Definition/General
Introduction:
Gastric adenocarcinoma is the most common gastric malignancy accounting for >90% of gastric cancers
Cytological diagnosis is highly accurate when adequate samples are obtained
Lauren classification divides tumors into intestinal and diffuse types.
Origin:
Arises from gastric glandular epithelium
Intestinal type develops through adenoma-carcinoma sequence
Diffuse type arises de novo from normal mucosa
H
pylori infection major risk factor
Environmental and genetic factors contribute.
Classification:
Lauren classification: Intestinal, diffuse, mixed types
WHO classification: Papillary, tubular, mucinous, signet ring, mixed types
Grade: Well, moderately, poorly differentiated
TNM staging system used.
Epidemiology:
Second most common GI malignancy
Male predominance (2:1)
Peak age 50-70 years
Geographic variation: High in Asia
Declining incidence in developed countries
H
pylori association (60-80%).
Clinical Features
Presentation:
Epigastric pain (70%)
Weight loss (60%)
Anorexia
Early satiety
Nausea and vomiting
Dysphagia
GI bleeding.
Symptoms:
Abdominal discomfort
Postprandial fullness
Loss of appetite
Fatigue
Black stools
Hematemesis
Progressive symptoms.
Risk Factors:
H
pylori infection
Chronic atrophic gastritis
Intestinal metaplasia
Adenomatous polyps
Family history
Smoking
High salt diet.
Screening:
Endoscopic screening in high-risk areas
H
pylori testing
Serum pepsinogen
Family screening
Surveillance of precancerous lesions.
Master Gastric Adenocarcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Ulcerative lesions (most common)
Polypoid masses
Infiltrative thickening
Linitis plastica (diffuse type)
Mixed patterns.
Characteristics:
Irregular ulcerated surface
Firm consistency
Gray-white appearance
Necrosis and hemorrhage
Wall thickening.
Size Location:
Antrum (50%)
Body (25%)
Cardia (20%)
Pan-gastric (5%)
Variable size
Multifocal disease possible.
Multifocality:
Skip lesions
Synchronous lesions
Field cancerization
Lymphatic invasion
Peritoneal dissemination.
Microscopic Description
Histological Features:
Malignant glandular cells
Nuclear pleomorphism
Increased N/C ratio
Prominent nucleoli
Mitotic activity
Loss of polarity.
Cellular Characteristics:
Enlarged hyperchromatic nuclei
Irregular nuclear contours
Coarse chromatin
Variable cytoplasm
Signet ring cells (diffuse type)
Mucin production.
Architectural Patterns:
Glandular formations (intestinal)
Single cells (diffuse)
Sheets and clusters
Signet ring morphology
Mucinous lakes.
Grading Criteria:
Well-differentiated: Well-formed glands
Moderately differentiated: Irregular glands
Poorly differentiated: Solid sheets, signet rings
Undifferentiated.
Immunohistochemistry
Positive Markers:
CK7
CK20 (intestinal type)
CDX2 (intestinal)
MUC5AC (gastric)
MUC2 (intestinal)
CEA.
Negative Markers:
CK5/6
p63
TTF-1
Chromogranin (unless mixed)
Synaptophysin.
Diagnostic Utility:
Confirms adenocarcinoma
Type classification
Primary vs metastatic
Prognostic markers.
Molecular Subtypes:
MSI-high
EBV-positive
Genomically stable
Chromosomal instability.
Molecular/Genetic
Genetic Mutations:
TP53 (50%)
APC (30%)
PIK3CA (20%)
KRAS (15%)
ARID1A
CDH1 (diffuse).
Molecular Markers:
HER2 amplification (20%)
PD-L1 expression
MSI status
EBV status
TMB assessment.
Prognostic Significance:
Stage most important
Lauren type
HER2 status
MSI status
Grade.
Therapeutic Targets:
HER2-targeted therapy
PD-1 inhibitors
VEGF inhibitors
Targeted therapy.
Differential Diagnosis
Similar Entities:
High-grade dysplasia
Reactive changes
Metastatic adenocarcinoma
Lymphoma
Neuroendocrine tumors.
Distinguishing Features:
Adenocarcinoma: Invasive growth
Dysplasia: Surface intact
Reactive: Uniform features
Lymphoma: Hematologic markers.
Diagnostic Challenges:
Well-differentiated tumors
Small biopsies
Inflammatory background
Signet ring identification.
Rare Variants:
Hepatoid adenocarcinoma
Micropapillary
Adenosquamous
Undifferentiated with lymphoid stroma.
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
Gastric cytology, adequate for evaluation
Diagnosis
Malignant - Adenocarcinoma
Malignant Features
Malignant glandular cells with [nuclear atypia] and [architectural distortion]
Lauren Classification
Type: [Intestinal/Diffuse/Mixed] adenocarcinoma
Differentiation
Grade: [Well/Moderately/Poorly] differentiated
Special Studies
IHC: [markers] recommended
HER2 testing: [recommended]
Final Diagnosis
Gastric cytology: Adenocarcinoma