Fig. 16.35 ). They may be detected incidentally as a hepatic mass on abdominal imaging or when they cause symptoms. The most common symptom is pain, which may be caused by pressure placed on the liver capsule by the expanding mass or hemorrhagic necrosis of the tumor as it outstrips its blood supply. Hepatocellular adenomas occasionally rupture, an event that may lead to life-threatening intraabdominal bleeding.
Hepatic adenomas can be subclassified molecularly into tumors at low, intermediate, and high risk for malignant transformation. Sex hormone exposure (e.g., oral contraceptive pills, anabolic steroids) markedly increases the frequency of all types of hepatic adenoma, and cessation of exposure to sex hormones often—but not always—leads to tumor regression, clearly linking sex hormones to the growth and survival of tumor cells in some cases.
Malignant tumors occurring in the liver can be primary or metastatic. The latter are far more common. Our discussion here is focused on primary hepatic tumors. Most primary liver cancers arise from hepatocytes and are termed hepatocellular carcinoma (HCC). Much less common are cancers of bile duct origin, cholangiocarcinomas. Other types of primary liver cancers, such as hepatoblastoma (a childhood hepatocellular tumor) and angiosarcoma, are too rare to merit further discussion.
Globally, HCC, also erroneously known as hepatoma, accounts for approximately 5.4% of all cancers, but its incidence varies widely in different parts of the world. More than 85% of cases occur in countries with high rates of chronic HBV infection. The incidence of HCC is highest in Asia (southeast China, Korea, Taiwan) and sub-Saharan Africa, areas in which HBV is transmitted vertically and, as already discussed, the carrier state starts in infancy. Moreover, many of these populations are exposed to aflatoxin, which when combined with HBV infection increases the risk for HCC dramatically. The peak incidence of HCC in these areas is between 20 and 40 years of age and, in almost 50% of cases, the tumor appears in the absence of cirrhosis.
Fig. 16.35 Livercelladenoma.(A)Resectedspecimenofthelivermass.
(B)Microscopicviewshowingcordsofhepatocytes,withanarterialvascularsupply(arrow) andnoportaltracts.
In Western counties, the incidence of HCC is rapidly rising, largely owing to the increased prevalence of hepatitis C. The number of new HCC cases tripled in the United States in recent decades, but its incidence is still 8-fold to 30-fold lower than in some Asian countries. It is hoped that new, effective treatments for hepatitis C infection will stem the rising tide of HCC in the United States. In Western populations, HCC rarely manifests before 60 years of age, and in almost 90% of cases the malignancy emerges after cirrhosis becomes established. There is a pronounced male predominance throughout the world, about 3:1 in low-incidence areas and as high as 8:1 in high-incidence areas.
Chronic liver diseases are the most common setting for emergence of HCC. While usually identified in a background of cirrhosis, cirrhosis is not required for hepatocarcinogenesis. Rather, progression to cirrhosis and to hepatocellular cancer take place in parallel over many years to decades.
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