Hepatoblastoma

Clinical features

  • Most frequent primary liver tumour in children (40% of all paediatric hepatic tumours and 55% of all malignant tumours)
  • 88% occur at under 5 years of age; 68% during the first two years of life
  • Male predominance
  • More frequent in white patients
  • 60-70% in right lobe
  • Associations with: prematurity, low birth weight (< 1500 g), Beckwith- Wiedemann syndrome, trisomy 18 syndrome, familial polypoid adenomatosis and hemi hypertrophy
  • 80-90% have significant elevation of serum alpha-fetoprotein
  • lower levels of alpha-fetoprotein  may indicate a poorer prognosis
  • Paraneoplastic syndromes: thrombocytosis, human chorionic gonadotropin production (virilisation) and osteoporosis

 

Fig 76 – Hepatoblastoma – Clusters of uniform small appearing cells with high N: C ratio (H&E)
Fig 77 - Hepatoblastoma – Small hepatocytes with centrally placed unique nuclei and moderate granular cytoplasm (hepatocytes phenotype) (H&E)
Fig 78 - Hepatoblastoma –Pseudoacinar pattern (left corner- H&E). Cells arranged in a pseudoacinar pattern, with centrally placed nuclei and moderate well defined cytoplasm. High nuclear/cytoplasmic ratio (Giemsa)

 

Fig 79 – Liver neuroblastoma. Fine needle aspiration of a primitive neuroblastoma of the liver. Notice the scarce cytoplasm of these hyperchromatic cells, compared with the hepatocytes (H&E)

 

  • High cellularity
  • Small hepatocytes with high N/C ratio
  • Centrally placed nuclei
  • Nucleoli may be prominent
  • Sparse to moderate granular cytoplasm (depends on the degree of differentiation)
  • Cells occur singly or in trabeculae, acini, cords and rosettes (anaplastic subtype)
  • Nuclear moulding (anaplastic subtype)
  • Nuclear pyknosis
  • Hematopoietic elements (more frequent in the foetal subtype)
  • Mesenchymal elements: osteoid

 

Immunocytochemistry

  • Low molecular weight cytokeratin’s: positive
  • Alpha-fetoprotein: positive (75%); may be negative in anaplastic subtype
  • EMA: positive (except for the anaplastic subtype)
  • CEA: positive, with canaliculus staining pattern (except for the anaplastic subtype)
  • Chromogranin A: positive (focal) (50%)
  • HepPar1: positive
  • Vimentin: positive (75%); generally negative in anaplastic subtype
  • HCG: positive (giant cells)
  • glypican 3: positive
  • HMB45: positive (occasionally)
  • CD99: positive
  • CD56 (NCAM): positive
  • Neuroendocrine markers: positive
  • NB84: positive
  • Bcl-2 : positive
  • Desmin: positive
  • CD45: negative
  • Desmin: negative (except in teratoid tumours)

 

Genetic studies

  • No consistent pattern of chromosomal anomalies
  • P53 gene mutation

 

 

Differential diagnosis

  • Hepatocellular carcinoma
    • Differential diagnosis with the embryonic and macrotrabecular subtypes
    • Rare under three years of age
    • If present, is usually associated with previous hepatitis B infection, cirrhosis or metabolic diseases
    • In well-differentiated forms, there are great similarities between these entities, and distinguishing them is very difficult
    • Vimentin: negative
  • Metastatic Yolk sac tumour
    • May present hepatoid differentiation
    • Eosinophilic hyaline globules in intra or extracellular locations (visceral yolk sac differentiation)
    • Single cells or in spherical or papillary aggregates
  • Rhabdomyosarcoma
    • Other components of hepatoblastoma are not present
    • Muscular markers: positive
  • Small round blue cell “metastatic” tumours, e.g. neuroblastoma , Wilms’ tumour, lymphoma, Ewing’s sarcoma (Fig 79)
    • This may be a problem, especially in anaplastic subtypes
    • Small morphological details can help: rosettes, fibrillary background, tubular formation, mainly isolated cells, lymphoglandular bodies, dark and light cells, etc.
    • Immunocytochemistry may give a clue to the diagnosis

 

Main points

  • Embryonal tumour derived from pluripotent hepatic stem cells
  • High incidence of trisomy 20 and trisomy of all or part of chromosome 2
  • Main prognostic factor: complete resect ability
  • Other prognostic factors: tumour size, stage and multifocality
  • Foetal type is the only histological subtype that leads to changes in therapy regarding stage I tumours
  • Distant metastasis in 20% of the patients at diagnosis
  • Five-year survival rate is 75%
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