patho

1. STOMACH
PATHOLOGY

3. NORMAL ANATOMY/
HISTOLOGY

5. GASTRITIS
Inflammation of gastric mucosa
 Acute Gastritis
 Chronic Gastritis

6. Acute Gastritis
Transient mucosal acute inflammation
Frequently associated with:
 Heavy use of NSAIDs
 Excessive Alcohol consumption
 Heavy smoking
 Chemotherapeutic drugs
 Uremia
 Systemic infections (Salmonella, CMV)
 Severe stress –trauma, burns, surgery
 Ischemia & shock
 Suicidal ingestion of corrosive
 Gastric irradiation

7. Pathogenesis of Acute Gastritis
Pathogenesis poorly understood
Following influences thought to be operative
 Increased acid secretion with back diffusion
 Decreased production of HCO3 buffer
 Reduced blood flow
 Disruption of adherent Mucus layer
 Direct damage to epithelium
 Regurgitation of bile acids fron duodenum
 Inadequate synthesis of PG’s
 Idiopathic gastritis

8. Morphology
Mild – Mucosal hyperemia
 Lamina propria edema & congestion
 Surface epithelium intact,
 Scattered intraepithelial & intraluminal neutrophils (activity)
Severe –Mucosal erosion & hemorrhage
 Erosion denotes loss of surface epithelium generating defect in
mucosa that does not cross muscularis mucosae
 Rich inflammatory infiltrate
 Fibrinous purulent exudate into lumen
 Hemorrhage –punctate dark spots in hyperemic mucosa
Concurrent erosion & hemorrhage called acute erosive
hemorrhagic gastritis large areas of mucosa may be denuded
seen in alcoholics and NASIDs ingestion

9. ACUTE GASTRITIS

10. ERROSIONS

11. ACUTE GASTRITIS

12. ACID ALKALI INGESTION

13. C/F Of Acute Gastritis
 May be asymptomatic
 Epigastric pain
 Nausea & vomiting
 Overt hemorrhage
 Massive hematemesis & malena

14. Chronic Gastritis
Defined as chronic mucosal inflammatory
changes leading to eventually mucosal atrophy
and intestinal metaplasia usually in the absence
of erosions
Epithelial changes may become dysplastic
provide background for development of
carcinoma

15. CHRONIC GASTRITIS
HISTOLOGICAL CLASSIFICATION:
 Chronic superficial gastritis
 Chronic atrophic gastritis
 Gastric atrophy
CLASSIFICATION BASED ON PATHOGENESIS:
 Type A or immune gastritis
 Type B or non immune gastritis

16. Pathogenesis of Chronic Gastritis
Major etiologic associations are:
 H.Pylori chronic infection
 Autoimmune (P. Anemia)
 Toxic as with alcohol & cigarette smoking
 Post surgical- antrectomy with gastroenterostomy with reflux of
bile
 Motor & mechanical including obstruction, bezoars & gastric
atony
 Radiation
 Granulomatous (crohns disease)
 Uremia
 GVHD

17. Trichobezoars

18. CHRONIC GASTRITIS
CHRONIC SUPERFICIAL GASTRITIS:
 Inflammatory infiltrate limited to foveolar region, no
glandular atrophy
 ↓ cytoplasmic mucin, ↑ nuclear and nucleolar size and some
↑ in foveolar mitosis—may be seen
CHRONIC ATROPHIC GASTRITIS:
 Extensive inflammation, glandular atrophy
 Grade: mild, moderate, severe—estimated by thickness of
glands to whole mucosal thickness
 ↑ in distance between glands
GASTRIC ATROPHY:
 Thinning of mucosa in absence of inflammation
 End stage of chronic atrophic gastritis

19. CHRONIC GASTRITIS
TYPE A/ IMMUNE GASTRITIS:
 Site: fundus, spares antrum
 Antibodies against parietal cells, Intrinsic Factor, acid
producing enzymes- hypo or achlorhydria, ↑ serum gastrin and
pernicious anemia
 Also seen Hashimoto thyroiditis, Addisons disease & type 1
diabetes
 Patient are at risk of developing carcinoma / carcinoid tumours
TYPE B/ NON IMMUNE GASTRITIS:
 Site: begins in antrum and progress proximally to fundus
 Associated with H.pylori, alcohol, Cigarette smoke
 Types:
 Hypersecretory gastritis: restricted to antrum and

20. CHRONIC GASTRITIS
Endoscopically:
Thin, smooth mucosa with prominent submucosal vessels—
atrophic gastritis and gastric atrophy

21. H. Pylori
 Colonizes gastric mucosa esp antrum and cardia by:
1. Surface adhesion
2. Free in mucus
3. Intercellularly Intracellular colonization
4. → ↑↑ epithelial damage
 Disintegration and loss of apical mucin, epithelial
pits, erosions and ulceration
 Lymphoid follicles
 Special stains: Giemsa, Warthin-Starry stain or
IHC
 Found in 90% chronic gastritis, 95% duodenal ucler,

22. Giemsa stain H. Pylori

23. Diagnostic tests for H. pylori
 Serological tests for H.pylori antibodies
 Fecal bacterial detection
 Urea breath test (production of NH3 by
bacterial urease)
 Gastric biopsy demonstration of bacteria,
bacterial culture, rapid urease test
 Bacterial DNA detection by PCR

24. Diseases Associated with Helicobacter pylori
Infection
 Chronic gastritis Strong causal association
 Peptic ulcer disease Strong causal association
 Gastric carcinoma Strong causal association
 Gastric MALT lymphoma * Definitive etiologic role
* MALT, mucosa-associated lymphoid tissue

25. Gastric pathology
Part-II

26. Morphology of Chronic Gastritis
Regenerative Change.
Proliferative response to epithelial injury
Neck region of gastric glands mitotic figures increased
Enlarged epithelial cell with hyperchromatic nuclei and
higher N/C ratio & prominent nucleoli
Regenerative changes if severe with active inflammation
resemble dysplasia
Metaplasia.
Antral, body, and fundic mucosa may become partially
replaced by metaplastic columnar absorptive cells and
goblet cells of intestinal morphology (intestinal
metaplasia). Occasionally, villus-like projections or
features of colonic epithelium may be present. H.pylori
absent from areas of intestinal metaplasia

27. Morphology of Chronic Gastritis
Atrophy.
Marked loss in glandular structures associated with autoimmune
gastritis and pangastritis caused by H. pylori.
Persisting glands frequently undergo cystic dilatation. Atrophic
autoimmune gastritis or chronic gastritis treated by inhibitors of acid
secretion- hyperplasia of gastrin-producing G-cells in antral mucosa,
attributed to hypochlorhydria or achlorhydria arising from severe
parietal cell loss. Increased gastrinemia stimulates hyperplasia of
enterochromaffin-like cells in gastric body, provides background for
gastric carcinoid tumor
Dysplasia.
Long-standing chronic gastritis, epithelium develops cytologic
atypia-dysplasia. Intestinal metaplasia may precede dysplasia.
Dysplastic alterations if severe constitute in situ carcinoma. Dysplasia
thought to be precursor lesion of gastric cancer in atrophic
autoimmune gastritis and H. pylori- associated chronic gastritis.

28. Sydney System of
Grading Chronic Gastritis
1. Site: Antral, Corporal mucosa
2. Grading of: (Mild, Moderate, Marked)
 H-Pylori
 Chronic inflammation
 Activity
 Atrophy
 Intestinal metaplasia
*Normal lymphocytes & plasma cells in lamina propria = up to
5/HPF
*No Neutrophils in lamina propria

29. H. pylori
 H. pylori is a nonsporing, curvilinear gram-negative rod
measuring approximately 3.5 × 0.5 μm.
 Gastric mucus, which is lethal to most bacteria. The specialized
traits that allow it to flourish include:
• Motility (via flagella), allowing it to swim through viscous
mucus
• Elaboration of a urease, which produces ammonia and carbon
dioxide from endogenous urea, thereby buffering gastric acid in
the immediate vicinity of the organism
• Expression of bacterial adhesins, such as BabA, which binds to
the fucosylated Lewis B blood-group antigens, enhances binding
to blood group O antigen bearing cells
• Expression of bacterial toxins, such as cytotoxin association
gene A (CagA) and vacuolating cytotoxin gene A (VacA).

30. H.PYLORI
H&E STAIN GIEMSA STAIN

31. Moderate Gastritis

32. Chronic Gastritis

33. Intestinal Metaplasia

34. Anti-parietal cell antibody- bright
green immunofluorescence

35. OTHER TYPES OF
GASTRITIS
LYMPHOCYTIC ALLERGIC GASTRITIS:
GASTRITIS:  Seen in children associated with
 45-60% associated with diarrhea vomiting & growth failure
celiac disease  Eosinophilic infiltration
 Lymphocytosis of foveolar EOSINOPHILIC GASTRITIS:
ad surface epithelium mostly  Site: distal part of stomach and
T CD8+ lymphocytes proximal duodenum
 Typically affects middle-aged women
GRANULOMATOUS
GASTRITIS:  Allergic phenomenon, peripheral
 Cause: TB, mycosis, eosinophilia
 L/M: edema, prominent diffuse
sarcoidosis, Crohn’s disease
or idiopathic eosinophilic infiltration, eosiniphilic
microabscesses
 Narrowing & rigidity of
 Gastric outlet obstruction
antrum due to transmural  Related to eosinophlic enteritis
granulomas  D/D: inflammatory fibroid polyp

36. TYPES OF GASTRITIS
MELAKOPLAKIA: GRAFT VS HOST
 Histiocytic infiltrate conatining Michaelis- DISEASE:
Gutmann bodies  Bone marrow transplanted
REACTIVE GASTROPATHY patient
 Group of disorder characterized by foveolar  Apoptosis, gland
hyperpasia, loss of mucin , glandular destruction, sparse
regenerative changes, edema ,dilatation of lymphocytic infiltrate in
mucosal capillaries, smooth muscle lamina propria and granular
extending into lamina propria key to eosinophilic debris in
defination is absence of neutrophils
dilated glands
 Fairly common with Aspirin NSAID’s or
bile reflux MELAKOPLAKIA:
 Endoscopic longitudinal stripes of Histiocytic infiltrate conatining
erythematous mucosa alternating with less
severely mucosa (Water Melon Stomach)
Michaelis-Gutmann bodies

37. Clinical Features - Chronic Gastritis
 Nausea
 Vomiting
 Upper abdominal Discomfort- burning pain
 Hypochlorhydia due to parietal cell loss
 Pernicious Anemia in autoimmune gastritis

38. ACUTE GASTRIC ULCERATION
 Acutely developing mucosal defects
 Well known complication of NSAID’s therapy
 Causes: any debilitating illness, sepsis, shock, extensive
burns, severe trauma, intracranial injury , long term steroid
and aspirin ingestion, radio or chemotherapy
 Erosion- shedding of superficial epithelium
 Ulceration of mucosa deep lesion involving full mucosal
thickeness
 If muscle involved→ fibrosis and pit formation
 Deep ulcer may perforate, especially seen in radiotherapy
ulcers

39. TYPES-ACUTE GASTRIC ULCERS
1. STRESS ULCERS
• Due to severe physiologic stress of any nature
• Multiple lesions located mainly in stomach
• Range in depth from erosions to ulcers
• NSAID-induced ulcers related to decrease production of PG’s
which favors production of mucus ,HCO37 inhibit acid secretion
2. CURLING ULCERS
• Associated with severe burns or trauma
• Occurs in proximal duodenum
3. CUSHING ULCERS
• Gastric ,duodenal ,esophageal ulcers associated with Intracranial
injury, operations or tumours
• Direct stimulation of vagal nuclei by increase intracranial pressure
leading to hypersecretion of gastric acid- epithelial damage
• Carry high incidence of perforation

40. MORPHOLOGY Of ACUTE ULCER
GROSS:
 Acute stress ulcers usually less than 1 cm in diameter
 Circular and small.
 Ulcer base frequently stained a dark brown by the acid digestion of extruded
blood
 Unlike chronic peptic ulcers, acute stress ulcers found anywhere in stomach,
 Margins and base of ulcers not indurated.
 May occur singly, more often multiple stress ulcers throughout stomach &
duodenum.
MICROSCOPICALLY:
 Stress ulcers abrupt lesions, with essentially unremarkable adjacent mucosa.
 Depending on duration of ulceration, may be a suffusion of blood into
mucosa, submucosa and some inflammatory reaction.
 Conspicuously absent are scarring & thickening of blood vessels, as seen in
chronic peptic ulcers.
 Healing with complete reepithelialization, after causative factors removed.
 Time required for complete healing varies from days to several weeks.

41. Clinical Presentation of Acute Ulcer
 Bleeding from erosion or ulcers
 Associated history of critical illness

42. Multiple Stress Ulcers

43. PEPTIC ULCER
Ulcer defined as breach in mucosa of alimentary
tract that extends through out the muscularis
mucosa into submucosa or deeper
Peptic ulcers are chronic most often solitary occur in
any portion of GIT exposed to aggressive action of
acid/peptic juices(Usually less than 4cm in diameter)

44. Peptic Ulcer
SITE (In order of decreasing frequency)
 Duodenum first portion
 Stomach usually antrum (95% lesser curvature)
 G-E junction in setting of GERD/Barrett esophagus
 Margins of gastrojejunostomy
 Zollinger-Ellison syndrome
 Ileal Meckel diverticulum with ectopic gastric mucosa

45. Epidemiology
 In USA 4 million people have peptic ulcer
 5000die each year as a result of peptic acid disease
 Middle age to older adults, may first become
evident in young adult life
 Lifetime likelihood of developing peptic ulcer
about 10% for Americam males & 4% for females
 Male to female ratio is for duodenal ulcer is 3:1 &
for gastric ulcer is 1.5-2:1

46. Pathogenesis
Peptic ulcers produced by imbalance between gastroduodenal
mucosal defence mechanisms & damaging forces particularly
gastric acid & pepsin
 H.pylori infection major factor in pathogenesis of peptic ulcer
 Hyperacidity as in Zollinger-Ellison syndrome
 Chronic use of NSAID suppress PG synthesis
 Cigarette smoking impair mucosal blood flow & impair healing
 Alcoholic cirrhosis, increase incidence of peptic ulcer
 Corticosteroid in high dose or repeated use
 Chronic renal failure-uremia
 Hyperparathyroidism –hypercalcemia stimulate gastrin
production and acid secretion
 Personality and psychological stress
(10-20% of individuals worldwide infected by H. pylori actually
develops peptic ulcer)

48. H. Pylori –Pathogenesis of P. ulcer
 H. pylori does not invade tissues it induces an intense
inflammatory and immune response by increase production of
pro-inflammatory cytokines IL 1,6, & TNF and IL8 by mucosal
epithelial cells which recruits neutrophils
 Bacterial gene products involved in epithelial injury & induction
of inflammation, secrete urease which breakdown urea to form
toxic ammonium chloride & monochloramine, also elobrate
phospholipases that damage surface epithelial cells
 H.pylori enhances gastric acid secretion and impair duodenal
HCO3 production thus lowering luminal pH in duodenum
which favors gastric metaplasia in 1st part of duodenum,
provide environment for H. pylori colonization
 H.pylori protiens evoke immune response in mucosa with
activation of T & B lymphocytes. T cell dirven activation of B
cell may be involved in pathogenesis of gastric lymphomas
 Thrombotic occlusion of surface capillaries is promoted by
bacterial platelet activating factor

49. H. Pylori
Infection with CagA positive strain is associated with
 More organism in tissue
 More severe epithelial damage
 Greater acute and chronic inflammation
 Higher likelihood of peptic ulceration
 Increase risk of gastric cancer
* CagA gene is essential for expression of VacA
(Vacuolating toxin) which causes cell injury
* Over 80% patient with duodenal ulcers are
infected by CagA positive strain

50. MORPHOLOGY PEPTIC ULCER
 98% of peptic ulcers located in 1st part of duodenum or
in stomach in ratio of 4:1
 Most duodenal ulcers occur within a few cm of pyloric
ring
 Anterior wall of duodenum is affected more than
posterior wall
 Gastric ulcer predominantly located along lesser
curvature, less commonly anterior or posterior wall or
greater curvature
 Great majority are single ulcer
 10 to 20% of patient with gastric ulcers may have
coexistent duodenal ulcers

51. PEPTIC ULCER MORPHOLOGY
Gross:
 Small lesion less than 0.3cm are shallow erosions over 0.6cm are ulcers
 Over 50% of peptic ulcer are less than 2cm about 10% are greater than 4cm in
diameter
 Classic peptic ulcer oval to round sharply punched out defect with relatively straight
wall, converging mucosal folds extending to its margin
 Proximal ulcer margin-overhanging edges, distal-sloping borders
 Ulcer margins are level with surrounding mucosa
Cut Section:
 Undermining of edges, complete replacement of muscle by grayish white fibrous
tissue
 Base of ulcer is smooth & clean owing to peptic digestion of any exudate
 Subserosal fibrosis and inflammatory enlargement of regional lymph nodes
 Deep ulcers base formed by adherent pancreas ,omental fat
 Free perforation into peritoneal cavity
(Multiple biopsies recommended for standard size ulcer)

52. PEPTIC ULCER MORPHOLOGY
Microscopically:
In active ulcers Four Layers:
1. Surface coat purulent exudate, bacteria & necrotic fibrinoid
debris
2. Inflammatory infiltrate includes neutrophils
3. Granulation tissue infiltrated by mononuclear inflammatory
cells
4. Fibroous or collagenous scar replacing muscle wall &
extending into subserosa
 Muscularis mucosae fusion with muscularis externa at edges
 Hypertrophied nerve bundles
 Superimposed Candida infection on necrotic surface
 Chronic inflammation virtually universal in peptic ulcer and
persist after ulcer has healed but in healed erosion or stress
ulcers no chronic inflammation seen

53. GASTRIC ULCER

54. ULCER

55. CHRONIC PEPTIC ULCER
Healing phase:
 Regenerating epithelium grows over surface
 Epithelium may show intestinal metaplasia
Malignant transformation does not occur with duodenal
ulcer and is extremely rarely with gastric ulcers

56. Clinical Presentation
 Epigastric gnawing , burning or aching pain
 Bleeding, iron deficiency anemia
 Nausea, vomitin ,bloating, belching
 Weight loss
 Gastric ulcer pain immediately after taking meal
 Doudenal ulcer pain empty stomach reduced by
taking meal
 Milk reduces pain in gastric ulcer not in
duodenal ulcer

57. Complications of Peptic Ulcer Disease
 Bleeding
• Occurs in 15% to 20% of patients
• Most frequent may be life-threatening
• Accounts for 25% of ulcer deaths
 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

59. Hypertrophic Gastropathy
 Menetrier Disease
 Zollinger- Ellison Syndrome

60. MENETRIER’S DISEASE
 Associated with hypochlorhydria or achlorhydria,
hypoproteinemia
 Site: greater curvature of stomach, diffuse involvement of
fundus and sparing antrum
 Gross: marked hypertrophic rugae
 L/M: foveolar hyperplasia, tortuous cystically dilated glands
and extension into base of glands and beyond muscularis
mucosae
 Glandular componenet ↓ed
 Edematous and inflammed stroma
 Carcinoma may develop but incidence is same as that Ca
originating in atrophic gastritis
 D/D: carcinoma

61. ZOLLINGER-ELLISON
SYNDROME
 Accompanied by gastric changes radiographically and
grossly similar to Menetrier’s disease
 L/M: hyperplasia affecting secretory rather than foveolar
part of fundic gland
 Hyperplasia of mainly parietal cells, but ECL cells also ↑ed
 Fundic gland polyps and intramucosal cysts maybe seen
 May be associated with MEN

62. Gastric Pathology
Part III

63. GASTRIC TUMOURS
 NON-NEOPLASTIC POLYPS 90%
 NEOPLASTIC 10%
BENIGN
MALIGNANT

64. WHO Histologic Classification of Gastric Tumors
EPITHELIAL TUMORS
Intraepithelial neoplasia: adenoma
Adenocarcinoma *
••• Papillary adenocarcinoma
••• Tubular adenocarcinoma
••• Mucinous adenocarcinoma
••• Signet-ring cell carcinoma
••• Undifferentiated carcinoma
••• Adenosquamous carcinoma
Small-cell carcinoma
Carcinoid tumor
NON-EPITHELIAL TUMORS
Leiomyoma
Schwannoma
Granular cell tumor
Leiomyosarcoma
Gastrointestinal stromal tumor (GIST) (gradation from benign to malignant)
Kaposi sarcoma
MALIGNANT LYMPHOMA
* The Laurén classification subdivides adenocarcinomas into intestinal and diffuse
types

65. Gastric Polyps-Classification
1. Hyperplastic
2. Adenomas Intestinal adenomatous
villoglandular
3. Mixed villous
4. Fundic gland Gastric
5. Inflammatory fibroid polyp
Familial polyposis
6. Polyposis syndrome Gardner syn.
7. others PJ syn.
Cowden syn.
Cronkhite-canada syn.
Focal hyperplasia
Antral gland hyperplasia

66. Hyperplastic polyps
Associated with
 Hypochlorhydria
 Dec. pepsinogen
 Hypergastrinemia
 Ch. Gastritis
 Gastric atrophy
95% of gastric polyps
Gross:
 Small, sessile, may be multiple up to 20
 Located in antrum
 Several cm in diameter
Microscopically:
 Hyperplastic (regenerative) surface epithelium
 Cystically dilated glands
 Inflammatory cells and smooth muscle in lamina propria
 No Malignant transformation

67. Gastric Hyperplastic Polyps

68. Fundic gland
 Fundic gland hyperplasia, hamartomatous cystic
polyp,
 Site: multiple polyps in fundus
 Microscopy:
 Microcysts with fundic epithelium (oxyphil
cells)
 Crypts are short
 Increase smooth muscles in pericystic area
 Associated With
 Zollinger ellison syndrome
 Proton pump use (prolonged)

69. Peutz-Jeghers polyps
 Gastric P-J polyps seen as a part of P-J
syndrome
 Juvenile polyps seen as part of juvenile polyposis
syndrome

70. Inflammatory Fibroid polyp
 Eosinophilic granuloma, inflammatory pseudotumor
 Associated with hypochlorhydria
 Site: antrum
 Gross: elevated, sessile
 Microscopy:
 Submucosal
 Vascular+fibroblatic proliferation, whorling around blood
vessels
 Polymorphic infiltrate, numerous eosinophils
 Many fibers are myofibroblastic
 Immunohistochemictry: CD34, bcl-2 +ve

71. Inflammatory Fibroid Polyp

72. Adenomatous Polyps/Adenomas
o Proliferative dysplastic epithelium with malignant potential
o Back ground chronic gastritis /intestinal metaplasia or autoimmune
gastritis
o Site: antrum
o 5-10% of polypoid lesion in stomach
o Increase with age, seventh decade
Gross:
Single, large, sessile/ pedunculated, grow up to 3-4cm
Some time adenomatous change cover large area of gastric mucosa without
forming mass lesion
Microscopy:
 Dysplatic glands
 Pseudostratified epithelium, abnormal nuclei
 Increase mitoses
 Type: Gastric or intestinal (Tubular/Villous)
 40% contain carcinoma at time of diagnosis
 Risk of malignancy in adjacent mucosa is 30%

73. Gastric Adenomatous polyp

75. GASTRIC
CARCINOMAS

76. Epidemiology of Gastric cancer
 Second most common tumor in the world
 High in Japan, Chile, Costa Rica, China, Colombia,
Portugal, Russia and Bulgaria
 Four to six fold less common in USA, UK, Canada,
Australia, New Zealand, France & Sweden
 Male to female ratio 2:1
 Intestinal type develops in high risk areas from
precursor lesion with mean age of incidence 55yrs,
male to female ratio of 2:1, drop in incidence
occurred in this type
 Diffuse type no precursor lesion with mean age of
incidence 48yrs, equal male to female ratio

77. Factors Associated with Increased Incidence of Gastric Carcinoma
Environmental Factors
Infection by H. pylori
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
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
• 40% harbor cancer at time of diagnosis
• 30% have adjacent cancer at time of diagnosis
Barrett esophagus
Genetic Factors
Slightly increased risk with blood group A
Family history of gastric cancer
Hereditary non-polyposis colon cancer syndrome
Familial gastric carcinoma syndrome (E-cadherin mutation)

78. MOLECULAR GENETIC FEATURES
 Aneuploidy—intestinal > diffuse
 Germline mutations of E-cadherin gene in families with
hereditary Ca of diffuse type
 Microsatellite instability —20% of gastric Ca,
 Accumulation of p53 mutation—50%
 Somatic mutation of APC gene—4%
 Overexpression of ras p21 product
 Membrane immunostaining for c-erbB-2—few cases
 Loss of p16—1/4th gastric Ca
 Bcl-2 and Bax expression—intestinal>diffuse
 Loss of Fhit expression—diffuse type and Krukenberg tumor
 Overexpression of cyclin D1

79. Morphology
 Gross
 Microscopic
 Special stains
 Immunohistochemistry
 Metastases- Virchow node
 Krukenberg Tumour- Bilateral ovarian
 Sister Mary Joseph nodule- paraumbilical

80. Morphology
GROSS:
Location;
 Pylorus and Antrum 50-60%
 Body and Fundus 25%
 Lesser curvature 40%
 Greater curvature 12%
Gastric carcinoma is classified on the basis of
1. Depth of invasion
2. Macroscopic growth pattern
3. Histologic subtype
Morphologic feature having the greatest impact on
clinical out come is the depth of invasion

81. Morphology
Early gastric carcinoma
Lesion confined to mucosa and submucosa
regardless of presence or absence of
perigastric lymph node metastases
Advanced gastric carcinoma
A neoplasm extended below submucosa into
muscular wall
Three Macroscopic Pattern
 Exophytic
 Flat /Depressed
 Excavated (Ulcerated)

82. Malignant Gastric Ulcer
 Heaped-up, beaded margins
 Shaggy necrotic bases
 Overt neoplastic tissue extending into
surrounding mucosa and wall
Linitis plastica
Rigid thickened leather bottle wall infiltrated by
Malignancy

83. Morphology
Histologic Types
 Intestinal- Glandular
 Diffuse- Signet Ring Cell
(more than 50% signet ring
cell)- PAS positive, CK +,
EMA+, CEA+
Histologic Grade
 Well-differentiated
 Moderately-differentiated
 Poorly-differentiated
 Undifferentiated

84. Clinical Presentation
 Generally asymptomatic
 Anorexia ,vomiting
 Abdominal pain
 Weight loss
 Dysphagia
 Anemia
 Hemorrhage
Diagnosis
 Radiographic techniques for exophytic lesions
 Endoscopy
 Biopsy

85. Virchow node: Mets from Carcinoma of
stomach to supraclavicular lymph node
(Sentinel)
Metastatic Cancers of stomach Includes Mets from
 Systemic lymphoma,
 Malignant melanoma,
 Ca breast ,
 Ca lung

86. Gastric Malignant Ulcer
(with depth of invasion)


87. ADENOCARCINOMA

88. Gastric Adenocarcinoma

89. Intestinal & Diffuse type of
Adenocarcinoma

90. DIFFUSE INFILTRATIVE CA

91. PAS Positive Signet Ring Cell

92. Prognosis of Gastric Carcinoma
 Depends on
 Depth of invasion
 Extent of Lymph Node involvement
 Distant metastases
 Histologic type
 Resection margins
 DNA Ploidy , P53 mutation
 Five year S.R of surgically treated early carcinoma is 90-
95% in advanced cases it is 15%

93. Gastrointestinal Stromal Tumors
 Non- epithelial neoplasms of gut
 Site: stomach, small bowel, other portions of gut,
omentum, mesentry, retroperitonium
 60% submucosal, 30% subserosal, 10% intramural
 Origin interstitial cell of Cajal
PROGNOSIS:
 Tumor size, mitoses, necrosis,
 Stomach GIST has better prognosis than intestinal

94. New Concept-GIST
Smooth muscle Neuronal (GANT) Both Undifferentiated
Sm. Muscle Actin NeuronSp.Enolase Morpholigically & Unable to classify
Desmin Leu 7 immunohistoche-
mically exhibit
Myosin S-100
both sm. muscle Usually CD34+ve
and neuronal
differentiation C-Kit positive
(CD117)

95. GIST c-KIT Positive

96. Stomach Lymphoma
 Classification:
 Low grade: Small lymphoid cells
 High/ intermediate: large lymphoid cells
 Rare…1-4% of GI malignancies
 Primary GI lymphoma exhibit no evidence of liver,
spleen, mediastinal lymph node or bone marrow
involvement at time of diagnosis
 Regional lymph node involvement may be present
 Collision tumors:
 Lymphoma+adenocarcinoma
 Carcinoma can develop after treatment of lymphoma

97. Grading system indicating degree of
certainty of diagnosis of MALT
Lymphoma
Grade 0 (Normal) Scattered plasma cells in lamina propria.
NO lymphoid follicles
Grade 1 (Active chronic Small clustes of lymphocytes in lamina
gastritis) propria. NO follicles/ LELs
Grade 2 (Active chronic gastritis Prominent follicles with surrounding
with florid follicles) mantle zone+plasma cells. NO LELs
Grade 3 (suspicious lymphoid Follicles surrounded by small lymphocytes
infiltrate in lamina propria, infiltrate diffusely in lamina propria and
reactive probably) Occasionally into epithelium
Grade 4 (suspicious lymphoid Folicles surrounded by MZ cells diffuse
infiltrate in lamina propria, infiltrate in lamina propria and into
lymphoma probably) epithelium in small gps.
Grade 5 (low grade B-Cell Dense diffuse infiltrate of MZ cells in
lymphoma of MALT) lamina propria with prominent LELs

98. MALT

99. MALT Lynphoma

100. NEUROENDOCRINE DIFFERENTIATION
1. Well differentiated neuroendocrine tumors (carcinoid):
 Slow growing
 Neuroendocrine cells of gastric mucosa
2. Atypical carcinoid/ neuroendocrine carcinoma/ large cell
neuroendocrine ca
 Tumors with obvious morphological features of neuroendocrine
differentiation but obvious atypia:
 Trabaculae, rosettes, insulae; dense core secretory granules,
NSE+
 Atypia—invasiveness, necrosis, mitosis
3. Small cell carcinoma:
 Analogous to pulmonary counterpart
 Aggressive behavior
4. Otherwise typical adenocarcinoma of diffuse or intestinal
type having cells with argyrophilia or neuroendocrine
differentiation

101. Carcinoid