Hepatoblastoma

Epidemiology and Etiology:

· Most common liver tumour of young childhood

· 80-90% <5y

· Associations with congenital conditions (up to 30%)

· Chromosomal abnormalities

· Trisomy 21

· Trisomy 18

· Metabolic / Pathophysiologic abnormalities

· Cystathioninuria

· Glycogen storage diseases

· Hypoglycemia

· Heterozygous alpha-1-antitrypsin deficiency

· Isosexual precocity

· Prematurity

· Very low birth weight

· Total parenteral nutrition

· Inherited Tumour Syndromes:

· Beckwith-Wiedemann syndrome

· Familial polyposis coli (FAP)

· Li Fraumeni

· Polyposis coli

· Other syndromes:

· Budd-Chiari

· Schinzel-Geidon syndrome

· Malformations:

· Cleft palate

· Renal malformations

· Diaphragmatic hernia

· Hemihypertrophy

· Other malformations

· Environmental exposures (in utero):

· Alcohol

· HIV

· HBV

· Clomiphene citrate

· Pergonal

· OCP

· Osteoporosis

Common sites:

·

Gross features:

· Large usually

· Liver not cirrhotic usually

· Hemorrhage and necrosis

·

Histologic features:

· Pure epithelial type

· Embryonal pattern:

· Small cells with fairly round to oval nuclei and scant basophilic cytoplasm

· Acini or tubules

· Fetal type

· Larger cells than embryonal type and larger than normal hepatocytes

· higher N:C ratio than normal hepatocytes

· Round nuclei

· Moderate amount of eosinophilic and or clear cytoplasm

· Scattered array of lipids and glycogen may give alternating clear and eosinophilic appearance

· Plates or cords

· Mitoses rare

· May have a better prognosis

· Extramedullary hematopoiesis maybe

· Macrotrabecular pattern:

· Fetal or embryonal cells in cords or clusters of 20 or more cells (as opposed to 2-6 cell-thick cords or plates)

· Mixed epithelial and mesenchymal type

· Mixture of 2 epithelial types as well as foci of mesenchymal differentiation

· Osteoid is common

· With or without teratoid features

· Intestinal glandular epithelium

· Neuroid-melanocytic

· Rhabdoid type

· Extramedullary hematopoiesis often

· small cell undifferentiated (formerly “anaplastic”) pattern:

· resemble neuroblastoma

Immunophenotype:

Marker:	Sensitivity:	Specificity:
AFP	Often	Also seen in HCC
Chromogranin A (focal)	“has been reported”

· No good immunostains to distinguish from HCC

Molecular features:

· Beta-catenin deletions or mutations (80%)

· Wnt / Beta-catenin signaling pathway frequently activated

· APC mutations as well

· Trisomies:

· Chromosome 2 and 20 most commonly

· Chromosome 8

· Trisomy 8 or 20 may impart adverse prognosis

· Unique translocation in small cell undifferentiated type

· LOH:

· 11p15 (shared with other embryonal tumours)

Other features:

· Serum AFP elevated (nearly all)

· Generally higher than in HCC

· Can be used to monitor treatment and recurrence

· Nonspecific – also may be present in any other hepatic mass

· Small cell undifferentiated less likely to have elevated AFP

· Prognostic factors:

· Resectability is single most important

· 67% are not amenable to primary surgery

· Histology

· Small cell undifferentiated (poor prognosis)

· “favorable” histology:

· Pure epithelial, purely fetal

· Mitotically inactive ( <= 2 / 10 HPF)

· “less favorable” histology:

· Not favorable or unfavorable histology

· “unfavorable” histology:

· Predominantly (>75%):

· Small cell undifferentiated

· Rhabdoid component

· Significance of lesser amounts of these histologies is unkown

· Immunohistochemistry

· MIB-1 < 10% good

· PCNA low levels good

· Beta-catenin nuclear bad

· Ploidy

· Diploid good survival

· Aneuploid bad survival

· COG staging:

· Stage I:

· Completely resected

· Stage II:

· Microscopic residual tumour

· Stage III:

· Gross residual tumour

· Stage IV:

· Metastatic disease

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.

· Silverberg SG, DeLellis RA, Frable WJ, LiVolsi VA, Wick MR. Silverberg's Principles and Practice of Surgical Pathology and Cytopathology: 2-Volume Set. 4th ed. Churchill Livingstone; 2005.

· Russo P, Ruchelli ED, Piccoli DA. Pathology of Pediatric Gastrointestinal and Liver Disease. 1st ed. Springer; 2004:358.