Pediatric liver tumors and hepatic ontogenesis: Common and distinctive pathways

Abstract

Several types of pediatric liver tumors exhibit structural features apparently reflecting processes which normally occur during hepatic ontogenesis: some hepatoblastomas mimic distinct phases of hepatogenesis, including the formation of mesenchymal structures closely associated with immature epithelia, and there are tumors almost exclusively consisting of complex mesenchymal patterns. Current classifications of hepatoblastomas refer to the identification of more or less mature (differentiated) single or mixed components seen in histologic preparations. These do not, however, attempt to integrate ontogenic pathways, in contrast for example, to nephroblastoma and associated lesions, where such a view has proved to be highly fruitful. Based on the fact that an enormous amount of knowledge has recently been accumulated regarding hepatic ontogenesis, time may have come to look at these tumors with a new eye. In what follows, we aim at trying to analyze distinct features of pediatric hepatic tumors (except vascular tumors) within the background of ontogenesis. Some key steps of hepatogenesis and the regulatory factors involved may, in the future, deliver an armamentarium to search for novel molecular mechanisms involved in tumorigenic pathways.

HGF/c-Met related activation of β-catenin in hepatoblastoma

“…These include wholly epithelial tumours, with pure fetal and mixed fetal/embryonal histology; tumours with mixed epithelial and mesenchmyal features; and several types of transitional, small and large cell undifferentiated tumours [5]. This heterogeneous tumour spectrum appears to reflect distinct patterns of hepatic embryogenesis, indicating a developmental origin for HB, and such tumour heterogeneity may account for their variation in clinical behaviour [6]. …”

Undifferentiated (Embryonal) Sarcoma of the Liver: An Intriguing Diagnosis in a Child

“…! Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare and highly malignant hepatic neoplasm of mesenchymal origin affecting almost exclusively the pediatric population, mainly between the ages of 5-10 years, without a gender predilection [2,5,17]. The tumor is located in the right lobe of liver in the majority of the patients, and rarely involves both lobes [1,6].…”

“…The tumor is located in the right lobe of liver in the majority of the patients, and rarely involves both lobes [1,6]. It may grow exophytically and may be covered with omentum [9,10,15,17]. The main presenting symptoms are typically an abdominal mass and abdominal pain of a few weeksʼ or monthsʼ duration.…”

“…Tumor rupture and resultant acute abdomen is an unusual presentation [7,8,12,14]. There are no reliable laboratory data, but typically the serum alpha-fetoprotein (AFP) level is normal [5,7,17]. It is usually a large tumor, up to 4 kg, and composed of solid and cystic parts, the latter often containing necrotic material and hemorrhage [2,3,7].…”

“…It is usually a large tumor, up to 4 kg, and composed of solid and cystic parts, the latter often containing necrotic material and hemorrhage [2,3,7]. The tumor cells range from spindle shaped or satellite to pleomorphic multinucleated giant cells [2,5,7,[15][16][17]. The authors report on a child with UESL who became symptomatic following blunt trauma.…”