Page 653 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

A distinctive clinicopathologic variant of HCC is the
fibrolamellar carcinoma. It occurs in young male and
female adults (20 to 40 years of age) with equal incidence
and has no association with cirrhosis or other risk factors. It
usually consists of a single tumor with fibrous bands coursing
through it, superficially resembling focal nodular hyperplasia.
The fibrolamellar variant has a better prognosis than that of
the other, more common variants.
Clinical Features
Although HCC may manifest with silent hepatomegaly, it
is more often encountered in persons with symptomatic
cirrhosis of the liver. In these persons, a rapid increase in liver
size, sudden worsening of ascites, or the appearance of bloody
ascites, fever, and pain call attention to the development of
a tumor. There are no good serologic screening tests
for hepatocellular carcinoma. The most commonly used
marker is serum alpha-fetoprotein level, but it rises only
with advanced tumors and only in 50% of patients. Fur-
thermore, false-positive results are obtained in yolk-sac
tumors, and many non-neoplastic conditions such as cir-
rhosis, chronic hepatitis, normal pregnancy, and massive
liver necrosis. Hence the test is neither specific nor sensi-
tive. Radiologic screening of patients with cirrhosis at 6-month
intervals, looking for dysplastic nodules or early, small hepatocel-
lular carcinomas, is the current clinical frontier.
The overall prognosis with advanced HCC is grim.
Resection or ablation may be curative for a single small
lesion (most often those with the uncommon fibrolamellar
variant), but does not prevent de novo emergence of new
HCCs in a chronically diseased liver. Transplantation can
DISORDERS OF THE GALLBLADDER AND THE EXTRAHEPATIC
BILIARY TRACT
Disorders of the gallbladder and biliary tract affect a large
proportion of the world’s population. Cholelithiasis (gall-
stones) accounts for more than 95% of these diseases. About
2% of the United States federal health budget is spent on
cholelithiasis and its complications. In this section, gall-
bladder diseases (cholelithiasis and cholecystitis) are dis-
cussed first, followed by consideration of some disorders
of the extrahepatic bile ducts. It should be kept in mind
that lesions of the extrahepatic biliary tract may extend to
intrahepatic bile ducts, and that tumors of the biliary tract
(cholangiocarcinomas, described later) may have intra- or
extrahepatic locations.
GALLBLADDER DISEASES
Cholelithiasis (Gallstones)
Gallstones afflict 10% to 20% of adults residing in Western
countries in the Northern Hemisphere, 20% to 40% in Latin
American countries, and only 3% to 4% in Asian countries.
In the United States, about 1 million new cases of gallstones
are diagnosed annually, and two thirds of persons so
Gallbladder Diseases 639
be curative, however. Without resection, median survival
is 7 months. Recent clinical trials have shown that treat-
ment with sorafenib, a broad-spectrum tyrosine kinase
inhibitor, provides some benefit to those with advanced
disease. In some countries such as Taiwan, HBV immuni-
zation programs have lowered the incidence of HCC sub-
stantially, proving that preventive measures can alleviate
the terrible toll taken by this disease in endemic regions.
S U M M A RY
Liver Tumors
• The most common malignant tumors of the liver are
metastatic carcinomas, most often from colon, lung, and
breast.
• The main primary malignancy is hepatocellular carcinoma.
It is common in regions of Asia and Africa, and its inci-
dence is increasing in the United States.
• The main etiologic agents for hepatocellular carcinoma
are hepatitis B and C, alcoholic cirrhosis, hemochromato-
sis, and, more rarely, tyrosinemia and α1-antitrypsin (AAT)
deficiency.
• In the Western population, about 90% of hepatocellular
carcinomas develop in cirrhotic livers; in Asia, almost 50%
of cases develop in noncirrhotic livers.
• The chronic inflammation and cellular regeneration asso-
ciated with viral hepatitis may be predisposing factors for
the development of carcinomas.
• Hepatocellular carcinomas may be unifocal or multifocal,
tend to invade blood vessels, and recapitulate normal liver
architecture to varying degrees.
affected undergo surgery, with retrieval of as much as 25
to 50 million tons of stones! There are two main types of
gallstones: cholesterol stones, containing crystalline choles-
terol monohydrate (80% of stones in the West), and pigment
stones, made of bilirubin calcium salts.
PAT H O G E N E S I S
Bile formation is the only significant pathway for elimination
of excess cholesterol from the body, either as free choles-
terol or as bile salts. Cholesterol is rendered water-soluble
by aggregation with bile salts and lecithins. When cholesterol
concentrations exceed the solubilizing capacity of bile (super-
saturation), cholesterol can no longer remain dispersed and
crystallizes out of solution. Cholesterol gallstone formation
is enhanced by hypomobility of the gallbladder (stasis),
which promotes nucleation, and by mucus hypersecre-
tion, with consequent trapping of the crystals, thereby
enhancing their aggregation into stones.
Formation of pigment stones is more likely in the presence
of unconjugated bilirubin in the biliary tree, as occurs in