eMedicine Specialties > Gastroenterology > Liver

Hepatocellular Adenoma: Differential Diagnoses & Workup

Author: Brian S Berk, MD, Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of End Stage Liver Disease, Section of Gastroenterology, Dartmouth Hitchcock Medical Center
Coauthor(s): Kenneth Ingram, PAC, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University
Contributor Information and Disclosures

Updated: Aug 3, 2006

Differential Diagnoses

Cholangiocarcinoma
Colon Cancer, Adenocarcinoma
Hepatic Carcinoma, Primary
Malignant Melanoma
Metastatic Cancer, Unknown Primary Site

Other Problems to Be Considered

Echinococcal cyst
Focal fatty change
Focal nodular hyperplasia
Hepatoblastoma
Infiltrative liver disease
Inflammatory pseudotumor
Leiomyosarcoma
Lymphoma
Nodular regenerative hyperplasia

Workup

Laboratory Studies

• Serologically, hepatocellular adenomas are a diagnosis of exclusion. No specific serologic studies exist.
• Serum aminotransferase (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) levels are mildly elevated in approximately 50% of patients, likely due to the mass effect of the tumor.
• Serum alpha-fetoprotein (AFP) levels are within the reference range in patients with hepatocellular adenoma. Elevations are noted in 50% of hepatocellular carcinoma (HCC) cases. Thus, finding an elevated AFP represents either a primary carcinoma or an adenoma that has undergone malignant transformation. An AFP level within the reference range does not eliminate HCC from the differential diagnosis.
• Elevated carcinoembryonic antigen (CEA) levels suggest metastasis from the colon.
• Serologies for amoebiasis and echinococcus should be considered if the lesion appears cystic.

Imaging Studies

• Findings on imaging studies in cases of hepatocellular adenomas generally are nondiagnostic because the mass often is solitary and well demarcated. Distinguishing characteristics generally are absent. Ultrasound and CT imaging are more specific if intralesional hemorrhage is noted.
• Ultrasound
  • A nonspecific finding reveals a hypoechoic lesion, which usually is subcapsular (7% pedunculated), well circumscribed, ranges from 2-20 cm, and is located predominantly in the right lobe of the liver.
  • Doppler flow patterns in adenomas are venous, as compared to the arterial pattern noted in focal nodular hyperplasia.
• Computed tomography imaging
  • A nonspecific, well-circumscribed mass that has a low density on noncontrast and a marked centripetal pattern of enhancement on arterial phase
  • The lesion can have a central necrotic area or calcifications.
  • Most adenomas are encapsulated on CT scan.
• Magnetic resonance imaging
  • Variable appearance due to the presence or absence of hemorrhage
  • Hyperintense heterogeneous signals on T1- and T2-weighted imaging often due to lipids contained within the lesion
  • Hemorrhagic hepatocellular adenomas also may have hyperintense T1 imaging with subcapsular hemosiderin rings.
  • Kupffer cell–specific MRI agents (superparamagnetic iron oxides [SPIO] and ultrasmall superparamagnetic iron oxides [USPIO]) can be administered during the scan. They show no uptake due to a lack of endothelial-reticular cells.
  • Manganese–dipyridoxal diphosphate (DPDP), gadolinium, or gadobenate dimeglumine (Gd-BOPTA) can be administered during the scan. They show strong uptake due to the presence of hepatocytes.
  • Unfortunately, HCC also has a predominance of hepatocytes, which makes these agents unable to differentiate between hepatocellular adenomas and HCC.
• Nuclear scans
  • Adenomas appear as cold nodules on technetium Tc 99m sulfur colloid scans.
  • This is due to the altered blood flow through the lesions and the lack of phagocytic activity of Kupffer cells.
• Arteriography
  • Well-defined, round or ovoid, hypervascular mass with hepatic arterial branches entering from the periphery
  • Vessels within the mass are tortuous and of varying calibers with flow moving centrally from the periphery.
  • Avascular areas and intralesional hematomas are indicators of hepatocellular adenoma.

Procedures

• Results of histological evaluation with a liver biopsy are nondiagnostic and insensitive because the mass is comprised of normal-appearing hepatocytes.
• Resection and evaluation may be required as the most specific way to confirm diagnosis.

Histologic Findings

In a gross examination, hepatocellular adenomas appear as sharply circumscribed, light brown to yellow tumors that are soft in consistency and may or may not be encapsulated. Their sizes range to over 20 cm in diameter. Hypervascularity is present upon the surface of the lesion. Because adenomas contain no portal vein branches, their blood supply is entirely arterial. Multiple lesions, ranging in diameter from 1-20 cm, may be present within a single liver. Adenomas may hang on a stalk from the surface of the liver.

In a microscopic examination, the hallmark of adenomas is the normal appearance of the hepatocytes. These are arranged in sheets and have no malignant features. These cells tend to be larger than normal hepatocytes, and their cytoplasm often contains fat or glycogen. Generally, few, if any, portal tracts are present, and no central veins or bile ducts are present. Kupffer cells are reduced in number or absent. Vessels, when observed, tend to have thickened walls. Areas of thrombosis and infarction may be observed. Most hepatocellular adenomas contain a variable degree of microscopic collections of fat. Differentiation from a high-grade HCC can be difficult, if not impossible. Adenomas tend to lack malignant-appearing mitotic structures, the cell plates generally are only 2 cells thick, and no cellular infiltration (invasion) into the capsule or surrounding liver parenchyma occurs. Unfortunately, these features also may be absent in HCC, especially if it is well differentiated.

The tendency for these lesions to bleed may be related to their increased vasculature, which is made up of thin-walled, dilated sinusoids carrying blood at arterial pressure.

• Search for CME/CE on This Topic »

• Hepatic Adenoma (Radiology)

• HBV Reduces Recurrence-Free Survival After Surgery for Hepatocellular Carcinoma

• Morbidity and Mortality After Liver Resection for Benign and Malignant Hepatobiliary Lesions