1. CARCINOMA OF THE
GALLBLADDER

2. INTRO
• Most common malignancy of the extrahepatic
biliary tract
• Slightly more common in women
• Occurs most frequently in the seventh decade of
life
• Mean 5-year survival rate has remained for many
years at about 5% to 12% despite surgical
intervention

3. • The most common sites of involvement are the
fundus and the neck; about 20% involve the lateral
walls.

4. ETIOLOGY
• The most important risk factor associated with
gallbladder carcinoma is gallstones (cholelithiasis),
which are present in 95% of cases
• However, it should be noted that only 0.5% of
patients with gallstones develop gallbladder cancer
after twenty or more years

5. • Carcinogenic derivatives of bile acids are believed
to play a role.
• Genetic factors
• Previous surgery on the biliary tract
• IBD

6. MORPHOLOGY
• Carcinomas of the gallbladder show two patterns of
growth: infiltrating and exophytic

7. • The infiltrating pattern is more common and usually
appears as a poorly defined area of diffuse thickening
and induration of the gallbladder wall that may cover
several square centimeters or may involve the entire
gallbladder.
• Deep ulceration can cause direct penetration of the
gallbladder wall or fistula formation to adjacent viscera
into which the neoplasm has grown.
• These tumors are scirrhous and have a very firm
consistency

8. • The exophytic pattern grows into the lumen as an
irregular, cauliflower mass but at the same time
invades the underlying wall.
• The luminal portion may be necrotic, hemorrhagic,
and ulcerated

9. The opened gallbladder contains a large, exophytic tumor
that virtually fills the lumen

10. HISTOLOGY
• Most carcinomas of the gallbladder are
adenocarcinomas.
• Some of the carcinomas are papillary in
architecture and are well to moderately
differentiated; others are infiltrative and poorly
differentiated to undifferentiated
• About 5% are squamous cell carcinomas or have
adenosquamous differentiation

11. NORMAL ADENOCARCINOMA

12. Malignant glandular structures Papillary pattern
are present within a densely
fibrotic gallbladder wall.

13. • By the time these neoplasms are discovered, most
have invaded the liver centrifugally, and many
have extended to the cystic duct and adjacent bile
ducts and portal-hepatic lymph nodes.
• The peritoneum, gastrointestinal tract, and lungs
are common sites of seeding.

14. GASTRIC ADENOCARCINOMA

15. INTRO
• Adenocarcinoma is the most common malignancy
of the stomach, comprising over 90% of all gastric
cancers
• Early symptoms resemble those of chronic gastritis.
As a result, these tumors are often discovered at
advanced stages,

16. EPIDEMIOLOGY
• Gastric cancer incidence varies markedly with
geography
• The cause of the overall reduction in gastric cancer
is unknown.

17. • One possible explanation is the decreased
consumption of dietary carcinogens, such as N-
nitroso compounds and benzopyrene, because of
reduced use of salt and smoking for food
preservation and the widespread availability of
food refrigeration.
• Conversely, intake of green, leafy vegetables and
citrus fruits, which contain antioxidants such as
vitamin C, vitamin E, and beta-carotene, and is
correlated with reduced risk of gastric cancers,
may have increased as a result of improved food
transportation networks.

18. • Gastric cancer is more common in lower
socioeconomic groups and in individuals with
multifocal mucosal atrophy and intestinal
metaplasia.
• PUD does not impart an increased risk of gastric
cancer, but patients who have had partial
gastrectomies for PUD have a slightly higher risk of
developing cancer in the residual gastric stump as
a result of hypochlorhydria, bile reflux, and chronic
gastritis.

19. • Although overall incidence of gastric
adenocarcinoma is falling, cancer of the gastric
cardia is on the rise.
• This is probably related to Barrett esophagus and
may reflect the increasing incidence of chronic
GERD and obesity.

20. ETIOPATHOGENESIS
• Helicobacter Pylori Infection:
• Chronic H. pylori infection is the most important cause of
distal gastric adenocarcinoma
• It commonly generates chronic gastritis, and over several
decades may induce mucosal atrophy, which in some
patients precedes the development of cancer .
• Bacterial virulence factors, such as CagA and Vac A
(vacuolating enzyme), play an important role in the severity
of gastritis and intestinal metaplasia

21. • Dietary and Lifestyle Factors:
• Smoking and dietary habits (high intake of salt-preserved
and/or smoked foods) also play a role in increasing cancer
risk, either individually or by compounding the role of H.
pylori infection
• Genetic Susceptibility
• Some individuals are at increased risk of developing gastric
cancer, as well as other malignancies, because of
dominantly inherited cancer predisposition syndromes, such
as FAP, Lynch syndrome, and Li-Fraumeni syndrome .
Patients with Peutz-Jeghers are also at risk for developing
gastric cancers

22. • Hereditary Diffuse Gastric Cancer (HDGC):
• Familial diffuse gastric cancer with autosomal dominant
inheritance, caused by germline mutation of E-
cadherin(CDH1), is a recently reported syndrome
• Precursor Lesions
• Whether in H. pylori-associated chronic gastritis or
autoimmune gastritis, atrophy followed by intestinal
metaplasia develops over time, beginning a sequence of
events that may culminate in neoplasia, particularly
adenocarcinoma of tubular type.

23. • Gastric Polyps: Various polypoid lesions have the
potential to develop into adenocarcinoma
• Adenomatous Polyps: The risk of malignant transformation is
related to size (>2 cm) and the presence of high-grade
intraepithelial neoplasia/dysplasia
• Non-neoplastic Polyps: Hyperplastic polyps and rare
syndromic examples, as well as hamartomatous polyps that
generally occur as part of hereditary polyposis syndromes
(Peutz-Jeghers polyp, juvenile polyp, Cronkhite-Canada
syndrome-associated polyp), also may undergo malignant
transformation

24. MORPHOLOGY
• Most gastric adenocarcinomas involve the gastric
antrum; the lesser curvature is involved more often
than the greater curvature
• Gastric tumors with an intestinal morphology tend to
form bulky tumors composed of glandular
structures , while cancers with a diffuse infiltrative
growth pattern are more often composed of signet-
ring cells

25. Gastric adenocarcinoma. Intestinal-type adenocarcinoma
consisting of an elevated mass with heaped-up borders and
central ulceration.

26. NORMAL HISTOLOGY

28. Gastric adenocarcinoma. Intestinal-type adenocarcinoma
composed of columnar, gland-forming cells infiltrating through
desmoplastic stroma.

29. • When there are large areas of infitration, diffuse
rugal flattening and a rigid, thickened wall may
impart a leather bottle appearance termed linitis
plastica
• Breast and lung cancers that metastasize to the
stomach may also create a linitis plastica–like
appearance.

30. Linitis plastica. The gastric wall is markedly thickened, and
rugal folds are partially lost.

31. Signet-ring cells can be recognized by their large
cytoplasmic mucin vacuoles and peripherally displaced,
crescent-shaped nuclei.

32. CLINICAL FEATURES
• Intestinal-type gastric cancer predominates in high-
risk areas and develops from precursor lesions
including flat dysplasia and adenomas. The mean
age of presentation is 55 years, and the male-to-
female ratio is 2 : 1.
• In contrast, the incidence of diffuse gastric cancer is
relatively uniform across countries, there are no
identified precursor lesions, and the disease occurs
at similar frequencies in males and females.

33. • The depth of invasion and the extent of nodal and
distant metastasis at the time of diagnosis remain
the most powerful prognostic indicators for gastric
cancer

34. • In advanced cases gastric carcinoma may first be
detected as metastases to the supraclavicular
sentinel lymph node, also called Virchow's node.
• Gastric tumors can also metastasize to the
periumbilical region to form a subcutaneous
nodule, termed a Sister Mary Joseph nodule, after
the nurse who first noted this lesion as a marker of
metastatic carcinoma.

35. • Local invasion into the duodenum, pancreas, and
retroperitoneum is also characteristic. In such cases
efforts are usually focused on chemotherapy or
radiation therapy and palliative care

36. • Surgical resection remains the preferred treatment
for gastric adenocarcinoma.
• After surgical resection, the 5-year survival rate of
early gastric cancer can exceed 90%, even if
lymph node metastases are present. In contrast, the
5-year survival rate for advanced gastric cancer
remains below 20%

37. THANK YOU ..