Approximately 1% of all childhood malignancies are primary malignant tumors of the liver. With an annual incidence of 0.9 per 1 million children, hepatoblastoma is the most prevalent of them. 1 Though still regarded as a rare disease, hepatoblastoma's global incidence increased more than any other pediatric cancer due to an increase in low birth weights, early discovery, and improved imaging modalities. 2, 3, 4

If upfront resection is not an option, the current approach for diagnosing hepatoblastoma is a liver biopsy. 5 The purpose of the biopsy is tissue diagnosis in order to differentiate malignant (embryonal sarcoma and pediatric hepatocellular carcinoma) or benign (mesenchymal hamartoma, adenomas, and localized nodular hyperplasia) liver tumors from hepatoblastomas. This is due to the fact that the traditional PLADO (Sorafenib and cisplatin/doxorubicin) chemotherapy protocol has been shown to effectively treat hepatoblastomas. 

In this study, the clinicoradiological and histopathological characteristics of hepatoblastoma diagnosed in a tertiary care center were examined. Additionally, the survival rate was estimated in relation

The Institutional Research and Ethics Committee gave its approval for this research. Since no patients were directly involved in this retrospective analytical investigation, no consent was obtained. Included were 41 cases of hepatoblastoma (HB) that were diagnosed in the Department of Oncopathology throughout a five-year period, beginning in January 2018 and ending in December 2022. Alpha-fetoprotein (AFP) serum levels and pertinent clinical information were recorded at the time of the initial diagnosis. The size and location of the tumor, focality, and existence of metastases were among the radiological findings. The radiologic results were reported or used to establish the PRETEXT (pretreatment extent of disease) staging as specified in the 2019 WHO classification.

This investigation contained biopsies as well as slides for review. After being embedded in paraffin, fixed in 10% formalin, and sectioned into 4 micron-thick pieces, they were stained with hematoxylin and eosin. Two pathologists independently inspected the slides again after that. The subtyping of hepatoblastoma was done taking into account the 2019 WHO tumor classification system.

A total of 41 biopsies, including slides for review, received during a 5-year period from 2018 to 2022 were examined. The age range in this study was 5 months to 12 years (mean 2.6 years). The male-female ratio was 1.6:1 (25 and 16). The most common clinical presentation was abdominal mass (38.2%), followed by fever (31%) and abdominal pain (14.6%). None of the patients showed any association with genetic syndromes like familial adenomatous polyposis or Beckwith-Weidmann syndrome.

The AFP levels were >65000 ng/ml (the upper limit of AFP in our biochemistry lab is 65000 ng/ml) in 38/41 (92%). Three out of forty-one cases had low AFP levels at diagnosis. Liver function tests and beta HCG levels were within normal limits in all the cases. None of the cases were positive for HBsAg or HCV.

On radiology, the masses ranged from 5 to 14 cm in size, with 10/41 (24%) cases having multifocal lesions and 4 cases having lung metastases at presentation. None of the cases showed radiologic evidence of macrovascular invasion. Details about the PRETEXT stage were available to all patients. Ten patients (24%) belonged to PRETEXT-I, 24/41 (59%) to PRETEXT-II, 7/41 (17%) to PRETEXT-III, and none to PRETEXT-IV.

The most common epithelial subtype was fetal in 35/41 (85%). Other subtypes included embryonal, mixed epithelial, and mesenchymal types.

A recurrence was not found in any patient. Metastasis was documented in 10/41 (%) patients, with the most common site of distant metastases being the lung in 5/10 (50%) cases. Survival data was available for 31/41 patients, and 10 (42.9%) died due to disease. Overall median (range) survival was 70.7 (1.7 to 109.9) months. It was found that a higher number of patients in PRETEXT I succumbed to the disease despite being of the fetal subtype. The survival of those patients receiving Cispaltin+Doxorubicin according to the conventional PLADO protocol was improved (P≤0.05) compared to those who received Irinotecan+Vincristine+Fluorouracil in addition to the PLADO protocol.

Figure 1

The most frequent primary malignant tumor of the liver in children is hepatoblastoma. In children ages five or younger, it makes up 90% of tumors.⁶ It is an embryonal tumor that develops from hepatocellular precursors, which frequently mimic various phases of the development of the liver. Therefore, it is rare for these tumors to include only one kind of cell; instead, a mixture of epithelial, mesenchymal, undifferentiated, and other histological components are typically present. 6, 7, 1

According to previous studies, 70% of the participants in this study presented within the first two years of their lives, with a mean age of 2.6 years. 8, 9 A modest male preponderance of 1.7:1 10 is seen in this tumor, which is consistent with what our study found.

Due to the early advancement and adverse outcome in these cases, a link has been identified with extreme preterm and very low birth weight (< 1000 g). 10 Likewise, correlations have been demonstrated with Beckwith-Weidman syndrome 11, familial adenomatous polyposis 12, Gardner's syndrome, hemihypertrophy, and adrenal agenesis. In this study, only 4 out of 41 instances (10%) had premature births, and none of the cases had any syndromic associations.

According to a study by Buckley et al. 5, this occurrence was more common in children of mothers who were significantly overexposed to metals used in welding and soldering, as well as lubricants and protective greases both before and during pregnancy. 13 There was also more metal exposure among the fathers. The parents of patients in our study had no history of any kind of exposure.

In 90% of HB patients, serum AFP, a highly sensitive test, is increased. In our analysis, 92% of patients had a high AFP at the time of presentation. Reduced AFP levels in 8% of instances were not linked to the small cell undifferentiated subtype that has been seen in other research. 12

Compared to PRETEXT III and IV phases, patients in PRETEXT I and II had better overall survival (OS), and as reported in other studies, more patients in PRETEXT III and IV died from the disease than in PRETEXT I and II (P≤0.001). 14, 15 However, a contradicting fact that came out in our study was that greater proportion of patients with PRETEXT I died of the tumor.

When comparing histological subtypes with adverse effects, it has been noted that the fetal subtype had a decreased frequency of metastasis, mortality, recurrence, and MVI. 16, 17 Nevertheless, there was no discernible correlation between survival and histological subtype in our investigation. These results were in line with those of Gupta et al. 18 and Conran et al. 19

Five instances (12%) had distant metastases, with the lung being the most often observed location. 20 Who, in contrast to those without, had a shorter overall survival (3.2 months). 21, 22 Ten of the 41 cases (or 24%) had a disease-related death. This is comparable to findings from studies conducted in North India 18 and Germany 23, which showed just 21% and 23% of deaths, respectively.

Our patients' overall median survival was 70.7 months, and their 5-year OS was 60%, which is comparable to the 6-year OS of 63% and 58.7% reported in other studies. 24, 25 For PRETEXT I, II, III, and IV, they reported 5-year OS values of 100%, 87.1%, 89.7%, and 78.3%, respectively. In this study, the 5-year OS for metastatic disease was 49%.

Survival is not correlated with the histological subtyping on the biopsy. In order to identify the hepatoblastoma subtype, radiological characteristics must also be considered, as evidenced by the decreased survival of patients in PRETEXT stage I while having a fetal pattern on histology.