You are in: eMedicine Specialties > Radiology > GASTROINTESTINAL Hepatocellular CarcinomaArticle Last Updated: May 10, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Daniel R Jacobson, MD, MS, Clinical Instructor, Department of Radiology, University of Rochester School of Medicine, Radiology Residency Program Director, Rochester General Hospital Daniel R Jacobson is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, and Radiological Society of North America Editors: John L Haddad, MD, Clinical Associate Professor, Department of Radiology, Weill Medical College of Cornell University; Director of Body MRI, Department of Radiology, Methodist Hospital in Houston; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Udo P Schmiedl, MD, PhD, Clinical Professor, Department of Radiology, University of Washington; Consulting Staff, Swedish Medical Center, University of Washington Medical Center, Seattle Radiologists; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; John Karani, MBBS, FRCR, Consulting Staff, Department of Radiology, King's College Hospital, London Author and Editor Disclosure Synonyms and related keywords: hepatoma, typical hepatocellular carcinoma, primary liver carcinoma, clear cell carcinoma of the liver, HCC INTRODUCTIONSection 2 of 12
  BackgroundHepatocellular carcinoma (HCC) is the most common primary hepatic tumor and one of the most common cancers worldwide. HCC is a primary malignancy of hepatocellular origin. PathophysiologyHCC is a malignant tumor of hepatocellular origin that develops in patients with risk factors such as alcohol abuse, viral hepatitis, and metabolic liver disease. It can also occur, rarely, in patients with normal liver parenchyma. There are 3 growth patterns exhibited by HCC:
Microscopically, HCC cells resemble normal hepatocytes and can be confused with cells of hepatic adenoma. Tumors that are more differentiated can produce bile. FrequencyUnited StatesHCC is rare in the InternationalHCC is more common in Asia and Africa than in the Mortality/Morbidity
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Clinical DetailsClinical presentations vary among high-incidence and low-incidence regions. In high-incidence regions (ie, Asia, Africa), the clinical presentation of HCC tends to be aggressive and includes bleeding, hepatic rupture, and hemoperitoneum. In low-incidence regions (ie, Western Hemisphere), the clinical presentation of HCC tends to be less aggressive and includes symptoms such as fever of unknown origin, abdominal pain, malaise, weight loss, and hepatomegaly. Jaundice is rare. Liver function tests can be normal. AFP levels may be elevated because this protein is commonly produced by HCC; however, this is an insensitive parameter because AFP levels may be normal in more than one third of patients. Preferred ExaminationCross-sectional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is most commonly used to detect HCC. CT is frequently the first examination; however, MRI has superior contrast resolution and may better detect lesions less than 1 cm in diameter. Nuclear medicine imaging, angiography, and plain films are less useful. Limitations of TechniquesPlain films are nonspecific but may show a mass in the upper abdomen if the HCC is large. Nuclear medicine provides relatively nonspecific findings. The HCC may present as a "cold" defect on a sulfur-colloid study or may demonstrate uptake of radiopharmaceuticals if the mass produces bile. Gallium uptake is seen in 90% of HCCs. The Perform CT in hepatic arterial, portal venous, and delayed phases. Similarly, if MRI is used, precontrast, arterial, venous, and delayed phases are essential. Enhancement patterns of regenerative, dysplastic, and HCC nodules overlap; therefore, nodules of cirrhosis may not be differentiated from small HCCs. Angiography study may show increased vascularity of other hepatic tumors, including benign masses. DIFFERENTIALSSection 3 of 12
Cholangiocarcinoma Focal Nodular Hyperplasia Hepatic Adenoma Hepatocellular Carcinoma, Fibrolamellar Other Problems to Be ConsideredMetastatic disease
RADIOGRAPHSection 4 of 12
FindingsNonspecific findings on plain film are standard. An abdominal mass may be visible. Calcification is rare in HCC but more frequent in other hepatic masses such as fibrolamellar HCC. Patients with hemochromatosis as a predisposing factor in the development of HCC may show deposition of calcium pyrophosphate in the cartilage of joints. Patients with prior exposure to Thorotrast may be identified by noting contrast material deposition in the liver and lymph nodes. Degree of ConfidencePlain films are completely nonspecific. False Positives/NegativesMany other causes of chondrocalcinosis exist, such as gout, hyperparathyroidism, Wilson disease, and degenerative joint disease. CT SCANSection 5 of 12
FindingsProper technical performance of CT with imaging in the hepatic arterial and portal venous phases, as well as delayed contrast images, is important in detecting HCC. Lesions may be missed if early vascular imaging is not performed. It is important to use high injection rates and appropriate bolus timing. Sensitivity of good-quality dual- or triple-phase CT for the detection of patients with tumors is 60-70%. The CT appearance of HCC varies depending on tumor size and the imaging phase. The most common attenuation pattern is iso-hyper-isoattenuation on prephase, arterial phase, and venous phase, respectively; however, this pattern is shared by other hepatocellular nodules, including regenerative and dysplastic nodules.
CT can also evaluate complications of HCC such as portal venous or hepatic venous invasion. In addition, be alert and evaluate for other complications such as bleeding within the tumor and hemoperitoneum. Evaluate underlying disease on CT, which can indicate the etiology of a hepatic mass. Look for signs of cirrhosis and hemochromatosis. Degree of ConfidenceIn the setting of an abnormal liver with elevated AFP, a vascular mass or a large necrotic mass strongly suggests HCC; however, other hepatic lesions both benign and malignant can mimic HCC on CT. MRI or nuclear imaging can assist in this differentiation. In addition, cirrhotic nodules cannot be reliably differentiated from small HCCs. Since success of therapy depends on early HCC detection, the distinction is important; MRI can assist with nodule differentiation. False Positives/NegativesFalse-negative CT imaging can occur. Even the best CT scanner may have difficulty detecting small lesions, especially if good-quality, triphasic scanning is not performed. Prospective detection rates of patients with tumors and of tumor nodules were reported as 59% and 37%, respectively, in a large series with pathologic correlation1. MRISection 6 of 12
FindingsHCC appearance varies on MRI depending on multiple factors, such as hemorrhage, degree of fibrosis, histologic pattern, degree of necrosis, and the amount of fatty change.
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape. Degree of ConfidenceSome well-differentiated HCCs can mimic cirrhotic nodules on MRI. Some HCCs can contain Kupffer cells, thus having signal characteristics similar to normal liver on images contrasted with superparamagnetic iron oxide. ULTRASOUNDSection 7 of 12
FindingsSmall HCCs can be homogeneously hyperechoic and can mimic hemangioma. This can result from a large proportion of fat being present in the tumor. Small HCCs also can appear hypoechoic, with larger HCCs frequently mixed in echogenicity. Vascular invasion can be adequately evaluated using color Doppler imaging with conventional gray-scale US. Look for tumor thrombus in hepatic and portal veins as well as in the inferior vena cava. Portal venous invasion is more common in HCC, but hepatic vein invasion is more specific for HCC. Degree of ConfidenceIn particular, small hyperechoic masses seen on US require further evaluation because they can represent hemangioma (most commonly), metastatic disease, or, less likely, HCC. Further imaging with CT or MRI during dynamic contrast enhancement shows the typical peripheral, nodular contrast enhancement pattern of hemangioma. MRI or CT can further characterize many nonspecific hepatic masses seen on US (described in MRI). NUCLEAR MEDICINESection 8 of 12
FindingsOn a gallium scan, up to 90% of HCCs demonstrate uptake of the radiopharmaceutical. Gallium may help distinguish regenerating nodules of cirrhosis from HCC, as regenerating nodules typically do not label with gallium. On a liver-spleen scan, a sulfur-colloid study typically demonstrates an area of decreased labeling in HCC. Look for signs of cirrhosis, such as heterogeneous labeling of the liver with a large spleen and colloid shift to the bone marrow. Prominent left and caudate lobes of the liver are also signs of cirrhosis. A "cold" defect in the liver with signs of cirrhosis strongly suggests HCC. Hepatobiliary scans can show labeling of HCC due to the presence of hepatocytes. HCC may have no uptake initially but may show delayed uptake as the rest of the normal liver clears. This is related to malignant hepatocytes, which are hypofunctional relative to normal hepatocytes. Positron emission tomography with fluorodeoxyglucose (FDG-PET) is primarily useful in assessing the degree of differentiation and in staging moderately and poorly differentiated tumors, rather than in primary lesion detection. Sensitivity of FDG-PET for the detection of HCC is 50-70%. This limited sensitivity is due to the low level of FDG uptake in well-differentiated tumors; however, FDG-PET may be superior to CT in detecting extrahepatic spread. Degree of ConfidenceOn a gallium scan, the liver normally labels early and may obscure HCC labeling. Differential diagnoses of a mass that shows labeling in the liver include other types of malignancy and infection. ANGIOGRAPHYSection 9 of 12
FindingsAngiography for the diagnosis of HCC has been replaced largely by cross-sectional imaging. Normal vasculature is typically displaced by a large mass. HCC is characteristically hypervascular with bizarre neovascularity and arteriovenous shunting. An enlarged hepatic artery may be present. Look for vascular invasion (portal veins, hepatic veins). INTERVENTIONSection 10 of 12
Percutaneous ethanol injection has been widely used for the treatment of focal, small HCC in cirrhotic livers. In addition to ethanol injection, acetic acid injection, interstitial laser hyperthermia, and microwave therapy have been used to treat HCC. Percutaneous radiofrequency ablation has also been advocated for treatment of small HCCs. Percutaneous radiofrequency ablation appears to be effective in achieving tumor necrosis in HCC. Embolization of particles such as Gelfoam into the hepatic artery can be performed to affect blood supply to the tumor. Response rates of 60-80% have been reported, but there has been no demonstration of increased survival. The prognosis of radiologic interventions is generally poor. Long-term survival does not appear to significantly differ from survival of those who undergo surgical treatment. Long-term survival rates for transplantation are 20-30%, while the rate for resection (possible in only about 15% of patients) is 30-40%. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Hepatocellular Carcinoma excerpt Article Last Updated: May 10, 2007 | ||||||||||||||
