Hepatoblastoma in the neonatal period: An unusual presentation.

Hepatoblastoma (HBL) is a rare primary malignant liver tumor affecting mainly pediatric patients in the age group 6 months to 3 years. Presentation of HBL in the neonatal period is rare. HBL can be diagnosed on cytology along with subtyping. Estimation of serum alpha-fetoprotein (AFP) is essential as a tumor marker. Fetal type HBL usually shows high AFP level. In this report, diagnosis of HBL in a 10-day-old baby with low serum AFP is being described for its unusual presentation.

Introduction

Hepatoblastoma (HBL) is a rare primary malignant liver tumor affecting mainly pediatric patients in the age group 6 months to 3 years.[1] Presentation of HBL in the neonatal period is rare. In this report, diagnosis of HBL in a 10-day-old baby with low serum alpha-fetoprotein (AFP) is being described for its unusual presentation.

Case Report

A 10-day-old male baby was brought to the emergency room with complaints of jaundice and respiratory distress. The baby was born at term by normal vaginal delivery and birth weight was 3 kg. On clinical examination, chest was clear and an abdominal lump was palpable in the right upper quadrant with smooth surface, moving with respiration. At the upper part of the lump, the lower border of liver was palpable and appeared to be separate from the lump. Ultrasonography (USG) of abdomen suggested an adrenal mass lying closely to upper pole of the right kidney. There was unconjugated hyperbilirubinemia and prothrombin time was normal. Vanillylmandelic acid (VMA) was not elevated. Next, USG-guided fine needle aspiration cytology (FNAC) was attempted. The smear [Figure 1] was highly cellular, composed of tumor cells arranged in trabeculae and acini. The cells had abundant cytoplasm with distinct borders. The nucleus was round with fine chromatin and some of the cells showed single central nucleoli. Some foci showed the trabeculae lined by endothelial cells on one side. Tumor cells did not show the presence of bile pigments. There was evidence of extramedullary hematopoiesis featured by the presence of erythroid precursors and megakaryocytes [Figure 2]. The cytomorphology suggested HBL of fetal type. AFP level was marginally elevated for age (9790.0 ng/ ml). Peripheral blood count (PBC) showed normal values. Laparotomy was done and a tumor was found projecting from undersurface of the liver, extending to cover the upper part of right kidney. PRETEXT staging (International Society of Pediatric Oncology) showed the tumor infiltrated the liver extensively with only the left lateral sector (segments II and III) free. The stage was III A I, E0 M0 P0 V0. A biopsy was taken including a margin of normal liver. The histopathology showed the tumor mass composed of cells resembling, but slightly smaller than normal hepatocytes and arranged in trabeculae. Cells mostly had clear cytoplasm, while some showed eosinophilic cytoplasm, resulting in alternate pink and white appearance. Nuclei were small and round with extramedullary hematopoiesis. No mitotic activity was found. Normal liver tissue was seen at the periphery. The histopathology thus confirmed the diagnosis of HBL of fetal type. The baby was put on chemotherapy regime of Cisplatin and Doxorubicin. Three cycles had been given at three weekly intervals. The baby is doing well and the mass has reduced in size as seen on computed tomography (CT) scan.

Figure 1

Smear shows cells arranged in trabeculae and acinar pattern. Cells have abundant cytoplasm and fine nuclear chromatin (MGG, ×400)

Figure 2

Smear shows extramedullary hematopoiesis: megakaryocyte and normoblasts (MGG, ×400)

Discussion

HBLs are rare tumors with an approximate incidence of 1.2 per million. They usually occur in children between the age of 6 months and 3 years.[1] Less than 10% of HBL cases are diagnosed in the neonatal period.[2] Reported incidence in the first year of life is 1 per million.[3] Tumors detected antenatally or after birth up to 3 months of age are considered congenital fetal tumors. The lesions can be benign or malignant, and early detection of the tumor can significantly affect neonatal care.[4] Congenital HBLs exhibit some important distinctive features when compared to HBLs diagnosed in children beyond the neonatal period.[5] These are: a different clinical presentation, a higher incidence of pure fetal histology, a significant risk for systemic metastases and a worse outcome.[6]

Incidence of HBL is more frequent in whites than in blacks.[7] There is slight male predominance (1.4–2:1), especially in patients under 5 years of age.

Histologically, HBL has two main types – epithelial and mesenchymal – with the epithelial type having four subtypes – fetal, embryonal, small cell type and macrotrabecular. HBL can be diagnosed on cytology along with its subtyping which is important for prognostication.[8] Histological confirmation of clinical and radiological diagnosis of HBL is essential if the patient is under 3 months of age. The small cell type has an unfavorable outcome and the fetal subtype possibly has a good prognosis.[9] In our case of fetal type HBL, though the tumor was extensive, there was no spread into portal vein or any metastasis.

Serum AFP is the most useful laboratory test for HBL and hepatocellular carcinoma. AFP is produced in the fetal liver and yolk sac, and levels decline to adult values during the first 6 months after birth. AFP can be used as a tumor marker for screening and confirmation of diagnosis. But it is not specific. Serum AFP levels can also be elevated in hepatocellular carcinoma, hepatitis, cirrhosis, germ cell tumor, hemangioendothelioma, testicular tumor and gallbladder carcinoma. High values should be compared to normal ones for the age. In patients with raised AFP value at the time of presentation, serial measurements can be used to monitor chemotherapeutic efficacy and to detect disease recurrence. In small cell type HBL, serum AFP may not rise because of lack of differentiation of the cells, but in better differentiated types like fetal HBL, serum AFP is usually elevated. But though the present case was of fetal type, AFP was marginally elevated. This is an unusual finding and only one report documents low AFP in well-differentiated HBL.[10] This low AFP value was disadvantageous as it could not be used for follow-up.

AFP levels have prognostic implications. Very high or low values have worse prognosis compared to average values. Very high values may be due to tumor extension or may reflect large tumor mass, whereas small cell type HBLs may fail to secrete AFP and they show poor response to chemotherapy.

Right lobe of liver is more commonly found to be affected by HBL, as was seen in our case. This could be related to the different blood supply of the two lobes, with low oxygen tension of portal supply to the right lobe in contrast to umbilical venous supply to the left lobe having some role in the embryological differentiation of HBL.[11]

Beckwith–Wiedemann syndrome, hemihypertrophy and low birth weight are common associations of HBL, though in the present case, no such association was noted.[1] Prematurity can also be a risk factor. Thrombocytosis is commonly found in HBL. Hepatic tumor in pediatric age group, if associated with thrombocytosis and raised AFP, strongly suggests the diagnosis of HBL.[12] In the present case, platelet count was within normal limits.

Extensive involvement of the liver by the tumor makes it non-resectable, as was observed in the present case. Chemotherapy followed by surgery is the treatment of choice in such cases. Short follow-up intervals are recommended.[5] Diagnosis of congenital tumors in the antenatal period is possible with the available imaging modalities. Early detection of HBLs allows for consideration of the mode of delivery, prompt treatment, and may lead to better outcomes.[6] Caesarean section is recommended when HBL is antenatally diagnosed as vaginal delivery may cause tumor rupture. In this case, the baby was delivered vaginally, but fortunately there was no tumor rupture.

To conclude, HBL is a rare tumor, but must be considered when a right upper abdominal mass lesion is found in a neonate. FNAC can give fairly accurate diagnosis including subtyping.[13] But serum AFP level may not be elevated in HBL and histology is necessary in such cases.