The existing literature on this very rare subset of primary n-NB liver tumors is scarce. A SEER cohort which included patients < 20 years of age over two-and-a-half decades reported 271 cases with primary hepatic malignancies, predominated by hepatoblastoma (67%) [2]. Primary n-HB liver tumors constituted 32.5% of the total cases, wherein HCC comprized 31% of the total cases. This publication is of an earlier cohort from 1973 to 1997 though, when rhabdoid tumor was not recognized as a specific entity and hence not reported. A recent analysis from a major liver transplant centre in India reported on 47 primary n-HB liver tumors in children over a 10-year period, with a preponderance of HCC (47%) [5]. There were no sarcomas or rhabdoid tumors reported in that cohort, probably due to a referral bias, the centre being a referral site for complex hepatic resections and liver transplantation. Our study documented nearly three-fourths of the primary liver tumors to be non-HCC, which is more than that reported in other studies. This disparity could be partly attributed to the fact that subjects were included from a recent time frame in a pediatric oncology unit, managing all types of malignancies including the newly recognized specific entities.

Most children with malignant liver tumors presented with abdominal pain and distension in our cohort, which are the common symptoms across liver malignancies, except in hepatoblastoma, where pain is typically absent unless the tumor is complicated by intra-tumoral bleeding or rupture [6, 7]. Jaundice was noted in fewer than 20% of the above cohort and data on its exact incidence in n-HB pediatric liver malignancies is limited. However, this is more observed in HCC unlike hepatoblastoma, where the liver function is usually normal [6, 7]. Serum AFP levels may be elevated in several non-hepatoblastoma liver tumors as observed in our cohort, too. Hence, a biopsy is warranted when radiologic findings or patient age are not consistent with hepatoblastoma.

Hepatocellular carcinoma predominated the primary n-HB hepatic tumors, which is concordant with previous reports. AFP was elevated in a majority of our patients with HCC (87.5%, n = 14/16), consistent with literature from both west and east, but slightly higher than a study from India [5]. The median AFP levels though were higher in our cohort (131,249 ng/mL) relative to what is observed in previous studies (2322–9677 ng/mL), except one which observed a higher mean AFP level of 446,927 ng/mL [6]. This elevated level in our subjects is despite a lower proportion of underlying cirrhosis (19%) in our study compared to more than 50% in the published cohorts, including a study from India with increased prevalence of tyrosinemia, which is known to be associated with elevated AFP levels [8]. This is relevant in cases when pathology cannot distinguish between hepatoblastoma and HCC because AFP levels may not provide a useful differentiation. The survival outcomes of the treated patients with HCC are comparable to the published literature, though there were more resections than transplants in our cohort, reflective of the non-cirrhotic origin of HCC [9].

A literature review of PubMed publications spanning four decades identified 34 patients with liver rhabdoid tumors, 62% of them with metastases and reported worse survival for liver site (12% survival, n = 4/34) [10]. This is commensurate with reported outcomes from the UK, revealing one-year survival of 14% for children with liver rhabdoid tumors [11]. Our study included 10 rhabdoid tumors of the liver, metastatic in 60% with three alive out of the treated cohort of four patients. This difference in the outcomes among the cohorts could probably be due to the selected treatment in non-metastatic subjects only in our centre. The incidence and survival of UESL in our study is similar to the published literature on a combined modality treatment protocol [12].

The study is limited in being a retrospective audit with survival data restricted by the small sample size in each sub-type of tumors. Nevertheless, this is a very rare subset treated at a single tertiary centre with data on demographic, clinical profile and outcomes. A referral bias for malignant tumors with slight underrepresentation of benign etiology is a possibility, with our centre mainly providing oncology services. This study is also limited by the unavailability of molecular and germline data in certain histological sub-types, such as rhabdoid tumors. A prospective national registry would further enhance our understanding of this ultra rare subset of liver tumors. Multicentre collaborative studies incorporating molecular and germline data could inform future therapies and strategies, especially defining the role of targeted agents in the context of pediatric liver cancers.

To conclude, the demographic profile of non-HB primary hepatic tumors in children mirrors that of the western world; however, our cohort exhibited a higher proportion of malignant tumors, particularly rhabdoid tumors and elevated median AFP levels in HCC. The overall outcomes of treated malignant tumors were relatively favorable, though limited by the sample size in this rare cohort.