Hepatoblastoma

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Hepatoblastoma Microchapters
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Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Epidemiology and Demographics
Risk Factors
Screening
Differentiating Hepatoblastoma from other Diseases
Natural History, Complications and Prognosis
Diagnosis
Staging
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2]

Synonyms and keywords: Epithelial hepatoblastoma; Fetal hepatoblastoma; Embryonal hepatoblatoma; Macrotrabecular hepatoblastoma; Mixed hepatoblastoma; Rhabdoid hepatoblastoma; Small cell hepatoblastoma; Undifferentiated hepatoblastoma; Cholangioblastic hepatoblastoma; Teratoid hepatoblastoma; Chondroid hepatoblastoma; Osteoid hepatoblastoma; Rhabdomyoblastic hepatoblastoma; Neuroid-melanocytic hepatoblastoma; Well differentiated hepatoblastoma; HB

Overview

Hepatoblastoma is the most common primary liver tumor occurs in infant and children, usually less than 3 years old, more frequently in male, and accounting for over 1% of pediatric cancers. The etiology is unknown and not well understood, but it has been associated with Beckwith-Weidemann syndrome, familial adenomatous polyposis, and other factors such as low birth weight, preeclampsia, hemihypertrophy. The primary treatment is surgical resection, however, chemotherapy plays an important role by increasing the number of tumors that are respectable, chemotherapeutic agents helps in shrinkage of the tumor and make it easier to be resected by surgery. Prognosis of the tumor depends on various criteria such as resectability of the tumor, distant metastasis, tumor size, PRETEXT staging, and recurrence of the tumor. The mainstay of treatment is surgery, but the adjuvant chemotherapeutic agents and liver transplantation also are helpful.

Historical Perspective

In 1898, the first case of hepatoblastoma was published in English literature, the tumor was diagnosed in a 6-week old boy in Prague, by a physician named Misick, who found a large tumor on the autopsy of his liver. Decades later on 1962 Willis used the term, hepatoblastoma for this type of liver tumor because of it's embryonal origin

Classification

• Hepatoblastoma are divided into two broad categories:
  • Epithelial type (E-HB)
    • Fetal, which has four subtypes:
      • Well differentiated
      • Crowded or mitotically active
      • Pleomorphic
      • Poorly differentiated
      • Anaplastic
    • Embryonal
    • Macrotubular small cell undifferentiated (SCU)
    • Cholangioblastic
  • Mixed epithelial and mesenchymal type (MEM-HB). The mixed type is subdivided into:
    • Stromal derivatives
    • Teratoid variants

Pathophysiology

• The exact pathogenesis of hepatoblastoma is not fully understood.
• Loss of function mutations in APC leads to intracellular accumulation of the protooncogene beta-catenin, which leads to germline mutation of Wnt signal transduction and pathway.
• Hepatoblastomas originate from primitive hepatic stem cells.
• B-catenin mutations have been shown to be common in the majority of sporadic hepatoblastomas.
• Studies revealed that tumor occurs more often in families affected by familial adenomatous polyposis(FAP), which is caused by inactivation of the adenomatous polyposis coli (APC), a tumor-suppressor gene that down-regulate the amount of beta-catenin.
• Immunohistochemical markers such as expression of CK19, beta-catenin and EpCAM were correlated with tumor behaviour, response to chemotherapy and survival.

Hepatoblastoma H&Esource:wikipedia

Causes

• Underlying causes of hepatoblastoma poorly understood and most tumors are sporadic but there are some risk factors and conditions that have a strong association with this tumor such as:
  • Beckwith-Weidemann syndrome
  • Familial adenomatous polyposis (FAP)
  • Down syndrome
  • Edward syndrome (trisomy 18)
  • Nephroblastoma,
  • Low birth weight infants are at higher risk of developing a hepatoblastoma
  • Preeclampsia
  • Parental tobacco smoking
  • Oxygen therapy
  • Certain medication (furosemide)
  • Radiation
  • Total parenteral nutrition (TPN)

• The most common genetic mutation which plays role in etiology of sporadic cases include:
  • The Wnt signaling pathway which results in the accumulation of beta-catenin.

Differentiating hepatoblastoma from Other Diseases

• Hepatoblastoma must be differentiated from other diseases that cause rapidly enlarging abdominal mass in pediatrics such as:
  • Hepatocellular carcinoma (HCC) of liver
  • Focal nodular hyperplasia of liver
  • Hepatic adenoma of liver
  • Lymphoma, and metastases to liver

Epidemiology and Demographics

• Hepatoblastoma is the most common primary liver cancer in infants and children, tumor involves right lobe of liver more often.
• The incidence/prevalence of hepatoblastoma is approximately 0.05–0.15 patients per 100000 population in children younger than 15 years.
• Peak incidence means of 18 months, mostly in infants and children younger than 3 years old, with a male predilection.
• Hepatoblastoma accounts for one percent of all primary malignancies in pediatrics.

Risk Factors

• Common risk factors in the development of hepatoblastoma include:
  • Low birth weight infants
  • Preeclampsia
  • Fetal distress
  • Premature labor
  • Chromosomal anomalies such as Down syndrome, Edwards syndrome.
  • Parental tobacco smoking before and during pregnancy
  • Oxygen therapy
  • Certain medication (furosemide)
  • Total parenteral nutrition (TPN)

Screening

• There is no screening method for detecting hepatoblastoma.
• Ultrasound is the main tool for suspected hepatic lesions in children.
• Serum alpha-fetoprotein (AFP) is the most important clinical marker of hepatoblastoma and helps to estimate malignant change, response to the treatment, and relapse.

Natural History, Complications, and Prognosis

• Prognosis is based on different factors including:
  • Age of diagnosis, younger children have a better prognosis.
  • Metastases,
  • Alpha-fetoprotein (AFP) levels, drop in AFP level after chemotherapy means better response to treatment.
  • Histologic subtype, the well-differentiated fetal subtype has a better prognosis compared with small cell undifferentiated ones.
  • Pretreatment extent of disease (PRETEXT) which was developed to stage the tumor before surgical removal and compare the efficacy of varous adjuvant chemotherapeutic agents. It is based on anatomy of liver and depending on tumor free sectors of liver.
• Complications of hepatoblastoma includes:
  • Pancytopenia
  • Anemia
  • Intraperitoneal tumor rupture
  • Complications related to chemotherapy such as renal failure
  • Post-transplant complications such as hepatic ductal obstruction, biliary leakage, thrombosis.
  • Psychosocial effects of treatment and painful procedures

Diagnosis

Diagnostic Study of Choice

• The diagnosis of hepatoblastoma is made when abdominal mass is detected on ultrasound or spiral CT scan, but a definitive diagnosis requires the histological evaluation of biopsy specimen after surgery.

History and Symptoms

• The majority of patients with hepatoblastoma have an abdominal mass or abdominal distension.
• Other symptoms of hepatoblastoma include:
  • Abdominal discomfort
  • Generalized fatigue
  • Loss of appetite (Anorexia)
  • Nausea and vomiting

• Ruptured tumor can cause symptoms of peritoneal irritation due to intraperitoneal bleeding such as severe abdominal pain, nausea, vomiting, and severe anemia.

Physical Examination

• Physical examination of patients with hepatoblastoma is usually remarkable for single, mildly painful, rapidly enlarging abdominal mass that is found in the right lobe of the liver.
• Most tumors are solitary; but can be multifocal as well.

Laboratory Findings

• Laboratory findings that help with the diagnosis of hepatoblastoma includes:
  • High levels of Alpha-fetoprotein (AFP)
  • Mild liver function disturbances
  • Anemia on complete blood count
  • Thrombocytosis (more frequent because of the effect of thrombopoietin)
  • Thrombocytopenia (less common)

Electrocardiogram

• There are no ECG findings associated with hepatoblastoma.

X-ray

• Chest x-rays can be useful especially since this tumor has the affinity to metastasize to lungs.

Ultrasound

• Imaging studies play an important role in the diagnosis, staging, and treatment of disease, most tumors can be resected surgically and ultrasound is often used in order to detect tumor size, also the initial diagnosis is made by abdominal ultrasound.

CT scan

• CT scan is very helpful to diagnose the disease, children with hepatoblastoma undergo either a CT or MRI scan at diagnosis.
• Surgeons prefer an angiographic or biphasic CT scan because of better depiction of the hepatic arterial, portal venous and hepatic vein and other liver structures.
• Concerns about radiation exposures in pediatrics has changed this modality in favor of MRI, although MRI is much lengthy exam than CT has the advantage of multiplanar soft-tissue characterization, and when diffusion-weighted imaging techniques are used, MRI is exquisitely sensitive for detecting tiny liver lesions.
• Spiral CT scan findings of hypervascular lesions in the liver with delayed contrast excretion are highly suggestive of a malignant liver tumor.

MRI

• MRI has the advantage of multiplanar soft-tissue characterization, lack of harmful ionizing radiation and when diffusion-weighted imaging techniques are used, MRI is exquisitely sensitive for detecting tiny liver lesions.

Other Imaging Findings

• Other imaging studies such as PET scan or even bone scan when there is evidence of metastasis to bone may be helpful in the diagnosis of hepatoblastoma. PET scan can be helpful in localizing recurrent hepatoblastoma.

Other Diagnostic Studies

• Other diagnostic studies for hepatoblastoma include evaluation of serum level of alpha-fetoprotein, serum hCG level in rare cases of precocious puberty.

Treatment

Medical Therapy

• The mainstay of therapy for hepatoblastoma is surgery, however, the vast majority of the tumors cannot be completely resected because of their large size or metastasis.
• Liver transplantation can be considered for tumors that cannot be removed by surgery.
• Chemotherapy is an important adjuvant therapy, and cisplatin is the most commonly used chemotherapeutic agent, it can reduce the volume of tumors that are too big for surgical removal.

Surgery

• Surgery is the mainstay of treatment for hepatoblastoma.
• The feasibility of surgery depends on the resectability of tumor at diagnosis.

Primary Prevention

• There are no established measures for the primary prevention of hepatoblastoma.

Secondary Prevention

• There are no established measures for the secondary prevention of hepatoblastoma.