Pediatric Hepatocellular Carcinoma Workup

Updated: Nov 05, 2015
  • Author: Paulette Mehta, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Laboratory Studies

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  • Laboratory profile in hepatocellular carcinoma (HCC) should include serologies for hepatitis B and C and should evaluate the extent of hepatic dysfunction shown by the presence of altered liver function tests, coagulopathies, or hyperammonemia. Tests for amebiasis and echinococcus may be helpful in patients who may have these diseases.

  • Approximately 50% of patients demonstrate elevated a-fetoprotein (AFP) levels and, to a lesser extent, abnormal levels of beta human chorionic gonadotropin (b-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. A serum sodium, calcium level should also be obtained , due to association of hypercalcemia and hyponatremia as part of 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

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  • Initial staging evaluation should include, but is not limited to, chest, abdomen, and pelvic CT scanning. If surgical resection is anticipated, use 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 to develop hepatocellular carcinoma. Hepatocellular carcinoma has a typical radiographic appearance of increased dye uptake during the arterial phase.

  • Additional scans that may be helpful in the staging workup include a bone scan and MRI 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.

A review by Chou et al that evaluated the test performance of imaging modalities for hepatocellular carcinoma found that CT and MRI are associated with higher sensitivity than ultrasonography without contrast for detection of hepatocellular carcinoma and that sensitivity was higher for MRI than CT. The study also added that for evaluation of focal liver lesions, the sensitivities of ultrasonography with contrast, CT, and MRI for hepatocellular carcinoma are similar. [2]




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

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

  • If definitive tumor resection is planned, this biopsy should preferable be performed by the surgeon who is eventually going to perform the hepatectomy.


Histologic Findings

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  • 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 specimen, 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 B12 binding protein are significantly elevated and rise and fall concomitantly with successful or unsuccessful disease control. Claims that the fibrolamellar variant is associated with a better prognosis compared with hepatocellular carcinoma have not been substantiated, and contradicting evidence is noted. [1]



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  • 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 affected patient.

  • The proposed staging system is as follows:

    • Clinical group 1 - Complete resection of the tumor

    • Clinical group IIa - Completely resectable after presurgical irradiation and/or chemotherapy.

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

    • Clinical group III - 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 and/or bone)