Carcinoma of the gallbladder is the most common malignancy of the extrahepatic biliary tract. It occurs most frequently in the seventh decade of life and has a poor 5-year survival rate of around 5-12% despite surgical intervention. The most important risk factor is gallstones, present in 95% of cases. Carcinomas of the gallbladder show infiltrating or exophytic patterns of growth and are usually adenocarcinomas, though some are squamous cell carcinomas. They typically invade the liver and involve lymph nodes by the time of discovery.

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%

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