Definition/General
Introduction:
Gastric adenocarcinoma is the most common malignant tumor of the stomach, representing 90-95% of gastric cancers
It is the fourth most common cancer worldwide and second leading cause of cancer-related death globally.
Origin:
Arises from gastric epithelium through multistep process
Intestinal type develops through gastritis-atrophy-intestinal metaplasia-dysplasia sequence
Diffuse type arises from normal mucosa.
Classification:
Lauren Classification: Intestinal type (gland-forming), Diffuse type (single cells), Mixed type
WHO Classification includes tubular, papillary, mucinous, signet-ring cell, and mixed carcinomas.
Epidemiology:
Higher incidence in East Asia, Eastern Europe, South America
Male predominance (2:1)
Peak incidence 60-70 years
Strong association with H
pylori infection.
Clinical Features
Presentation:
Epigastric pain
Early satiety
Weight loss
Nausea and vomiting
Gastrointestinal bleeding
Dysphagia (proximal tumors)
Palpable mass (advanced cases).
Symptoms:
Abdominal discomfort
Loss of appetite
Fatigue
Bloating after meals
Heartburn
Hematemesis or melena
Iron deficiency anemia.
Risk Factors:
Helicobacter pylori infection (strongest risk factor)
Chronic atrophic gastritis
Intestinal metaplasia
Family history
Dietary factors (high salt, smoked foods).
Screening:
Upper endoscopy in high-risk populations
Serum pepsinogen levels
H
pylori testing
CEA and CA 19-9 may be elevated
Imaging for staging.
Master Gastric Adenocarcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Variable gross appearance based on Borrmann classification
Type I: Polypoid/fungating
Type II: Ulcerated with raised margins
Type III: Ulcerated with infiltrating margins
Type IV: Diffusely infiltrating.
Characteristics:
Size ranges from small early cancers to large advanced tumors
Color varies from gray-white to hemorrhagic
Consistency depends on desmoplastic response.
Size Location:
Most common in antrum and lesser curvature
Early gastric cancer confined to mucosa/submucosa
Advanced cancer invades beyond submucosa.
Multifocality:
Usually unifocal
Multifocal disease in familial cases
Skip lesions possible
May involve multiple anatomic subsites.
Microscopic Description
Histological Features:
Intestinal type: Well-formed glands with intestinal-type epithelium
Diffuse type: Single cells or small clusters infiltrating stomach wall
Variable mucin production.
Cellular Characteristics:
Enlarged hyperchromatic nuclei
Loss of polarity
Increased mitotic activity
Signet-ring cells in diffuse type
Goblet cells in intestinal type.
Architectural Patterns:
Tubular (most common)
Papillary
Solid
Signet-ring cell pattern
Mixed architecture frequent
Mucinous areas possible.
Grading Criteria:
Well differentiated: >95% gland formation
Moderately differentiated: 50-95% glands
Poorly differentiated: <50% glands
Signet-ring cell type always poorly differentiated.
Immunohistochemistry
Positive Markers:
CK7 positive (70%)
CK20 positive (60%)
CEA positive
CDX2 positive (intestinal type)
MUC1 positive
MUC6 positive (gastric phenotype).
Negative Markers:
TTF-1 negative
PAX8 negative
WT1 negative
PSA negative
GATA3 negative
ER/PR negative.
Diagnostic Utility:
CK7+/CK20+ pattern supports gastric origin
CDX2 positivity in intestinal type
HER2 testing mandatory for treatment decisions.
Molecular Subtypes:
EBV-positive (9%)
MSI-H (22%)
Chromosomally stable (20%)
Chromosomally unstable (50%)
HER2 amplification (15-20%).
Molecular/Genetic
Genetic Mutations:
TP53 mutations (40-60%)
PIK3CA mutations (25%)
ARID1A mutations (25%)
CDH1 mutations (diffuse type)
RHOA mutations
HER2 amplification.
Molecular Markers:
Microsatellite instability testing
HER2 amplification by IHC/FISH
EBV in situ hybridization
PD-L1 expression assessment.
Prognostic Significance:
Lauren classification affects prognosis: intestinal type better than diffuse
HER2 amplification predicts response to trastuzumab
MSI-H better prognosis.
Therapeutic Targets:
HER2-targeted therapy (trastuzumab) if amplified
Immune checkpoint inhibitors for MSI-H tumors
Anti-VEGF therapy
Claudin18.2-targeted therapy.
Differential Diagnosis
Similar Entities:
Metastatic adenocarcinoma (breast, lung, pancreas)
Lymphoma
Gastrointestinal stromal tumor
Carcinoid tumor
Reactive/regenerative changes.
Distinguishing Features:
Primary gastric: CK7+/CK20+, gastric phenotype markers
Metastatic breast: ER+, GATA3+, GCDFP-15+
Lymphoma: CD45+, B/T-cell markers.
Diagnostic Challenges:
Distinction from metastatic lobular breast carcinoma (especially signet-ring cell type)
Recognition of early gastric cancer
Sampling of heterogeneous tumors.
Rare Variants:
Hepatoid adenocarcinoma (AFP+)
Lymphoepithelioma-like carcinoma (EBV+)
Mucinous adenocarcinoma (>50% mucin)
Adenosquamous carcinoma
Undifferentiated carcinoma.
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 Information
Gastrectomy specimen measuring [size] cm
Tumor Location
Tumor located in [antrum/body/fundus/cardia], [lesser/greater] curvature
Tumor Size
Tumor measures [X] x [Y] cm
Lauren Classification
[Intestinal/Diffuse/Mixed] type adenocarcinoma
Histologic Grade
[Well/Moderately/Poorly] differentiated
Depth of Invasion
Tumor invades [mucosa/submucosa/muscularis propria/subserosa/serosa] (pT[X])
Lymph Nodes
[X] of [Y] lymph nodes involved (pN[X])
Margins
Proximal margin: [negative/positive], Distal margin: [negative/positive]
Lymphovascular Invasion
Lymphovascular invasion: [Present/Absent]
Perineural Invasion
Perineural invasion: [Present/Absent]
HER2 Status
HER2: [Negative/Positive] by IHC, [if equivocal, FISH result]
TNM Staging
pT[X]N[X]M[X], Stage [I/II/III/IV]
Final Diagnosis
Final diagnosis: Gastric adenocarcinoma, [Lauren type], [grade], pT[X]N[X]M[X], Stage [X]