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Liver and intrahepatic bile ducts - tumor

Other malignancies


Reviewers: Deepali Jain, M.D. (see Reviewers page)
Revised: 9 January 2013, last major update February 2012
Copyright: (c) 2004-2013, PathologyOutlines.com, Inc.


● Malignant liver neoplasm almost exclusively in infants, composed exclusively of immature hepatocytic elements (WHO)
● Most common primary liver tumor in children (50% of liver malignancies in children)
● Existence in adults is controversial (J Hepatol 2012;56:1392)


● Can be congenital; 90% occur by age of 5 years, 70% by age of 2 years; 2/3 male, prevalence of 1 per 120,000 (1 per million children under age 15 years)
● Associated with familial colonic polyposis (APC gene, 500x risk), glycogen storage disease, hemihypertrophy (Beckwith-Wiedemann syndrome), Li-Fraumeni syndrome, low birth weight infants, Simpson-Golabi-Behmel syndrome, trisomy 18, Wilm’s tumor; not associated with cirrhosis
● Also associated with adenomatoid transformation of Bowman’s capsular epithelium in kidney
● Metastases to adrenal glands, bone marrow, brain, lung, lymph nodes (regional)
● Variable virilization due to hCG production by multinucleated giant cells
● Laboratory: thrombocytosis (Arch Dis Child 1993;69:171), elevated serum AFP (75%)
● Note: diagnosis difficult on needle biopsy; must sample generously


Based on Children’s Cancer Study Group:
Stage I: completely resected
Stage II: microscopic residual disease only
Stage III: gross residual disease or positive lymph nodes or spilled tumor
Stage IV: metastases

Note: can also stage using TNM

Prognostic factors

● Stage, age and sex
● Favorable: presence of osteoid
● Unfavorable: small cell / undifferentiated (Pediatr Blood Cancer 2009;52:328) and macrotrabecular patterns, increased mitotic activity; also AFP level < 100, nuclear beta catenin staining, low p27 / kip1, high cyclin D1, 4q deletions


● Preoperative chemotherapy and surgery; resect lung metastases; liver transplant if unresectable
● Long term survival now 60-70% with most recurrences detected within 3 years

Gross description

● Usually right lobe
● Usually solid, variegated, tan-green, solitary (70%), variable hemorrhage and cysts
● Mean 10 cm (range 3-20 cm), well-circumscribed; often partially encapsulated
● May be calcified or ossified in prominent mesenchymal component

Micro description

● Epithelial and mesenchymal elements in varying proportions and at variable stages of differentiation
● Pseudocapsule, canaliculi with bile formation, cords 2-3 cells thick with alternating light and dark pattern due to glycogen and fat
● Cells smaller than normal hepatocytes
● Extramedullary hematopoiesis common in fetal and embryonal subtypes
● Usually no pleomorphism, no intranuclear inclusions, no hyaline globules, rare / no tumor giant cells, no mitotic figures and no associated cirrhosis
● Rare rhabdoid cells

Epithelial type (56%)


Fetal pattern (31%):
● Tumor cells in trabeculae 2-3 cells thick (resembling fetal liver), separated by sinusoids lined by CD34+ endothelial cells
● Tumor cells are same size or smaller than in non-neoplastic liver
● Distinct cell membranes, uniform, polyhedral, slightly higher nuclear / cytoplasmic ratio, inconspicuous nucleoli and may contain bile
● Minimal pleomorphism, no / rare mitotic figures
● Have “dark” and “light” foci related to amount of glycogen and fat
● Extramedullary hematopoiesis common; no portal tracts, bile ducts or ductules at the periphery
● Reduced reticulin, rare mitosis
● Cholangoblastic if ductular differentiation (CK7/19 positive) prominent
● Crowded fetal type: crowded cells and 2+ mitotic figures/10 hpf

Embryonal pattern (19%):
● Sheets, ribbons, rosettes, papillary patterns or trabeculae of variable thickness with immature appearance, discohesive small cells with poorly defined cell borders, basophilic cytoplasm, high N/C ratio, prominent nucleoli, coarse chromatin and increased mitotic figures
● Extramedullary hematopoiesis, necrosis and vascular lakes are common; no fat, glycogen or bile

Macrotrabecular pattern (3%):
● Frequent trabeculae > 10 cells thick throughout the tumor, variable cytologic features

Small cell undifferentiated / anaplastic pattern (3%):
● Most primitive form
● Definition: 70%+ small cell areas; however, even small foci should be reported becaues associated with poor prognosis
● Discohesive sheets of small uniform keratin+ cells with minimal cytoplasm, indistinct cell borders, oval hyperchromatic nuclei, variable prominent nucleoli and increased mitotic figures (Mod Pathol 2003;16:930)
● Resembles small cell carcinoma at other sites
● May have mucoid stroma, hyalinized septae; bile
● Loss of INI1 associated with rhabdoid phenotype

Gross images

Epithelial hepatoblastoma

Patient with trisomy 18

Micro images

Cholangioblastic pattern

Fetal pattern

Fetal pattern in patient with trisomy 18

Macrotrabecular pattern

Mixed fetal and embryonal patterns

Small cell pattern

Mixed epithelial mesenchymal type (44%)


● Mixture of fetal / epithelial and mesenchymal cell types
● Teratoid (34%) or not (10%)
● Mesenchymal component has spindle-oval cells with minimal cytoplasm, frequent osteoid, fibrous septa, myxoid zones, hemorrhage and necrosis
● Teratoid features are keratinized squamous epithelium, intestinal epithelial, skeletal muscle, mature bone and cartilage, melanin and neuroectodermal structures

Micro images

Mixed pattern

Post-chemotherapy treatment effect

Positive stains

● Alpha fetoprotein (negative in small cell type), chromogranin (fetal, epithelial subtypes, usually focal), CK8/18 (fetal, epithelial subtypes), CK19 (embryonal subtypes)
● Also EMA, HepPar1 (negative in small cell type), polyclonal CEA (canalicular pattern), vimentin
● Variable hCG, occasional HMB45 and melanin
● Beta catenin (nuclear) in small cell and embryonal types, Delta-like protein (DLK), glypican-3 (negative in small cell type), glutamine synthase

Negative stains

● CD45 / LCA, desmin and neurofilament

Molecular description

● Gain of Xq in 60%, gain of Xp in 43%, also trisomy 2q (2q+) and trisomy 20, 1p-, 2q-, 4q-, 4q+
● Fetal type usually diploid, embryonal often aneuploid (Hum Pathol 2003;34:864)
● Deletion or translocation of 22q in small cell type (Front Biosci (Elite Ed) 2012;4:1287); also FOXG1 overexpression (Hum Pathol 2007;38:400), Yin Yang 1 (YY1) protein (Virchows Arch 2011;458:453), SERPINB3 overexpression (Eur J Cancer 2012;48:1219)

Electron microscopy description

● Immature hepatocytes

Differential diagnosis

Hepatocellular carcinoma - resembles macrotrabecular variant of hepatoblastoma, uncommon in children, larger more pleomorphic tumor cells, no extramedullary hematopoiesis

Metastatic tumors: more common than hepatoblastoma, primary tumor cells should not resemble hepatocytes
● Neuroblastoma
Undifferentiated sarcoma
● Wilms’ tumor
Yolk sac tumor: rare yolk sac cells may be present in hepatoblastoma

End of Liver and intrahepatic bile ducts - tumor > Other malignancies > Hepatoblastoma

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