Malignant tumors of the liver in children

https://doi.org/10.1053/j.sempedsurg.2016.09.002Get rights and content

Abstract

This article aims to give an overview of pediatric liver tumors; in particular of the two most frequently occurring groups of hepatoblastomas and hepatocellular carcinomas. Focus lays on achievements gained through worldwide collaboration. We present recent advances in insight, treatment results, and future questions to be asked. Increasing international collaboration between the four major Pediatric Liver Tumor Study Groups (SIOPEL/GPOH, COG, and JPLT) may serve as a paradigm to approach rare tumors. This international effort has been catalyzed by the Children’s Hepatic tumor International Collaboration (CHIC) formation of a large collaborative database. Interrogation of this database has led to a new universal risk stratification system for hepatoblastoma using PRETEXT/POSTTEXT staging as a backbone. Pathologists in this international collaboration have established a new histopathological consensus classification for pediatric liver tumors. Concomitantly there have been advances in chemotherapy options, an increased role of liver transplantation for unresectable tumors, and a web portal system developed at www.siopel.org for international education, consultation, and collaboration. These achievements will be further tested and validated in the upcoming Paediatric Hepatic International Tumour Trial (PHITT).

Introduction

Although rare, hepatoblastoma (HB) is the most frequent of the malignant pediatric liver tumors. After neuroblastoma and nephroblastoma, HB is the third most common abdominal solid tumor in very young children. Hepatocellular carcinoma (HCC) is most often seen in older children and adolescents.1 An interesting hybrid tumor, HB with features of HCC variably called transitional or “not-otherwise-specified” (NOS), exists on the age continuum between HB and HCC. In Asia and Africa, hepatocellular carcinoma (HCC) occurs more frequently than HB, which is probably a consequence of the higher prevalence of hepatitis B infection on those continents. Interestingly, the incidence of HCC seems to have decreased in some countries as a consequence of wide spread vaccination programs against hepatitis B infection in these areas.2 In today’s age of electronic communication, the possibility of collaboration on an international scale has increasingly facilitated treatment and research of these rare tumors. For example, in addition to international cooperative research and education services, advice on treatment of difficult cases is now possible with the support of a consultation service which can be accessed under the virtual consultation service tab on the international pediatric liver tumor website (www.siopel.org). This virtual consultation service gives any interested treating clinician, some of whom may see a pediatric liver tumor only once every few years, real time access to expert opinion from an international panel of pediatric liver tumor oncologists, pathologists, radiologists, and surgeons.

Section snippets

Hepatoblastoma (HB)

The treatment of hepatoblastomas has been one of the success stories of pediatric oncology. From a disease with a dreadful outlook with survival rates around 35% in the seventies of the last century, survival has now reached over 90% for patients with standard risk tumors, and 45–80% for patients with metastatic disease.3, 4, 5, 6, 7 Progress has been made due to improved surgical technique and better risk stratified chemotherapy based on increasingly refined risk factors. In addition, sharing

Timing of surgery

Over the past two decades the surgical approaches to HB have been different between SIOPEL and the other three major study groups. The SIOPEL group used a single strategy for all patients of delayed surgery following neo-adjuvant chemotherapy in order to make the tumor smaller, less prone to bleed, more demarcated from the surrounding normal hepatic parenchyma and thus more likely to be completely resected by smaller resections.24 In contrast COG, GPOH and JPLT have offered resection at

Hepatocellular carcinoma (HCC)

The incidence of HCC in the western world seems stable or slightly increased.43, 44 In adults, HCC occurs most commonly in the setting of chronic cirrhotic liver disease. In children, however, there are several distinct clinical and biologic patterns of HCC which cluster into two broad categories. First are the sporadic or “de novo” tumors where HCC arises in a normal liver without preceeding liver disease. An ongoing debate questions whether this de novo form of pediatric HCC biologically

Hepatocellular neoplasms-not otherwise specified (HC-NOS), or HB with HCC features

Hepatoblastoma (HB) with hepatocellular carcinoma (HCC) features are a small subset of malignant liver tumors primarily of children in an intermediate age group (5–10 years) that demonstrate features of both HB and HCC, thereby carrying the “transitional tumor” nickname.58 As classically described by Prokurat, the tumor cells themselves may have HCC features.59 Alternatively there may be geographic admixture of histologic patterns with some areas resembling typical HB histology admixed with

Fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma (FL-HCC) is more common in females and is primarily a tumor of adolescents and young adults. In fact, FL-HCC accounts for about 10–25% of HCC in adolescents and young adults, but only 1% of HCC in adults overall.60, 61, 62, 63, 64 There are no known metabolic diseases which predispose to the development of FL-HCC. In adults FL-HCC is felt to have an improved outcome.63 However, in studies of children this improved survival for FL-HCC was not seen.64, 65

Undifferentiated embryonal sarcoma of the liver (UESL)

UESL is a rare malignant neoplasm of mesenchymal origin,67 recently shown to share genetic features with its benign cousin, mesenchymal harmatoma. Age at diagnosis is usually between 6–10 years but some studies report an older presentation in young teenagers.68 Patients present with abdominal pain and palpable mass, occasionally fever and anorexia with more advanced cases. Because of their internal myxoid nature, imaging may appear centrally cystic and rupture with biopsy attempts is common (

Malignant rhabdoid tumor (MRT) of the liver

Most common in the kidney, the liver is one of several possible primary sites for malignant rhabdoid tumors (MRT) in children. In the kidney it is called rhabdoid tumor of the kidney; in the brain the term is atypical teratoid rhabdoid tumor; and when in the soft tissues or liver as malignant rhabdoid tumor (MRT). MRT can be sporadic or associated with predisposing germline mutations of SMARCB1.85 INI-1 is consistently negative and there is much speculation that before routine testing for

Other malignant tumors involving the liver (nested stromal epithelial, cholangiocarcinoma, hemangioendothelioma, hepatic involvement in hematologic malignancy, liver metastatic disease)

Nested stromal epithelial tumor (NSET) of the liver is a rare neoplasm presenting as a solitary hepatic mass, occurring in childhood and adolescents. Morphologically, the tumor has nests of epithelioid and spindle cells. Some cases have been associated with ectopic ACTH secretion and rarely even may present with Cushing syndrome.88, 89 It has been reported in one child with Beckwith–Wiedemann syndrome.90 Β-catenin mutations (also common in hepatoblastoma) have been reported in two tumors.91

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