Liver & intrahepatic bile ducts
Other malignancies
Hepatoblastoma


Topic Completed: 12 April 2021

Minor changes: 12 April 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Hepatoblastoma[TI] liver[TI] pathology

See also: Epithelial typeMixed epithelial mesenchymal type

Rui Caetano Oliveira, M.D.
Maria Augusta Cipriano, M.D.
Page views in 2020: 10,414
Page views in 2021 to date: 4,008
Cite this page: Oliveira RC, Cipriano MA. Hepatoblastoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livertumorhepatoblastoma.html. Accessed April 15th, 2021.
Definition / general
  • Malignant primary hepatic blastomatous tumor that reiterates the hepatic development
  • Variable combination of epithelial and mesenchymal components
Essential features
  • Most frequent liver tumor in children
  • Tumor cells recapitulating the embryological stages of hepatic development
  • Epithelioid pattern or mixed epithelioid and mesenchymal pattern
  • Mainly staged using the PRETEXT (PRE-Treatment EXTent of tumor) system
ICD coding
  • ICD-O: 8970/3 - Hepatoblastoma
  • ICD-11: 2C12.01 - Hepatoblastoma
Epidemiology
  • Most frequent liver tumor in children
  • 1 - 1.5 cases per million
  • Majority of cases (80 - 90%) between 5 months to 6 years old
  • Remaining cases in prenatal / neonatal and older children
  • Adult tumors are very rare (Surg Oncol 2016;25:339)
  • Slight male predominance
Sites
  • Liver; some authors refer a preference to the right lobe or state that the tumor starts at the right hepatic lobe (J Hepatol 2012;56:1392)
Pathophysiology
  • Current hypothesis is that hepatoblastoma arises from primary hepatoblasts or multipotent hepatic progenitor cells
Etiology
  • Majority of cases are sporadic
  • Some cases are associated with familial adenomatous polyposis (APC mutations), Beckwith-Wiedemann syndrome and trisomy 18 (Pediatr Blood Cancer 2018;65:e26892)
  • Strong association with low birth weight, especially if < 1,000 g and parental smoking
Clinical features
  • Usually presents with abdominal enlargement, mass or pain
  • Anorexia and weight loss may be reported
  • Jaundice is an uncommon feature
Diagnosis
  • Usually by a combination of clinical, laboratory and radiology findings (Clin Liver Dis 2018;22:753)
  • Biopsy / FNA may be necessary in some cases
Laboratory
  • Serum AFP is significantly elevated in the majority of patients (about 90%)
Radiology description
  • Ultrasound
    • Solid masses that are hyperechoic relative to the adjacent liver, although hypoechoic fibrotic septa can also be seen
    • Epithelial hepatoblastomas may appear homogeneous
    • Mixed epithelial / mesenchymal tumors exhibit heterogeneous imaging (due to osteoid, cartilaginous and fibrous tissue) and frequently have echogenic calcifications with acoustic shadowing and anechoic foci representing hemorrhage / necrosis (Radiol Bras 2017;50:68)
  • Computed tomography
    • Well defined mass with regular borders that is hypoattenuating in comparison with the adjacent hepatic parenchyma
    • Common diffuse heterogeneous contrast enhancement
    • Half of all hepatoblastomas appear lobulated or septated, especially on contrast enhanced images (Radiol Bras 2017;50:68)
Radiology images

Contributed by Rui Caetano Oliveira, M.D. and Maria Augusta Cipriano, M.D.

Hepatic ultrasonography

Hepatic CT

Staging
  • PRETEXT (PRE-Treatment EXTent of tumor) staging system is the recommended by the Pediatric Hepatic International Tumor Trial (PHITT) (Cancer Imaging 2016;16:21)
  • Composed by:
    • PRETEXT group describes the extent of tumor in the liver and therefore the amount that must be surgically removed
    • Liver is divided into 4 sections: left lateral section (Couinaud segments 2 and 3), left medial section (Couinaud segments 4a and 4b), right anterior section (Couinaud segments 5 and 6) and right posterior section (Couinaud segments 6 and 7)
      • PRETEXT I: 1 section is involved and the adjoining are free
      • PRETEXT II: 1 or 2 sections are involved and 2 adjoining are free
      • PRETEXT III: 2 or 3 sections are involved and no 2 adjoining sections are free
      • PRETEXT IV: all sections are involved
    • Annotation factors that describe additional risk factors
      • Hepatic venous / inferior vena cava involvement
      • Portal venous involvement
      • Extrahepatic spread of disease
      • Multifocal tumor
      • Tumor rupture
      • Caudate lobe involvement
      • Lymph node metastases
      • Distant metastases
Prognostic factors
  • PRETEXT stages I and II are associated with good prognosis and PRETEXT stage IV is a predictor of bad prognosis
  • Multifocal disease, extrahepatic and unresectable vascular involvement, tumor rupture and metastasis at diagnosis are factors of bad prognosis (in the pretreatment evaluation)
  • After treatment, poor response to chemotherapy, disease progression under chemotherapy, positive surgical margins and tumor relapse are associated with unfavorable prognosis
  • Age < 1 year (good prognosis) versus age > 6 years (worse prognosis) (Pediatr Blood Cancer 2020;67:e28350)
  • Normal or low levels of alpha fetoprotein (AFP) are associated with aggressive course and small cell undifferentiated histological subtype
  • Serum AFP reduction during treatment is a good prognosis and indicator of response to treatment (BMC Pediatr 2019;19:485)
  • Histological evaluation has impact: pure fetal pattern with low mitotic activity is related to good prognosis and small cell undifferentiated pattern is associated with bad prognosis
  • Based on staging system, metastases and AFP levels, 5 prognostic groups have been established, with group 1 exhibiting the best prognosis and group 5 the worst (Lancet Oncol 2017;18:122)


 Group 
Criteria
PRETEXT group
Metastasis at diagnosis
Serum AFP (μg/L)
1
I / II
No
> 100
2
III
No
> 100
3
IV
No
> 100
4
Any
Yes
> 100
5
Any
Any
≤ 100
Case reports
Treatment
Gross description
  • Single or multinodular tumor
  • Well defined boundaries
  • Tumors usually exhibit a tan-brown cut surface, especially in the fetal subtype (Medicine (Baltimore) 2018;97:e9647)
  • Small cell undifferentiated subtypes have a variegated appearance
  • Necrosis and hemorrhage are present in posttreatment specimens
  • If osteoid is present, the texture is firm and gritty
Gross images

Contributed by Rui Caetano Oliveira, M.D. and Maria Augusta Cipriano, M.D.

Gross examination

Microscopic (histologic) description
  • Classified by the International Pediatric Liver Tumor Consensus Classification as epithelial or mixed epithelial and mesenchymal
  • Epithelial hepatoblastoma may exhibit several patterns (alone or in combination): fetal, embryonal, small cell undifferentiated (SCUD), cholangioblastic and macrotrabecular (J Gastrointest Oncol 2018;9:326)
  • Fetal pattern (Pediatr Dev Pathol 2020;23:79)
    • Thin trabeculae or nests of small to medium sized cells resembling hepatocytes of the developing fetal liver
    • Clear or finely granular cytoplasm with variable amount of glycogen and lipids
    • Small round nucleus with indistinct nucleolus
    • Foci of extramedullary hematopoiesis are usually present
    • Typically has low mitotic activity, referred to as well differentiated hepatoblastoma
    • A subset has increased mitotic activity, with decreased cytoplasmatic glycogen and pleomorphic nuclei, referred to as mitotically active hepatoblastoma
  • Embryonal pattern (Pediatr Dev Pathol 2020;23:79)
    • Resembles the developing liver at 6 - 8 weeks of gestation
    • Solid nests or glandular / acinar morphology, with papillae and pseudorosettes
    • Dark and granular cytoplasm without glycogen or lipids
    • Enlarged nuclei with coarse chromatin, resembling blastemal cells
    • Extramedullary hematopoiesis is usually absent
    • Increased mitotic activity
  • Small cell undifferentiated pattern (Pediatr Dev Pathol 2020;23:79)
    • Solid sheets of discohesive small cells (small, round blue tumor)
    • Abundant mitoses, apoptosis and necrosis
  • Macrotrabecular pattern
    • Thick trabeculae (5 - 12 cells thick)
    • Trabeculae may be composed of fetal, embryonal, pleomorphic or hepatocellular carcinoma-like cells
  • Cholangioblastic pattern
    • Small ducts within or around hepatocellular components
  • Mesenchymal pattern (Pediatr Dev Pathol 2020;23:79)
    • Mature and immature fibrous tissue
    • Osteoid or osteoid-like tissue (more abundant after chemotherapy)
    • Hyaline cartilage
    • Small subset may exhibit teratoid features: endodermal, neuroectodermal (neuronal cells, glial tissue, melanin producing cells) and complex tissue (striated muscle)
Microscopic (histologic) images

Contributed by Rui Caetano Oliveira, M.D. and Maria Augusta Cipriano, M.D.

Hepatoblastoma patterns

Small cell undifferentiated pattern

Fetal component

Small nests


Therapy changes

Keratin staining

Polyclonal CEA

CK19 staining

Beta catenin staining

Cytology description
Positive stains
Negative stains
Molecular / cytogenetics description
  • Gene expression profile may be helpful in stratifying patients:
    • High risk tumors have upregulation of NFE2L2 activity, high LIN28B, HMGA2, SALL4 and AFP expression and high coordinated expression of oncofetal proteins and stem cell markers
    • Low risk tumors have LIN28B and let-7 expression and high HNF1A activity (Hepatology 2017;65:104)
Sample pathology report
  • Liver, hepatectomy:
    • Hepatoblastoma (see comment)
    • Comment: There is a neoplasia with well defined boundaries, composed of small to medium sized cells resembling hepatocytes of the developing fetal liver, arranged in trabeculae and with foci of extramedullary hematopoiesis. The tumor exhibits mostly a fetal pattern, with some areas with a cholangioblastic pattern and a small cell undifferentiated pattern in the periphery of the lesion. There is fibrosis, hemosiderin pigment and osteoid-like tissue in the center, with probable association with neoadjuvant chemotherapy, comprising circa 30% of the lesion volume. No vascular invasion was seen. Nontumoral parenchyma without changes.
Differential diagnosis
Board review style question #1
Regarding evaluation of hepatoblastoma, which staging system has the best prognostic value?

  1. AJCC
  2. LI-RADS
  3. PRETEXT
  4. TNM
Board review style answer #1
C. PRETEXT

Comment Here

Reference: Hepatoblastoma
Board review style question #2

A young boy is found to have a liver mass and undergoes resection. A diagnosis of hepatoblastoma is made. Which pattern does this picture represent?

  1. Cholangioblastic
  2. Embryonal
  3. Fetal
  4. Small cell undifferentiated
Board review style answer #2
D. Small cell undifferentiated

Comment Here

Reference: Hepatoblastoma
Back to top
Image 01 Image 02