Pathologic basis of gastric disease

Question 1

Gastritis vs gastropathy

Answer 1

gastritis: inflammation + injury
gastropathy: non-inflammatory injury

Question 2

Hypertrophic Pyloric Stenosis

Answer 2

Hyperplasia of pyloric muscularis propria → obstructs gastric outflow

M:F = 4:1
Presents in 2-3rd week of life with regurgitation and persistent projectile non-bilious vomiting
Firm ovoid abdominal mass

Treatment: Surgical splitting of muscularis propria (“myotomy”)

Question 3

Signs and symptoms of gastric disease

Answer 3

Epigastric Pain ~ Early satiety

Nausea and Vomiting ~ Melena ~ Hematemesis

Question 4

Stress-related Mucosal Disease

Answer 4

Morphologically resembles acute gastritis
Injury mediated by vasoconstriction/ischemia
Erosion and ulceration may be widespread

Occurs in 75% of critically ill patients
Trauma, shock, or sepsis (stress ulcers)
Burns (Curling ulcers)
Intracranial disease (Cushing ulcers)

Question 5

Chronic gastritis

Answer 5

Two most common causes: Helicobacter pylori infection and Autoimmune gastritis

Others:
Eosinophilic gastropathy
Allergic disease [e.g. cow’s milk] and parasitic infection
Lymphocytic gastropathy
associated with celiac disease
Granulomatous gastropathy
Crohn’s disease, sarcoidosis, infection

Question 6

Helicobacter pylori

Answer 6

Gram-negative bacillus adapted to gastric environment

Flagella to maneuver through gastric mucus
Adhesion molecules bind to gastric foveolar cells
Acid resistance through abundant urease
Elaboration of toxins cause tissue damage
Minimization and evasion of immune response

Oral-oral, fecal-oral, and environmental spread
Associated with poverty, household crowding, and rural areas

Question 7

Diseases associated with H. pylori

Answer 7

Gastritis
Gastric and duodenal ulcers (15% lifetime risk)
Gastric adenocarcinoma (1% lifetime risk)
Gastric lymphoma

Question 8

Autoimmune Gastritis

Answer 8

Corpus (body and fundus) restricted chronic atrophic gastritis
Anti-parietal cell and anti-intrinsic factor antibodies
+/- pernicious anemia (intrinsic factor mediates B12 uptake, so can get a deficiency and anemia)

Scandinavian and northern European descent

Lymphocyte and plasma cell infiltrate in the body of stomach and glandular atrophy

Intestinal metaplasia

Question 9

Peptic Ulcer Disease

Answer 9

acid-mediated ulceration of stomach & duodenum

Question 10

Mass-like inflammatory lesions

Answer 10

Gastritis cystica
Gastritis polyposa

Gastritis that cause

Question 11

Hypertrophic gastropathies

Answer 11

Ménétrier disease

Zollinger-Ellison syndrome

Question 12

Benign neoplasms

Answer 12

In order of prevalence:

Inflammatory / hyperplastic polyp: Rare progression to cancer; associated with H. pylori

Fundic gland polyp: very rare progression to cancer

Adenomatous polyp (adenoma): common progression to cancer

Question 13

Malignant (potentially)

Answer 13

Adenocarcinoma: transformation of gastric epithelium

Lymphoma: malignant transformation of resident B-cells; highly associated with H. pylori; varies in behavior

Carcinoid tumor: Epithelial tumor derived from neuroendocrine cells; variable behavior from indolent to malignant; some tumors are sporadic and others are associated with gastric atrophy (e.g. autoimmune gastritis)

Gastrointestinal stromal tumor: Stromal tumor derived from interstitial cells of Cajal; cKIT mutation

Question 14

Path findings with Inflammatory / hyperplastic polyp

Answer 14

Cystically dilated foveolae

Often in antrum of stomach

Hyperplasia

Question 15

Path findings with fundic Gland Polyp

Answer 15

Cystically dilated oxyntic gland

Question 16

Path findings with adenoma

Answer 16

Dark, atypical cells

Question 17

Adenocarcinoma

Answer 17

Accounts for 90% of all malignant gastric tumors

Second most common fatal malignancy in the world

But not in USA (accounts for only 2.5% of cancer deaths)

High incidence in Japan, Chile, and Eastern Europe

Risk factors: environment (diet) and Helicobacter

Symptoms
Early: dyspepsia, dysphagia, and nausea
Late: weight loss, anorexia, early satiety, anemia

High mortality unless disease detected early (hard to catch early because symptoms appear late)

Overall 5-year survival is 30% (90% for early gastric cancer)
Less than 20% of gastric cancers in USA detected early

Question 18

Mutations associated with adenocarcinomas

Answer 18

Wnt signalling pathway activation
Common in intestinal type cancers
Can occur with loss of APC (as in FAP)

Loss of CDH1 (mutation or methylation)
Common in diffuse type cancers
Germline loss of CDH1 in familial gastric cancer

Amplification of Her2/neu
Occurs in a minority of tumors (intestinal > diffuse)
Susceptible to tyrosine kinase inhibitor trastuzumab

Question 19

Gastrointestinal Stromal Tumor (GIST)

Answer 19

Mesenchymal neoplasm derived from interstitial cells of Cajal (pacemaker cells controlling peristalsis)

Most contain a mutation in the c-kit oncogene

Used as diagnostic aid on tissue
Targeted therapy with tyrosine kinase inhibitor imatinib

Variable clinical course – indolent to malignant

Risk assessment: location, mitotic rate, and size

Spindle cell proliferation

Question 20

What’s the mutation associated with GIST?

Answer 20

CKIT

Question 21

Carcinoid (Neuroendocrine) Tumor

Answer 21

a.k.a. “well-differentiated endocrine neoplasm”

Neoplastic proliferation of ECC in body/fundus

Variable behavior
Sporadic: higher rate of malignant behavior
Atrophy associated: typically indolent

Associated with gastric atrophy and MEN-I

Question 22

Lymphoma

Answer 22

Most extranodal lymphomas arise in GI tract and, in particular, the stomach

5% of gastric cancers are lymphomas

Most are MALT lymphomas (low-grade B-cell)
Given time, will transform to high-grade DLBCL

Associated with chronic gastritis and often driven by Helicobacter infection
Helicobacter eradication cures MALT lymphomas

Question 23

Path findings in lymphoma

Answer 23

B-cells infiltrate and disrupt gastric glands:

“lymphoepithelial lesions”

Question 24

Path findings of adenocarcinoma

Answer 24

Grossly (2 patterns):
Ulcerating pattern (not clean base like regular PUD)
Linitis plastica pattern (thickening of wall)

Microscopically (2 patterns): 
Instestinal type (gland-forming)
Diffuse type (signet ring cell)

Question 25

AJCC staging system (TNM)

Answer 25

Assigns a “stage of disease” to the tumor
Describes prognosis (i.e. survivial)
Determines optimal treatments

(T)umor characteristics
Depth of invasion into gastric wall

Regional lymph (N)ode metastases
Number of lymph nodes involved by tumor

Distant (M)etastatic disease