eMedicine Specialties > Pediatrics: General Medicine > Oncology

Hepatocellular Carcinoma: Differential Diagnoses & Workup

Author: Girindra G Raval, MD, Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine
Coauthor(s): Paulette Mehta, MD, MPH, Professor of Hematology/Oncology, Department of Internal Medicine, Co-Director of Fellowship Program, Medical Director of Hematology/Oncology at CAVHS, University Arkansas for Medical Sciences and Central Arkansas Veterans Hospital System
Contributor Information and Disclosures

Updated: Feb 23, 2009

Differential Diagnoses

Amebiasis
Hepatoblastoma

Other Problems to Be Considered

Capillary hemangioma
Cavernous hemangioma
Metastatic tumor from a nonhepatic primary site

Workup

Laboratory Studies

  • 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

  • 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.

Procedures

  • 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

  • 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

Staging

  • 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)

More on Hepatocellular Carcinoma

Overview: Hepatocellular Carcinoma
Differential Diagnoses & Workup: Hepatocellular Carcinoma
Treatment & Medication: Hepatocellular Carcinoma
Follow-up: Hepatocellular Carcinoma
References
[ CLOSE WINDOW ]

References

  1. Czauderna P, Mackinlay G, Perilongo G, et al. Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group. J Clin Oncol. Jun 15 2002;20(12):2798-804. [Medline].

  2. Evans AE, Land VJ, Newton WA, Randolph JG, Sather HN, Tefft M. Combination chemotherapy (vincristine, adriamycin, cyclophosphamide, and 5-fluorouracil) in the treatment of children with malignant hepatoma. Cancer. Sep 1 1982;50(5):821-6. [Medline].

  3. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. Jul 24 2008;359(4):378-90. [Medline].

  4. Alagille D, Odievre M. Liver and Biliary Tract Disease in Children. New York, NY: John Wiley & Sons; 1979:331.

  5. Berman MM, Libbey NP, Foster JH. Hepatocellular carcinoma. Polygonal cell type with fibrous stroma--an atypical variant with a favorable prognosis. Cancer. Sep 15 1980;46(6):1448-55. [Medline].

  6. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. Nov 2005;42(5):1208-36. [Medline].

  7. Chlebowski RT, Tong M, Weissman J, et al. Hepatocellular carcinoma. Diagnostic and prognostic features in North American patients. Cancer. Jun 15 1984;53(12):2701-6. [Medline].

  8. Degos F, Christidis C, Ganne-Carrie N, et al. Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut. Jul 2000;47(1):131-6. [Medline]. [Full Text].

  9. Evans AE, Land VJ, Newton WA, et al. Combination chemotherapy (vincristine, adriamycin, cyclophosphamide, and 5-fluorouracil) in the treatment of children with malignant hepatoma. Cancer. Sep 1 1982;50(5):821-6. [Medline].

  10. Farmer DG, Rosove MH, Shaked A, Busuttil RW. Current treatment modalities for hepatocellular carcinoma. Ann Intern Med. 1994;219:236-47. [Medline].

  11. Giacomantonio M, Ein SH, Mancer K, Stephens CA. Thirty years of experience with pediatric primary malignant liver tumors. J Pediatr Surg. Oct 1984;19(5):523-6. [Medline].

  12. Greensberg M, Filler RM. Hepatic tumors. In: Pizzo PA, Poplack DG, eds. Principles and Practices of Pediatric Oncology. Philadelphia, PA: JB Lippincott Co; 1993.

  13. Jeffers LJ, Dubow RA, Zieve L, et al. Hepatic encephalopathy and orotic aciduria associated with hepatocellular carcinoma in a noncirrhotic liver. Hepatology. Jan-Feb 1988;8(1):78-81. [Medline].

  14. Kew MC, Fisher JW. Serum erythropoietin concentrations in patients with hepatocellular carcinoma. Cancer. Dec 1 1986;58(11):2485-8. [Medline].

  15. Levy LJ, Swinburne LM, Boulton RP, Losowsky MS. Primary hepatocellular carcinoma presenting as fulminant hepatic failure in a young woman. Postgrad Med J. Dec 1986;62(734):1135-7. [Medline].

  16. Mitchell RB, Wagner JE, Karp JE, et al. Syndrome of idiopathic hyperammonemia after high-dose chemotherapy: review of nine cases. Am J Med. Nov 1988;85(5):662-7. [Medline].

  17. Morita K, Okabe I, Uchino J, et al. The proposed Japanese TNM classification of primary liver carcinoma in infants and children. Jpn J Clin Oncol. Jun 1983;13(2):361-9. [Medline].

  18. Noda T, Sasaki Y, Yamada T, et al. Adult capillary hemangioma of the liver: report of a case. Surg Today. 2005;35(9):796-9. [Medline].

  19. Paradinas FJ, Melia WM, Wilkinson ML, et al. High serum vitamin B12 binding capacity as a marker of the fibrolamellar variant of hepatocellular carcinoma. Br Med J (Clin Res Ed). Sep 25 1982;285(6345):840-2. [Medline].

  20. Ringe B, Wittekind C, Bechstein WO, et al. The role of liver transplantation in hepatobiliary malignancy. A retrospective analysis of 95 patients with particular regard to tumor stage and recurrence. Ann Surg. Jan 1989;209(1):88-98. [Medline].

  21. Schafer DF, Sorrell MF. Hepatocellular carcinoma. Lancet. Apr 10 1999;353(9160):1253-7. [Medline].

  22. Vaillo A, Rodriguez-Recio FJ, Gutierrez-Martin A, et al. Fine needle aspiration cytology of clear cell carcinoma of the gallbladder with hepatic infiltration: a case report. Acta Cytol. Jul-Aug 2004;48(4):560-4. [Medline].

  23. Winter SS, Rose E, Katz R. Hyperammonemia after chemotherapy in an adolescent with hepatocellular carcinoma. J Pediatr Gastroenterol Nutr. Nov 1997;25(5):537-40. [Medline].

  24. Young JL Jr, Miller RW. Incidence of malignant tumors in U. S. children. J Pediatr. Feb 1975;86(2):254-8. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

hepatocellular carcinoma, hepatoma, HCC, fibrolamellar carcinoma, malignant hepatoma, hepatocarcinoma, liver cell carcinoma, liver disease, liver dysfunction, parenchymal cells, liver, tumor, cancer, cirrhosis, hepatitis B, hepatitis C, hemochromatosis, Gaucher disease, Gaucher's disease, biliary atresia, infantile cholestasis, glycogen-storage disease, cirrhosis, hepatitis B, hepatitis C, liver dysfunction, tyrosinemia, pleural effusions

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Girindra G Raval, MD, Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Paulette Mehta, MD, MPH, Professor of Hematology/Oncology, Department of Internal Medicine, Co-Director of Fellowship Program, Medical Director of Hematology/Oncology at CAVHS, University Arkansas for Medical Sciences and Central Arkansas Veterans Hospital System
Paulette Mehta, MD, MPH is a member of the following medical societies: American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania
Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.