Hepatoblastoma: A Case Report
Hepatoblastoma is a primary, malignant tumour of the liver, most commonly seen in early childhood (usually less than 3 years of age). It is the most common hepatic malignancy in childhood but overall a rare tumour with a low incidence rate. Here we report a case of a 5-year-old child who presented with abdominal pain and distension. Histopathologic features of hepatoblastoma are discussed in detail.
Hepatoblastoma originates from primitive (immature) hepatic parenchymal cells. It is most commonly seen in early childhood (less than 3 years of age). It is usually unifocal and affects the right lobe more often than the left lobe. It can also metastasize rapidly. Hepatoblastomas are categorised into 2 types: 1) Epithelial type 2) Mixed epithelial/mesenchymal type. There is a slight predilection for boys.
The child usually presents with progressive abdominal distension with anorexia, failure to thrive, fever and jaundice. The concentration of serum alpha fetoprotein (AFP) is elevated serving both as a diagnostic and prognostic marker. The tumour grows rapidly and if untreated, causes death by haemorrhage, hepatic failure, and widespread metastasis.
Here we present a case of a 5-year-old child who presented with an acute abdomen with a chief complaint of abdominal pain and distension. This case was initially radiologically diagnosed as a liver abscess, however, the histopathological diagnosis showed that it was indeed a hepatoblastoma.
A 5-year-old female child was brought to the emergency room with a history of abdominal pain in the peri-umbilical region for one day. Abdominal ultrasound revealed a heterogeneous mass in segment V/VIII of liver measuring 3.3 x 2.2 x 2.2 centimetres (cm) and was seen to project from the surface of liver. Areas of calcification were noted in the inferior component of lesion. Lesion showed vascularity on colour doppler study. Contrast enhanced computed tomography (CECT) showed a heterogeneous enhancing mass in segment VI of liver with rupture and active extravasation of contrast. Massive hemoperitoneum was noted.
Emergent laparotomy with resection of mass was done under general anaesthesia. Approximately, 100 to 150 cc of blood clot was removed. Preoperative serum AFP could not be done as the case had presented as a surgical emergency with massive intraperitoneal haemorrhage.
Gross examination showed that the specimen was a part of the liver measuring 4.5 x 3 x 2 cm. The cut-section showed a circumscribed, capsulated, tumoural mass measuring 1.5 x 1.5 cm in size which was touching one margin of resection (Figure 1). The growth had a brownish-white fleshy appearance with areas of haemorrhage.
Microscopically, sections revealed a well-encapsulated tumoural mass in the liver (Figures 2 and 3) composed of two types of cells:
(i) small tumoural cells having round to oval nuclei, prominent nucleoli and scant cytoplasm arranged in cords and ribbons resembling embryonal liver.
(ii) cells with moderate eosinophilic cytoplasm arranged in plates and cords resembling foetal liver.
Massive areas of haemorrhages were seen. The surrounding liver showed increased mononuclear infiltrate in the portal tract. Other tissue specimens were also separately sent which were brownish-black which revealed tumoural haemorrhages. A final histopathological diagnosis of hepatoblastoma of epithelial type (mixed foetal and embryonal) was made.
Post-operatively serial serum AFP levels were done which showed AFP levels decreasing gradually and ultimately were within normal limits. The patient also received five cycles of chemotherapy with cisplatin and adriamycin and is being followed up with serial serum alpha fetoprotein levels.
The liver is the third most common site for intra-abdominal malignancy in children, following adrenal neuroblastoma and Wilm stumour. There are three forms of primary liver cell tumours occurring in children:
- Hepatoblastoma which is the predominant form.
- Hepatocellular carcinoma (HCC) which is usually found in the teenage population with underlying predisposing factors such as tyrosinemia.
- Hepatocellular neoplasm not otherwise specified which appears in late childhood and early adolescence. This entity was previously known as transitional liver cell tumour (TLCT) because it exhibited a mixture of histological patterns overlapping hepatoblastoma and hepatocellular carcinoma.
Hepatoblastoma is a rare malignancy occurring primarily in young children <3 years of age with a very low worldwide incidence (<2 cases per million children under 18 years of age). Approximately, only a hundred cases are diagnosed in the United States every year. Due to the extreme rarity of hepatoblastoma, conclusive risk factors have not been identified but associations with several genetic syndromes or parental environmental exposures have been described.
Some of the well-known risk factors are Beckwith-Wiedemann syndrome, Wilmstumour of kidney, glycogen storage disease, familial colonic polyposis, parental exposure to metals, tobacco smoking of both parents and very low birth weight babies (VLBW).[6-8] Hepatoblastoma has also been reported in single instances with foetal alcohol syndrome, oral contraceptive use during pregnancy, and maternal liver transplantation with immunosuppressive therapy. Other maternal factors found to correlate are preeclampsia, polyhydramnios, oligohydramnios, high maternal pre-pregnancy weight and women receiving treatment for infertility.
Types of Hepatoblastoma
Grossly, hepatoblastoma is a solid, well-circumscribed, and solitary more often than multiple, tumour. Microscopically, most of the tumour is exclusively composed of immature hepatocytic elements and are referred to as pure or epithelial. Some of these known as foetal, consist of hepatocytes arranged in irregular laminae around two-cell thick recapitulating the foetal liver. Others are termed as embryonal, which are more immature in appearance with a predominant solid growth pattern and may also exhibit ribbons, rosettes and papillary formations. Some tumors termed as anaplastic are largely composed of anaplastic small cells, others show a tubular component with cholangiolar features (cholangioblastic hepatoblastoma). Foci of extra medullary haematopoiesis and multinucleated giant cells may be seen. A macrotrabecular type resembling liver cell carcinoma has been described. However, around 25% of hepatoblastomas are of the mixed type, containing in addition a stromal component that may be undifferentiated or develop into bone or cartilage, resembling Wilms tumour.
Immunohistochemically, reactivity has been found for keratin, EMA (epithelial membrane antigen),vimentin,polyclonal CEA (carcinoembryonic antigen), HepPar-1, AFP (α–fetoprotein), α 1-antitrypsin, CD 99, CD 56, human chorionic gonatropin (hCG), transferrin receptor and delta like protein.
The International Childhood Liver Tumour Strategy Group (SIOPEL) has defined a prognostic stratification system of hepatoblastoma patients considering PRETEXT stage, metastatic disease, serum α-fetoprotein levels, multifocality, age and histology characterized by small undifferentiated cells. Based on gene expression profiling, two prognostic subtypes of hepatoblastoma called C1 and C2, which have different pathological, clinical and molecular characteristics have been identified.
As far as molecular abnormalities are considered, the frequency of mutations in hepatoblastoma is very low (1-2%) compared to adult HCC (35-75%) of which CTNNB1, encoding β-catenin, is the most frequent one.[14,15]
Though several advances have been made in ascertaining the molecular profile and prognostic stratification of hepatoblastoma, its etiopathogenes is still remains obscure and complex. It is essential for different investigation groups to join hands to provide additional insight into the pathogenesis of this rare tumour.
- http://hepatoblastoma.mditv. com/generalinfo
- Weinberg AG, Finegold MJ. Primary hepatic tumors of childhood. HumPatho 1983; 14:512-537.
- Willert JR. Pediatric hepatoblastoma. 2017: EMedicine by MedScape.
- Pediatric Liver Tumors Update. Medscape. Sept 2016.
- Macias RIR, Armengol C, Marin JJG. Hepatoblastoma etiopathogenesis. J Carcinog Mutagen. 2016; 7:(1).
- Ito E, Sato Y, et al. Type 1a glycogen storage disease with hepatoblastoma in siblings. Cancer. 1987; 59:1776-1780.
- Pateva IB, Egler RA, Stearns DS. Hepatoblastoma in an 11-year-old:Case report and a review of the literature. Medicine. January 2017; 96(2):e5858.
- Rosai J. Liver tumors and tumor like conditions. Rosai and Ackerman’s Surgical Pathology. 10th edition. 2011. Elsevier Mosby: 953-955
- Khan A, Bader JL, Hoy GR, et al. Hepatoblastoma in a child with fetal alcohol syndrome. Lancet. 1979; 1:1403-4.
- OttenJ, SmetsR, DeJager R, et al. Hepatoblastoma in an infant after oral contraceptive use during pregnancy. N Engl J Med. 1977; 297: 222.
- Roll C, Luboldt HJ, Winter A, et al. Hepatoblastoma in a 2-year-old child of a liver transplanted mother. Lancet. 1997; 349:103.
- Maibach R, Roebuck D, Brugieres L, Capra M, Brock P, et al. Prognostic stratification for children with hepatoblastoma: the SIOPEL experience. Eur J Cancer. 2012; 48: 1543-1549.
- Cairo S, Armengol C, De Reyniès A, Wei Y, Thomas E, et al. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell. 2008; 14:471-484.
- Buendia MA. Unravelling the genetics of hepatoblastoma: few mutations, what else? J Hepatol. 2014; 61(6):1202-4.
- Armengol C, Cairo S, Fabre M, Buendia MA. Wnt signaling and hepatocarcinogenesis: the hepatoblastoma model. Int J Biochem Cell Biol. 2011; 43(2):265-70.