64. Gastric precancerous conditions, polyps and other tumours

1. Definition

• Precancerous conditions → diseases with a raised risk of gastric cancer: atrophic gastritis, intestinal metaplasia, pernicious anaemia, adenomas, gastric remnant, Ménétrier's disease
• Precancerous lesion → dysplasia (intraepithelial neoplasia), low or high grade
• Gastric polyp → any lesion raised above the mucosa
• Other gastric tumours:
  • GIST (gastrointestinal stromal tumour)
  • Gastric lymphoma (MALT and diffuse large B-cell)
  • Neuroendocrine tumour (NET, carcinoid)
  • Benign → leiomyoma, lipoma, schwannoma, ectopic pancreas

2. Epidemiology

• Gastric polyps → found in about 6% of gastroscopies
  • Fundic gland polyps → about 75% (in the West; PPI users)
  • Hyperplastic polyps → about 15–20%
  • Adenomas → under 10% (more where H. pylori is common)
• GIST → most common mesenchymal tumour of the gut; 60% in the stomach, 30% small bowel; median age 60
• Gastric lymphoma → stomach is the commonest site of extranodal lymphoma (about 5% of gastric cancers)
• Gastric NETs → under 2% of gastric tumours; rising with more endoscopy

3. Aetiology and risk factors

• H. pylori → chronic gastritis, atrophy, metaplasia, adenomas, MALT lymphoma
• Autoimmune (pernicious anaemia) gastritis → body atrophy, high gastrin → type 1 NETs, cancer
• Fundic gland polyps → long-term PPIs; many small polyps in familial adenomatous polyposis (FAP) (dysplasia possible)
• Hyperplastic polyps → chronic gastritis (H. pylori, autoimmune), around gastroenterostomy stomas
• Adenomas → atrophic gastritis, FAP
• Polyposis syndromes → Peutz-Jeghers (hamartoma), juvenile polyposis, Cowden
• Gastric remnant → 15–20 years after Billroth II (bile reflux)
• Ménétrier's disease → giant rugal folds, protein loss; TGF-alpha excess
• GIST → KIT (CD117) mutation (about 80%) or PDGFRA (about 10%); neurofibromatosis type 1, Carney triad, SDH-deficient (young)
• NETs:
  • Type 1 → atrophic gastritis
  • Type 2 → Zollinger-Ellison syndrome in MEN1
  • Type 3 → sporadic

4. Pathogenesis

• Correa cascade → gastritis → atrophy → intestinal metaplasia → dysplasia → cancer
• Risk rises with the extent of atrophy and metaplasia (OLGA and OLGIM stages III–IV = high risk)
• Adenoma → dysplasia-carcinoma sequence; risk rises with size over 2 cm
• Hyperplastic polyp → cancer risk low (1–2%), more if over 1 cm
• GIST → from interstitial cells of Cajal (gut pacemaker cells); grows outwards (exophytic); spreads by blood to liver and peritoneum; rarely to nodes
• MALT lymphoma → H. pylori drives B-cell growth in gastric lymphoid tissue; t(11;18) translocation predicts poor response to eradication
• High gastrin (types 1 and 2) → enterochromaffin-like (ECL) cell hyperplasia → small, multiple NETs

5. Classification

Gastric polyps

• Non-neoplastic → fundic gland, hyperplastic, inflammatory fibroid, hamartomatous
• Neoplastic → adenoma (tubular, villous, tubulovillous), neuroendocrine, GIST and other submucosal

Dysplasia (Vienna)

• Low-grade, high-grade, intramucosal carcinoma, invasive

GIST risk (modified NIH / Miettinen)

• Based on size, mitotic count (per 5 mm²), site (gastric better than small bowel), rupture
• Very low, low, intermediate, high

Gastric NETs

• Type 1 (70–80%) → atrophic gastritis; high gastrin; small, many, benign
• Type 2 (5%) → gastrinoma (MEN1); high gastrin; many, low risk
• Type 3 (15–20%) → sporadic; normal gastrin; single, large, malignant

Gastric lymphoma

• MALT (marginal zone, low grade)
• Diffuse large B-cell lymphoma (high grade) → most common
• Lugano staging

6. Clinical picture

Symptoms

• Precancer and most polyps → no symptoms; found at endoscopy
• Large polyps → bleeding (anaemia), pyloric obstruction (prolapse through the pylorus)
• GIST → upper GI bleeding (ulcerated mucosa over it), abdominal mass, early satiety, pain; many found by chance
• Lymphoma → epigastric pain, weight loss, bleeding; B symptoms (fever, night sweats) in high-grade disease
• Pernicious anaemia → tiredness, neuropathy (B12)
• NET → usually none; carcinoid syndrome rare (liver metastases, type 3); type 2 → ulcers, diarrhoea
• Ménétrier's → oedema (protein loss), epigastric pain

Signs

• Pallor
• Epigastric mass (GIST, lymphoma)
• Hepatomegaly (metastases)

7. Diagnosis

• Gastroscopy with biopsies:
  • Updated Sydney protocol (2 antrum, 1 incisura, 2 body) → atrophy, metaplasia, H. pylori
  • Remove or biopsy polyps; image-enhanced endoscopy (narrow-band imaging)
  • Gastrin and parietal cell or intrinsic factor antibodies (autoimmune gastritis)
• Submucosal mass:
  • Endoscopic ultrasound (EUS) → layer of origin (GIST from the muscularis propria, layer 4); size, features
  • EUS-guided fine-needle biopsy → CD117 (KIT) and DOG1 staining for GIST
  • Avoid percutaneous biopsy of a resectable GIST (rupture, seeding)
• CT → GIST size, spread; lymphoma staging; NET staging
• Lymphoma → biopsy (histology, H. pylori, t(11;18)), PET-CT, bone marrow
• NET → serum gastrin, chromogranin A, Ki-67 index (grade), gallium-68 DOTATATE PET
• Mutation testing → GIST (KIT exon 11, 9; PDGFRA D842V → resistant to imatinib)

8. Differential diagnosis

• Polyps → early gastric cancer, submucosal tumours, ectopic pancreas, varices
• Submucosal mass → GIST, leiomyoma, lipoma, schwannoma, external pressure (spleen, pancreas)
• Thick folds → lymphoma, Ménétrier's, linitis plastica, Zollinger-Ellison

9. Treatment

Conservative

• Eradicate H. pylori in everyone with gastritis, metaplasia or polyps
• Surveillance of extensive atrophy or intestinal metaplasia (MAPS II guideline):
  • Extensive (antrum and body) or family history → endoscopy every 3 years
  • Low-grade dysplasia without a visible lesion → repeat in 12 months
• Fundic gland polyps → no follow-up if under 1 cm; review PPI need
• Hyperplastic polyps → eradicate H. pylori; many regress
• MALT lymphoma (stage I, H. pylori positive) → H. pylori eradication alone → remission in about 75%
  • No response, t(11;18) → radiotherapy; rituximab-based chemotherapy for advanced disease
• Diffuse large B-cell lymphoma → R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) ± radiotherapy; surgery not first-line
• GIST:
  • Imatinib (tyrosine kinase inhibitor):
    • Adjuvant for 3 years in high-risk resected GIST
    • Neoadjuvant to shrink large tumours (organ-sparing)
    • First-line in metastatic disease
  • Second line → sunitinib, then regorafenib, ripretinib; avapritinib for PDGFRA D842V
  • GIST under 2 cm with no high-risk EUS features → EUS surveillance
• Type 1 NET under 1 cm → endoscopic surveillance or endoscopic removal
• Metastatic NETs → somatostatin analogues (octreotide, lanreotide), PRRT (lutetium-177 DOTATATE), everolimus

Surgical

• Endoscopic resection:
  • Adenomas → remove all (EMR or ESD)
  • Hyperplastic polyps over 1 cm → remove (cancer focus possible)
  • Fundic gland polyps over 1 cm, or with dysplasia → remove
  • High-grade dysplasia or early cancer → ESD
  • Type 1 and 2 NETs over 1 cm → EMR or ESD
• GIST → surgical resection is the only cure:
  • Wedge or segmental resection with clear margins (1–2 cm enough); no lymphadenectomy (nodes rarely involved)
  • Avoid tumour rupture (high recurrence risk)
  • Laparoscopic resection for tumours up to about 5 cm
  • Large or near the cardia or pylorus → neoadjuvant imatinib, then partial or rarely total gastrectomy
• Type 3 NET → gastrectomy with lymphadenectomy (as adenocarcinoma)
• Type 2 NET → remove the gastrinoma (duodenum or pancreas)
• Type 1 NET, many or recurrent → antrectomy (removes gastrin source)
• Lymphoma → surgery only for complications (perforation, bleeding, obstruction)
• Polyposis → endoscopic removal; prophylactic gastrectomy for CDH1 carriers
• Ménétrier's → anti-EGFR antibody (cetuximab); gastrectomy for severe protein loss or dysplasia

10. Complications

• Precancer → gastric cancer
• Polyps → bleeding, obstruction, cancer
• GIST → bleeding, rupture, liver and peritoneal metastases; imatinib side effects (oedema, rash, diarrhoea, myelosuppression)
• Lymphoma → perforation during chemotherapy, bleeding
• NETs → liver metastases, carcinoid syndrome (rare)
• Endoscopic resection → bleeding, perforation