Pathologic basis of gastric disease Flashcards
Gastritis vs gastropathy
gastritis: inflammation + injury
gastropathy: non-inflammatory injury
Hypertrophic Pyloric Stenosis
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”)
Signs and symptoms of gastric disease
Epigastric Pain ~ Early satiety
Nausea and Vomiting ~ Melena ~ Hematemesis
Stress-related Mucosal Disease
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)
Chronic gastritis
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
Helicobacter pylori
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
Diseases associated with H. pylori
Gastritis
Gastric and duodenal ulcers (15% lifetime risk)
Gastric adenocarcinoma (1% lifetime risk)
Gastric lymphoma
Autoimmune Gastritis
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
Peptic Ulcer Disease
acid-mediated ulceration of stomach & duodenum
Mass-like inflammatory lesions
Gastritis cystica
Gastritis polyposa
Gastritis that cause
Hypertrophic gastropathies
Ménétrier disease
Zollinger-Ellison syndrome
Benign neoplasms
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
Malignant (potentially)
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
Path findings with Inflammatory / hyperplastic polyp
Cystically dilated foveolae
Often in antrum of stomach
Hyperplasia
Path findings with fundic Gland Polyp
Cystically dilated oxyntic gland
Path findings with adenoma
Dark, atypical cells
Adenocarcinoma
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
Mutations associated with adenocarcinomas
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
Gastrointestinal Stromal Tumor (GIST)
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
What’s the mutation associated with GIST?
CKIT
Carcinoid (Neuroendocrine) Tumor
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
Lymphoma
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
Path findings in lymphoma
B-cells infiltrate and disrupt gastric glands:
“lymphoepithelial lesions”
Path findings of adenocarcinoma
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)
AJCC staging system (TNM)
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
