Oesophageal & Gastric Pathology
Pathology · GIT & Liver · lean revision notes
Oesophageal & Gastric Pathology
High-yield morphology-driven topic: Barrett oesophagus, oesophageal carcinomas (squamous vs adeno), gastric carcinoma (Lauren classification), Helicobacter pylori disease and Menetrier disease. NEET PG loves the histology images here — goblet cells and signet-ring cells are the classic image-recall traps.
1. Normal mucosa & a quick orientation
The oesophagus is lined by non-keratinised stratified squamous epithelium. The stomach is lined by simple columnar epithelium with foveolar (surface mucous) cells, and glands that differ by region:
- Cardia/antrum → mucous glands (and G-cells secreting gastrin in the antrum).
- Body/fundus → oxyntic (gastric) glands with parietal cells (HCl + intrinsic factor) and chief cells (pepsinogen).
The squamo-columnar junction is the Z-line (gastro-oesophageal junction). Disease tends to arise where one epithelium is forced to behave like another (metaplasia) — the recurring theme of this topic.
High-yield: Metaplasia is a reversible change of one differentiated cell type into another, usually as an adaptive response to chronic stress. It is the soil from which dysplasia and carcinoma grow.
2. Gastro-oesophageal reflux disease (GERD) & Barrett oesophagus
GERD basics
Reflux of acidic gastric contents → reflux oesophagitis. Histology shows basal zone hyperplasia, elongation of lamina propria papillae, and intra-epithelial eosinophils, neutrophils and lymphocytes. (Pure eosinophilic infiltrate with rings/furrows on endoscopy in a young atopic patient → think eosinophilic oesophagitis, >15 eos/HPF, treated with topical steroids/dietary elimination — a classic differential.)
Barrett oesophagus — the star of this topic
Chronic GERD → the distal squamous mucosa is replaced by metaplastic columnar epithelium containing goblet cells (intestinal metaplasia).
- Endoscopy: salmon-pink/red velvety tongues of mucosa extending upward above the GE junction (contrast with the normal pale, glistening squamous mucosa).
- Histology (image item): columnar-lined epithelium with goblet cells that stain with Alcian blue at pH 2.5 (acid mucins). The goblet cell is the sine qua non of Barrett in the classic (American) definition.
- Risk: white males, obesity, smoking, hiatus hernia.
High-yield: Goblet cells = intestinal metaplasia = Barrett oesophagus. Their presence (not just columnar lining) defines Barrett in the conventional definition tested in NEET PG.
High-yield: Barrett oesophagus is the single most important risk factor for oesophageal adenocarcinoma, increasing risk roughly 30–40 fold. The sequence is: GERD → Barrett (intestinal metaplasia) → low-grade dysplasia → high-grade dysplasia → adenocarcinoma.
Surveillance & management flow: Confirm Barrett on biopsy → grade dysplasia → act on grade.
- No dysplasia → endoscopic surveillance (e.g. every 3–5 years) + PPI.
- Low-grade dysplasia → confirm by second pathologist → endoscopic eradication or close surveillance.
- High-grade dysplasia/intramucosal carcinoma → endoscopic mucosal resection / radiofrequency ablation (definitive).
Dysplasia is recognised by nuclear enlargement, hyperchromasia, stratification, loss of polarity and increased mitoses without invasion through the basement membrane.
3. Oesophageal carcinoma
Two dominant histological types — the comparison is a perennial favourite.
| Feature | Squamous cell carcinoma (SCC) | Adenocarcinoma |
|---|---|---|
| Worldwide frequency | Most common type globally | Most common in USA / West (rising) |
| Usual site | Middle third (also upper) | Distal third / GE junction |
| Precursor | Squamous dysplasia | Barrett oesophagus |
| Major risk factors | Alcohol, tobacco/smoking, hot beverages, nitrosamines, achalasia, Plummer-Vinson, tylosis, HPV, lye stricture | GERD, obesity, smoking, Barrett |
| Race/sex bias | Higher in certain Asian/African belts | White males |
| H. pylori | — | Protective (less reflux) |
High-yield: Globally the commonest oesophageal cancer is squamous cell carcinoma; in the USA/Western countries adenocarcinoma has overtaken it owing to GERD/Barrett and obesity.
Named associations (eponym recall):
- Plummer-Vinson (Paterson-Kelly) syndrome = dysphagia + iron-deficiency anaemia + oesophageal webs (upper/post-cricoid) → predisposes to post-cricoid SCC.
- Tylosis (palmoplantar keratoderma, RHBDF2 mutation) → SCC.
- Achalasia → mid-oesophageal SCC (food stasis).
- Lye (corrosive) stricture → SCC years later.
Clinical features: progressive dysphagia (solids → then liquids), weight loss, odynophagia, retrosternal pain, hoarseness (recurrent laryngeal involvement), and late presentation because the oesophagus has no serosa → early spread. Lymphatic spread depends on level (upper → cervical nodes; middle → mediastinal; lower → coeliac/gastric nodes).
Investigation of choice: upper GI endoscopy with biopsy (diagnosis); CT/PET and endoscopic ultrasound (EUS) for T and N staging. Barium swallow may show the classic irregular "rat-tail"/apple-core narrowing but is not diagnostic.
4. Gastric pathology — gastritis spectrum
Acute gastritis
NSAIDs, alcohol, severe stress (burns = Curling ulcer; raised ICP/CNS injury = Cushing ulcer), uraemia. Neutrophilic, erosive.
Chronic gastritis — two big buckets
| Feature | Type A (Autoimmune) | Type B (H. pylori) |
|---|---|---|
| Frequency | Less common (~10%) | Most common |
| Location | Body/fundus | Antrum (can extend) |
| Antibodies | Anti-parietal cell, anti-intrinsic factor | — |
| Acid | Achlorhydria (parietal cell loss) | Variable/↑ early |
| Gastrin | High (loss of acid feedback) | Normal/variable |
| Vit B12 | Deficient → pernicious anaemia | Usually normal |
| Cancer link | Intestinal-type adenocarcinoma, carcinoid (ECL hyperplasia) | Adenocarcinoma + MALT lymphoma |
High-yield: Autoimmune gastritis → loss of parietal cells → ↓ intrinsic factor → B12 deficiency / pernicious anaemia, hypergastrinaemia, and ECL-cell hyperplasia that can produce gastric carcinoid tumours.
5. Helicobacter pylori-associated pathology
A spiral, microaerophilic, urease-positive, oxidase- and catalase-positive Gram-negative rod that colonises the gastric mucous layer (and areas of gastric metaplasia in the duodenum).
Virulence & mechanism: urease (neutralises acid, makes ammonia), flagella (motility), adhesins, CagA and VacA (cytotoxins → inflammation, epithelial injury).
Disease spectrum (image/association recall):
- Chronic antral gastritis (most common cause).
- Peptic ulcer disease — H. pylori causes the majority of duodenal ulcers (~70–90%) and many gastric ulcers.
- Gastric adenocarcinoma (intestinal type, via chronic gastritis → atrophy → intestinal metaplasia → dysplasia → carcinoma).
- Gastric MALT lymphoma (extranodal marginal zone B-cell lymphoma).
High-yield: H. pylori is a WHO/IARC Group 1 (definite) carcinogen for gastric adenocarcinoma. It is the only bacterium classified as a definite human carcinogen — a favourite one-liner.
High-yield: Low-grade gastric MALT lymphoma is the classic tumour that can regress with H. pylori eradication (triple therapy) alone — antibiotics treating a cancer. Translocation t(11;18) predicts non-response to eradication.
Diagnosis:
- Non-invasive: urea breath test and stool antigen (best for confirming eradication; stop PPI/antibiotics before testing to avoid false negatives). Serology cannot distinguish current vs past infection.
- Invasive (endoscopy): rapid urease test (CLO test), histology (organisms on the surface mucus, best seen with Giemsa/Warthin-Starry/immunostain), and culture.
Treatment: PPI-based triple therapy (PPI + clarithromycin + amoxicillin/metronidazole) or quadruple therapy with bismuth in resistant areas.
6. Gastric carcinoma — Lauren classification (core image topic)
Adenocarcinoma is by far the commonest gastric malignancy (>90%). The Lauren classification splits it into intestinal and diffuse types — distinguish them cold.
| Feature | Intestinal type | Diffuse type |
|---|---|---|
| Histology | Gland-forming, cohesive cells (resembles colonic Ca) | Discohesive signet-ring cells, no/poor glands |
| Signet-ring cells | Few/none | Hallmark (mucin pushes nucleus to periphery — "signet ring") |
| Background | Chronic atrophic gastritis, intestinal metaplasia, H. pylori, diet (nitrosamines, smoked food) | Often no precursor; CDH1 / E-cadherin loss |
| Age / trend | Older, declining incidence | Younger, relatively stable |
| Spread/macroscopy | Bulky/ulcerated mass | Linitis plastica ("leather bottle" rigid stomach) |
| Prognosis | Relatively better | Worse |
| Genetics | APC, p53, microsatellite instability | CDH1 mutation (also hereditary diffuse gastric cancer) |
High-yield (image item): Signet-ring cell = cytoplasm distended by mucin pushing a crescentic nucleus to the cell periphery → diffuse-type gastric carcinoma. Mucicarmine / PAS highlight the intracytoplasmic mucin.
High-yield: Diffuse infiltration of the stomach wall → linitis plastica ("leather bottle" stomach), classically signet-ring/diffuse type with loss of E-cadherin (CDH1). Hereditary diffuse gastric cancer = germline CDH1 mutation (prophylactic gastrectomy considered).
Other gastric tumours to keep separate:
- MALT lymphoma (H. pylori, lymphoepithelial lesions).
- GIST (gastrointestinal stromal tumour) — spindle/epithelioid cells, c-KIT (CD117) +, DOG1+, arises from interstitial cells of Cajal; treated with imatinib.
- Carcinoid (NET) — from ECL cells, chromogranin/synaptophysin +, associated with autoimmune gastritis/MEN-1/ZES.
Macroscopic patterns (Borrmann): I polypoid, II fungating, III ulcerated, IV diffuse/infiltrative (linitis).
Spread & eponymic metastases (classic short-answer recall):
- Virchow node — left supraclavicular node (Troisier sign).
- Krukenberg tumour — bilateral ovarian metastasis of signet-ring cells.
- Sister Mary Joseph nodule — periumbilical metastasis.
- Blumer shelf — palpable rectouterine/rectovesical deposit on PR.
- Irish node — left axillary node.
Investigation of choice: upper GI endoscopy + biopsy for diagnosis; CT / EUS / staging laparoscopy for staging. Early gastric cancer = confined to mucosa/submucosa regardless of nodal status (Japanese definition) and has an excellent prognosis.
7. Menetrier disease (hyperplastic, hypoproteinaemic gastropathy)
A rare, characteristic entity beloved of exams.
- Pathology: massive foveolar (surface mucous) cell hyperplasia → giant, cerebriform rugal folds in the body/fundus with glandular atrophy.
- Driver: excessive TGF-α signalling (EGFR pathway).
- Clinical: protein-losing enteropathy → hypoalbuminaemia, oedema, weight loss, epigastric pain; often hypochlorhydria.
- Mnemonic: "Menetrier = More mucosa, More mucus, Less protein, Less acid."
High-yield: Giant gastric rugal folds + hypoproteinaemia/oedema + foveolar hyperplasia = Menetrier disease; it is a (low) premalignant condition. Contrast with Zollinger-Ellison syndrome, where rugal hyperplasia is driven by gastrin and acid is high.
8. Putting differentials together
Giant gastric folds DDx: Menetrier (↓acid, hypoproteinaemia) vs Zollinger-Ellison (↑gastrin, ↑acid, ulcers) vs lymphoma vs diffuse carcinoma/linitis.
Dysphagia DDx: carcinoma (progressive, older, weight loss) vs achalasia (both solids & liquids early, bird-beak) vs benign stricture (GERD) vs web/ring (Plummer-Vinson, Schatzki).
Oesophageal columnar mucosa: Barrett (goblet cells, intestinal metaplasia) vs simple cardiac-type columnar metaplasia (no goblet cells).
Recently asked / exam angle
- Image of goblet cells in oesophageal biopsy → identify Barrett oesophagus; name the special stain → Alcian blue (pH 2.5); name the cancer it predisposes to → adenocarcinoma.
- Signet-ring cell photomicrograph → diffuse gastric carcinoma; gene → CDH1/E-cadherin; gross → linitis plastica.
- Commonest oesophageal cancer worldwide vs in the West (SCC vs adenocarcinoma) — repeated single-best-answer.
- Only bacterium that is a definite (Group 1) human carcinogen → H. pylori.
- Tumour that regresses with antibiotics → gastric MALT lymphoma; non-responder marker → t(11;18).
- Best test to confirm H. pylori eradication → urea breath test / stool antigen (off PPI).
- Krukenberg / Virchow / Sister Mary Joseph — match the eponym to gastric cancer metastasis.
- Autoimmune gastritis → antibody (anti-parietal/anti-IF), vitamin (B12), tumour risk (carcinoid).
- Giant rugal folds + hypoalbuminaemia → Menetrier; cytokine → TGF-α.
- CLO/rapid urease test principle → bacterial urease splitting urea (colour change).
Rapid revision
- Barrett = goblet cells (intestinal metaplasia), salmon-pink mucosa above Z-line; Alcian blue +; → oesophageal adenocarcinoma (distal third).
- SCC = commonest oesophageal cancer worldwide, middle third; alcohol, tobacco, achalasia, Plummer-Vinson, lye, tylosis.
- Adenocarcinoma = commonest in the West, distal third, from Barrett/GERD/obesity.
- Plummer-Vinson = web + iron-deficiency anaemia + dysphagia → post-cricoid SCC.
- H. pylori = urease-positive spiral rod, Group 1 carcinogen; antral gastritis, duodenal ulcer, gastric adenoca, MALT lymphoma.
- MALT lymphoma regresses with eradication therapy; t(11;18) = won't respond.
- Lauren intestinal = glands, cohesive, H. pylori/metaplasia background, APC/p53/MSI.
- Lauren diffuse = signet-ring cells, CDH1/E-cadherin loss, linitis plastica, worse prognosis.
- Autoimmune (Type A) gastritis = body/fundus, anti-IF Ab, B12 deficiency/pernicious anaemia, ↑gastrin, carcinoid risk.
- Gastric cancer mets: Virchow (L supraclavicular), Krukenberg (ovary), Sister Mary Joseph (umbilicus), Blumer shelf (PR).
- Menetrier = giant rugae + foveolar hyperplasia + hypoproteinaemia/oedema + low acid, driven by TGF-α.
- Diagnostic IOC for both oesophageal & gastric cancer = endoscopy + biopsy; stage with EUS/CT/PET.