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Flashcards in 12 Pathology of the Stomach Deck (21):
1

Major Anatomic Regions of the Stomach (p.3-5)

2

Acute gastritis (p.6-8+12-14)

  • ?
  • The most severe form of injury
  • Causes

  • A nonspecific term for transient mucosal injury (with or without actual inflammatory cell infiltrates) that can vary in severity.
  • The most severe form of injury is gastric ulceration.
  • Causes—imbalance of damaging forces and protective forces
    • H. pylori, CMV, other acute infection
    • “Chemicals” (NSAIDs, cytotoxic chemotherapeutic drugs, iron pills, EtOH)
    • bile acid reflux
    • “stress”--severe illness leading to loss of protective factors (e.g. blood flow)—e.g. Curling and Cushing’s ulcers
      • Occurs in a high proportion of ICU patients—hence, the importance of prophylaxis (PPIs, H2RA, sucralfate)

3

Acute gastritis (p.9-11)

  • Morphology
  • Diagnosis involves/
  • treatment involves/

  • Morphology (not all are present in every case; represents increasing severity):
    • Edema and congestion
    • Acute inflammation
    • Epithelial necrosis
    • Hemorrhage
    • Surface erosion
    • Ulcer
  • Diagnosis involves
    • evaluating possible causes of injury or loss of protection
    • documenting the non-specific gastric injury (erosions, hemorrhage, perforation, ulcer, gastritis);
  • treatment involves ulcer prophylaxis

4

Peptic ulcer disease

  • Primary risk factors
  • Mechanism
    • H. pylori infection can cause/
      • patients with H. pylori pangastritis tend to have/
    • NSAIDs

  • Primary risk factors:
    • H. pylori infection,
    • NSAID use
  • Mechanism:
    • H. pylori infection can cause acid hypersecretion (especially antral predominant HP gastritis) resulting in duodenal ulcers;
      • patients with H. pylori pangastritis tend to have normal to low acid secretion but develop gastric ulcers possibly due to loss of protective factors
    • NSAIDs
      • inhibit COX enzymes
      • reduce protective prostaglandin synthesis
      • results in loss of protective factors

5

Chronic (atrophic) gastritis (p.16+24-25)

  • Over time, persistent gastritis due a variety of etiologies
    • can result in/
    • usually accompanied by/
    • this type of gastritis is referred to as/
  • 2 forms distinguished based on etiology and pathology

  • Over time, persistent gastritis due a variety of etiologies
    • can result in loss of glands (atrophy) that causes visible thinning and flattening of the mucosa
    • usually accompanied by intestinal metaplasia
    • this type of gastritis is referred to as metaplastic atrophic gastritis (MAG).
  • 2 forms distinguished based on etiology and pathology 
    • environmental metaplastic atrophic gastritis (EMAG)
      • caused by H. pylori or other chronic sources of injury
    • autoimmune metaplastic atrophic gastritis (AMAG)

6

Chronic H. pylori gastritis/Environmental Metaplastic Atrophic Gastritis (p.17-18)

  • H. pylori 
  • H. pylori exclusively colonizes/
  • Epidemiology
    • highly prevalent in
    • at highest risk
    •  transmission
  • Virulence factors
  • Host factors/

  • H. pylori
    • one of the most common chronic bacterial infections in humans;
    • an organisms that is adapted to living in the human stomach
  • H. pylori exclusively colonizes gastric type epithelium
    • when the organism is found outside the stomach it is colonizing metaplastic gastric epithelium (e.g. gastric foveolar metaplasia in the duodenum)
  • Epidemiology:
    • highly prevalent in developing regions and dense living conditions with contaminated water
    • young children are at highest risk of acquiring infection and re-infection;
    • person to person transmission is likely (fecal-oral; oral-oral or gastric oral)
  • Virulence factors:
    • flagella (motility),
    • urease (decrease acidity also antigenic for inflammatory response and byproducts of urea metabolism are toxic),
    • adhesins (e.g. BabA, mediate specific attachment to gastric foveolar epithelium--Lewis b antigen),
    • CagA genes (risk factor for ulcers and cancer);
    • catalase (metabolizes reactive oxygen species produced by inflammatory response)
  • Host factors influence pathogenicity of infection

7

Chronic H. pylori gastritis/Environmental Metaplastic Atrophic Gastritis:
Morphology (p.19-23+25)

  • characteristic/
  • surface/
  • organisms/
  • Active inflammation/
  • In some patients, chronic gastritis remains/
  • In classic EMAG,
    • atrophy with intestinal metaplasia/
    • acid secretion/
    • develop/
    • have a higher risk of developing/

  • characteristic superficial band like lamina propria inflammatory infiltrate comprised of lymphocytes, plasma cells, neutrophils invade the epithelium;
  • surface epithelial injury and vacuolization
  • organisms are adherent to the surface of epithelial cells and float in the mucous
  • Active inflammation is antral predominant, but can involve the entire stomach (pangastritis).
  • In some patients, chronic gastritis remains predominantly antral without significant atrophy
    • these patients tend to have high acid output and develop duodenal ulcers
  • In classic EMAG,
    • atrophy with intestinal metaplasia
      • is distributed throughout the stomach (involves the antrum and body)
      • tends to be multifocal or patchy rather than continuous;
    • acid secretion is low to normal in these patients;
    • develop gastric ulcers
    • have a higher risk of developing cancer

8

Chronic H. pylori gastritis/Environmental Metaplastic Atrophic Gastritis:
Sequelae (p.18+26)

  • Peptic ulcer disease
  • Intestinal metaplasia
    • reduces the bacterial burden
    • correlates with development of pangastritis;
    • risk factor for subsequent development of dysplasia and cancer
  • Dysplasia and gastric adenocarcinoma
    • intestinal type
  • MALT lymphoma
    • low grade lymphoma that may be cured by H. pylori eradication;
    • chromosomal translocations and high grade lymphoma predict treatment failure

9

Autoimmune gastritis (p.27)

  • involving/
  • associated with/
    • mediated by/
    • associated with the development of/
  • frequency vs. EMAG
  • race
  • prevalence
  • what may initiate the autoinflammatory process
  • Associated with/

  • involving the gastric body,
  • associated with the production of auto-antibodies (anti-parietal cell and anti-intrinsic factor Abs)
    • mediated by self reactive T cells directed against oxyntic glands;
    • associated with the development of pernicious anemia.
  • Less common than EMAG;
  • occurs in all racial groups (not just people of N. European descent);
  • not rare--prevalence in up to 2% of patients over 60;
  • H. pylori infection may initiate the autoinflammatory process.
  • Associated with other autoimmune endocrinopathies such as autoimmune thyroiditis and diabetes mellitus.

10

Autoimmune gastritis:
Morphology (p.29+32)

  • involves/
  • results in/
    • after destruction of the oxyntic glands, they are replaced with/
  • This combination of findings is highly characteristic if/
  • Early on the inflammation in the body and fundus/

  • involves only the body and fundus of the stomach
    • antrum is uninvolved by this chronic inflammatory process
  • results in loss of the acid producing glandular epithelium (atrophy) due to autoimmune inflammation
    • after destruction of the oxyntic glands, they are replaced with antral type glands (“antralization”), intestinal metaplasia and hyperplasia of ECL cells (a type of endocrine cell in the stomach);
  • This combination of findings is highly characteristic if we are sure ther ei sno gastritis in the antrum and there is no H. pylori
  • Early on the inflammation in the body and fundus is directed at the deeper glands so
    • the distribution of inflammation is both superficial and deep
    • lymphocytes (T cells) are seen infiltrating residual oxyntic glands

11

Autoimmune gastritis (p.27-28+30-31)

  • Mechanism of ECL cell hyperplasia and carcinoid tumor formation: 
  • Sequelae:

  • Mechanism of ECL cell hyperplasia and carcinoid tumor formation:
    • due to achlorhydria, compensatory hypergastrinemia results
    • gastrin (produced by antral G cells, attempting to stimulate acid production) stimulates endocrine cells of the body resulting in endocrine hyperplasia and formation of carcinoid tumors
  • Sequelae:
    • Loss of intrinsic factor and Vitamin B12 deficiency which may result in pernicious anemia
    • Increased risk of dysplasia and cancer
    • Carcinoid tumors (always benign, frequently multiple, always occur in the body of the stomach)

12

Other forms of gastritis (p.33-34)

  • patterns recognized on biopsy;
  • clinical importance is in the differential diagnosis:
  • Reactive (or “chemical”) gastropathy: bile reflux, NSAIDs, EtOH, other
  • Eosinophilic gastritis: primary or secondary (to other causes of peripheral eosinophilia)
  • Lymphocytic gastritis: H. pylori or celiac disease
  • Granulomatous gastritis: sarcoidosis, Crohn’s disease, infection, foreign material, other

13

Hypertrophic gastropathy (p.15)

  • the appearance of/
  • Malignant
  • Other
    • Menetrier’s disease
    • Zollinger-Ellison syndrome
    • Others

  • the appearance of enlarged gastric folds usually in the body
  • Malignant:
    • Diffuse type adenocarcinoma
    • Lymphoma
  • Other:
    • Menetrier’s disease
      • protein losing hypersecretory gastropathy;
      • associated with excessive TGFalpha production that stimulates epithelial hyperplasia via EGFR; 
      • in children associated with CMV
      • hypertrophy of foveolar epithelium and atrophy of glands
    • Zollinger-Ellison syndrome
      • gastrin producing endocrine tumor stimulating gastric hyperplasia and hypersecretion
      • severe GERD and gastroduodenal ulcers, often multiple
      • hypertrophy of oxyntic glands of the body/fundus
    • Others: acute H. pylori infection, lymphocytic gastritis, eosinophilic gastroenteritis, amyloidosis, sarcoidosis

14

Gastric carcinoma (p.37-38+41)

  • Adenocarcinoma
  • Symptoms
    • early
    • later
  • Epidemiology
  • It is important to differentiate/

  • Adenocarcinoma
    • the most common histologic subtype
    • has a couple of subtypes
  • Symptoms:
    • early: dyspepsia, dysphagia, nausea;
    • later: weigh loss, anorexia, change in bowel habits, anemia, hemorrhage
  • Epidemiology:
    • a common malignancy worldwide,
    • incidence is declining due to recognition of risk factors like H. pylori;
    • worldwide regional variation in incidence.
  • It is important to differentiate tumors located in the gastric “cardia” near the junction with the esophagus from more distal gastric cancers, because many of these tumors are related to obesity, GERD and Barrett’s esophagus.
    • Incidence is rising for these.

15

Gastric carcinoma (p.40+44-46)

  • Environmental risk factors for developing gastric carcinoma
  • two infectious organisms linked to gastric carcinoma
  • Lauren classification of gastric adenocarcinoma
    • 2 types
    • based on/

  • Environmental risk factors for developing gastric carcinoma:
    • H. pylori infection, Salt and salt preserved foods, nitroso compounds, smoking
    • obesity? (all gastric cancer or predominantly cardia cancers), 
    • fruits and veggies are protective
  • two infectious organisms linked to gastric carcinoma:
    • H. pylori
    • Epstein Barr Virus
  • Lauren classification of gastric adenocarcinoma
    • 2 types:
      • Intestinal type
      • diffuse type
    • based on the histologic appearance of the tumors

16

Gastric carcinoma:
Intestinal type (p.43+47-48)

  • Comprised predominantly of
  • Gross appearance
  • arises in/
  • Strong association with/
    • also associated with/
  • more common in intestinal type tumors

  • Comprised predominantly of gland-like structures rather than infiltrating single cells
  • Gross appearance: solitary mass lesion (exophytic or ulcerated)
  • arises in a background of intestinal metaplasia and dysplasia:
    • the cascade of events leading from intestinal metaplasia to dysplasia and eventually to cancer is believed to give rise to most intestinal type cancers
  • Strong association with H. pylori;
    • also associated with autoimmune atrophic gastritis
  • HER2 amplification is more common in intestinal type tumors (important therapeutic target)

17

Gastric carcinoma:
Diffuse type (p.47+49-51)

  • Comprised of/
  • Classic gross appearance
  • Less association with/
  • what plays a pathogenic role

  • Comprised of single infiltrating cells often with signet ring morphology
  • Classic gross appearance
    • diffuse thickening of the wall of the stomach (leather bottle stomach or linitis plastica);
    • frequently no dominant mass lesion;
    • can impart appearance of thickened and enlarged gastric folds
  • Less association with
    • H. pylori
    • intestinal metaplasia and dysplasia;
    • no well-defined precursor lesion
  • Loss of e-Cadherin function plays a pathogenic role

18

Gastric carcinoma:
Heredtary gastric cancer (p.52-56)

  • Familial diffuse type gastric cancer
    • mutation
    • develop/
    • inheritance pattern
    • females are at risk for/
  • Familial adenomatous polyposis syndrome
    • mutations
    • patients
      • have/
      • are at risk for developing/

  • Familial diffuse type gastric cancer
    • mutation in E-cadherin gene (CDH1);
    • develop multifocal gastric cancers with diffuse-type morphology (signet ring cells) at an early age (<40);
    • dominant inheritance pattern;
    • females are at risk for lobular carcinoma of the breast
  • Familial adenomatous polyposis syndrome;
    • mutations in APC gene;
    • patients
      • have gastric fundic gland polyps or gastric adenomas
      • are at risk for developing intestinal type cancers

19

Gastric carcinoma:
Molecular pathogenesis (p.43)

  • Oncogenes (e.g. KRAS) and tumor suppressor genes (e.g. p53 and p16, APC)/
  • Amplification of receptor tyrosine kinase genes/
  • HER2
    • can be inhibited by/
    • amplification/

  • Oncogenes (e.g. KRAS) and tumor suppressor genes (e.g. p53 and p16, APC) that are mutated in other forms of cancer are mutated in gastric cancer
  • Amplification of receptor tyrosine kinase genes is seen in up to 40% of gastric cancers (HER2, EGFR, cmet).
  • HER2
    • can be inhibited by targeted chemotherapeutic agents
      • improves the survival of patients with gastric cancer in combination with conventional treatment compared to conventional treatment alone.
    • amplification is much more common in intestinal type tumors

20

Benign Gastric Polyps (p.57)

  • Hyperplastic polyps
  • Adenomas
  • Fundic gland polyps
  • Combination = FAP

21

Other tumors of the stomach (p.58-61)

  • distinguished from one another by/
  • tumors

  • distinguished from one another by the gross appearance, types of cells that comprise the tumor, molecular pathogenesis, epidemiology, and therapy.
  • tumors
    • Neuroendocrine tumors (aka Carcinoid tumors)
    • Lymphoma
    • GI stromal tumor