3. Acute Gastritis
Chronic Gastritis
PEPTIC ULCER DISEASE
Gastric Polyps and Tumors

4. transient mucosal inflammatory process
Acute Gastritis
Acute gastritis is a
transient mucosal inflammatory process
asymptomatic or cause variable degrees of epigastric pain, nausea, and vomiting
In more severe cases
mucosal erosion, ulceration, hemorrhage

5. Acute Gastritis Pathogenesis
Acute or chronic gastritis can occur following
disruption of gastroduodenal mucosal protective mechanisms

6. Mechanisms which protect the gastric mucosa
Mucin secreted by surface foveolar cells forms a thin layer of mucus
bicarbonate ion secretion by surface epithelial cells
rich vascular supply to the gastric mucosa
epithelial barrier
Elaboration of prostaglandin
Epithelial regenerative capacity

7. Etiopathogenesis NSAID (e.g., aspirin) H. pylori infections alcohol
smoking
stress (trauma, burns, surgery)
Uremia
Treatment with cancer chemotherapeutic drugs
Systemic bacterial or viral infections

8. Etiopathogenesis Ischemia and shock
Suicidal attempts, as with acids and alkali
Gastric irradiation or freezing
Mechanical trauma (e.g., nasogastric intubation)
Distal gastrectomy

10. Morphology of acute gastritis
surface epithelium is intact
presence of neutrophils above the basement membrane in direct contact with epithelial cells is abnormal in all parts of the GI tract and signifies active inflammation

11. Morphology of acute gastritis
severe mucosal damage, erosions and hemorrhage
(erosion denotes loss of the superficial epithelium, generating a defect in the mucosa that is limited to the lamina propria)
Concurrent erosion and hemorrhage is termed acute erosive hemorrhagic gastritis

12. ACUTE GASTRIC ULCERATION
Focal, acutely developing gastric mucosal defects
Stress ulcers - shock, sepsis, or severe trauma
Curling ulcers - severe burns or trauma
Cushing ulcers - intracranial disease

13. Chronic Gastritis Chronic infection by H. pylori
Immunologic (autoimmune), in association with pernicious anemia
Toxic, as with alcohol and cigarette smoking
Postsurgical, especially following antrectomy with gastroenterostomy with reflux of bilious duodenal secretions

14. Less common etiologies
Radiation
Granulomatous conditions (e.g., Crohn disease)
Miscellaneous-amyloidosis, graft-versus-host disease,
uremia

15. Pathogenesis
result of an imbalance between gastroduodenal mucosal defenses and damaging forces that overcome those defenses

16. Pathogenesis
H. pylori infection is the most common cause of chronic gastritis
H. pylori gastritis may progress to pangastritis resulting in multifocal atrophic gastritis

17. Four features are linked to H. pylori virulence
Flagella - allow the bacteria to be motile in viscous mucus
Urease - generates ammonia from endogenous urea and thereby elevates local gastric pH
Adhesins - enhance their bacterial adherence to surface foveolar cells
Toxins - such as cytotoxin-associated gene A (CagA)

18. Morphology H. pylori are typically found in the antrum
demonstrate H. pylori in superficial mucus overlying epithelial cells

19. Morphology H. pylori–infected antral mucosa is
erythematous & nodular appearance
inflammatory infiltrate includes
-variable numbers of neutrophils
-large numbers of plasma cells
- Lymphocytes& macrophages
pit abscesses
thickened rugal folds

20. Morphology
Long-standing H. pylori gastritis extend to involve the body and fundus, and the mucosa can become atrophic
Lymphoid aggregates, some with germinal centers represent an induced form of mucosa-associated lymphoid tissue, or MALT, that has the potential to transform into lymphoma

21. Clinical Features symptoms less severe but more persistent
Nausea and upper abdominal discomfort , vomiting
fecal bacterial detection
urea breath test (+)ve
noninvasive serologic test for antibodies to H. pylori

22. AUTOIMMUNE GASTRITIS
Antibodies to parietal cells and intrinsic factor that can be detected in serum and gastric secretions
Reduced serum pepsinogen I concentration
Antral endocrine cell hyperplasia
Vitamin B12 deficiency
Defective gastric acid secretion (achlorhydria)

23. AUTOIMMUNE GASTRITIS < 10% of gastritis cases
seen with other autoimmune diseases
a) type 1 diabetes
b) Addison's disease
c) Hashimoto thyroiditis
high risk of gastric CA and endocrine tumors (carcinoid tumors)

24. AUTOIMMUNE GASTRITIS diffuse mucosal damage a) fundus and body
b) lymphocytes and plasma cells
c) active inflammation  neutrophils !
d) atrophy is frequently associated;
and with pangastritis (H. pylori)
e) hyperplasia of G cells ( gastrin)
i) due to  H+ production
ii) hypergastrinemia

25. Complications of Chronic Gastritis PEPTIC ULCER DISEASE
Peptic ulcers are chronic, most often solitary, lesions that occur
in any portion of the gastrointestinal tract exposed to
the aggressive action of acidic peptic juices

26. Peptic Ulcers
SITE
most common in the gastric antrum and first portion of the duodenum
occur in the esophagus as a result of GERD
Gastric mucosa within a Meckel diverticulum

27. Pathogenesis
Two conditions are key for the development of peptic ulcers
(1) H. pylori infection, which has a strong causal relationship with peptic ulcer development
(2) mucosal exposure to gastric acid and pepsin

28. Pathogenesis
peptic ulcers are created by an imbalance between the gastroduodenal mucosal defenses and
the damaging forces that overcome such defenses

29. Pathogenesis The gastric hyperacidity that drives PUD may be caused by
H. pylori infection
parietal cell hyperplasia
excessive secretory responses
impaired inhibition of stimulatory mechanisms such as gastrin release
For example, Zollinger-Ellison syndrome

30. Pathogenesis More common cofactors in pepticulcerogenesis include
chronic NSAID use
cigarette smoking
high-dose corticosteroids

31. Pathogenesis Duodenal ulcers are more frequent in
individuals with alcoholic cirrhosis
chronic obstructive pulmonary disease
chronic renal failure
self-imposed or exogenous psychologic stress

32. Helicobacter pylori Causes 80% of gastric peptic ulcers
Causes 100% of duodenal peptic ulcers
Causes chronic gastritis
Causes gastric carcinomas
Causes MALT lymphomas 32

33. Morphology SITE Peptic ulcers four times more common in the proximal
duodenum than in the stomach
Duodenal ulcers
few centimeters of the pyloric valve and involve the anterior duodenal wall
Gastric ulcers
along the lesser curvature near the interface of the body and antrum 33

34. Morphology 2 to 4 cm in diameter SIZE NUMBER SHAPE Usually Solitary
less than 0.3 cm in diameter tend to be shallow while those over 0.6 cm are likely to be deeper ulcers
NUMBER
Usually Solitary
SHAPE
round to oval, sharply punched-out defect 34

35. Morphology Margin overhang the base slightly or
level with the surrounding mucosa
Depth
limited by the thick gastric muscularis propria or by adherent pancreas, omental fat, or the liver
Hemorrhage and fibrin deposition are often present on the gastric serosa 35

36. Morphology BASE OF ULCER
smooth and clean as a result of peptic digestion of exudate with evident blood vessels
In active ulcers the base may have a thin layer of fibrinoid debris
neutrophilic inflammatory infiltrate
active granulation tissue infiltrated with mononuclear leukocytes
fibrous or collagenous scar forms the ulcer base 36

38. Clinical Manifestations

39. “PEPTIC” ULCERS Epigastric pain (burning, aching,)
Fe deficiency anemia
Acute hemorrhage
Penetration, perforation:
Pain in BACK
Pain in CHEST
Pain in LUQ
Malignant transformation of peptic ulcers is very rare 39

40. PEPTIC ULCERS Bleeding Perforation Obstruction from edema or scarring
Occurs in 15% to 20% of patients
Most frequent complication
May be life-threatening
Perforation
Occurs in about 5% of patients
Accounts for two thirds of ulcer deaths
Obstruction from edema or scarring
Occurs in about 2% of patients
Most often due to pyloric channel ulcers
May also occur with duodenal ulcers
Causes incapacitating, crampy abdominal pain
Rarely, may lead to total obstruction with intractable vomiting 40

42. GASTRIC TUMORS BENIGN: MALIGNANT POTENTIALLY MALIGNANT
POLYPS (HYPERPLASTIC vs. ADENOMATOUS)
LEIOMYOMAS (Same gross and micro as sm. muscle)
LIPOMAS (Same gross and micro as adipose tissue)
MALIGNANT
(ADENO)Carcinoma
LYMPHOMA
POTENTIALLY MALIGNANT
G.I.S.T. (Gastro-Intestinal “Stromal” Tumor)
CARCINOID (NEUROENDOCRINE) 42

43. WHO GASTRIC NEOPLASMS Epithelial Tumors: Adenomatous polyps
Adenocarcinoma (papillary, tubular, mucinous, signet ring, adenosquamous, unclassified),
Small cell, Carcinoid (neuroendocrine)
Nonepithelial Tumors: Leiomyooma, Leimyosarcoma,
Schwannoma, GIST, Granular Cell Tumor, Kaposi sarcoma
Malignant Lymphomas: 43

44. ADENOCARCINOMA H. pylori associated, MASSIVELY!!!
Japan, Chile, Costa Rica, Colombia, China, Portugal, Russia, and Bulgaria
M>>F
Socioeconomically related

45. Factors Associated with Increased Incidence of Gastric Carcinoma
Environmental Factors
Infection by H. pylori
Present in most cases of intestinal-type carcinoma
Diet
Nitrites derived from nitrates (water, preserved food)
Smoked and salted foods, pickled vegetables, chili peppers
Lack of fresh fruit and vegetables
Low socioeconomic status
Cigarette smoking

46. Host Factors
Chronic gastritis
Hypochlorhydria: favors colonization with H. pylori
Intestinal metaplasia is a precursor lesion
Partial gastrectomy- Favors reflux of bilious, alkaline intestinal fluid
Gastric adenomas
Barrett esophagus
Increased risk of gastroesophageal junction tumors

47. Genetic Factors
Slightly increased risk with blood group A
Family history of gastric cancer
Hereditary nonpolyposis colon cancer syndrome
Familial gastric carcinoma syndrome (E-cadherin mutation)

48. ADENOCARCINOMA RISK FACTORS
H. pylori
Nitrites, smoked meats, pickled, salted, chili peppers, socioeconomic, tobacco
Chronic gastritis, Barrett’s, adenomas
Family history

49. Morphology SITE - Favoured location is the
lesser curvature of the antropyloric region
Gastric carcinoma is classified on the basis of
- depth of invasion
- macroscopic growth pattern
- histologic subtype

50. Morphology Early gastric carcinoma
lesion confined to the mucosa and submucosa
regardless of the presence or absence of perigastric lymph node metastases
Advanced gastric carcinoma
neoplasm that has extended below the submucosa into the muscular wall
spread more widely

51. Morphology
(1) exophytic, with protrusion of a tumor mass into the lumen
(2) flat or depressed, in which there is no obvious tumor mass within the mucosa
(3) excavated, whereby a shallow or deeply erosive crater is present in the wall of the stomach.

52. ADENOCARCINOMA GROWTH PATTERNS
I hope these are logical anatomic or “geometric” descriptions, and NOT exact classifications. 52

53. Morphology Exophytic tumors may contain portions of an adenoma.
Flat or depressed malignancy presents only as regional effacement of the normal surface mucosal pattern
Excavated cancers may mimic, in size and appearance, chronic peptic ulcers, although more advanced cases show heaped-up margins

54. Morphology
a broad region of the gastric wall, or the entire stomach, is extensively infiltrated by malignancy.
The rigid and thickened stomach is termed a leather bottle stomach, or linitis plastica; metastatic carcinoma from the breast and lung may generate a similar picture.

55. Morphology
Histologic appearances of gastric cancer are best classified into the intestinal type and diffuse type
intestinal variant is composed of malignant cells forming neoplastic intestinal glands resembling those of colonic adenocarcinoma
diffuse variant is composed of gastric-type mucous cells that generally do not form glands but rather permeate the mucosa and wall as scattered individual "signet-ring" cells or small clusters in an "infiltrative" growth pattern.

56. Morphology
all gastric carcinomas eventually penetrate the wall to involve the serosa, spread to regional and more distant lymph nodes, and metastasize widely.
The earliest lymph node metastasis may sometimes involve a supraclavicular lymph node (Virchow node)
Intraperitoneal spread in females is to both the ovaries, giving rise to the so-called Krukenberg tumor

57. Morphology Gastric carcinoma.
showing an ill-defined, excavated central ulcer
surrounded by irregular, heaped-up borders.

58. Gross: Linitis plastica carcinoma diffusely infiltrates the entire gastric wall without forming an intraluminal mass. The wall of the stomach is typically thickened to about 2-3 cm. and has a leathery, inelastic consistency.

59. Gastric carcinoma. Intestinal type gland formation by malignant cells,
Diffuse type demonstrating
signet-ring carcinoma cells.

60. Clinical Features The symptoms include weight loss, abdominal pain,
anorexia,
vomiting,
altered bowel habits,
less frequently dysphagia,
anemic symptoms
hemorrhage

61. Prognosis depends primarily on
the depth of invasion and the extent of nodal and distant
metastasis at the time of diagnosis
The prognostic value of biomarkers
p53 mutation and c-ERB-B2
Early gastric cancer
five-year survival rate of surgically treated is 90% to 95%
Advanced gastric cancer
five-year survival rate for remains below 15%.

62. G.I.S.T. TUMORS Can behave and/or look benign or malignant
Usually look like smooth muscle, i.e., “stroma”
Are usually POSITIVE for
c-KIT (CD117), i.e., express this antigen on immunochemical staining, the tumor cells are derived from the interstitial cells, of Cajal, a “neural” type of cell

63. G.I.S.T. TUMORS c-KIT (receptor for stem cell factor) mutations
platelet-derived growth factor receptor-a. (PDGFRA) mutations
tyrosine kinase inhibitor (STIS71) has been shown to be effective in treatment

64. CARCINOID TUMOR
arise from the diffuse components of the endocrine system
majority are found in the GI tract, and more than 40% occur in the small intestine
tracheobronchial tree and lungs

65. Gastric carcinoids may be associated with endocrine cell hyperplasia
chronic atrophic gastritis
Zollinger-Ellison syndrome
well-differentiated neuroendocrine carcinomas

66. Gastric carcinoids
release peptide and nonpeptide hormones to coordinate gut function
carcinoids are intramural or submucosal masses that create small polypoid lesions

67. Gastric carcinoids
Histologically composed of islands, trabeculae, strands, glands, or sheets of uniform cells with scant, pink granular cytoplasm and a round to oval stippled nucleus
Immunohistochemical stains are typically positive for endocrine granule markers, such as synaptophysin and chromogranin A

68. Gastric carcinoids Symptoms are determined by the hormones produced
Zollinger-Ellison syndrome
carcinoid syndrome

69. Carcinoid syndrome characterized by cutaneous flushing, sweating
Bronchospasm
colicky abdominal pain & diarrhea
right-sided cardiac valvular fibrosis

70. Foregut carcinoid tumors Midgut carcinoid tumors
The most important prognostic factor for GI carcinoid tumors is location
Foregut carcinoid tumors
rarely metastasize and are generally cured by resection
Midgut carcinoid tumors
Aggressive, greater depth of local invasion, increased size, and presence of necrosis and mitosis are associated with poor outcome
Hindgut carcinoids occur in appendix & rectum
in appendix almost uniformly benign < 2cm
Rectal carcinoid rarely metastsize

71. lymphoepithelial lesion (LEL) is a hallmark
GASTRIC LYMPHOMA
Primary :
Mucosa (gut)-associated lymphoid tissue tumor
Previously called
MALToma, MALT-type lymphoma, or MALT lymphoma,
Now called
Extranodal marginal zone B-cell lymphoma of MALT type
lymphoepithelial lesion (LEL) is a hallmark
Secondary
spread from adjacent lymph nodes

72. Predisposing factors:
Gastric LYMPHOMA
Predisposing factors:
Helicobacter pylori-associated chronic gastritis
Autoimmune diseases
Immunodeficiency syndromes (eg, AIDS)
Long-standing immunosuppressive therapy (eg, post transplantation)

73. Distribution of GI Lymphoma
55-65%
20-35%
7-20%
Courtesy of Dr. Alyssa Krasinskas 73

74. Molecular MALT Genetics t(11;18)(q21;q21) API2/MALT1 gene fusion
~25% of gastric MALT lymphomas
t(1;14)(p22;q32)
BCL10 deregulated by coming under control of Ig gene
Some intestinal MALT lymphomas
t(14;18)(q32;q21)
MALT1/Ig fusion
<5% of gastric MALT lymphomas
Trisomy 3, 12, 18 (often associated with t(1;14)
p53 mutation; methylation of p15 and p16 promoters
Mutations of fas 74