Carcinoma of the Stomach: Intestinal vs. Diffuse Type

Learning Objectives

• Etiopathogenesis of gastric cancer
• Differences between intestinal and diffuse types of gastric cancer

Gastric Adenocarcinoma

• Most common stomach malignancy

• 90% of all gastric cancers

• Epidemiology: Higher incidence in Japan, Chile, Costa Rica, Eastern Europe; lower in North America, Northern Europe, Africa, Southeast Asia
• More common in lower socioeconomic groups, individuals with multifocal mucosal atrophy, and intestinal metaplasia

Risk Factors

Environmental Factors

• Gender: Males, typically in the 6th-8th decade
• Helicobacter pylori (CAG strain)
• Diet: Rich in nitrosamines (smoked fish, meat)
• Smoking and tobacco
• Previous gastric surgery

Host Factors

• Pernicious anemia
• Menetrier's disease
• Hypertrophic gastropathy
• Autoimmune or atrophic gastritis
• Gastric ulcers and dysplasia

Genetic Factors

• Blood group A
• Hereditary non-polyposis colon cancer syndrome
• Familial adenomatous polyposis

Classification of Gastric Cancers

Based on Depth of Invasion

• Early: Confined to mucosa/submucosa
• Advanced: Invades muscularis propria and beyond

Based on Macroscopic Growth Pattern

• Flat type
• Exophytic type
• Ulcerated type
• Diffuse type

Based on Microscopic Type (Lauren Classification)

• Intestinal type
• Diffuse type

Pathogenesis

Intestinal Type

• Increased Wnt pathway signaling (APC Gene, beta-catenin mutations)
• Other mutations: TGF signaling, apoptosis regulation, cell cycle control (e.g., CDK2A)

Diffuse Type

• Loss of E-cadherin (CDH1 mutation or promoter hypermethylation)
• Sporadic forms are usually intestinal; familial are diffuse type

Morphology

Intestinal Type

• Bulky tumors: Exophytic mass, ulcerated tumor, polypoid, or fungating growth

Diffuse Type

• Infiltrative tumors
• Desmoplastic response, gastric wall stiffening (linitis plastica or leather bottle stomach)

Microscopic Features

Intestinal Type

• Glandular structures with mucin vacuoles

Diffuse Type

• Signet ring cells (mucin vacuoles push the nucleus to periphery)

Clinical Features

Similarities

• Early symptoms: Dyspepsia, dysphagia, nausea (often neglected)
• Advanced symptoms: Weight loss, anorexia, early satiety, anemia, hemorrhage

Differences

• Intestinal: High-risk areas, precursor lesions, mean age ~55 years, male predominance (2:1), associated with H. pylori, dietary factors
• Diffuse: Uniform global distribution, younger age onset, no gender predominance

Prognosis and Treatment

• Prognostic Indicators: Depth of invasion, extent of nodal/distant metastasis
• Common Metastasis Sites: Supraclavicular nodes (Virchow node), umbilicus (Sister Mary Joseph nodules), ovaries (Krukenberg tumor), axillary lymph node, pouch of Douglas
• Treatment: Surgery (preferred), chemotherapy/radiation in advanced cases, palliative care
• 5-Year Survival Rates: >90% in early stages, <30% in advanced stages