Step 1 · Gastrointestinal

Esophageal & Gastric Pathology

Name: Esophageal & Gastric Pathology
Creator: Veli Bakalov, MD

From reflux and rupture to signet-ring cancer and the Virchow node

Gastrointestinal·Oral, Esophageal & Gastric Pathology·5 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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GERD → Barrett esophagus (distal squamous epithelium replaced by columnar epithelium with goblet cells) → dysplasia → distal esophageal adenocarcinoma.
Esophageal SCC = upper two-thirds, most common worldwide (alcohol + tobacco, hot liquids, caustic strictures, achalasia, Plummer-Vinson); adenocarcinoma = lower third, most common in the US (GERD, Barrett, obesity).
Achalasia = loss of NO/VIP inhibitory neurons in the myenteric plexus → LES fails to relax, no peristalsis, bird-beak on barium, dysphagia to solids AND liquids; Chagas disease is a secondary cause; raises SCC risk.
Mallory-Weiss = partial-thickness mucosal GE-junction tear with hematemesis after retching; Boerhaave = transmural rupture with pneumomediastinum, subcutaneous emphysema, Hamman crunch (surgical emergency).
Curling ulcer = burns (hypovolemia → mucosal ischemia); Cushing ulcer = CNS injury (↑ vagal tone → ↑ acid).
Type A gastritis = autoimmune, body/fundus, anti-parietal and anti-IF antibodies, achlorhydria, high gastrin, pernicious anemia, carcinoid and adenocarcinoma risk; type B = H. pylori, antrum, PUD, MALT lymphoma, adenocarcinoma.
Gastric ulcer pain worsens with meals (weight loss) and needs biopsy; duodenal ulcer pain improves with meals (weight gain), is ~90% H. pylori, and is almost always benign.
Posterior duodenal ulcer bleeds from the gastroduodenal artery; anterior duodenal ulcer perforates (free air under the diaphragm).
Diffuse gastric cancer = E-cadherin (CDH1) loss, signet-ring cells, linitis plastica; spread to Virchow node (left supraclavicular), Sister Mary Joseph nodule (umbilicus), Krukenberg tumor (ovaries), Blumer shelf (pouch of Douglas).

Reflux, Barrett esophagus, and esophageal cancer

GERD. Acid refluxes through an incompetent lower esophageal sphincter (LES), causing heartburn and regurgitation; extraesophageal clues are chronic cough and adult-onset asthma. Hiatal hernia, obesity, pregnancy, and scleroderma all weaken the antireflux barrier. Complications are erosive esophagitis, peptic stricture, and Barrett esophagus.

Barrett esophagus. Chronic acid injury drives metaplasia of the distal esophagus: nonkeratinized stratified squamous epithelium is replaced by columnar epithelium with goblet cells (intestinal metaplasia). Barrett is the key precursor of distal esophageal adenocarcinoma, so patients undergo surveillance endoscopy for dysplasia.

GERDWeak LES, acid reflux
Barrett metaplasiaColumnar epithelium with goblet cells
DysplasiaDetected on surveillance endoscopy
AdenocarcinomaDistal esophagus

Reflux to cancer

Two cancers, two locations. Both types present with progressive dysphagia, first to solids and then to liquids, plus weight loss. They spread early because the esophagus has no serosa.

Esophageal cancer types

Feature	Squamous cell carcinoma	Adenocarcinoma
Location	Upper two-thirds	Lower third
Most common	Worldwide	In the US
Risk factors	Alcohol and tobacco (synergistic), hot liquids, caustic strictures, achalasia, Plummer-Vinson syndrome	GERD, Barrett esophagus, obesity, smoking

Achalasia and esophageal bleeding

Achalasia. Loss of inhibitory neurons (NO and VIP) in the myenteric (Auerbach) plexus leaves the LES unable to relax and abolishes peristalsis. Dysphagia is to BOTH solids and liquids from the start, unlike the solids-then-liquids progression of an obstructing cancer. Barium swallow shows a dilated esophagus tapering to a bird-beak; manometry shows high LES pressure with incomplete relaxation and absent peristalsis. Secondary achalasia follows Chagas disease (Trypanosoma cruzi destroys the plexus) or malignancy at the gastroesophageal junction. Long-standing achalasia raises the risk of esophageal squamous cell carcinoma. Treatment targets the LES: pneumatic dilation, surgical myotomy, or botulinum toxin.

Esophageal varices. Dilated submucosal veins that form in portal hypertension where the left gastric (portal) vein meets the azygos (systemic) system. Rupture causes painless, massive hematemesis and is a leading cause of death in cirrhosis. An acute bleed is treated with octreotide, endoscopic banding, and antibiotics; nonselective β-blockers help prevent bleeding.

Mallory-Weiss vs Boerhaave. Severe retching (alcoholics, bulimia) can tear the gastroesophageal junction, and the depth of the tear defines the disease:

Mallory-Weiss syndrome: a partial-thickness, longitudinal mucosal tear causing hematemesis, often with epigastric or back pain; usually self-limited.
Boerhaave syndrome: full-thickness transmural rupture, usually of the distal esophagus. Air and gastric contents enter the mediastinum, producing pneumomediastinum, subcutaneous emphysema, and Hamman crunch (crackling synchronous with the heartbeat). It is a surgical emergency.

Gastritis and H. pylori

Acute (erosive) gastritis. Results from disrupted mucosal defense: NSAIDs (↓ PGE2, so less mucus, bicarbonate, and mucosal blood flow), alcohol, and stress ulcers. Curling ulcer follows severe burns, where hypovolemia causes mucosal ischemia (Curling = Cutaneous burns). Cushing ulcer follows CNS injury, where increased vagal tone raises ACh and acid (Cushing = Cranial injury).

Chronic gastritis. Type A (Autoimmune) is a T-cell–mediated attack on parietal cells, often in patients with other autoimmune diseases such as Hashimoto thyroiditis or vitiligo. Type B (Bacterial) is H. pylori infection and is by far the more common.

Chronic gastritis: type A vs type B

Feature	Type A (autoimmune)	Type B (H. pylori)
Location	Body/fundus	Antrum
Diagnosis	Anti-parietal cell and anti-intrinsic factor antibodies	Urea breath test, stool antigen, biopsy
Acid and gastrin	Achlorhydria, high gastrin	Antral disease often raises acid (duodenal ulcers)
Consequences	Pernicious anemia (B12 deficiency)	Peptic ulcer disease
Neoplasia	Gastric adenocarcinoma; carcinoid (gastrin-driven ECL hyperplasia)	MALT lymphoma, intestinal-type adenocarcinoma

H. pylori. A urease-positive, curved gram-negative rod whose urease generates ammonia to buffer its niche. It colonizes the antrum and drives most peptic ulcers, gastric MALT lymphoma, and intestinal-type adenocarcinoma. Diagnose noninvasively with the urea breath test or stool antigen, or by biopsy. Eradicate with bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline), now preferred because clarithromycin resistance is common; clarithromycin triple therapy (PPI + clarithromycin + amoxicillin) is reserved for known-susceptible strains.

Gastric MALT lymphoma often regresses after H. pylori eradication alone.

Peptic ulcer disease

Gastric vs duodenal ulcer

Feature	Gastric ulcer	Duodenal ulcer
Main causes	H. pylori (~70%), NSAIDs (↓ mucosal protection)	H. pylori (~90%) with ↑ acid; Zollinger-Ellison syndrome
Pain with meals	Worse → weight loss	Relieved → weight gain
Malignant potential	Can be malignant: biopsy required	Almost always benign
Other	Usually lesser curvature	Brunner gland hypertrophy

Location predicts the complication. A posterior duodenal ulcer erodes into the gastroduodenal artery and causes brisk bleeding. An anterior duodenal ulcer perforates into the peritoneal cavity, causing free air under the diaphragm and peritonitis. A lesser-curvature gastric ulcer can bleed from the left gastric artery.

Gastric adenocarcinoma

Intestinal type. Gland-forming tumor arising from chronic gastritis and intestinal metaplasia. Risks are H. pylori, dietary nitrosamines (smoked foods), smoking, and achlorhydria. It typically sits on the lesser curvature as an ulcer with raised, heaped-up margins.

Diffuse type. Not tied to H. pylori. Loss of E-cadherin (CDH1) lets tumor cells detach and infiltrate singly as signet-ring cells, in which intracellular mucin pushes the nucleus to the periphery. Diffuse infiltration with desmoplasia produces linitis plastica, a thick, rigid "leather-bottle" stomach. Paraneoplastic skin signs of gastric cancer include acanthosis nigricans and the Leser-Trélat sign.

Named metastases. Gastric cancer classically announces itself at distant sites:

Virchow node: left supraclavicular lymph node.
Sister Mary Joseph nodule: periumbilical subcutaneous deposit.
Krukenberg tumor: bilateral ovarian metastases packed with signet-ring cells.
Blumer shelf: implant in the rectal pouch of Douglas, palpable on rectal exam.