Targets:
H
pylori eradication (triple/quadruple therapy)
Proton pump inhibitors (acid suppression)
NSAID cessation
Cytoprotective agents (sucralfate, misoprostol)
H2 receptor antagonists
Antacids for symptom relief.
Differential Diagnosis
Similar Entities:
Gastric adenocarcinoma (ulcerated)
Lymphoma (MALT, DLBCL)
Crohn disease
Cytomegalovirus ulcer
Ischemic ulceration
Radiation-induced ulcer
Behçet disease.
Distinguishing Features:
Benign ulcer: Smooth margins, no mass, benign histology
Carcinoma: Irregular margins, mass lesion, malignant cells
Lymphoma: Monoclonal B-cells, lymphoepithelial lesions
CMV: Viral inclusions, immunopositive
Crohn: Skip lesions, granulomas.
Diagnostic Challenges:
Distinguishing benign vs malignant ulcer endoscopically
Identifying H
pylori in treated patients
Recognizing healing vs recurrent ulcer
Sampling adequacy for histology
Drug-induced ulcers (bisphosphonates, KCl).
Rare Variants:
Stress ulcers (critically ill patients)
Curling ulcers (burn patients)
Cushing ulcers (CNS pathology)
Cameron ulcers (hiatal hernia)
Dieulafoy lesions (vascular malformation).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen
Gastric biopsy from ulcer [location]
Ulcer Features
[Acute/Chronic] peptic ulcer with [depth and characteristics]
H. pylori
H. pylori organisms: [present/absent] [by H&E/immunostain]
Inflammation
[Acute/chronic] inflammatory infiltrate, granulation tissue
Malignancy
No evidence of malignancy in sampled tissue
Diagnosis
Gastric peptic ulcer, [acute/chronic], H. pylori [positive/negative]