1

Pathology of upper
Pathology of upper 
gastrointestinal tract
gastrointestinal tract

Komson Wannasai, M.D., FRCPath.
Wannasai M D FRCPath
Department of Pathology
Faculty of Medicine
Chiang Mai University 
 E h
Esophagus and EG junction
d EG j ti

 Normal Esophagus 
 Hollow, muscular tube
 Pharynx ‐ EG junction (T11/T12)
Pharynx ‐ EG junction (T11/T12)
 23‐25 adult (10 ‐11 cm in neonate) 
 Luminal narrowings
 Cricoid cartilage
 Aortic arch
 Left main bronchus/left atrium
L ft i b h /l ft t i

 
2
 E h
Esophagus and EG junction
d EG j ti
 Structure 
 High pressure areas
 Upper esophageal sphincter (UES) ‐
pp p g p ( )
cricopharyngeus
 Lower esophageal sphincter (LES) 
Lower esophageal sphincter (LES) ‐ diaphragm
 Histology
 Mucosa ‐
M nonkeratinizing
k i i i squamous epithelium
i h li
 Submucosa ‐ loose connective tissue
 Muscularis propria ‐ proximal (6‐8 cm)  
 Adventitia
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4
5
 Signs and symptoms of 
g y p
esophageal disease   
 Heartburn
 Most commonly due to gastroesophageal
Most commonly due to gastroesophageal reflux disease 
reflux disease
 Dysphagia for solids alone
 Symptom of an obstructive lesion
Symptom of an obstructive lesion
 Examples‐esophageal cancer, esophageal web, stricture 
 Dysphagia for solids and liquids
for solids and liquids
 Symptom of a motility disorder
 Oropharyngeal (upper esophageal) dysphagia
(upper esophageal) dysphagia
 Striated muscle weakness
 Lower esophageal dysphagia
Lower esophageal dysphagia
 Smooth muscle dysmotility
 
6
 Tracheoesophageal
T h h l fistula
fi t l
 Characteristics 
 Proximal esophagus ends blindly
P i l h d bli dl
 Distal esophagus arises from the trachea. 
 Clinical findings 
 Maternal polyhydramnios
Maternal polyhydramnios (excess amniotic fluid) 
(excess amniotic fluid)
 Swallowed amniotic fluid cannot be reabsorbed in the 
small intestine 
 Abdominal distention in newborn 
 Air in the stomach from tracheal fistula 
 Difficulty with feeding 
 Food regurgitates out of the mouth. 
Food regurgitates out of the mouth.
 Chemical pneumonia from aspiration  7
8
VATER syndrome 
Vertebral abnormalities 
Anal atresia
TE fistula 
fistula
Renal disease and absent radius  9
 Lesions Associated with Motor 
Dysfunction: Achalasia  
 Failure to relax
 Pathogenesis 
Pathogenesis
 Incomplete relaxation of LES 
 Absent ganglion cells in myenteric
Absent ganglion cells in myenteric plexus 
plexus
 Decreases proximal smooth muscle contraction 
 Loss of vasointestinal peptide (normally relaxes 
p p ( y
LES) 
 Dilation of esophagus proximal to LES with 
absent peristalsis 
b i li
 Acquired cause is Chagas' disease. 
 Destruction
Destruction of ganglion cells by leishmanial
of ganglion cells by leishmanial
forms 

10
 Lesions Associated with Motor 
Dysfunction: Achalasia  
 Clinical findings 
 N
Nocturnal regurgitation of 
t l it ti f
undigested food 
 Abnormal barium swallow 
Ab lb i ll
 Dilated, aperistaltic esophagus 
with a beak‐like tapering at distal 
end 
 Abnormal esophageal 
manometry
 Detects aperistalsis and failure of 
LES relaxation 
11
 Lesions Associated with Motor 
Dysfunction: Hiatal hernia 
 Separation of the diaphragmatic 
crura
 Widening of the space between the 
Wid i f th b t th
muscular crura and the esophageal 
muscular crura and the esophageal
wall

12
 Lesions Associated with Motor 
Dysfunction: Hiatal
Dysfunction: Hiatal hernia 
hernia 
 Sliding hernia 
 Most
Most common type 
common type
 Herniation of proximal 
stomach through a 
widened diaphragmatic 
hiatus 
 Clinical findings 
Cli i l fi di
 Heartburn and 
oc u a ep gas c
nocturnal epigastric
distress from acid reflux 
 Hematemesis (vomiting  Paraesophageal hernia 
bl d) l
blood), ulceration, 
ti Portion of stomach herniates
stricture  alongside the distal esophagus. 

13
 Lesions Associated with Motor 
Dysfunction: Diverticulum
Dysfunction: Diverticulum  
 Types of diverticulum
 True diverticulum
True diverticulum
 Outpouching lined by mucosa, submucosa, muscularis propria, 
and adventitia 
 False, or pulsion diverticulum
 Weakness in underlying muscle wall 
 Outpouching
O hi of mucosa and submucosa
f d b i
into area of weakness 
f k
 Zenker's diverticulum
 Pulsion type located in upper esophagus 
 Area of weakness is cricopharyngeus muscle. 
 Clinical findings 
Clinical findings
 Painful swallowing 
 Halitosis (entrapped food), diverticulitis 
Halitosis (entrapped food), diverticulitis

  14
 Lesions Associated with Motor 
D f ti
Dysfunction: Mallory‐
Dysfunction: Mallory
M ll ‐Weiss syndrome
W i d

 Mucosal tear in the proximal stomach 
and distal esophagus 
d di t l h
 Due to severe stretching in alcoholics or 
g
bulimia 
 Causes hematemesis
C h t i
 Boerhaave syndrome
 Distal esophageal 
Distal esophageal 
rupture and 
rupture  and mediastinitis
mediastinitis

15
 Corrosi e esophagitis
Corrosive esophagitis
 Ingestion of strong alkali (e.g., lye) 
or acid (e.g., HCl) 
 Complications 
C li ti
 Stricture formation, perforation, 
Stricture formation perforation
squamous cell carcinoma 

16
 Infectio s esophagitis
Infectious esophagitis
 Usually a complication of AIDS 
 Pathogens 
P th
 Herpes simplex virus 
 See multinucleated squamous cells with intranuclear
inclusions 
 Cytomegalovirus (CMV) 
 See basophilic intranuclear inclusions 
 Candida
 See yeasts and pseudohyphae (extended yeast forms) 
 Present with painful swallowing (i.e., 
odynophagia) 
odynophagia)
17
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 Esophageal varices
Esophageal varices
 Epidemiology and pathogenesis 
 Dil
Dilated submucosal left gastric coronary veins 
t d b l l ft ti i
 Complication of portal hypertension from cirrhosis 
 portal hypertension
lh i
 Alcohol abuse is the most common cause. 
 Viral hepatitis B and C
 Clinical findings 
 Rupture with massive hematemesis   (vomiting 
blood) )
 Most common cause of death 
in cirrhosis 
20
21
 Refl esophagitis
Reflux esophagitis
 Risk factors 
 Smoking, alcohol, caffeine, fatty foods, 
chocolate, hiatal hernia 
 Pathogenesis
 Transient relaxation of lower esophageal 
sphincter (LES) 
 Reflux of acid and bile into the distal esophagus 
 Ineffective
Ineffective esophageal clearance of reflux 
esophageal clearance of reflux
material 
22
 Refl esophagitis
Reflux esophagitis
 Pathology 
 Mild: simple hyperemia
 Inflammatory cells: E  N
Inflammatory cells: E 
 Basal zone hyperplasia – 20%  
 Elongation of the lamina propria papillae
 Clinical features
Clinical features
 Noncardiac chest pain, nocturnal cough, nocturnal 
asthma 
th
 Heartburn, acid injury to enamel 
 Barrett's esophagus 23
24
25
 Refl esophagitis
Reflux esophagitis
 Diagnosis
 Endoscopic exam 
 Examination of the contraction of 
the esophagus and LES
the esophagus and LES 
 Measure the pH
Measure the pH
 Barium swallow radiograph 
g p
 
  26
 Refl esophagitis
Reflux esophagitis
 Treatment
 Change life style 
 Medication 
M di ti
 Antacid
 Foaming agent; Gaviscon 
 H2 blocker; cimetidine, famotidine, 
bl k d f d
nizatidine, ranitidine 
 Surgery; Fundoplication 
  27
 Barrett esophagus
Barrett esophagus
 Intestinal metaplasia within the esophageal 
squamous mucosa
squamous mucosa
 Long‐standing gastroesophageal reflux
 10% of patients with symptomatic GERD 
 Distal squamous mucosa is replaced by 
Distal squamous mucosa is replaced by
metaplastic columnar epithelium
 Criterias
 Endoscopic
Endoscopic evidence of columnar epithelial lining 
evidence of columnar epithelial lining
above the gastroesophageal junction 
 Histologic evidence of intestinal metaplasia
Histologic evidence of intestinal metaplasia
28
 Barrett esophagus
Barrett esophagus
 Classified as long segment (≥ 3 cm) or 
short segment (< 3 cm)
h t t( 3 )
 Pathology
 Gross: endoscopic features 
 One or several tongues or patches of red, 
velvety mucosa 
 Extending upward from the EGJ
 Microscopic features  
Microscopic features
 Metaplastic columnar epithelium with mucous 
glands
29
 Dysplasia: low grade and high grade  
 Barrett esophagus
Barrett esophagus
 Clinical features: GERD 
 Secondary complications
 Adenocarcinoma 30‐40 folds
30‐40 folds
 

30
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Primar esophageal t mors
Primary esophageal tumors 
 Epithelial  Malignant (cont’)
 Benign  Adenocarcinoma 
 Squamous
q  Mucoepidermoid
papilloma CA 
 Adenoma
 Malignant 
M li t
 Malignant melanoma 
 Squamous
S cell 
ll
 Choriocarcinoma 
carcinoma
 Spindle cell   Undifferentiated 
Undifferentiated
carcinoma  CA 
(
(Carcinosarcoma) )
34

 
Primar esophageal t mors
Primary esophageal tumors 
 Non epithelial 
 Benign 
 Leiomyoma
 Granular cell tumors
 Malignant 
 Soft tissue sarcoma 
f
 Lymphoma
y p
 Neurogenic sarcoma 
  35
36
 Squamous
q cell carcinoma of 
esophagus 
 Epidemiology
 Most common type of carcinoma of 
the esophagus worldwide
the esophagus worldwide
 Male to female ratio of 2:1
 African Americans have a higher risk 
than whites
h hi

37
 Squamous cell carcinoma
q of 
esophagus 
 Etiology
 Smoking and alcohol use
 Dysphagia due to esophagitis
due to esophagitis or 
or
achalasia
 Increases exposure of mucosa to toxins
I f i
 Plummer‐Vinson syndrome
y
 Deficiency of vitamin A 

38
 Squamous
q cell carcinoma of 
esophagus 
 Morphology
 Begin as intraepithelial neoplasm 
or carcinoma in situ
i i i
 When they become overt
When they become overt
 20% upper third
20% upper third
 50% middle third
 30% lower third  
39
 Squamous cell carcinoma
q of 
esophagus 
 Early lesions: plaque like lesion
 Advance lesion
Advance lesion
 Tumorous masses 
 Encircle the lumen
E i l th l
 Three morphologic patterns 
 Protruded (60%)
 Flat (15%)
 Excavated (ulcerated; 25%)
 Invasion
Invasion into lamina propia, muscularis
into lamina propia, muscularis
mucosae, submucosa, muscular layer 
adventitia
40
 Squamous cell carcinoma
q of 
esophagus 
 Well or moderately differentiated 
 Sheet‐like growth pattern with polygonal 
shape cells showing hyperchromatic
shape cells showing hyperchromatic
nuclei with prominent nucleoli  
 Keratin pearls; intercellular bridges; 
single cell keratinization
single cell

41
42
43
44
 Squamous cell carcinoma
q of 
esophagus 
 Clinical Features
 Insidious onset 
 Progressive dysphagia
Progressive dysphagia 
 Esophageal obstruction 
 Extreme weight loss 
 Hemorrhage 
Hemorrhage
 Sepsis 
 Aspiration 

45
 Ad
Adenocarcinoma of esophagus  
i f h
 Etiology
 Pre‐existant Barrett esophagus 
 Secondary to reflux esophagitis it is worth 
Secondary to reflux esophagitis it is worth
reviewing esophageal reflux
 Epidemiology
E id i l
 Mean age 64 yrs
Mean age 64 yrs
 Male > Female 
 Common found in Barrett esophagus

46
 
 Ad
Adenocarcinoma of esophagus 
i f h

 Pathogenesis
 Reflux esophagitis 
 Metaplastic
M t l ti Barrett esophageal 
B tt h l
mucosa
 Glandular epithelial dysplasia 
 Adenocarcinoma 
 
 
47
 Ad
Adenocarcinoma of esophagus 
i f h
 General Gross Description
 Arise from dysplastic mucosa in the setting 
of Barrett esophagus
 Distal one‐third of the esophagus 
 Invade the subjacent gastric cardia
I d th bj t ti di
 Flat or raised patches
p
 Large nodular masses
 Deeply ulcerative or diffusely infiltrative 
D l l i diff l i fil i
features
  48
 Ad
Adenocarcinoma of esophagus 
i f h

 Microscopic Description
 Invasive glandular structures
 Mucin‐producing glandular tumors 
M i d i l d l t
 Intestinal‐type features
yp
 Keeping with the morphology of the 
preexisting metaplastic mucosa
preexisting metaplastic

49
50
51
52
 Ad
Adenocarcinoma of esophagus 
i f h

 Clinical feature
 Occur in patients over 40 years
 More common in men and white
M i d hit
 The symptoms like other forms of 
The symptoms like other forms of
esophageal carcinoma 
 Poor prognosis

53
 Stomach
Normal structure 
 Sac, 1200‐1500 ml, max 3000 mL
 Narrowing area: incisura angularis
 Anatomic regions: cardia, fundus, body 
Anatomic regions: cardia fundus body
(corpus), antrum, and pylorus
 Mucosa: surface foveolar cells, mucous 
neck cells and glands (cardia, gastric or 
g ( ,g
oxyntic, antral or pyloric glands)
 Cells: mucous, parietal, chief , endocrine
C ll i l hi f d i
 
54
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56
 Stomach
Mucosal physiology
p y gy
 Acid secretion 
 Cephalic, gastric and intestinal phases
 Parietal cells (acid)
Parietal cells (acid)
 Mucosal protection 
 Mucous secretion 
 Bicarbornate secretion
Bicarbornate secretion
 Epithelial barrier 
 Mucosal blood flow 

57
 A t G t iti
Acute Gastritis
Acute transient mucosal inflammatory process
Acute transient mucosal inflammatory process

 Pathogenesis  Uremia
Uremia 
 NSAIDs; particularly   Systemic bacterial or viral 
aspirin
aspirin  infections 
 Excessive alcohol   Severe stress 
consumption   Ischemia and shock 
 Heavy smoking   Suicidal attempts
 Treatment with cancer   Gastric irradiation or 
chemotherapeutic drugs  freezing 
 Mechanical trauma 
 Distal gastrectomy
 

58
 A t G t iti
Acute Gastritis
 Increased acid secretion 
 Decreased production of 
bi b
bicarbonate 
t
 Reduced blood flow
Reduced blood flow
 Disruption of the adherent mucus 
Disruption of the adherent mucus
layer
 Direct damage to the epithelium
59
60
 A t G t iti
Acute Gastritis
 Morphology 
 Intraepithelial neutrophils
 Erosion
 Loss of superficial epithelium above muscularis
mucosae accompanied by hemorrhage and
mucosae, accompanied by hemorrhage and 
variable acute inflammatory infiltrate 
 Defect in the mucosa is limited to the lamina 
D f i h i li i d h l i
propria 
 Clinical features 
 Asymptomatic ‐
Asymptomatic severe bleeding
severe bleeding
61

 
 Massive gastric 
hemorrhage

Erosion and 
h
hemorrhagic spots
h i t

62
63
Loss of superficial epithelium above muscularis mucosae, 
acco pa ed by e o age a d a ab e acute
accompanied by hemorrhage and variable acute 
inflammatory infiltrate  64
 A t
Acute gastric ulceration
ti l ti
 Focal, acutely developing gastric mucosal 
d f t
defects 
 Etiologic association 
Etiologic association
 NSIADs association 
 Severe physiologic stress
 Curling ulcers: Severe burn or trauma
Curling ulcers: Severe burn or trauma
 Proximal duodenum 
 Cushing ulcers: Intracranial injury, operation, 
Cushing ulcers: Intracranial injury operation
tumor 
 Stomach, duodenum, esophagus
S h d d h
65
 A t
Acute gastric ulceration
ti l ti

 Morphology 
 Single or multiple
 Any sites
 Less than 1 cm
h
 Sharply demarcated
Sharply demarcated
 Clinical features
Clinical features
 Bleeding
66
67
 Ch i
Chronic gastritis
t iti
 Chronic mucosal inflammatory 
changes leading to mucosal atrophy 
and epithelial metaplasia usually
and epithelial metaplasia, usually 
without erosions 
 May develop carcinoma
 
 

68
 Ch i
Chronic gastritis
t iti
 Pathogenesis
 Chronic infection by H. pylori
Ch i i f ti b H l i
 Autoimmune
 Toxic
 Postsurgical; antrectomy with gastroenterostomy
 Motor and mechanical 
 Radiation 
Radiation
 Granulomatous conditions 
 Mi ll
Miscellaneous 

69
 Ch i
Chronic gastritis
t iti
 Morphology
 Chronic
Chronic inflammation with/without 
inflammation with/without
neutrophils
 Plasma cells, lymphocytes, occasional lymphoid 
l ll l h ll h d
follicles 
 Intestinal metaplasia
 Replacement by metaplastic
p y p ggoblet cells of 
intestinal morphology, absorptive cells and 
Paneth cells
 
  70
 Chronic gastritis
Chronic gastritis
 Complete intestinal metaplasia: mucosal 
pattern resembles small bowel
pattern resembles small bowel 
epithelium with goblet and absorptive 
cells, villi
ll illi and crypts
d
 Incomplete intestinal metaplasia:
p p no 
absorptive cells, columnar cells 
resemble gastric foveolar cells
resemble gastric foveolar

71
The lamina propria
The lamina propria
contains a moderate 
chronic
inflammatory infiltrate 

Intestinal metaplasia;
Intestinal metaplasia;
complete type 

72
73
 Ch i
Chronic superficial gastritis
fi i l t iti
 Involve superficial epithelium, gastric 
pits and upper lamina propria
it d l i i
 Without involving gland
Without involving gland
 Inflammatory cell infiltrate 
 Lymphocytes, plasma cells, eosinophils
A
Active chronic gastritis; neutrophils
ti h i t iti t hil
 

74
The mucosa adjacent to the ulcer shows chronic 
gastritis.  Note
t iti N t theth discrete
di t band of
b d f chronic
h i inflammation 
i fl ti75
in the most superficial portion of the mucosa.  
 Ch i t hi
Chronic atrophic gastritis
t iti
 Chronic gastritis accompanied by 
glandular atrophy (mild, moderate, 
severe)
 Usually secondary to chronic
Usually secondary to chronic H. 
H.
pylori infection
 Atrophy of gland
 Collapse and condensation of 
reticulin 76
77
78
79
• Helicobacter pylori.
pylori A 
A
Steiner silver stain 
demonstrates the
numerous darkly 
stainedd Helicobacter
l b
organisms along the 
luminal surface of the 
ggastric epithelial
p cells. 
Note that there is no 
tissue invasion by
bacteria.
  80
 Mi ll
Miscellaneous Conditions
C diti
 Bezoars
 Phytobezoars
 Trichobezoars (hair
(hair ball)
ball)
 Hypertrophic gastropathy
 Zollinger‐Ellison syndrome
 Menetrier
Menetrier’ss disease

81
Ti h b
Trichobezoar

82
Hypertrophic  Gross feature
Hypertrophic Gross feature Histologic Clinical 
Clinical
gastropathy feature  feature 
Zollinger‐Ellison  Enlarged rugal Glandular  Peptic ulcer, 
syndrome fold  hyperplasia;   hypergastrinemi
l
large parietal 
l a ,steatorrhea 
h
cells ,often  and diarrhea 
nearer to
nearer to 
surface than 
normal 

Menetrier’s Thick strand of  Foveolar hyper  Protien lossing

disease  mucus ;  plasia ;  gastropathy 
“polypoid” areas  glandular 
in some
in some atrophy
atrophy 

83
84
 Stomach : Tumors
Stomach : Tumors
 Adenoma 
 C i
Carcinoma
 Stromal tumor
Stromal tumor
 Lymphoma 
 Others
 Lipoma
 Germ cell tumor  
 Metastatic carcinoma 
  85
 WHO Histologic Classification of 
g
Gastric Tumors  
 Epithelial Tumors
 Intraepithelial neoplasia: adenoma
I t ith li l l i d
 Adenocarcinoma*
 Papillary adenocarcinoma 
 Tubular adenocarcinoma 
 Mucinous adenocarcinoma 
 Signet‐ring cell carcinoma 
 U diff
Undifferentiated carcinoma 
ti t d i
 Adenosquamous carcinoma 
 Small‐cell carcinoma
S ll ll i
 Carcinoid tumor 
86
 WHO Histologic Classification of 
g
Gastric Tumors  
 Nonepithelial Tumors
 LLeiomyoma
i
 Schwannoma
 Granular cell tumor
 Leiomyosarcoma
 Gastrointestinal stromal tumor (GIST) (gradation 
from benign to malignant)
g g )
 Kaposi sarcoma
 Others
 Malignant Lymphoma 
87
 G ti
Gastric carcinoma
i
 Adenocarcinoma of stomach is the most 
important tumor of the stomach
important tumor of the stomach 
 High incidence in Japan, Chile, Northern 
g p
Italy, China, Portugal, Russia
 2/3 men
2/3

88
 Factors Associated with Increased 
Incidence of Gastric Carcinoma  
 Environmental Factors
 Infection by H. pylori
I f ti b H l i
 Present in most cases of intestinal‐type carcinoma 
 Diet
Di
 Nitrites derived from nitrates (water, preserved food) 
 Smoked and salted foods, pickled vegetables, chili 
peppers 
 Lack of fresh fruit and vegetables 
Lack of fresh fruit and vegetables
 Low socioeconomic status
 Cigarette smoking
Ci ki

89
 Factors Associated with Increased 
Incidence of Gastric Carcinoma 
 Host Factors
 Chronic gastritis
Ch i t iti
 Hypochlorhydria: favors colonization with H. pylori
 Intestinal metaplasia is a precursor lesion 
I t ti l t l i i l i
 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
 Increased risk of gastroesophageal junction tumors 

90
 Factors Associated with Increased 
Incidence of Gastric Carcinoma 

 Genetic Factors
 Slightly increased risk with blood 
group A
group A
 Family history of gastric cancer
y y g
 Hereditary nonpolyposis colon cancer 
syndrome
d
 Familial gastric carcinoma syndrome 
Familial gastric carcinoma syndrome
(E‐cadherin mutation) 
91
 G ti
Gastric carcinoma
i
 Pathology
 Gross morphology
 Three main growth patterns 
Th i th tt
 Polypoid
yp pattern 
p
 Present early 
 Traumatized and bleeds
d d bl d
 Giving a feeling of gastric discomfort
g g g
 Most amenable to surgical excision
 Best prognosis 92
 G ti
Gastric carcinoma
i
Ulcerative pattern 
 Most common type 
 Ulcer: raised
Ulcer: raised edge
 Necrotic shaggy
ggy base
 Radiating folds are absent 
Diffuse
ff infiltrative
fl pattern
 Present very late
 Linitis plastica 
93
94
95
96
97
 G ti
Gastric carcinoma
i
 Microscopic appearance (Lauren’s 
classification)
l ifi ti )
 Intestinal pattern (well differentiated)
p ( )
 Neoplastic intestinal glands resembling colonic 
adenocarcinoma
 Contain apical mucin vacuoles 
 Diffuse infiltrative pattern (poorly 
iff i fil i ( l
differentiated)
 Compose of sheet of anaplastic cell
 Cell have single vacuole of mucin, displacing 
Cell have single vacuole of mucin, displacing
nucleus to one side (signet‐ring cell) 98
99
100
101
102
103
104
 G ti
Gastric carcinoma
i
 Early gastric cancer 
 Mucosa and submucosa
 Small, flat mucosal thickening
 Minimal polyploid and ulcerative 
l l l d d l
component
 Good prognosis 
p g
 
105
 G ti
Gastric carcinoma
i
 Late gastric cancer 
 Invade muscle wall
 Mass protrude into the lumen
Mass protrude into the lumen
 Malignant ulcer with raised ,everted edges 
 Ulcer resembling the chronic peptic ulcer
 Diffusing infiltrating lesion causing thickening
Diffusing infiltrating lesion causing thickening 
and contraction of stomach 
 

106
107
 G ti
Gastric carcinoma
i
 Symptom 
 Loss appetites
 Food intolerance (small capacity of 
F di t l ( ll it f
stomach))
 Melena
 
 

108
 G ti
Gastric carcinoma
i
 Spreading
 Direct invasion
 Through the wall of the stomach 
 Lymphatic spread
L h ti d
 Through the thoracic duct
Through the thoracic duct
 Virchow’s node 
 Sister Mary Joseph nodule 
109
 G ti
Gastric carcinoma
i
 Hematogenous spread  
To liver, lung, brain 
To ovary (Krukenberg’s tumor)
 Transcelomic spread
Malignant ascites
M li i
 

110
 G ti
Gastric carcinoma
i
 Prognosis
 Restrict to the mucosa and submucosa
 35% 5 years survival
y
 Invade muscle wall not lymph nodes
 30% 5 years survival
30% 5 i l
 Full thickness of the wall and lymph nodes
 5% 5 years  survival
 

111
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Originate from interstitial cells of Cajal
( t i t ti l
(gastrointestinal pacemaker cells that control 
k ll th t t l
gut motility)
 Mutation mostly in the c‐kit protooncogene 
coding for c‐KIT
coding for c KIT (CD 117) of PDGFRA
(CD 117) of PDGFRA
 The c‐KIT protooncogene protein is a 
transmembrane
b receptor for a growth factor 
f hf
known as stem cell factor (SCF) 

112
 S ti
Santiago Ramón Cajal
R ó C j l
 1 May 1852 – 17 October 1934
 

113
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Incident / Frequency 
 2‐3% of gastric malignancies
2 3% f ti li i
 Usually older adults, median age 60‐65 years
 Male = female incidence
 Stomach (60%), jejunum and ileum (30%), 
duodenum (5%), colorectum (5%), rarely 
esophagus, appendix, retroperitoneum, abdomen 
(extra‐GI stromal tumors)
 MC clinical manifestation: Hemorrhage (61.3%)
g ( )
 Consistent expression of  CD117/c‐kit, CD34; also 
DOG1, vimentin
,
  114
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Clinical description 
 M
Mesentery ,omentum
t t and retroperitoneum
d t it
 Clinical presentation depend on the size and site of 
tumor
 Small asymtomatic GISTs, usually less than 2 cm in 
diameter
 Larger tumor present with vague abdominal 
discomfort , acute or chronic gastrointestinal 
haemorrhage, dysphagia, intestinal obstruction. 
 

115
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Gross
 Unencapsulated but well 
circumscribed masses
circumscribed masses 
 Well‐demarcated spharical masses 
p
that appear to arise from the 
muscularis propria layer of GI wall
muscularis propria layer of GI wall
 May have overlying mucosal 
y y g
ulceration
116
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Larger GISTs nearly always outgrow 
th i
their vascular supply, cystic 
l l ti
g
degeneration or central necrosis and 
hemorrhage
 Diameter of GISTs –
f a few millimeters 
f ll
to more than 30 cm.
 
 
117
118
119
120
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Histological pathology
 Spindle cell GISTs (70‐80%)
 Bland spindle cells with pale to 
Bland spindle cells with pale to
eosinophilic fibrillar cytoplasm
 Whorls or short intersecting fascicles
 Frequent and prominent nuclear 
Frequent and prominent nuclear
pallisading, numerous perinuclear
vacuoles, extensive stromal
l t i t l hyalinization
h li i ti
 Minimal pleomorphism; < 2 mitotic 
figures/50 HPFs 121
122
123
124
125
126
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Histological pathology
 Epithelioid GISTs (20‐30%)
 Predominantly sheets of epithelioid
d i l h f i h li id cells
ll
 Condensed rim of eosinophilic
p cytoplasm 
y p
adjacent to nucleus and peripheral 
cytoplasmic clearing
 Well defined cell membranes, round 
nuclei with small nucleoli
 Also scattered bizarre or multinucleated 
cells  127
128
 P
Prognotic criteria of GISTs
ti it i f GIST
Size cm  Mitotic count/50hpf 
Very low risk <2  <5
Low risk
Low risk 2‐5
2 5  <5
Intermediat risk  <5  6‐10 
5‐10  <5 
Hi h i k
High risk >5 
5 >5
5
>10  anyy
any  >10 
129
 G t i t ti l St
Gastrointestinal Stromal Tumors
lT

 Treatment
 Complete surgical excision is the 
treatment of choice for localised
treatment of choice for localised 
GISTs.
 Imatinib mesylate (Glivec) is now 
considered to be the drug of choice
considered to be the drug of choice 
for metastasic and inoperable GISTs. 
 
130
 G t i t ti l L
Gastrointestinal Lymphoma
h
 Primary lymphoma
 No other palpable LN or enlarged 
mediastinal LN
 Normal WBC count
 Normal liver and spleen
N l li d l
 Lesion found only GI tract
y
 Secondary lymphoma 
 Metastasis lymphoma 
 
131
 G ti l
Gastric lymphoma
h
 1‐7% of gastric malignancies
 55‐75% of primary gastrointestinal 
lymphomas are gastric
lymphomas are gastric
 Most common: Diffuse large B‐cell 
lymphoma, then extranodal marginal 
zone (MALT) lymphoma
zone (MALT) lymphoma
 Most patients age 60+

132
 G ti l
Gastric lymphoma
h
 Usually arise at sites of chronic 
i fl
inflammation
ti
 Chronic H. pylori infection (MALToma)
Chronic H pylori infection (MALToma)
 MALTomas can transform into more 
aggressive tumors (DLBCL)
 Eradication of  H. pylori 
Eradication of H p lori  remissions 
remissions
with low rates of recurrence
 
133
 G t i t ti l L
Gastrointestinal Lymphoma
h
 Morphology (DLBCL) 
 Large polypoid or lobulated mass with 
superficial or deep ulceration; often in distal 
stomach, but sparing pylorus
 Infiltrative pattern of high grade, 
Infiltrative pattern of high grade
centroblast like cells; multinucleated forms 
may resemble Reed‐Sternberg cells
bl R d St b ll

134
135
136
 G t i t ti l L
Gastrointestinal Lymphoma
h
 Morphology (MALToma) 
 Dense, monotonous population of 
centrocyte‐like cells, often with residual 
germinal centers and lymphoepithelial
lesions 
lesions
 May have plasmacytoid differentiation
 Commonly lymphoepithelial lesions 
(
(infiltration of glandular epithelium by 
g p y
lymphocytes) or follicular colonization 

137
138