Hepatic Tumours Flashcards
How are primary liver tumors classified?
Tumors are classified clinically as benign or malignant. According to their cell of origin, liver tumors are classified into three groups:
- Liver cell tumors (liver cell adenoma, hepatoblastoma, and hepatocellular carcinoma)
- Bile ductal tumors (cholangiocarcinoma)
- Vascular tumors (hemangioma and angiosarcoma)
What is the most common benign tumor of the liver?
It is hemangioma. These small tumors, composed of blood vessels, are found incidentally in 7% of livers. Usually, they are asymptomatic and of no clinical significance. Larger tumors are visible on computed tomography (CT) scans and are included in the differential diagnosis of hepatic nodular lesions, such as adenomas and focal nodular hyperplasia.
What is the clinical significance of liver cell adenomas?
Liver cell adenomas are benign tumors composed of well-differentiated hepatocytes. Tumor cells resemble normal liver cells. Most tumors cause no symptoms and are diagnosed incidentally (e.g., by CT scan). Large tumors discovered by CT scan may be confused with hepatocellular carcinoma. Although malignant transformation of these adenomas is rare, it is advisable to resect all liver tumors that measure more than a few centimeters in diameter. Subcapsular adenomas may be vascular and are prone to rupture. Massive bleeding may cause hematoperitoneum and hypovolemic shock. Liver cell adenomas occur more often in women than in men and are thought to be induced by estrogen. Tumors found in women taking oral contraceptives may regress on discontinuation of contraceptives.
What is focal nodular hyperplasia (FNH)?
FNH is a circumscribed nodule found in an otherwise normal liver. It represents a hamartoma composed of liver cells arranged around a central fibrotic scar containing thick-walled vessels. The scar and the fibrous septa radiating from it contain infiltrates of lymphocytes and proliferating bile ducts. These findings are similar to those encountered in cirrhosis. Hence, FNH is also known as localized cirrhosis.
FNH is usually diagnosed incidentally during surgery or CT scan. It should be distinguished from other nodular lesions. FNHs do not undergo malignant transformation.
List key facts about the epidemiology of hepatocellular carcinoma (HCC).
HCC, also known as malignant hepatoma, is the most common liver tumor worldwide. Important facts about the epidemiology of this tumor are as follows:
- Incidence shows broad geographic variation. In the United States, the incidence is 3 per 100,000. In areas of Africa (e.g., Mozambique) and Asia (e.g., Korea, Taiwan, and south China), the incidence is 50 times higher (i.e., 150:100,000)
- High incidence of HCC in areas of the world correlates with the prevalence of HBV and virus-related cirrhosis in these countries.
- HBV and HCV play a role in the carcinogenesis of HCC.
- Aflatoxins, fungus-derived carcinogens that are widespread in some underdeveloped countries, probably play a pathogenetic role as well.
- Men are more often affected, but the male-to-female ratio also shows geographic variability, from 4:1 in the United States to 9:1 in endemic areas of Asia and Africa.
Do all hepatocellular carcinomas develop in cirrhotic livers?
No. Most (80%) cases of HCC develop in the background of cirrhosis. The remaining 20% of HCC cases arise in normal livers or from preexisting adenomas. Fibrolamellar HCC, a tumor with a better prognosis than classical HCC, typically occurs in otherwise normal livers of young people.
Describe the macroscopic features of hepatocellular carcinoma.
HCC appear in three forms:
- Unifocal: The tumor may present as a large mass replacing part of the liver or a nodule of a different color and consistency in a cirrhotic liver.
- Multifocal: These tumors present as nodules involving parts of the liver. The nodules may be grouped or widely scattered.
- Diffusely infiltrative: These tumors permeate and diffusely enlarge the liver. Tumor cells penetrate the cirrhotic liver, becoming imperceptibly intermixed with the remaining liver cells.
Describe the typical histologic features of hepatocellular carcinoma.
HCCs present histologically as well differentiated, moderately well differentiated, and poorly differentiated carcinomas.
- In well-differentiated tumors, the tumor cells resemble normal liver cells. For example, tumor cells may secrete bile, which accumulates in the intercellular canaliculi.
- In undifferentiated tumors, the cells are anaplastic, retaining only a vague resemblance to hepatocytes. Such cells may be small with a high nuclear-to-cytoplasmic ratio or large and even multinucleated.
Tumor cells grow in several histologic patterns described as trabecular, pseudoglandular, acinar, or otherwise. Recognition of these patterns is useful for the histologic diagnosis of HCC but is of no clinical significance.
Do all histologic forms of HCC have the same prognosis?
No. HCCs generally have an abysmal prognosis, and in most instances death occurs within 1 year of diagnosis. Those with small, resectable tumors, accounting for 20% to 30% of cases, have a better survival. In that group, the best prognosis is assigned to fibrolamellar carcinomas. These tumors are composed of large cells with well-developed cytoplasm. Strands of tumor cells are enclosed in dense connective tissue. Surgical resection of fibrolamellar hepatocellular carcinomas is associated with a 60% 5-year survival rate.
What is the significance of alpha-fetoprotein (AFP) in the diagnosis of hepatocellular carcinoma?
AFP, a protein normally secreted by fetal hepatocytes, is found only in minute amounts in adult blood (<40 ng/dL). Serum levels of AFP are markedly elevated in most patients (85%) harboring an HCC. Accordingly, AFP is a useful serologic marker of HCC.
List common symptoms and signs of hepatocellular carcinoma.
- Abdominal pain (stretching of liver capsule) and fever (cytokines, tumor necrosis)
- Weight loss and weakness (tumor acts as parasite)
- Enlarged liver may be palpated
- Ascites may increase in size (portal vein occlusion by tumor) and become hemorrhagic
- Liver failure (tumor replacing normal liver)
- Bleeding from esophageal varices or tumor ruptured into abdominal cavity
- AFP elevated in blood 10 to 100 times above normal
- CT and ultrasound may demonstrate masses in the liver
- Radiologically guided or open surgical biopsy essential for definitive histologic typing of the tumor
How do hepatocellular carcinomas metastasize?
HCCs have a tendency to invade vascular spaces and metastasize via blood. Hematogenous metastases are most often found in the lungs. Local extension to hilar lymph nodes is also common. Intraabdominal spread is usually found in advanced cases.
List important facts about cholangiocarcinoma.
- It is an adenocarcinoma arising from bile ducts.
- It is a rare tumor in the United States, affecting mostly the elderly (>60 years old).
- Risk factors include PSC; in China, it is related to infestation with Clonorchis sinensis.
- It originates either from intrahepatic or extrahepatic bile ducts.
- Symptoms are usually nonspecific.
- Extrahepatic tumors may present with early biliary obstruction.
- Prognosis is poor (20%–30% 5-year survival)
Are there any serologic markers for cholangiocarcinoma?
Cholangiocarcinomas are adenocarcinomas, and like adenocarcinomas in other sites, they secrete carcinoembryonic antigen. However, this serologic marker has low sensitivity and specificity and is of limited value in the diagnosis of cholangiocarcinomas, or for distinguishing it from other adenocarcinomas that have metastasized to the liver.
Is liver biopsy essential for the definitive diagnosis of cholangiocarcinoma?
Yes. Liver biopsy must be performed to determine the nature of the clinically identified liver mass. Cholangiocarcinomas present histologically as adenocarcinomas and are readily distinguished from hepatocellular carcinomas. Unfortunately, cholangiocarcinoma cannot always be distinguished from other adenocarcinomas (e.g., carcinoma of the pancreas or colon) that may have metastasized to the liver. Because metastatic adenocarcinomas are more common than primary hepatic adenocarcinomas, a search for another possible primary tumor should always be undertaken.
