Q2 LONG ANSWER 10M ★ High-yield

Describe the aetiology, classification, morphology and spread of gastric carcinoma.

Pathology · 2nd Professional — Para-Clinical

Introduction

Gastric carcinoma is a malignant epithelial tumour of the stomach, accounting for over 90% of gastric malignancies.

Incidence varies greatly by region — very high in Japan, Korea, China and parts of South America; in India it is commonest in the south and north-east
Male to female ratio about 2:1; usually over 50 years
Site — 50–60% in the pylorus and antrum, and more on the lesser curvature than the greater

Aetiology

Factor	Detail
Helicobacter pylori	A WHO class I carcinogen; causes chronic gastritis → atrophy → intestinal metaplasia → dysplasia → carcinoma. Also causes gastric malt lymphoma
Diet	Nitrosamines; smoked, salted and pickled foods; low intake of fresh fruit and vegetables (vitamins C and E are protective)
Precursor conditions	Chronic atrophic gastritis, intestinal metaplasia, dysplasia, pernicious anaemia (autoimmune gastritis), gastric adenomatous polyps, menetrier disease, previous partial gastrectomy (after 15–20 years)
Genetic	Blood group A; family history; germline E-cadherin (CDH1) mutation causes hereditary diffuse gastric cancer; HNPCC; familial adenomatous polyposis
Other	Smoking; low socioeconomic status; Epstein–Barr virus in about 10%

Classification

Early and advanced gastric carcinoma

Type	Definition	Prognosis
Early gastric carcinoma	Confined to the mucosa and submucosa, regardless of lymph node involvement	5-year survival above 90%
Advanced gastric carcinoma	Extends beyond the submucosa into the muscularis propria or further	5-year survival under 20%

The definition of "early" depends on depth, not on nodes or size — a common examination trap
Japan detects a high proportion at the early stage through population endoscopic screening, which is why its survival figures are so much better

Macroscopic (Borrmann) types of advanced carcinoma

I — polypoid or fungating
II — ulcerated with sharply raised, heaped margins
III — ulcerated with diffuse infiltration of the margins
IV — diffusely infiltrative; when the whole stomach is involved it becomes a rigid, thickened, contracted organ — "linitis plastica" or the leather-bottle stomach

Lauren Histological Classification

Feature	Intestinal type	Diffuse type
Differentiation	Well differentiated; forms glands resembling intestinal epithelium	Poorly differentiated; NO gland formation
Cells	Columnar, cohesive	Signet ring cells — a mucin vacuole displacing the nucleus to the periphery; discohesive and infiltrate singly
Age	Older, over 50	Younger patients
Sex	Male predominance	Equal
Precursor lesion	Chronic atrophic gastritis with intestinal metaplasia	None identified
Genetics	APC, p53, microsatellite instability	E-cadherin (CDH1) loss — explaining the loss of cell cohesion
Macroscopic form	Polypoid or ulcerated mass	Linitis plastica
Spread	Haematogenous, to liver	Transcoelomic; krukenberg tumour
Environmental link	Strong — declining in incidence	Weak — incidence stable
Prognosis	Better	Worse

CLINICAL PEARL

Loss of E-cadherin explains the entire diffuse phenotype. E-cadherin is the molecule that holds epithelial cells to one another. Lose it and the cells cannot form glands, infiltrate singly rather than as a mass, and spread diffusely through the wall — producing linitis plastica and the signet-ring morphology. One molecular defect accounts for the histology, the naked-eye appearance and the poor prognosis together.

Spread and Clinical Features

Route	Sites
Direct	Pancreas, transverse colon, liver, omentum, spleen
Lymphatic	Perigastric nodes; then the left supraclavicular node — virchow node (troisier sign)
Haematogenous	Liver (commonest), lung, bone, brain
Transcoelomic	Peritoneal seeding; bilateral ovarian deposits = krukenberg tumour (signet-ring cells in a fibrous stroma); "sister MARY JOSEPH nodule" at the umbilicus; BLUMER shelf in the rectovesical pouch

Early disease is asymptomatic or gives vague dyspepsia, which is why most present late
Later — weight loss, epigastric pain, anorexia (especially for meat), vomiting, iron deficiency anaemia, a palpable epigastric mass
Paraneoplastic — acanthosis nigricans, the sign of Leser–Trelat, migratory thrombophlebitis, dermatomyositis, microangiopathic haemolytic anaemia

Applied Aspects

Endoscopy with multiple biopsies is the investigation of choice; a single biopsy from an ulcer edge may miss the tumour, and at least 6 to 8 should be taken
Linitis plastica may yield negative mucosal biopsies, because the tumour infiltrates the submucosa and muscularis while sparing the surface — deep or endoscopic ultrasound-guided biopsy may be needed
H. Pylori eradication reduces the risk, and is the main preventable factor; refrigeration and fresh food have driven the worldwide decline in incidence
Staging by CT and laparoscopy; peritoneal disease found at laparoscopy spares the patient a futile laparotomy
Surgery is the only curative treatment, with perioperative chemotherapy; HER2 testing guides trastuzumab in advanced disease
Gastric lymphoma (malt) must be separated from carcinoma — it may regress completely with H. Pylori eradication alone, and so has a far better outlook
Gastrointestinal stromal tumour (GIST) is the other important gastric neoplasm — arising from the interstitial cells of Cajal, CD117 (kit) positive, and treated with imatinib
Prognosis depends on depth of invasion and nodal status, which is why detecting disease while it is still "early" matters so much more than any treatment advance
Population endoscopic screening is justified only where incidence is high, as in Japan and Korea; it is not cost-effective in low-incidence populations

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