Pathology of the Stomach and Small Bowel Flashcards
Hypertrophic pyloric stenosis
Congenital
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”)
Gastritis vs gastropathy
gastritis: inflammation + injury
Gastropathy: non-inflammatory injury
Drugs (NSAIDs)
H. pylori
alcohol, tobacco
chemical injury (bile, strong acids/bases)
Stress related mucosal disease
-resembles acute gastritis:
injury mediated by vasoconstriction/ischemia
erosion and ulceration may be widespread
Occur in 75% of critically ill pts
- trauma, shock, or sepsis (stress ulcers)
- Burns (Curling ulcers)
- Intracranial disease (Cushing ulcers)
Chronic gastritis
- H. pylori infection
- Autoimmune gastritis
-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
H. pylori gastritis
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
Histology of h. pylori gastritis
- Lymphocyte and plasma cell infiltrate
- neutrophilic infiltrate
- can see H. pylori on high mag
Diseases assoc w/ H. pylori
Gastritis
Gastric and duodenal ulcers (15% lifetime risk)
Gastric adenocarcinoma (1% lifetime risk)
Gastric lymphoma
Autoimmune Gastritis
Corpus restricted chronic atrophic gastritis
Anti-parietal cell and anti-intrinsic factor antibodies
+/- pernicious anemia
Scandinavian and northern
European descent
On histology:
intestinal metaplasia
lymphocyte and plasma cell infiltrate in body of stomach and glandular atrophy
Peptic ulcer disease
acid mediated ulceration of stomach and duodenum
Bleeding 15%, perforation 5%, obstruction 2%
Causes: H pylori Cigarette use COPD illicit drugs NSAIDs alcohol psych stress endocrine cell hyperplasia Zollinger Ellison syndrome (PUD of stomach, duod, jejunum) Viral infection (CMV, HSV)
Gross: mucosa hangs over the edge and ulcer has a “clean base”
Necrotic debris in ulcer bed
Mass-like inflammatory lesions
gastritis cystica
gastritis polyposa
Hypertrophic gastropathies
Menetrier disease (leads to markedly enlarged RUGAE of stomach) Zollinger-Ellison Syndrome
Benign neoplastic diseases
inflammatory/hyperplastic polyp (rare progression to cancer, assoc with helicobacter and other chronic gastritidies)
Histology: inflamm, edema, cystically dilated foveolae
fundic gland polyp (very rare progression to cancer– in FAP pts; FAP assoc and sporadic, usally PPI assoc)
Histology: cystically dilated oxyntic gland
adenomatous polyp (adenoma) (common progression to cancer, increased incidence in FAP, Helicobacter gastritis, and other chronic gastritides)
Potentially Malignant neoplastic diseases
adenocarcinoma
lymphoma
carcinoid tumor
GI stromal tumor
Adenocarcinoma
Epithelial tumor derived from malignant transformation of gastric epithelium; malignant behavior; associated with chronic gastritis (especially Helicobacter) and diet
90% of all malignant gastric tumors
second most common fatal malignancy in world (in US 2.5% of cancer deaths)
High incidence: Japan, Chile, E. Europe
Sx:
early: dyspepsia, dysphagia, and nausea
Late: weight loss, anorexia, early satiety, anemia
High mortality unless detected early
5 yr: 3-% survival (90% for early gastric cancer)
-Less than 20% of gastric cancers in USA detected early
Histology:
can see signet ring cell (diffuse type)
or intestinal type
Ulcerating pattern (heaped edges, no clean base) or linitis plastica (thickened wall)(see pics!!)
lymphoma
Lymphoid tumor usually derived from malignant transformation of resident B-cells; malignant behavior but varies from low-grade to high-grade; associated with Helicobacter gastritis
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)
GI stromal tumor
Stromal tumor derived from interstitial cells of Cajal; variable behavior from indolent to malignant; tumors harbor activating mutations in the tyrosine kinase CKIT or PDGFRA
Adenocarcinoma mutation
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
TNM staging
T: tumor characteristics (depth of invasion into gastric wall)
N: regional lymph node mets
M: distant metastatic disease
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. often driven by Helicobacter infection
(eradication cures MALT lymphomas)
Histology of MALT lymphoma:
diffuse infiltrate of B cells
-B cells disrupt gastric glands (lymphoepithelial lesions)
Carcinoid (Neuroendocrine) Tumor
-“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
GI stromal tumor (GIST)
- mesenchymal neoplasm of interstitial cell of Cajal
- mutation in CKIT oncogene
- targeted therapy with TKI imatinib
Variable clinical course: indolent to malignant
risk: location, mitotic rate, size
Key Points
Inflammatory gastric diseases occur when there is a mismatch between protective and damaging “forces”
Stress-related gastritis very common in sick patients
Helicobacter infection is a huge “player” in gastric disease
Adenocarcinoma is the most common cancer in the stomach, is decreasing in incidence in the USA, and typically presents at an advanced stage
Many gastric lymphomas can be cured with antibiotics
Gastrointestinal stromal tumors have a variable behavior and many are driven by CKIT mutations
