Hepatoblastoma C22.2

Hepatoblastoma (HB) is a malignant liver tumor in children (Herold 2022).

The classification of HB into a specific disease stage as well as the treatment protocols refer to the so-called PRETEXT group I - IV (pre-treatment extension [von Schweinitz 2016]). This is determined by the number of contiguous tumor-free sections of the liver (Honda 2022).

Hepatoblastoma is now one of the most common primary malignant liver tumors in children - with an increasing incidence (Wu 2022). The rising incidence is partly due to the improved survival rates of premature babies (Honda 2022).

The incidence of HB is currently approx. 1 - 2 per million children under the age of 15 (Nussbaumer 2022) and thus accounts for approx. 1 % of all malignant diseases in children (Song 2022). There is a male predisposition (von Schweinitz 2016), as HB occurs 1.2 - 3.3 times more frequently in boys than in girls (Eberherr 2021).

HB presumably arises from defects in embryonic development, while cancers in adults are due to acquired mutations (Eberherr 2021).

The actual etiology of HB is still unknown. Predisposing factors to date include:

- Low birth weight (especially < 1,500 g)

- Maternal nicotine consumption during pregnancy (although this is still controversial)

- Previous infertility treatment (also controversial to date) (Nussbaumer 2022)

However, certain congenital diseases show a significantly increased incidence of hepatoblastomas. These diseases include:

- Beckwith- Wiedemann spectrum

- Familial adenomatous polyposis

- Simpson-Golabi-Behmel syndrome

- Trisomy 18 (Nussbaumer 2022)

If one of these genetic disorders is detected, screening protocols are recommended with regular abdominal ultrasounds and determination of the alpha-fetoprotein for early detection of HB (Nussbaumer 2022).

HB develops from primitive precursor cells of the liver parenchyma, which can be differentiated according to the respective liver development into:

- Fetal

- Embryonic

- Macrotrabecular

- Cholangioblastic (von Schweinitz 2016)

Mesenchymal structures may also be present, such as:

- Cartilage

- osteoid

- Rhabdomyoblast-like structures

- Smooth muscle (von Schweinitz 2016)

Hepatoblastoma predominantly manifests in the first two years of life (Sharma 2017) with a pronounced age peak between 6 months and 3 years (von Schweinitz 2016).

HB is predominantly localized in the right lobe of the liver. Only in very rare cases is HB found extrahepatic (von Schweinitz 2016).

HB can cause the following symptoms:

- Fever

- fatigue

- Disturbance of eating and drinking behavior

- jaundice

- Palpable abdominal tumor

- Pubertas praecox

- Acute abdomen in the event of tumor rupture, although this only occurs rarely (von Schweinitz 2016)

Physical examination

Physical examination reveals a palpable, indolent (Eberherr 2021) tumor in the abdominal region (von Schweinitz 2016).

Abdominal sonography with color Doppler

This usually shows the tumor well (von Schweinitz 2016).

Diffusion-weighted MRI

This plays a particularly important role in the preoperative assessment with regard to the detection of satellite lesions (Honda 2022).

Punch biopsy

Diagnostic punch biopsy is strongly recommended in cases of suspected HB. Biopsy under sonographic or laparoscopic control has proven to be successful. A fine needle aspiration biopsy should not be performed, as this provides too little tissue to assess the tumor (Murawski 2023).

Alpha-fetoprotein (AFP)

This is elevated in the serum of approx. 80 - 90 % of patients and is the most important tumor marker. HB with low AFP is generally more aggressive and associated with a very poor prognosis (von Schweinitz 2016). It should be noted that alpha-fetoprotein is still highly elevated in the first period after birth and only decreases within the first 10 weeks (Eberherr 2021).

Thrombocytosis

Thrombocytosis is very rare (von Schweinitz 2016).

Beta HCG

Beta- HCG can be elevated in approx. 20 % of patients (von Schweinitz 2016).

HB exhibits a high degree of heterogeneity (Song 2022). Histopathologically, 56% are epithelial subtypes and 44% are mixed epithelial / mesenchymal subtypes. The epithelial subtypes are further subdivided into fetal (31%), embryonal (19%), macrotrabecular (3%) and also 3% small cell undifferentiated and cholangioblastic subtypes (Eberherr 2021).

Small cell undifferentiated HB is associated with a significantly less favorable prognosis (Murawski 2023).

Metastasis

Around 20% of patients already have metastases at the time of diagnosis of HB. Lung metastases are the most common (Honda 2022). Metastases can also form in the brain and bones (Eberherr 2021).

The treatment of hepatoblastoma has changed significantly over the last three decades (Sharma 2017). The therapeutic options now include both chemotherapy and surgery. Radiotherapy, on the other hand, has not proven to be effective (von Schweinitz 2016).

Chemotherapy

Almost all patients initially receive neoadjuvant cisplatin-based chemotherapy (von Schweinitz 2016).

Some patients respond well to chemotherapy, while others - depending on the tumor signatures - show a high level of resistance to chemotherapy (Song 2022).

Neoadjuvant cisplatin-based therapies in particular have led to around 50 - 85 % of initially inoperable HB ultimately becoming resectable (Honda 2022).

Both resection and liver transplantation now play a decisive role in the treatment of HB. In particular, the possibilities offered by technological advances in the development of 3D image processing software and virtual stimulation of a hepatectomy are being utilized (Honda 2022).

Surgical resection

To achieve safe and complete resection of even extensive liver tumors, the ALLPS procedure was developed, which is also used for hepatoblastoma (Honda 2022).

In the case of lung metastases that do not respond completely to cisplatin, additional surgical resection of the remaining metastases should be performed (Horiike 2020).

Liver transplantation

Liver transplantation is particularly important in cases of non-surgically removable HB (Eberherr 2021).

Since it is known that the tumor may still be present histologically even in the absence of imaging findings, liver transplantation is also an important treatment option in this case (Honda 2022).

The prognosis for HB has improved significantly over the last three decades. Thanks to innovative advances in both chemotherapy and surgery, the survival rate has risen from 30% to 80% (Honda 2022).

The prognosis ultimately depends on the possibility of radical surgical resection; even with aggressive resection of metastases, the prognosis can be good (Honda 2022).

The 5-year survival rate after a liver transplant has risen from 50% to 90%. Even with existing lung metastases, cisplatin-based chemotherapy can achieve a complete remission of the metastases in up to 50% of cases (Honda 2022).

There is no real prophylaxis to date (von Schweinitz 2016).

If certain genetic disorders such as Beckwith- Wiedemann spectrum, familial adenomatous polyposis, Simpson-Golabi- Behmel syndrome and trisomy 18 are detected, screening protocols are recommended with regular abdominal sonograms and determination of alpha fetoprotein for early detection of HB (Nussbaumer 2022).

The tumor markers alpha-fetoprotein and beta-HCG are the most important follow-up parameters. Follow-up care in the first p. o. year with physical examination and determination of AFP in the serum should initially be carried out every 6 weeks, and every 3 months an abdominal ultrasound and a chest X-ray in 2 planes.

In the 2nd and 3rd year, the sonography and chest X-ray should be performed every 3 months and from the 4th year every 6 months (von Schweinitz 2016).

After 5 years, only annual checks for possible long-term effects of chemotherapy in the form of determination of:

- liver values

- creatinine

- phosphate

- ECG

- Echocardiogram

- Audiogram

The last two examinations only if anthracycline was given (von Schweinitz 2016)

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