Hepatoblastoma

Hepatoblastomas usually present with as a single, mildly painful, rapidly enlarging abdominal mass that arises in the right lobe of the liver in 55% to 60% of cases.[10] Rapid enlargement of these tumors rarely results in tumor rupture and hemorrhage. Tumors may reach up to 25 cm in size. Most tumors are solitary; however, up to 15% of tumors are multifocal. Some cases are associated with non-specific symptoms such as weight loss, failure to thrive or anorexia.[7] Significant elevations of alpha-fetoprotein (AFP) are observed in 90% of patients, and rarely, a paraneoplastic syndrome can occur.

Ultrasound (US) and either computed tomography (CT) or magnetic resonance imaging (MRI) are the imaging modalities used to define the extent of tumor involvement of the liver and aid in pre-surgical planning. A chest CT can help detect lung metastasis; the lung is the most common location of metastases and up to 20% of cases present with metastases.[7] After imaging, a biopsy, alpha-fetoprotein level, liver function tests, and a hepatitis panel are performed as needed. Consent for participation in biologic studies should be requested before the biopsy is performed so the specimen can be properly allocated and handled.[9]

Surgical resection is the mainstay of treatment with resectability of the tumor determining the need for neo-adjuvant or adjuvant chemotherapy. At presentation, approximately 60% of tumors are unresectable.[11] If unresectable and chemotherapy fails to shrink the tumor to a resectable size, a liver transplant can be done and has a good long-term survival rate.[12] The benefit of radiation therapy is unclear, with some unresectable cases responding well. Alpha-fetoprotein levels are useful for tracking surgical success and whether the tumor has metastasized.[10] An increased risk of post-transplant lymphoproliferative disorder after immunosuppression for liver transplant has been suggested in some publications.[6]

The differential diagnosis includes hepatocellular carcinoma (HCC), focal nodular hyperplasia, hepatic adenoma, lymphoma, and metastases. HCC can appear similar to the macrotrabecular subtype of hepatoblastoma, however, usually affects an adult patient population with risk factors such as metabolic disorders, liver cirrhosis, or childhood hepatitis B infection. Focal nodular hyperplasia usually affects older children and adults. Hepatic adenoma can resemble pure fetal hepatoblastomas; however, these rarely occur in persons under 5 years of age unless they have an underlying metabolic disorder.

The Children’s Hepatic Tumors International Collaboration (CHIC) constructed a staging and risk stratification system intended to standardize the assessment of this tumor across the globe. This new staging system is called the Children’s Hepatic Tumors International Collaboration – Hepatoblastoma Stratification and incorporates confirmed prognostic factors from prior risk stratification systems with new additional factors to stratify patients into 4 risk groups.

Found to be most predictive are AFP levels, patient age, Pretreatment Extent of Disease (PRETEXT) group (I, II, III, or IV), the presence of metastases, and PRETEXT annotation factor. PRETEXT group is based on the extent of the tumor in the liver. PRETEXT annotation factor is determined to be positive if at least 1 of the following 5 factors are present: involvement of the vena cava or all 3 hepatic veins, or both (V); involvement of portal bifurcation or both right and left portal veins, or both (P); extrahepatic contiguous tumor extension (E); multifocal liver tumor (F); tumor rupture at diagnosis (R). Gender, low birth weight, prematurity, and Beckwith-Wiedemann syndrome were not found to be significant. Of note, the histologic type was not included in this risk stratification system but may be incorporated at a future date. Validation of these risk groups is in progress.[2][13]

Prognosis is based on numerous factors including age of diagnosis, PRETEXT group, metastases, alfa fetal protein (AFP) levels, histologic subtype, completeness of resection, and clinical stage of the disease.  With certainty, the well-differentiated fetal subtype is associated with a better prognosis compared with small cell undifferentiated and macrotrabecular, which are linked to unfavorable prognosis.[13] Of note, the histologic subtype is only prognostically valuable before treatment with chemotherapy. Alfa-fetoprotein is typically high upon diagnosis, but a significant drop after neo-adjuvant chemotherapy portends a better response to treatment. Younger age of diagnosis has historically been a poor prognostic factor; however, recent studies have called this into question, providing evidence that these younger patients do just as well as older children.[14]  Specifically, children younger than 1 year of age have a better prognosis and children greater than 6 years of age have a worse prognosis.[2] Tumor presence at the resection margin, multifocality, and metastases have been shown to be poor prognostic factors. Beta-catenin expression has been shown to be associated with a lower period of event-free survival, while EpCAM expression has been associated with higher tumor viability and a poorer response to neo-adjuvant chemotherapy.[15][16]

• Intraperitoneal tumor rupture
• Complications related to chemotherapy
• Post-transplant complications
• Psychosocial effects of treatment and painful procedures

Improved clinical outcomes are achieved when hepatoblastomas are managed by an interprofessional team which may include a pediatrician, oncologist, radiologist, pediatric surgeon, hepatologist and a transplant specialist.[17] After surgical resection, these children are monitored by intensive care unit (ICU) nurses, therapists, dietitians, and an intensivist.