Gastric Carcinoma

Overview

90% of gastric malignancies. Leading cancer-death cause in high-incidence countries. Peak 4th-6th decade, 2x male.

Etiology

H. pylori — 3-6x risk. Also linked to gastric MALT lymphoma
Dietary — MOST significant. Gastric canal clustering (lesser curvature/antrum, longest irritant exposure). ↑risk: smoked food, high salt, pickled veg, nitrates/nitrites. PROTECTIVE: green leafy veg, citrus, animal fats. Also tobacco+alcohol
Geographic — high: Japan/Chile/Italy; low: US/UK/Canada. Migration studies (Japanese→US) show shift toward HOST country rate within a generation — strong ENVIRONMENTAL evidence
Racial — variation within country (Black, American Indian, Indonesian Chinese, North Welsh higher)
Genetic — only ~4% family history. BLOOD GROUP A predisposes (contrast: peptic ulcer = group O — easily confused pair). Germline E-CADHERIN mutation (AD) → hereditary diffuse/occult gastric cancer, younger patients
Premalignant conditions: atrophic gastritis+intestinal metaplasia+hypo/achlorhydria; adenomatous polyps; chronic gastric ulcer (rare, “ulcer-cancer” <1%); gastric stump carcinoma (post-partial gastrectomy)

Morphology/classification

Located mainly gastric canal (lesser curvature/pylorus/antrum); less often body/cardia/fundus.

Sequential evolution: EGC (mucosa/submucosa-confined) → penetrates muscularis → Advanced gastric carcinoma.

2 complementary classification axes:

By invasion depth: I. EGC, II. Advanced (5 subtypes below)
By growth pattern: Expanding (“intestinal type” — cohesive clusters, lateral invasion) vs Infiltrating (“diffuse type” — poorly-defined border, single/small-group invasion)

EGC

Mucosa/submucosa-confined. Endoscopy-enabled diagnosis. 35% of Japanese new diagnoses (intensive screening). 3 gross patterns: Type I (polypoid), Type II (superficial elevated/flat/depressed = IIa/IIb/IIc), Type III (ulcerated). Usually WELL-DIFFERENTIATED. EXCELLENT prognosis — 5yr survival 93-99%.

Distinguish from: epithelial dysplasia (atypia in intestinal metaplasia) and carcinoma in situ (severe atypia, NO basement membrane invasion) — EGC = invasion present but confined to mucosa/submucosa.

Advanced gastric carcinoma — 5 patterns

Ulcerative carcinoma (COMMONEST) — flat, infiltrating, ulcerative, irregular necrotic base, raised margin. Gastric canal. POORLY-differentiated, deep invasion, tubular/acinar.
Fungating (polypoid) carcinoma — cauliflower-like, FUNDAL. Necrosis/infection prone. WELL-differentiated, often papillary.
Scirrhous carcinoma (LINITIS PLASTICA) — desmoplasia thickens wall = “LEATHER-BOTTLE STOMACH.” Localised (antral) or diffuse (cardia-pylorus). Reduced lumen, no ulcer, prominent rugae. Adenocarcinoma or SIGNET-RING cell; desmoplasia can hide tumour cells histologically.
Colloid (mucoid) carcinoma — fundal, gelatinous, copious mucus. Mucin pools + scattered (±signet-ring) tumour cells.
Ulcer-cancer — cancer in pre-existing chronic gastric ulcer, RARE (<1%). Most are malignant from onset, not true transformation. Needs classic peptic ulcer histology demonstrable + carcinomatous change elsewhere.

Spread

Direct — COMMONEST pattern. Submucosa→muscularis/serosa. Transcoelomic after serosal breach → peritoneal seeding → bilateral ovarian KRUKENBERG TUMOURS. Submucosal spread favours UPWARD (oesophagus, structural continuity) over DOWNWARD (duodenum, blocked by pyloric sphincter+Brunner’s glands). Direct invasion: omentum, pancreas, liver, CBD, diaphragm, spleen, transverse colon.

Lymphatic — early, esp. SCIRRHOUS type. Lesser/greater curvature, cardia, suprapancreatic nodes. VIRCHOW’S NODE (Troisier’s sign, left supraclavicular) = can be PRESENTING feature.

Haematogenous — liver, lungs, brain, bone, kidney, adrenal. More with POORLY-differentiated tumours.

Staging: TNM, Tis N0 M0 (intraepithelial) → T-any N-any M1.

Clinical features

Diverse: abdominal pain, distension/vomiting, weight loss, anorexia, anaemia/weakness. COMMONEST complication: HAEMORRHAGE (haematemesis/melaena). Also obstruction, perforation, jaundice.

Clinical relevance

Blood group pair (A=gastric cancer, O=peptic ulcer) = compact easily-confused fact, cross-reference against Peptic Ulcer Disease — shared anatomic region+risk factors makes mixing up easy. Krukenberg tumour = one of highest-yield “named metastasis” facts — bilateral solid ovarian masses (esp. mucin-producing signet-ring histology) should point back to occult GI (esp. gastric) primary — tested reasoning pattern. EGC vs advanced distinction (93-99% vs poor prognosis) = direct rationale for endoscopic screening in high-incidence populations (Japan) — this staging distinction matters more than histologic subtype for outcome. Linitis plastica’s desmoplasia obscuring tumour cells = genuine diagnostic trap — biopsy can look deceptively benign if it samples stroma not sparse signet-ring cells — clinical/radiologic suspicion must sometimes override falsely reassuring biopsy.

Overview

Gastric carcinoma is >90% of all gastric malignancies and the leading cancer-death cause in high-incidence countries. Peak 4th–6th decades, 2× male preponderance.

Etiology

H. pylori infection — seropositivity confers 3–6× risk; the same organism is also linked to gastric MALT lymphoma (see Non-Hodgkin Lymphoma).
Dietary factors — considered the most significant etiologic category, supported by multiple lines of evidence: cancer clustering along the “gastric canal” (lesser curvature/pyloric antrum) where irritant foods act longest; high risk with smoked food, high salt, pickled vegetables, dietary/water nitrates, meat-preservative nitrites; protective effect of green leafy vegetables, citrus fruits, animal fats; carcinogenic contribution from tobacco (smoke and chewing) and alcohol.
Geographic factors — highest death rates in Japan, Chile, Italy; low in US/UK/Canada. Migration studies (Japanese immigrants to the US) show incidence shifts toward the host country’s rate within a generation — strong evidence for environmental (not purely genetic) causation.
Racial factors — variation even within a country (e.g. higher in Black, American Indian, Indonesian Chinese, North Welsh populations).
Genetic factors — only ~4% have a family history. Blood group A predisposes (contrast: peptic ulcer favours blood group O — worth holding these as a paired, easily-confused fact). Germline E-cadherin gene mutation (autosomal dominant) causes hereditary diffuse (occult) gastric cancer in younger patients.
Premalignant gastric mucosal conditions:
- Atrophic gastritis with intestinal metaplasia and hypo-/achlorhydria.
- Adenomatous (neoplastic) gastric polyps.
- Chronic gastric ulcer (rare — “ulcer-cancer,” <1%) with achlorhydria association.
- Gastric stump carcinoma after partial gastrectomy.

Morphology and Classification

Most commonly located in the gastric canal (lesser curvature, pylorus, antrum); less often body, cardia, fundus.

Gastric carcinoma follows a sequential evolution — in situ/mucosal-confined early gastric carcinoma (EGC) progressively penetrates the muscularis to become advanced gastric carcinoma. Two classification schemes are used together:

By stage of invasion:

I. Early gastric carcinoma (EGC) — confined to mucosa/submucosa.
II. Advanced gastric carcinoma — crosses into muscularis propria or beyond; five gross subtypes (below).

By growth pattern (a separate, complementary axis):

Expanding (formerly “intestinal type”) — cohesive tumour cell clusters, laterally-invading margin.
Infiltrating (formerly “diffuse type”) — poorly-defined border, single/small-group cell invasion.

Early Gastric Carcinoma (EGC)

Cancer limited to mucosa/submucosa — a diagnosis made possible by fibreoptic endoscopy; comprises 35% of newly-diagnosed Japanese cases (reflecting intensive screening). Three gross patterns: Type I (polypoid/protruded), Type II (superficial — elevated/IIa, flat/IIb, depressed/IIc), Type III (ulcerated). Histologically typically a well-differentiated glandular adenocarcinoma. Excellent prognosis after resection — 5-year survival 93–99%.

Distinguish from: epithelial dysplasia (cellular atypia in intestinal metaplasia, e.g. atrophic gastritis/pernicious anaemia) and carcinoma in situ (severe atypia without basement membrane invasion) — EGC specifically implies invasion into (but confined to) mucosa/submucosa, distinct from both.

Advanced Gastric Carcinoma — Five Gross Patterns

Ulcerative carcinoma (commonest) — flat, infiltrating, ulcerative growth with irregular necrotic base, raised margin; typically in the gastric canal. Histologically poorly-differentiated adenocarcinoma, deeply invasive, tubular/acinar pattern.
Fungating (polypoid) carcinoma — cauliflower-like intraluminal growth (resembling colonic carcinoma), more often fundal; prone to necrosis/infection. Histologically well-differentiated, often papillary.
Scirrhous carcinoma (linitis plastica) — extensive desmoplasia thickens the stomach wall (“leather-bottle stomach”); localised (antral) or diffuse (cardia-to-pylorus); reduced lumen, no ulcer, prominent rugae. Adenocarcinoma or signet-ring cell carcinoma; marked desmoplasia can make tumour cells genuinely hard to find histologically.
Colloid (mucoid) carcinoma — usually fundal; gelatinous masses from copious mucus secretion; abundant mucin pools with scattered tumour cells, sometimes signet-ring.
Ulcer-cancer — cancer arising in a pre-existing chronic gastric ulcer — genuinely rare (<1%); most “ulcer-cancers” are actually malignant from the outset rather than true benign-ulcer-to-cancer transformation. Confirmation requires demonstrating classic peptic ulcer histology in one part of the lesion with carcinomatous change elsewhere in the base/margin.

Spread

Direct — the most common spread pattern; submucosal extension, then muscularis/serosa; transcoelomic dissemination after serosal breach can seed the peritoneal cavity, classically producing bilateral ovarian Krukenberg tumours. Submucosal spread favours upward extension into the oesophagus (structural continuity) over downward into the duodenum (blocked by the pyloric sphincter and Brunner’s glands). Direct invasion of omentum, pancreas, liver, common bile duct, diaphragm, spleen, transverse colon can occur.
Lymphatic — early metastasis, especially with scirrhous carcinoma; nodes along lesser/greater curvature, cardia, suprapancreatic region. Virchow’s node (Troisier’s sign) — left supraclavicular node involvement — can be the presenting feature.
Haematogenous — liver, lungs, brain, bone, kidney, adrenal; more common with poorly-differentiated tumours.

Staging: TNM system, from Tis N0 M0 (intraepithelial) to T-any N-any M1 (any metastatic disease).

Clinical Features

Diverse presentation: persistent abdominal pain, gastric distension/vomiting, weight loss (cachexia), anorexia, anaemia/weakness/malaise. Commonest complication: haemorrhage (haematemesis/melaena); also obstruction, perforation, jaundice.

Clinical Relevance

The blood-group association pair (group A → gastric cancer, group O → peptic ulcer) is a compact, easily-confused fact worth deliberately cross-referencing against Peptic Ulcer Disease — the two diseases share an anatomic region and several risk factors, making it easy to mix up which blood group goes with which condition.
Krukenberg tumour is one of the highest-yield “metastasis named after its secondary site” facts in pathology — recognising bilateral solid ovarian masses in a patient (especially with a mucin-producing signet-ring cell histology) as a strong pointer back to an occult gastric (or other GI) primary is a genuinely tested clinical reasoning pattern, not just a name to memorise.
The EGC-versus-advanced distinction, and EGC’s dramatically better prognosis (93–99% vs the generally poor outlook of advanced disease), is the direct rationale for endoscopic screening programmes in high-incidence populations (Japan) — this single staging distinction, more than histologic subtype, is what determines whether gastric cancer is a highly curable or a life-threatening diagnosis.
Linitis plastica’s marked desmoplasia obscuring the tumour cells histologically is a genuine diagnostic trap — a biopsy from a linitis plastica stomach can appear deceptively bland or even benign if it samples desmoplastic stroma without capturing the sparse infiltrating signet-ring cells, which is why clinical/radiologic suspicion (diffuse wall thickening, “leather-bottle” appearance) must sometimes override a falsely reassuring biopsy.

EGC-to-advanced sequential evolution with the five advanced-carcinoma gross subtypes branching off
Three spread routes (direct/lymphatic/haematogenous) with Krukenberg tumour and Virchow’s node marked