Gastric carcinoma
Dr.Ashraf Abdelfatah Deyab
Assistant professor of Pathology
Faculty of medicine- Majma’ah University
Gastric Carcinoma- Objectives
Discuss its epidemiology & Impact.
Explain the causes and risk factors.
Describe the morphology & laboratory
diagnosis.
Discuss screening & prevention (Japan
experience).
(Robbins Basic Pathology, 8th ed. P. 598- 600).
Gastric adenocarcinoma
Most common malignancy of stomach > 90% of
all gastric tumor4 th commonly occurring cancer in the world.
2nd cancer related to the death .
With Significant geographical distribution,
Japan, Chile, italy,east europe > 20 fold of USA,
north Europe, Africa, SE ASIA. Preventable???
Marked drop recently in USA+ Europe suggested
control of Enviromental & Dietary factors.
>> common in:(1) lower socioeconomic groups.
2) Multifocal mucosal atrophy& intestinal metaplasia.
Stomach- normal anatomy
Cardia
Pylorus
Fundus
Normal gastric fundus;
note specialized
ParietalAntrum
Cell: oxyntic
mucosa\pink.
Chief cells)= purple beneath
the top layer
of mucus glands..
Etiology& Risk group
Genetic factors: ( BLOOD group A, Family
history, Familial hereditary syndrome)
Host factors: (chronic gastritis, intestinal
metaplasia, partial Gastrectomy, gastric adenoma,
dysplasia, reflux, Barrett's esophagus, Autoimmune
gastritis –hypochlorhydra& PH change).
Environmental factors: ( H.pylori infection,
Diet “smoked food-fish-meat-salt, lack of fresh fruit
and vegetable”= N-nitroso,, cigarette smoking)
Gastric carcinoma Pathogenesis
The majority of gastric ca. pathogenesis is closely
related to environmental factors (not genetic)
interaction between host genetic background and
environmental factors still play a major role
multistep progression, from chronic gastritis to
intestinal metaplasia, dysplasia, and carcinoma.
1) Genetic
factors: molecular genetics of
gastric cancer has been established:
a) Allelic loss has been identified at a variety of
loci on various chromosomes.
Gastric carcinoma Pathogenesis
b) CDH gene mutations are identified in
familial gastric cancer, (Encode E-cadherin)- lead to
Diffuse type gastric ca
CDH mutations are present in about 50% of
sporadic cases of diffuse gastric tumors .
c) P53 mutations are present in the majority of
sporadic gastric cancers.
d) FAP individual: associated with increased risk
of intestinal-type
Gastric carcinoma Pathogenesis
2) Host & environmental factors:
a) Gastric PH change >> promotes the growth of
bacteria>> reduce dietary nitrate to nitrite then
>>convert dietary amines, in the presence of this
nitrite, into carcinogenic N-nitroso compounds.
B) H.pylori infection through its role in the
development of chronic gastritis
b) Coexistence of chronic atrophic gastritis
“controversial”
Gastric adenocarcinoma-morphology
classified according to their location in the
stomach: (Ant.\post. wall+ lesser, greater, curv.)
The gastric antrum & lesser curvature are
involved > >> often greater curvature.
Histological Types divided into :
1) Intestinal type adenocarcinoma
2) Diffuse type gastric adenocarcinoma
Note:” Early” gastric carcinoma variant described by Japanese
Chronic Atrophic Gastritis with intestinal metaplasia
Early’ gastric carcinoma : confined to
mucosa, submucosa (not extending into muscularis ),
Intestinal type of gastric adenocarcinoma
Different gross macroscopic appearance;
1)Exophytic (bulky, polypoidal).
2)Endophytic (invasive, ulcerative,excavated).
Microscopic pattern: infiltrating neoplastic glands in
varying degree of differentiation (tubular or papillary).
a\w H.pylori chronic gastritis with intestinal metaplasia &
atrophy “precursor” -
Also a\w FAP individual patients “rare”.
Gastric adenocarcinoma-morphology
macroscopic growth pattern
Gastric carcinoma- intestinal type
Diffuse type of gastric adenocarcinoma
Rigid gastric wall. “Leather bag”= linitis plastica.
Composed of diffuse sheet of dyscohesive signet
ring cells.
Background of variable amount of “pools”
mucin lacks with Desmoplastic stroma.
a\w CDH gene mutations- dyscohesive distrubtion.
Diffuse gastric carcinoma- linitis plastica
Mucinous (mucoid)carcinoma
WHO classification of stomach
carcinoma (Histologic variants)
The diagnosis is based on the predominant
histological pattern.
Tubular adenocarcinomas
Mucinous adenocarcinomas
Papillary adenocarcinomas
Signet-ring cell carcinomas
Adeno-squamous carcinoma
Squamous cell carcinoma
Undifferentiated carcinoma
Grading of Gastric Adenocarcinoma
G1, G2, G3
Adenocarcinoma may be graded into:
Well-differentiated (> 95% of tumor composed of
glands).
Moderately differentiated (50% to 95%
composed of glands).
Poorly differentiated (49% or less composed of
glands)
Gastric ca. clinical features
Intestinal type (better prognosis >> intestinal type)
-
The mean age of presentation is 55 years .
Male-to-female ratio is 2 : 1, arise from.
Considered as precursor: flat dyplasia & adenoma.
Closely associated with atrophic + metaplasia.
Diffuse type: “poor prognosis”
(Rarely in elderly, occasional in child).
No identified precursors.
With similar frequency between male and female.
The depth of invasion and the extent of local nodal and
distant metastasis at the time of diagnosis .
Gastric carcinoma- Clinical Findings
Symptoms& Signs:
If the tumor is located in the cardiac or pyloric
areas, it may produce obstruction relatively early
Otherwise “non-specific”; weight loss, dyspepsia,
abdominal pain, anorexia, vomiting\ Pyloric
obstruction, altered bowel habits, dysphagia,
anemia, and hemorrhage.- mimic chronic
gastritis.
These tumors are often discovered at advanced
stages, +\- left supra-clavicular region Virchow node.
Gastric ca. clinical features
Metastasize to (trans-coelmic, lymphatic, haematogenous)
- Supra-clavicular sentinel lymph node= Virchow's node
- Peri-umbilical region to form subcutaneous nodule,
termed a Sister Mary Joseph nodule .
Ovarian involvement generates Krukenberg tumors
Local invasion duodenum, pancreas, and
retroperitoneum.
Management: Surgical resection with
chemotherapy or radiation therapy + or
palliative management in advanced cases.
Spread of gastric carcinoma
(Virchow node)
Spread of gastric carcinoma
Lymphatic spread: mucosal or sub-mucosal
plan- (greater& lesser curvature LN, paraaortic, supra-clavicular” virchow sign” )
Hematogenous spread: liver, lung.
Trans-coelomic – both ovaries.
Direct spread to adjacent structure-
Metastatic tumors to the stomach are
relatively uncommon
Screening & prevention (Japan experience).
Gastric ca. is leading cause of death –Japan, 1983
Japan MOH: set National guidelines,
adopted a successful Mass screening
program “nationwide for the resident” for
early detection and prevention, 35% - are
early gastric cancer.
Screening tools: Barium studies, Upper GI
endoscopy. Serum pepsinogen tests- for atrophic
gastritis Dx. + screening for H. pylori Antibodies
Others preventive measures
Screening & prevention (Japan experience).
Target group: Screening for > 40 years, also
some specific patients.
Duration ; every 2 year.
Unfortunately, mass screening programs are not
cost-effective in low incidence area – USA
Prevention
overall reduction in gastric cancer incidence is
unknown?? how to modify the Risk factors
1) Decreased consumption of dietary carcinogens,
( e.g N-nitroso compounds ).
2) Reduced use of salt and smoked food.
3) Increase intake of green, fresh leafy vegetables
and citrus fruits, which contain antioxidants such
as vitamin C, vitamin E, and beta-carotene.
4) Improved food transportation networks.
5)Widespread availability of food refrigeration
for food preservation..
END