Page 657 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

Tumors 643
findings do not distinguish between biliary atresia and
intrahepatic cholestasis, but a liver biopsy provides evi-
dence of bile duct obstruction in 90% of cases of biliary
atresia. Liver transplantation is the definitive treatment.
Without surgical intervention, death usually occurs within
2 years of birth.
S U M M A RY
Diseases of the Gallbladder and Extrahepatic
Bile Ducts
• Gallbladder diseases include cholelithiasis and acute and
chronic cholecystitis.
• Gallstone formation is a common condition in Western
countries.The great majority of the gallstones are choles-
terol stones. Pigmented stones containing bilirubin and
calcium are most common in Asian countries.
• Risk factors for the development of cholesterol stones
are advancing age, female gender, estrogen use, obesity, and
heredity.
• Cholecystitis almost always occurs in association with
cholelithiasis, although in about 10% of cases it occurs in
the absence of gallstones.
• Acute calculous cholecystitis is the most common reason
for emergency cholecystectomy.
• Obstructive lesions of the extrahepatic bile ducts in adults
can give rise to ascending infection (cholangitis) and sec-
ondary biliary cirrhosis.
• Infants born with congenital biliary atresia present with
neonatal cholestasis and require liver transplantation for
cure.
TUMORS
Carcinoma of the Gallbladder
Although uncommon, carcinoma of the gallbladder is the
most frequent malignant tumor of the biliary tract. It is 2
to 6 times more common in women and occurs most fre-
quently in the seventh decade of life. Carcinoma of the
gallbladder is more frequent in the populations of Mexico
and Chile, presumably due to the higher incidence of gall-
stone disease in these regions. In the United States the
incidence is highest in Hispanics and Native Americans.
Only rarely is it discovered at a resectable stage, and the
mean 5-year survival rate is a dismal 5%. Gallstones are
present in 60% to 90% of cases. In Asia, where pyogenic
and parasitic diseases of the biliary tree are more common,
gallstones are less important. Presumably, gallbladders
containing stones or infectious agents develop cancer as a
result of recurrent trauma and chronic inflammation. The
role of carcinogenic derivatives of bile acids is unclear.
MORPHOLOGY
Cancers of the gallbladder may exhibit exophytic or infil-
trating growth patterns. The infiltrating pattern is more
Figure 15–37 Adenocarcinoma of the gallbladder. The opened gallblad-
der contains a large, exophytic tumor that virtually fills the lumen.
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 involve the entire
gallbladder. These tumors are scirrhous and very firm. The
exophytic pattern grows into the lumen as an irregular,
cauliflower-like mass but at the same time also invades the
underlying wall (Fig. 15–37). Most are adenocarcinomas,
which may be papillary or poorly differentiated. About 5%
are squamous cell carcinomas or demonstrate adenosqua-
mous differentiation, and rare neuroendocrine tumors also
occur. By the time gallbladder cancers are discovered, most
have invaded the liver or have spread to the bile ducts or to
the portal hepatic lymph nodes.
Clinical Features
Preoperative diagnosis of carcinoma of the gallbladder is
the exception, being reported in less than 20% of patients.
Onset of symptoms is insidious, and presenting manifesta-
tions typically are indistinguishable from those associated
with cholelithiasis: abdominal pain, jaundice, anorexia,
and nausea and vomiting. The fortunate person develops
early obstruction and acute cholecystitis or undergoes cho-
lecystectomy for coexistent symptomatic gallstones before
the tumor spreads to other sites.
Cholangiocarcinomas
Cholangiocarcinomas are adenocarcinomas that arise from
cholangiocytes lining the intrahepatic and extrahepatic
biliary ducts. Extrahepatic cholangiocarcinomas constitute
approximately two thirds of these tumors and may develop
at the hilum (known as Klatskin tumors) or more distally
in the biliary tree. Cholangiocarcinomas occur mostly in
persons of 50 to 70 years of age. Because both intra- and
extrahepatic cholangiocarcinomas generally are asymp-
tomatic until they reach an advanced stage, the prognosis
is poor, and most patients have unresectable tumors. Risk
factors include primary sclerosing cholangitis, fibropoly-
cystic diseases of the biliary tree, and infestation by Clonor-
chis sinensis or Opisthorchis viverrini.
All risk factors for cholangiocarcinomas cause chronic
cholestasis and inflammation, which presumably promote
the occurrence of somatic mutations in cholangiocytes.