Liver Masses: A Clinical, Radiologic, and Pathologic Perspective

Sudhakar K. Venkatesh; Vishal Chandan; Lewis R. Roberts


Clin Gastroenterol Hepatol. 2014;12(9):1414-1429. 

In This Article

Initial Clinical Evaluation

A careful review of the personal history and physical examination findings often helps in narrowing the differential diagnoses of liver masses. A history of chronic hepatitis or the features or complications of cirrhosis identifies individuals at risk for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. Similarly, a history of primary sclerosing cholangitis alerts the physician to the significant risk for cholangiocarcinoma and long-term oral contraceptive use predisposes certain women to hepatic adenoma. The family history is also of value in the initial clinical evaluation. A family history of young-onset diabetes mellitus, for example, may predispose to hepatic adenomatosis. Physical complaints such as abdominal pain are often nonspecific but may be the reason for seeking medical attention. Other physical symptoms are more suggestive of the underlying disease, for example, pruritus, dark urine, and pale stools observed in biliary obstruction. A history of constitutional symptoms such as fever may be useful in the diagnosis of hepatic abscesses; fever can also be associated with malignancy. Constitutional features of malignancy also include anorexia, weight loss, and fatigue. The physical examination may show features of chronic liver disease such as spider angiomas, a periumbilical caput medusa indicative of portal hypertension, hepatomegaly, or splenomegaly. Painless jaundice is highly suggestive of a malignancy such as cholangiocarcinoma or pancreatic adenocarcinoma whereas advanced malignant infiltration and some benign masses may be associated with palpable hepatomegaly, which may be nodular in patients with cirrhosis or focal masses.

The history and physical examination are complemented by laboratory tests that may show active hepatitis, a low platelet count caused by chronic liver disease with cirrhosis, portal hypertension and hypersplenism, or hyperbilirubinemia. The use of serum α-fetoprotein (AFP) level in surveillance for HCC is controversial because of low sensitivity for the detection of early stage disease.[2,3] AFP is well established as a predictor of risk of HCC in individuals with cirrhosis and can be extremely useful for HCC diagnosis in individuals with diffuse HCCs.[3] Although one-time AFP determinations have a high false-positive rate, particularly in patients with chronic hepatitis C virus, trends and patterns in AFP levels can be useful for early diagnosis of HCC.[4] A high AFP level is also prognostic for the outcomes of patients with HCC.[5] The AFP-L3 and des-gamma carboxyprothrombin also predict risk of HCC and are used extensively in Asia, particularly in Japan.[6] However, they are not yet in wide clinical use in Europe or the United States. The carbohydrate antigen 19-9 level is helpful in the diagnosis and prognostic prediction of patients with cholangiocarcinoma.[7] In the absence of acute cholangitis, a carbohydrate antigen 19-9 level greater than 1000 units/mL usually indicates the presence of extrahepatic disease.[7] The carcinoembryonic antigen level is valuable in assessing colorectal cancer metastatic to the liver, and the chromogranin A and 24-hour urine 5-hydroxyindoleacetic acid levels are useful for assessing neuroendocrine carcinomas metastatic to the liver.[8,9] In general, these markers are of value in determining the nature of malignant liver lesions when present, while having a relatively low specificity in the absence of detectable lesions. An increased lactate dehydrogenase level and widespread intra-abdominal lymphadenopathy may be clues to liver infiltration by lymphoma masquerading as primary liver cancer.