Hepatic Tumors
Paul Imbach
Forms – 188 Incidence – 188
Pathology and Genetics – 189 Macroscopic Features – 189 Microscopic Features – 189
Clinical Manifestations – 189 Laboratory Diagnosis – 189 Radiological Diagnosis – 190
Differential Diagnosis of Hepatoblastoma and Hepatocellular Carcinoma – 190
Staging – 190 Therapy – 190
Surgical Management – 190 Liver Transplantation – 190 Radiotherapy – 190 Chemotherapy – 191 Prognosis – 191
188 Chapter 17 - Hepatic Tumors
Forms
Hepatic tumors and frequency
Hepatoblastoma 43%
Hepatocellular carcinoma 23%
Sarcoma 6%
Benign vascular tumors (hemangioendothelioma) 13%
Hamartoma 6%
Others 9%
Incidence (Except Benign Hepatic Tumors)
One percent of all neoplasias in childhood
Annually 1.4 in 1 million children less than the age of 16 years are newly diagnosed
Ratio of boys to girls 1.4–2.0:1.0
Different incidences worldwide, e.g. Far East more than Europe or the USA
Relationship to hepatitis B in Taiwan: Due to systematic hepatitis B vaccination the number of patients with hepatic carcinoma has been reduced
Relationship to preterm birth rate: Inverse relationship between birth weight and frequency – 15 times higher risk in infants with birth weight less than 1,000 g
High incidence in genetically associated syndromes: Beckwith-Wiedemann syn- drome, familial adenomatous polyposis, trisomy 18, glycogen storage disease, he- reditary tyrosinemia type 1, Alagille syndrome, Li-Fraumeni syndrome, ataxia-te- langiectasia, tuberous sclerosis, Fanconi anemia
Hepatoblastoma: Mostly in infants, rarely after the age of 3 years. Intrauterine de- velopment of hepatoblastoma possible
Hepatocellular Carcinoma: Mostly in children older than 4 years of age; more com- mon in adolescents. Histologically identical with carcinoma in adulthood
Pathology and Genetics Macroscopic Features
Large, solid tumor mass; diameter less than 1 inch to more than 3 inches
Main occurrence in right hepatic lobe
Minority with multinodular, bilateral spread (15–30%) Microscopic Features
Hepatoblastoma: Two patterns of differentiation:
– Epithelial type with embryonal or fetal features
– Mixed epithelial-mesenchymal type, partly with osteoid formation – Some variants with variable embryonal differentiation
Hepatocellular carcinoma: Histologically similar to hepatocellular carcinoma of adults
Karyotype (hepatoblastoma):
– Commonly trisomy of chromosomes 2 and 20, rarely of chromosome 8 are asso- ciated
– Loss of heterozygosity (LOH) of chromosome 1p15 (as in other embryonal tu- mors, e.g. nephroblastoma or rhabdomyosarcoma)
Clinical Manifestations
Expansive palpable mass in the upper abdomen or generalized enlargement of the abdomen
Weight loss
Anorexia
Vomiting
Abdominal pain
Pallor
Jaundice and ascites
Occasionally precocious puberty in hepatocellular carcinoma
Metastatic pattern: Commonly in lungs; rarely in bone, brain and bone marrow
Laboratory Diagnosis
Serum a-fetoprotein levels elevated in 70% of children with hepatoblastoma, in 40%
with hepatocellular carcinoma; serum human β-chorionic gonadotropin (β-HCG) levels can be high in both; both parameters are markers of diagnosis, therapeutic response and follow-up
Level of bilirubin increased in about 15% of children with hepatoblastoma and in about 25% of children with hepatocellular carcinoma
Often anemia, occasionally thrombocytopenia or more commonly thrombocytosis are observed
Radiological Diagnosis
Ultrasound and X-ray of abdomen: Enlarged liver with displacement of stomach and colon, elevated diaphragm on the right side; occasionally calcification within the tumor mass is observed
CT scan and MRI useful for determination of extension and involvement of adher- ent organs
Liver scintigraphy: Useful to obtain additional information about localization of tumor, postoperative regeneration of liver or relapse
Differential Diagnosis of Hepatoblastoma and Hepatocellular Carci- noma
Hemangioendothelioma
Adenoma
Cavernous hemangioma
Malignant mesenchymoma of the liver
Mesenchymal hematoma of the liver
Liver metastases of other tumors
Staging
Stages I–IV similar to other solid tumors
Therapy
Surgical Management
Initially more than 50% of liver tumors are not totally resectable
Presurgical chemotherapy often leads to making large tumors resectable, particu- larly for hepatoblastoma
Complete resection is required for cure with lobectomy often necessary Liver Transplantation
In patients with incomplete surgical resection of tumor or with unsatisfactory re- sponse to chemotherapy (see below) liver transplantation may be indicated
Five-year survival rate is more than 60% by partial liver-lobe donation or liver do- nation postmortem
Radiotherapy
Only rarely useful or curative
190 Chapter 17 - Hepatic Tumors
Chemotherapy
Initial tumor reduction before surgery
Active drugs: Vincristine, doxorubicin, 5-fluorouracil, actinomycin D, cisplatin Prognosis
After complete tumor resection and chemotherapy survival 65–75% in children with hepatoblastoma and 40–60% in children with hepatocellular carcinoma
Some patients may be cured with only complete resection
Prognosis dependent on:
– Stage of tumor: two-thirds of children with hepatoblastoma initially have high risk of stages III or IV (the key is surgical resectability)
Rare subgroup with exclusive fetal form of hepatoblastoma and primary total re- section is prognostically favorable without chemotherapy
