Pediatric Hepatocellular Carcinoma Workup

Updated: Mar 12, 2020
  • Author: Paulette Mehta, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Laboratory Studies

The laboratory profile in hepatocellular carcinoma (HCC) should include serologies for hepatitis B and C. Additionally, the extent of hepatic dysfunction, as demonstrated by the presence of altered liver function tests, coagulopathies, or hyperammonemia, should be evaluated. Tests for amebiasis and echinococcosis may be helpful in patients who are at risk for these diseases.

Approximately 50% of patients have elevated α-fetoprotein (AFP) levels and, to a lesser extent, abnormal levels of β-human chorionic gonadotropin (β-hCG). These serum markers of fetal hepatocytic function are useful not only for diagnostic purposes, but also for monitoring tumor response to therapy.

Rarely, polycythemia occurs because of extrarenal erythropoietin production by the malignantly transformed hepatocytes. Serum sodium and calcium levels should also be obtained, because of the association of hyponatremia and hypercalcemia with the paraneoplastic syndrome secondary to excess production of parathyroid hormone–related protein (PTH-rP) and antidiuretic hormone (ADH).

Vitamin B12–binding protein levels may be elevated in children with the fibrolamellar variant of hepatocellular carcinoma. These levels may be followed as markers of disease burden.


Imaging Studies

The initial staging evaluation should include, but is not limited to, chest, abdomen, and pelvic computed tomography (CT) scanning. Hepatocellular carcinoma has a typical radiographic appearance of increased dye uptake during the arterial phase.

If surgical resection is anticipated, use magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the liver to best determine tumor margins and vasculature. Ultrasonography may be helpful to screen patients at high risk for hepatocellular carcinoma.

Additional scans that may be helpful in the staging workup include a bone scan and an MRI scan of the brain to determine the status of metastatic spread to the skeleton and neuraxis, respectively.

Chest radiography is an important tool to monitor pulmonary metastatic disease and, when appropriate, malignant pleural effusions.

Because affected patients may have underlying hepatic dysfunction or deficits in liver function because of bulky tumor burden, deficiencies in coagulation function may occur. In this setting, deep venous thromboses may complicate the patient's course. If extremity swelling, edema, or pain is noted, venous Doppler studies may be performed to exclude the possibility of deep venous thromboses.

Chou et al evaluated the test performance of imaging modalities and found that CT and MRI have higher sensitivity than ultrasonography without contrast for detection of hepatocellular carcinoma and that the sensitivity of MRI is higher than that of CT. The investigators also found that for evaluation of focal liver lesions, the sensitivities of ultrasonography with contrast, CT, and MRI for hepatocellular carcinoma are similar. [13]




Liver biopsy is the most important procedure to consider when hepatocellular carcinoma is suspected and when imaging studies combined with the AFP level do not provide a conclusive diagnosis.

Needle biopsies are generally not recommended, especially in the setting of cirrhosis, because it may be easy to overlook the findings of malignantly transformed hepatocytes in a small specimen, and the diagnosis may be missed. Seeding the biopsy tract with tumor during a needle biopsy is also a concern.

If definitive tumor resection is planned, the biopsy should preferably be done by the surgeon who will eventually perform the hepatectomy.


Histologic Findings

Histologic examination of tumor tissue in children with classic hepatocellular carcinoma reveals large polygonal cells with central nuclei, frequent mitotic figures and, often, invasion into surrounding hepatic tissue or adjacent abdominal structures. Areas of hemorrhage and necrosis, which may complicate the interpretation of needle biopsy specimens, are common.

A distinct histologic variation, termed fibrolamellar carcinoma, occurs with relatively high frequency in children and young adults. Tumor cells in this subtype are circumscribed characteristically by bundles of acellular collagen, creating either trabeculae or large nodules of tumor islands. Interestingly, in the fibrolamellar variant, levels of vitamin B12-binding protein are significantly elevated and rise and fall concomitantly with successful or unsuccessful disease control. Claims that the fibrolamellar variant has a better prognosis than hepatocellular carcinoma have not been substantiated, and contradicting evidence is available. [2]



Although no staging system has been uniformly adopted, a staging method proposed by the Children's Cancer Group and Southwest Oncology Group incorporates tumor bulk with surgical resection. The staging and classification for hepatocellular carcinoma draw on location, resectability, and response to any presurgical therapy given to the patient.

The proposed staging system is as follows:

  • Clinical group I: Complete resection of the tumor.

  • Clinical group IIa: Completely resectable after presurgical irradiation or chemotherapy.

  • Clinical group IIb: Residual disease confined to either left or right lobe of the liver after presurgical irradiation or chemotherapy.

  • Clinical group IIIa: Residual or unresectable tumor involves both left and right lobes of the liver.

  • Clinical group IIIb: Regional node involvement.

  • Clinical group IV: Distant metastatic spread (usually to the lungs or bone).