Gastric Adenocarcinoma

 

Epidemiology & Etiology:

    • 2nd most common tumour in the world (…?)
      • Leading cause of cancer death worldwide (…?)
      • Decline in incidence and mortality over the past 6 decades (intestinal type)
      • Higher incidence in (intestinal type):
        • Japan
        • Chili
        • Costa Rica
        • Columbia
        • China
        • Portugal
        • Russia
        • Bulgaria
      • Lower incidence in (intestinal type):
        • USA
        • UK
        • Canada
        • Australia
        • New Zealand
        • France
        • Sweden
    • M:F ~ 2:1 (intestinal type)
    • 55y mean (intestinal type)
      • 48y mean diffuse type
    • Risk factors (intestinal type):
      • H. pylori (HR 5-6)
      • Diet:
        • Nitrites derived from nitrates (water, preserved food)
        • N-nitroso compounds
        • Smoked and salted foods, pickled vegetables, chili peppers
        • Lack of fresh fruits and vegetables
          • Green leafy vegetables
          • Citrus fruits
        • Lack of refrigeration
        • benzopyrene
      • Low socioeconomic status
      • Cigarette smoking (inconclusive)
      • Chronic gastritis
        • Autoimmune
        • Bile reflux
      • Menetrier disease
      • Partial gastrectomy
      • Intestinal metaplasia / gastric adenomas (precursor lesions)
      • Barrett esophagus (GE junction tumours)
      • Ethnicity (likely environment rather than genetic):
        • Blacks
        • Native Americans
        • Hawaiians
      • Genetic:
        • Blood group A
        • Family history (8-10%)
        • HNPCC
        • Familial gastric carcinoma syndrome
          • E-cadherin mutation (CDH1)
          • Also increased risk of lobular breast cancer
        •  

 

Common sites:

    • 50-60% in pylorus and antrum
    • 40% lesser curvature
      •  

 

Gross features:

    • 3 macroscopic growth patterns:
      • Exophytic
        • May contain portions of an adenoma
      • Flat or depressed
        • No obvious tumour mass in the mucosa
        • Linitis plastica – leather bottle consistency of a portion or entire stomach
      • Excavated
        • Heaped up, beaded margins
        • Shaggy necrotic base
        • Overt neoplastic tissue extending into surrounding mucosa and wall
    • Intestinal type:
      • Bulky
    • Diffuse type:
    • Virchow node (left supraclavicular)
    • Sister Mary Joseph nodule (subcutaneous umbilical)
    • Widespread peritoneal seeding
      • One or both ovaries

 

Histologic features:

    • intestinal type (Laurén classification):
      • glands resembling those of colonic adenocarcinoma
      • expanding growth pattern
      • often apical mucin vacuoles, abundant mucin in gland lumens
      • gastritis -> atrophy -> intestinal metaplasia -> dysplasia -> adenocarcinoma
    • diffuse type (Laurén classification):
      • gastric-type mucous cells
      • scattered individual cells or small clusters
      • infiltrative growth pattern
      • signet ring cells
      • often strong desmoplastic reaction with scattered malignant cells within
      • intestinal metaplasia is not associated
    • WHO classification (based on histologic appearance)
      • Papillary adenocarcinoma
      • Tubular adenocarcinoma
      • Mucinous adenocarcinoma
      • Signet ring cell carcinoma (>50% signet ring morphology)
      • Undifferentiated carcinoma
      • Adenosquamous carcinoma
    • Depth of invasion (important in stagining and classification)
      • Carcinoma in situ – confined to surface epithelium
      • Early gastric carcinoma is confined to mucosa and submucosa
      • Advanced gastric carcinoma extends into the muscularis propria
    • Frequent occurrence of a minor (< 30%) component of cells with neuroendocrine differentiation
      • Should not prevent its classification as adenocarcinoma

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

    • Intestinal type:
      • No clear sequence of events
      • Mutations:
        • P53
      • Allelic losses
      • Microsatellite instability
        • TGFßRII
        • BAX
        • IGFRII
      • E-cadherin expression abnormalities
      • c-ERB-B2 amplification

 

Other features:

    • Steady decline in mortality in past 6 decades
    • 5 year survival rates remain poor (~20% in the US)
      • Early gastric cancer 90-95% 5-year survival
    • Intestinal metaplasia is a precursor lesion

 

References:

·       Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004:1552.

·       Bosman FT, Carneiro F, Hruban RH, Theise ND (eds.)  WHO Classification of Tumours of the Digestive System (2010)

·       Some notes taken

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