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Prenatal Diagnosis of Congenital Hepatoblastoma

Wang, Jia-Yan1,2,3; Zheng, Qi-Zhen1,2,3; Cao, Ding-Ya1,2,3; Xie, Yi-Nong1,2,3; Song, Ting4; Jiang, Qing-Ping5; Chen, Min1,2,3,∗

Editor(s): Li, Yan-Li; Pan, Yang

Author Information
doi: 10.1097/FM9.0000000000000022
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To editor:

Although rare, hepatoblastoma is the most common hepatic malignancy in newborns.1 Its etiology is unclear. The definitive diagnosis relied on the histopathology examination. Growing evidence suggests hepatoblastoma may arise from fetal life.1,2 Prenatal diagnosis may help parents to discuss with the neonatologist and pediatric surgeons to plan for the postnatal management. To date, only a few cases have been detected in utero.3–5 Here, we summarised the ultrasound, magnetic resonance imaging (MRI), and pathological features of a fetus with hepatoblastoma detected at 33 weeks of gestation.

Case presentation

A 28-year-old, gravida-4-para-1 woman was referred to our hospital at 33 weeks of gestation due to fetal abnormalities. She had received regular prenatal examinations from 6 weeks of pregnancy. The nuchal translucency scan in the first trimester and the anomaly scan in the 2nd trimester was unremarkable. She had acerebral-micro angioma operated 3 years ago without complication. The ultrasound examination showed a hyperechoic mass of 7.3 cm × 5.3 cm × 8.1 cm located in the left hepatic lobe. It was solid and well-demarcated. Color doppler showed extensive vascularity, and the peak systolic flow velocity inside the tumor was 66 cm/s. Below the solid tumor was a hypoechoic cystic lesion of 6.5 cm × 5.1 cm × 7.7 cm and was divided by collagenous septa. No blood flow was detected by color Doppler (Fig. 1). Bilateral hydrocele and polyhydramnios were also identified. No evidence of fetal hydrops was observed.

Figure 1
Figure 1:
Transverse section of the fetal abdomen at 33 weeks’ gestation. A large hyperechoic mass was located in the left upper abdominal cavity. It was well-demarcated and heterogeneous. It was highly vascularized with color Doppler. Below the solid mass, there was a hypoechoic cystic lesion, which was divided by collagenous septa. Color Doppler reveals no blood flow to the region, suggesting an area of bleeding.

Fetal MRI revealed a large irregular mass in the left superior abdomen. The mass measured 9.8 cm × 9.7 cm × 6.6 cm in size and displaced the remaining liver tissue, left kidney, and intestines. The gallbladder, right kidney, and bladder were normal (Fig. 2). Primary impression by MRI was hepatic hemangioendothelioma. There was no evidence of metastasis on the MRI.

Figure 2
Figure 2:
T2-weighted sagittal MRI image of the huge solid intra-abdominal mass. Polyhydramnios and hydrocele were present as a consequence of mass effect. MRI: Magnetic resonance imaging.

The parents opted for termination of the pregnancy. With the approval of the hospital ethics committee, Feticide was performed by intracardiac injection of potassium chloride (2 mL). Induction of labor by vaginal misoprostol was performed. A male baby, 3335 g, was delivered vaginally. A postmortem needle biopsy of the mass was performed. Microscopic examination showed the mass was composed of spindle cells. The nuclei displayed mild to moderate atypia with mitotic figures. A few glands were scattered and the cartilage was locally visible. Normal hepatic foci of extramedullary hematopoiesis were seen (Fig. 3). Based on the immunohistochemical expression of alpha-fetoprotein (AFP), and low molecular weight cytokeratin, a diagnosis of hepatoblastoma of mixed type was made.

Figure 3
Figure 3:
Hepatoblastoma of mixed epithelial-mesenchymal type (hematoxylin-eosin staining). A Mesenchymal component with spindle cells. B Mesenchymal component with cartilage. C Epithelial component with scattered glands. D Hepatocytes with hematopoietic foci.


While hepatoblastoma is the most common liver malignancy in children, the incidence was only about one per million.6 It usually presents as single solid and well-circumstanced echogenic lesion detected by ultrasound examination during the early third trimester. Its etiology remains unknown. Previously reported associations included cytogenetic abnormalities, such as gain of chromosome 2, 8, 18, or 20. Others were associated with familial adenomatous polyposis, Beckwith-Wiedemann syndrome and hemihypertrophy.2,6 Obstetrical complications include small for gestational age and premature birth. The mass effect may cause polyhydramnios, hydrops, or compression of the lungs, resulting in respiratory distress. Metastases to the brain, bone, and placenta were reported.1

There are no fetal interventions for hepatoblastoma. Serial ultrasound monitoring for tumor growth, early signs of hydrops, and amniotic fluid volume is critical as polyhydramnios can develop secondary to gastrointestinal compression. Delivery should be planned at a tertiary referral center with neonatology, pediatric surgery, and pediatric oncology.

A definitive diagnosis of hepatoblastoma was commonly reached by histopathologic analysis. There are two main types of hepatoblastoma based on histology: the epithelial type (subclassified as pure fetal type, fetal and embryonal type, pure embryonal, and small cell types) and the mixed epithelial-mesenchymal subtype. This categorization has been shown to have prognostic and therapeutic implication.

Although congenital hepatoblastoma was reported to be associated with poor outcomes, recent studies show the survival rate had been improved by the use of combined surgical dissection and chemotherapy.7–10

Current postnatal treatment is guided by the degree of local tumor burden as determined by the pre-treatment and post-treatment extent of disease system. While conventional surgical resection remains the standard of management, advances in chemotherapy and orthotopic liver transplant offer additional therapies in unresectable cases. Using an evidence-based risk stratification treatment algorithm, current 5-year event-free survival rates for patients with lower risk hepatoblastoma approach 80% but maybe worse (30%–40%) for relapsed or higher risk hepatoblastoma.2,7–10

A correct diagnosis of the size and classification of a hepatoblastoma is essential to guide treatment during the perinatal period. The exclusion of additional liver lesions and metastatic conditions is mandatory.

Differential diagnoses of congenital hepatoblastoma include infantile hepatic hemangioma/hemangioendothelioma, mesenchymal hamartoma, and hepatocellular carcinoma (HCC). Less commonly, metastatic neuroblastoma or embryonal rhabdomyosarcoma, and leukemia or infiltrative lymphoma were seen.1,11,12 Antenatally, the initial suspicion of congenital hepatoblastoma is often entertained by two-dimensional sonographic imaging if the tumor has the characteristic features of being single solid, well-demarcated and located in the right hepatic lobe. Nevertheless, these findings were not specific enough to exclude the diagnosis of HCC or other metastatic lesions. A tumoral peak systolic flow velocity of 40 cm/s or greater was previously reported to be associated with malignant hepatic tumor rather than a hemangioma in patients of all ages.13 In addition, the tumor vascularization assessed by three-dimensional power Doppler is helpful in distinguishing hepatoblastoma from HCC and metastatic hepatic tumors.4 Mesenchymal hamartoma typically appears as a multilocular cystic structure with a variable soft tissue component.1

Other imaging techniques such as computerized tomography, or MRI are well-described screening tools for hepatoblastoma, prenatally, or postnatally. However, the sensitivity and specificity of these tests is limited and the result remains inconclusive.10 An erroneous diagnosis of hemangioendothelioma by ultrasound and computerized tomography scan contributed to the treatment of a neonate with prednisone and postponed diagnosis of hepatoblastoma.14 In our case, the vascularity of the lesion on the antenatal ultrasound, the presence of polyhydramnios and absence of cardiac failure, the peak systolic flow velocity of 66 cm/s all supported the diagnosis of hepatoblastoma. However, this was hampered by the preceding MRI, which suggested a diagnosis of hemangioendothelioma. We assumed that the polyhydramnios weakened the quality of MRI in evaluating the nature of the tumor. It remains a dilemma to diagnose hepatoblastoma accurately without histopathologic analysis.

Fine needle aspiration under ultrasound-guidance is useful in preoperative diagnosis and categorization in most cases of hepatoblastomas in pediatric units. In country where late termination of pregnancy is still legally and ethically possible, the pregnancies may be terminated at a very late stage because of late-appearing sonographic findings suspected of hepatoblastoma. In the prenatal setting, needle aspiration biopsy can be used to verify fetal hepatoblastoma or not though the supporting data is limited.

Although perinatal autopsy is necessary for confirmation, the conventional autopsy could be declined because of parental refusal.15 In these cases, fine needle aspiration biopsy could serve as a good alternative. The previous study indicated that final pathological diagnoses after fetal death was available in 68% (17/25) of cases. Tissue collection by needle biopsy varied from 92% for the liver to 20% for the spleen.16

Our case demonstrated needle aspiration biopsy could also be used as an autopsy technique.


The gray-scale and Doppler ultrasound remain the first-tier diagnostic technique for prenatal diagnosis of hepatoblastoma. MRI offers the ability to evaluate the boundary of a neoplasm and assessing local or distant metastasis. The ability of MRI to assess the hepatoblastoma may be interfered by the presence of polyhydramnios. Fine needle aspiration biopsy is of potential value when the conventional autopsy is not available.



Conflicts of Interest



[1]. Lim IIP, Bondoc AJ, Geller JI, et al. Hepatoblastoma – the evolution of biology, surgery, and transplantation. Children (Basel) 2018;6(1):1. doi: 10.3390/children6010001.
[2]. Towbin AJ, Meyers RL, Woodley H, et al. 2017 PRETEXT: radiologic staging system for primary hepatic malignancies of childhood revised for the Paediatric Hepatic International Tumour Trial (PHITT). Pediatr Radiol 2018;48(4):536–554. doi: 10.1007/s00247-018-4078-z.
[3]. Ergin H, Yildirim B, Dagdeviren E, et al. A prenatally detected case of congenital hepatoblastoma. Pathol Oncol Res 2008;14(1):97–100. doi: 10.1007/s12253-008-9001-8.
[4]. Shih JC, Tsao PN, Huang SF, et al. Antenatal diagnosis of congenital hepatoblastoma in utero. Ultrasound Obstet Gynecol 2000;16(1):94–97. doi: 10.1046/j.1469-0705.2000.00168.x.
[5]. Ammann RA, Plaschkes J, Leibundgut K. Congenital hepatoblastoma: a distinct entity? Med Pediatr Oncol 1999;32(6):466–468. doi: 10.1002/(sici)1096-911x(199906)32:6<466::aid-mpo20>;2-1.
[6]. Puchmajerová A, Křepelová A, Indráková J, et al. [Hepatoblastoma, Etiology, Case Reports]. Klin Onkol 2016;29(Suppl 1):S78–S82. doi: 10.14735/amko2016S78.
[7]. Miura Y, Saito J, Shimanuki Y, et al. Diagnosis and treatment of a preterm infant with inoperable congenital hepatoblastoma – a case report. J Pediatr Hematol Oncol 2015;37(3):e188–e190. doi: 10.1097/MPH.0000000000000200.
[8]. Huang LC, Ho M, Chang WC, et al. Prenatal diagnosis of fetal hepatoblastoma with a good neonatal outcome: case report and narrative literature review. Pediatr Hematol Oncol 2011;28(2):150–154. doi: 10.3109/08880018.2010.536299.
[9]. Catanzarite V, Hilfiker M, Daneshmand S, et al. Prenatal diagnosis of fetal hepatoblastoma: case report and review of the literature. J Ultrasound Med 2008;27(7):1095–1098. doi: 10.7863/jum.2008.27.7.1095.
[10]. Trobaugh-Lotrario AD, Chaiyachati BH, Meyers RL, et al. Outcomes for patients with congenital hepatoblastoma. Pediatr Blood Cancer 2013;60(11):1817–1825. doi: 10.1002/pbc.24655.
[11]. Miller JH, Greenspan BS. Integrated imaging of hepatic tumors in childhood. Part II: Benign lesions (congenital, reparative, and inflammatory). Radiology 1985;154(1):91–100. doi: 10.1148/radiology.154.1.3880615.
[12]. Miller JH, Greenspan BS. Integrated imaging of hepatic tumors in childhood. Part I: malignant lesions (primary and metastatic). Radiology 1985;154(1):83–90. doi: 10.1148/radiology.154.1.2981115.
[13]. Numata K, Tanaka K, Mitsui K, et al. Flow characteristics of hepatic tumors at color Doppler sonography: correlation with arteriographic findings. AJR Am J Roentgenol 1993;160(3):515–521. doi: 10.2214/ajr.160.3.8381573.
[14]. Ingram JD, Yerushalmi B, Connell J, et al. Hepatoblastoma in a neonate: a hypervascular presentation mimicking hemangioendothelioma. Pediatr Radiol 2000;30(11):794–797. doi: 10.1007/s002470000320.
[15]. Sebire NJ, Weber MA, Thayyil S, et al. Minimally invasive perinatal autopsies using magnetic resonance imaging and endoscopic postmortem examination (“keyhole autopsy”): feasibility and initial experience. J Matern Fetal Neonatal Med 2012;25(5):513–518. doi: 10.3109/14767058.2011.601368.
[16]. Garg S, Punia RP, Basu S, et al. Comparison of needle autopsy with conventional autopsy in neonates. Fetal Pediatr Pathol 2009;28(3):139–150. doi: 10.1080/15513810902772482.

Hepatoblastoma; Prenatal diagnosis; Ultrasound; Magnetic resonance imaging

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