Hepatocellular carcinoma

Classification according to ICCC : VII.b (Hepatic carcinoma)

Epidemiology

Hepatocellular carcinoma (HCC) is rare in children, and is more common in adolescents. HCC accounts for about 0.5% of all childhood cancers.

Clinical symptoms

  • there are no symptoms for a long time; the patient himself/herself usually palpates a tumour mass
  • loss of appetite, weight loss, general weakness, increased fatigue – rarely
  • jaundice, ascites or abdominal pain are usually not present

Aetiology

  • cause of origin is unknown in most cases of hepatocellular carcinoma
  • risk factors:
    • tyrosinaemia, glycogen storage disease (GSD) type I and III, alpha-1 antitrypsin deficiency
    • chronic hepatitis C and B
    • long-term use of anabolic steroids
    • aflatoxin, thorotrast, vinyl chloride, pesticides, alcoholism
    • it rarely accompanies biliary atresia and other types of biliary cirrhosis

Unlike in adults, 75% cases of hepatocellular carcinoma in children develop in healthy liver without any signs of cirrhosis or another high-risk condition.

Diagnosis

The diagnostic algorithm is the same as in hepatoblastoma.

Medical history:

  1. birth weight, presence of congenital anomalies and syndromes
  2. ruling out inborn errors of metabolism (IEMs)
  3. infections, vaccinations, travelling to high-risk regions

Laboratory examination:

  1. haematology: blood count (paraneoplastic thrombocytosis, anaemia), coagulation
  2. biochemistry: liver function tests, total protein, albumin, ammonia
  3. serological testing for hepatitis, virological testing (EBV, CMV)
  4. tumour markers – AFP, older children and adolescents also CEA, Ca19-9

Imaging examination:

  1. abdominal ultrasound
  2. CT scans of abdomen, lungs and brain
  3. abdominal MRI scan
  4. 18F-FDG PET +/-

Differential diagnosis

Differential diagnosis of hepatic tumours depends on the size and character of the tumour, as well as on the patient’s age. In the differential diagnostic procedure, the following should be ruled out:

  1. non-cancerous causes:
    • haematoma
    • abscess (bacterial, mycotic, granulomatous)
  2. benign tumours:
    • mesenchymal hamartoma
    • adenoma, haemangioma
    • focal nodular hyperplasia
    • teratoma
    • infantile haemangioendothelioma
  3. secondary tumours (metastases) in the liver:
    • neuroblastoma
    • Wilm’s tumour
    • soft tissue sarcomas
    • germ cell tumours
  4. other primary hepatic tumours:
    • haemangiosarcoma
    • undifferentiated sarcoma
    • rhabdomyosarcoma of the biliary tract

Treatment

Surgical treatment

Similarly to hepatoblastoma, radical surgical removal of the tumour is crucial in the treatment of hepatocellular carcinoma. Radical resection provides the only real chance of curing the patient.

Surgical treatment modalities:

  • biopsy
  • radical resection of the tumour
  • liver transplantation

Factors influencing the radicality of surgical procedure:

  1. size of the primary tumour and the number of affected liver segments
  2. location in the liver – relation to large vessels (portal area and hepatic hilus)
  3. presence of extrahepatic tumour(s)

Chemotherapy

Hepatocellular cancer:

  • is usually resistant to conventional chemotherapy
  • only localised disease can be cured, after a radical surgery
  • advanced hepatocellular carcinoma belongs to incurable cancer types

New trends:

  • antiangiogenic therapy (thalidomide, bevacizumab)
  • biological therapy (multikinase inhibitors – sorafenib, sunitinib, …)

Locoregional treatment

Locoregional treatment is employed as a palliative procedure in cases where radical surgery cannot be performed, and where liver transplantation is contraindicated. Its objective is to decrease the size of tumour, and to prolong the patient’s survival. Locoregional treatment involves the following procedures:

  • radiofrequency thermal ablation
  • chemoembolisation
  • alcohol embolisation

Prognosis

Factors influencing the prognosis:

  1. extent of the disease (presence of extrahepatic tumours)
  2. radicality of the surgical procedure (30% of tumours are resectable)
  3. dysfunction of liver parenchyma
  4. general state of patient’s health (performance status)

Prognosis is much worse when compared to hepatoblastoma, because hepatocellular carcinoma does not respond well to chemotherapy. Only about 25% of patients survive 5 years after diagnosis.