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Hepatoblastoma: A Case Report

 

Article By

D.M. Shirodkar

R.G.W. Pinto

 

Abstract

This article presents a case of recurrence of hepatoblastoma in a patient one-year post-resection. Clinical features and histopathological diagnosis are presented.

 

Introduction:

Hepatoblastoma is the most common malignant liver tumor of early childhood. It constitutes of 1% of paediatric malignancies. Most of these tumors are seen before 5 years of age.[1] Surgery remains the primary means of curative therapy but the role of chemotherapy in both the adjuvant and neoadjuvant settings, has become increasingly important over the past three decades.

 

Case Report:

This is a case report of a 5-year-old girl who presented with recurrence of hepatoblastoma. She had been diagnosed a year ago and had undergone a prior resection of the tumor. She had presented with an abdominal mass and weight loss. At the time of examination, she was anemic and had hepatomegaly. She was born prematurely but her developmental milestones were normal. Radiological examination revealed a large solid tumor in the right lobe of the liver. Serum alpha fetoprotein level (AFP) was raised. Histopathological examination confirmed hepatoblastoma of fetal type. Now, the patient presented with recurrence of disease after one year. Current presentation showed a nodule in the lower lobe of the liver seen on contrast enhanced computed tomography (CECT). Lab investigations revealed hemoglobin of 8.8 g/dL (grams per decilitre) and raised alpha fetoprotein levels. Liver function tests (LFTs) were normal and there was no evidence of Hepatitis B or C infection.

A laparotomy with resection of tumor with hepatectomy was performed. A biopsy was taken from the nodule and sent for histopathological examination. Microscopic examination revealed hepatoblastoma –fetal type.

Tumor cells in trabeculae are 2-3 cells thick (resembling fetal liver), tumor cells are same size or smaller than in non-neoplastic liver, distinct cell membranes, uniform, polyhedral, slightly higher nuclear cytoplasmic ratio, inconspicuous nucleoli and may contain bile (Figure 1 and 2). They show minimal pleomorphism, no/rare mitotic figures, and have dark and light foci related to the amount of glycogen and fat. 

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Treatment was initiated and the patient received chemotherapy. However, due to distant metastasis eventually the patient expired.

 

Discussion:

The most common primary malignant liver neoplasm in children is hepatoblastoma. Two thirds of cases occur before 2 years of age and 90% of cases are found below 5 years with a slight male predominance.[2]

It is considered to be an embryonal tumor that is related to developmental disturbance of cell proliferation and differentiation during hepatic organogenesis. Most cases are sporadic. There is a significant correlation between gestational age and stage of disease.[3-5] In this case the child was born at gestational age of 32 weeks.

Most patients present with an enlarging abdominal mass. The right lobe is involved three times more often than the left lobe involvement seen in 20%-30%, and multicentric involvement in 15%.[6,7] The theory behind the involvement of the right lobe is that left lobe derives oxygenated blood totally from the umbilical vein.  The right lobe derives blood from portal vein with lower oxygen concentration. Anemia and platelet abnormalities have been reported.[6] Although low platelet counts can occur in hepatoblastoma, thrombocytosis is commonly reported.[8,9] Our patient had anemia and low platelet count. Less common symptoms are anorexia, weight loss, and pain.[7] Association with precocious puberty has been reported.[6]

There is no clear correlation between AFP and outcome, however, persistence or recurrence of elevated AFP is a sensitive marker of disease. There is a correlation between AFP and extent of disease for all stages,[10] and the rate of decline in AFP with treatment is prognostic.[10,11] Metastasis at diagnosis occurs in 10%-20% of patients,[6,13-15] with the lung being the predominant site of metastases both at presentation and relapse. Other sites of distant metastases, including brain and bone, are rare and usually occur in the setting of relapsed disease.[6,13,16,17]   

Hepatoblastoma usually appears as a focal or multifocal solid tumor. Stippled or chunky calcifications can be detected in 40%-50% of patients, which is significantly higher than in patients with benign lesions such as hemangiomas and hemangioendotheliomas.[18,19]

Intralesional calcification closely correlates to histologically detected osteoid matrix. While magnetic resonance imaging (MRI) is not as sensitive as computed tomography (CT) for the detection of calcification, the presence of calcification is not essential for diagnosis.

 

Pathology:

Hepatoblastoma is classified by histology as epithelial (56%) or mixed epithelial/mesenchymal (44%).[20] Epithelial hepatoblastoma is further broken down to pure fetal (31%), embryonal (19%), macro trabecular (3%), and small-cell undifferentiated (3%). The most common mesenchymal elements are osteoid and cartilage. In one study, osteoid made up a small component of 36% of untreated hepatoblastoma, but was increased in treated hepatoblastoma to 82% and composed up to 90% of the tumor area.[7] The presence of mesenchymal elements has been associated with improved prognosis in patients with advanced disease.[21] In completely resected tumors, pure fetal histology confers a better prognosis, while small-cell undifferentiated histology is associated with a poor prognosis.[21]

Multiple cytogenetic abnormalities have been noted in hepatoblastoma with the gain of chromosome 20 being the most common, followed by gain of chromosome 2 or 8.[22,23] Hepatoblastoma is also associated with familial adenomatous  polyposis, and trisomy 20 is a common finding in colon adenomas.[24] Many congenital syndromes have been described in patients with hepatoblastoma, but only Edward’s Syndrome, familial adenomatous polyposis and Beckwith-Wiedemann Syndrome have been clearly shown to increase the risk of hepatoblastoma.[5]

The differential diagnosis for hepatoblastoma is impacted by the age of the patient. In infants, hemangiomas, hemangioendotheliomas and hamartomas are common liver tumors. However, a liver tumor in an adolescent is more likely to be a hepatocellular carcinoma (HCC).[25]

Complete surgical excision of the primary tumor was felt to correlate with cure. Complete resection of the tumor remains the best hope for long-term survival; however, the advent of effective chemotherapy may permit cure in the presence of initially unresectable or metastatic disease.[26]

 

Conclusion:

Hepatoblastoma is the most common primary liver tumor in children. The primary treatment is surgical resection and the use of pre-resection chemotherapy can increase the number of tumors that are resectable. The prognosis for patients with resectable tumors is good in combination with chemotherapy. However, the outcome for those with nonresectable or recurrent disease remains poor and newer therapies are needed.

 

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