Pathology of the Stomach

Question 1

Acute Gastritis

Answer 1

acute mucosal inflammatory process, usually of a transient nature
Neutrophils present
With or without ulceration
Rarely associated with infection
No signs or pain, vomiting (sometimes blood)

Question 2

Acute hemorrhagic (erosive) gastritis

Answer 2

Associated with NSAIDS, particularly aspirin
Heavy alcohol intake (spirits), “alcoholic gastritis”
Heavy smoking
Stress
Ulcer base is frequently stained brown to black by acid digestion of extravasated blood and may be associated with transmural inflammation and local serositis

Question 3

Stress Ulcers – Acute Gastric Ulceration

Answer 3

Commonly encountered in patients with shock, extensive burns, sepsis, or severe trauma….. critically ill
Considered to be the result of local ischemia due to systemic hypotension or stress-induced splanchnic arterial vasoconstriction

Question 4

Gastropathy

Answer 4

Usually inflammatory cells absent Repair process associated with chronic or repeated episodes of acute gastritis (usually chemically induced)

Question 5

Cushing ulcers

Answer 5

Gastric mucosal injury associated with intracranial injury.
Thought to be caused by direct stimulation of vagal nuclei.
vagus nerve mediates the cephalic phase of gastric acid secretion.
Pts with head injuries are routinely placed on omeprazole

Question 6

Chronic Gastritis

Answer 6

Presence of chronic mucosal inflammatory changes leading to atrophy and metaplasia, usually in absence of erosions.
May become dysplastic leading to development of carcinoma.
Usually secondary to H. pylori.
Autoimmune gastritis including pernicious anemia is < 10%,
- increased risk of gastric cancer

Question 7

Chronic Gastritis - Clinical

Answer 7

Nausea and upper abdominal discomfort may occur, sometimes with vomiting, but hematemesis is uncommon.
Autoimmune gastritis is the most common cause of atrophic gastritis

Question 8

H. Pylori Infection and Chronic Gastritis

Answer 8

Most often presents as a predominantly antral gastritis with high acid production, despite hypogastrinemia.
Increased risk of gastric adenocarcinoma.
Four features are linked to H. pylori virulence: flagella, urease activity, adhesins, toxins such as (CagA)

Question 9

Pathologic Changes Associated with H. Pylori Chronic Gastritis

Answer 9

Acute inflammation w/PMNs
Chronic inflam w/diffuse lymphocytes plus plasma cells in lamina propria, & lymphoid follicles.
Intestinal metaplasia
Mucosal atrophy - usually patchy (marker for increased cancer risk)
Peptic ulcer disease
Dysplasia - ADCA sequence
MALT lymphoma

Question 10

Autoimmune Gastritis

Answer 10

Typically spares the antrum and includes hypergastrinemia (but achlorhydria).
Antibodies to parietal cells and intrinsic factor that can be detected in serum and gastric secretions.
Atrophic histological appearance.
When severe is associated with Pernicious Anemia.
Associated with increased risk of gastric cancer and carcinoid tumors.

Question 11

Autoimmune Gastritis - Patho

Answer 11

CD4+T cells against parietal cell components including the H+,K+ -ATPase.
- Chief cells also get destroyed
Reduced serum pepsinogen I concentration
- poor digestion
- delayed gastric emptying
Antral/fundic endocrine cell hyperplasia can result in carcinoid tumors.
Vitamin B12 deficiency.
Defective gastric acid secretion (achlorhydria).

Question 12

Autoimmune Gastritis - Morpho

Answer 12

Characterized by diffuse mucosal damage of the oxyntic (acid-producing) mucosa within the body and fundus.
With diffuse atrophy, the oxyntic mucosa of the body and fundus appears markedly thinned, and rugal folds are lost.
Antral endocrine cell hyperplasia
Intestinal metaplasia

Question 13

Reactive gastropathy

Answer 13

Gastric mucosa, showing hyperplasia of foveolar surface epithelial cells, glandular regenerative changes, and smooth muscle fibers extending into lamina propria.
Chemical injury, NSAID use, bile reflux, and mucosal trauma
(Gastric antral vascular ectasia …watermelon stomach…unknown etiology)

Question 14

Peptic Ulcer Disease

Answer 14

Chronic, most often solitary, lesions that occur in any part of the GI tract exposed to aggressive action of acid/peptide juices.
Usually in background of chronic gastritis. Associated with H. Pylori and NSAIDs.
95% within short distance of gastro duodenal-junction.
Most H. pylori related.
Can occur in GERD or Meckels

Question 15

Peptic Ulcer Disease - Morpho

Answer 15

Sharp Demarcation of Mucosa with Ulcer.
The ulcer is small (2 cm) and “punched-out”. Unlike cancerous ulcers, the margins are not elevated. The ulcer base is clean.
Perforation into the peritoneal cavity is a surgical emergency that may be identified by the presence of free air under the diaphragm on upright radiographs of the abdomen.

Question 16

Possible returns from nasogastric tube

Answer 16

Coffee grounds = slow bleeding or oozing.
Red blood/clots = active ongoing bleed.
Bile stained = no active bleeding above the Treitz ligament. A bile stained NG aspirate would make active bleeding proximal to the third portion of the duodenum most unlikely.
Clear = GI bleeding is often times intermittent and can stop spontaneously. The clear return suggests a competent pylorus and bleeding could be still occurring in the bulb and going postbulbar

Question 17

Hypertrophic Gastropathy

Answer 17

Menetrier Disease & Zollinger-Ellison Syndrome
Two important points:
- may mimic carcinoma or lymphoma
- may have severe peptic ulcer disease [Z-E]
Shows markedly thickened “cerebriform” gastric folds

Question 18

Menetrier disease

Answer 18

Excessive secretion of TGF-α
Protein-losing enteropathy
Weight loss, diarrhea, peripheral edema
Body and fundic involvement
Increased risk of ADCA in adults
Pediatric disease is usually self-limited and often follows respiratory infection
High-protein diet should be recommended to replace protein loss in patients with hypoalbuminemia

Question 19

Zollinger-Ellison Syndrome

Answer 19

Cause: gastrin-secreting tumor, i.e. gastrinoma
Chronic diarrhea, multiple peptic ulcers
Doubling of oxyntic mucosal thickness due to a 5x increase in the number of parietal cells
Rx: Block acid production, find & remove tumor

Question 20

Zollinger-Ellison Syndrome - Patho

Answer 20

Caused by a non–beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach.
May be sporadic or autosomal dominant familial syndrome called multiple endocrine neoplasia type 1 (MEN 1).
MEN I patients have tumors in their pituitary gland and parathyroid glands, in addition to tumors of the pancreas.
Octreotide is the best drug for pharmacologic management.
Cure is tumor removal w/chemo.

Question 21

Inflammatory and Hyperplastic Polyps:

Answer 21

75% of gastric polyps, usually small (1.5cm] polyps)

Corkscrew-shaped foveolar glands

Question 22

Fundic Gland polyps

Answer 22

Sporadic and FAP pts, F>M 5:1
Proton pump inhibitor related (2ndary to increased gastrin)
Lined by parietal, chief, and foveolar cells.

Question 23

Gastric Adenomas (Adenomatous polyps)

Answer 23

Contain proliferative dysplastic epithelium
Arise in chronic gastritis with atrophy and intestinal metaplasia
5-10% of gastric polyps, M>F 3:1
Marked association with subsequent carcinoma (~30%), greater if >2cm
Presence of epithelial dysplasia

Question 24

Stomach Carcinoma: Intestinal-type (non-signet ring)

Answer 24

3-fold decline in incidence over last 50 years**
M>F 2:1
Association with prior H. pylori infection and precursor lesions (atrophy, dysplasia, adenoma)
- Toll-like receptor 4 (TLR4)
FAP-related (APC/WNT pathway), HNPCC-related, p53
5-year survival rates 30% after resection (overall 10-15% 5 yr)
Occurs predominately in gastric antrum/pylorus; lesser > greater curvature
Malignant gland formation

Question 25

Stomach Carcinoma: Diffuse-type (signet-ring)

Answer 25

No decline, increasing in incidence (now 50%)
M=F
No association with H. pylori or precursor lesion
CDH1/ E-cadherin mutations, p53
Loss of E-cadherin function seems to be a key step in the development
Dismal 5-year survival, none to 1 or 2%
Occur throughout the stomach
Intracytoplasmic mucin droplet
Desmoplasia

Question 26

Stomach Carcinoma: Early

Answer 26

Tumor is confined to the mucosa and submucosa and may exhibit an exophytic, flat or depressed, or excavated conformation

Question 27

Stomach Carcinoma: Late

Answer 27

Carcinoma extends into the muscularis propria and beyond. Linitis plastica is an extreme form of flat or depressed advanced gastric carcinoma.

Question 28

Lymphoma

Answer 28

“Most common site of extra-nodal lymphoma”
Two types:
- Indolent extra-nodal marginal zone B-cell lymphomas (MALToma, H. pylori related.)*
- Diffuse large B-cell lymphoma (high grade) [rare large T-cell]

Question 29

Gastric MALT (B-cell) Lymphoma

Answer 29

Many are H. pylori related  
(~50% disappear on antibiotic Rx)
CD19+, CD20+
May show monoclonal light chains
May ‘transform’ to High Grade
Lymphoepithelial lesions 
Translocations that activate NF-kB

Question 30

Mesenchymal (Gastro-Intestinal Stromal Tumor [GIST])

Answer 30

Arise from the interstitial cells of Cajal (pacemaker cells).
Most common abdominal mesenchymal tumor, 50-60% occur in the stomach
M>F, ave. age 60 yr
Submucosal is most common presentation.
Tumors are mesenchymal in origin.
80 % show tyrosine kinase c-KIT (CD117) mutations / 15% PDGFRA mutations
Most are non-aggressive, but may recur; minority metastasize
Respond to Gleevec (imatinib) Rx if c-KIT or PDGFA positive …..(remember CML!!)…Develop resistance
Can be seen as part of tumor syndromes
Spindle cell feature