RESIDENT CASE STUDIES

Week 7 June 2 - June 6, 2003: Case 4 

Table of Contents | List of Diagnoses | Case 1 | Case 2 | Case 3 | Case 4

14 month old male infant with a liver mass measuring 12 cm in widest dimension. The mass remarkably decreased after several months of chemotherapy.

Discussion 
Hepatoblastoma is a malignant embryonal tumor with divergent differentiation. It is the most common liver tumor in children, and 90% is seen most commonly in the first 5 years of life.¹ It usually occurs as a single mass in most cases and often presents with a painless, enlarging abdominal mass. 

A variety of histological patterns may be present in varying proportions in hepatoblastomas. The histologic patterns may be entirely, a) fetal epithelial cells, b) small undifferentiated cells (small blue round cells), c) hepatic fetal epithelial and embryonal cells, d) connective tissue, e) osteoid-like material, f) skeletal muscle fibers, g) nests of squamous epithelial cells, and h) cells with melanin pigments.^9,10  

Hepatoblastomas are accompanied by anemia in about 70% of cases and by thrombocytosis (platelet counts of > 500 × 10⁹ /L) in 35% of cases.⁷

Rarely, human chorionics gonadotropin may be produced by hepatoblasts / tumor cells and this can lead to precocious puberty with young boys displaying genital enlargement, pubic hair, and a deepening voice.^2,3 

Alpha-fetoprotein (AFP), however, is the major laboratory parameter used in diagnosing and following the course of hepatoblastoma. It is elevated in as many as 90% of patients, and can both reliably predict the outcome of the disease and parallel its course. At one end of the spectrum, hepatoblastomas with little differentiation (small cell undifferentiated tumors) may show little or no AFP elevation. At the other end, tumors with wide extension or metastasis may have levels of AFP exceeding 1,000,000 ng/mL. Both extremes (<100 or >10⁶) are associated with an unfavorable outcome.^{8, 9} 

Hepatoblastoma is associated with several conditions including prematurity, Gardner syndrome, familial adenomatous polyposis, and the Beckwith-Wiedemann syndrome among others.^4,5,6 Trisomy for chromosome 2 and loss of heterozygosity for the telomeric portion of 11p (the material lost is usually of maternal origin).¹⁰ 

Differential diagnoses include small round blue cells tumors (when the histologic pattern is small round blue cell). Other differential diagnoses may be considered depending on the histologic pattern. Note however, that hepatocellular carcinoma is extremely rare in infants. 

References:

¹Ishak K, Goodman Z, Stocker J: Tumors of the Liver and Intrahepatic Bile Ducts. Washington, DC, Armed Forces Institute of Pathology, 2000. 

²Heimann A, White PF, Riely CA, et al: Hepatoblastoma presenting as isosexual precocity. The clinical importance of histologic and serologic parameters. J Clin Gastroenterol 9:105–110, 1987.

³Helmberger TK, Ros PR, Mergo PJ, et al: Pediatric liver neoplasms: A radiologic-pathologic correlation. Eur Radiol 9:1339–1347, 1999.

⁴Koishi S, Kubota M, Taniguchi Y, et al: Myelodysplasia in a child with Beckwith-Wiedemann syndrome previously treated for hepatoblastoma with multi-agent chemotherapy [letter]. J Pediatr Hematol Oncol 18:419–420, 1996

⁵Kurahashi H, Takami K, Oue T, et al: Biallelic inactivation of the APC gene in hepatoblastoma. Cancer Res 55:5007–5011, 1995.

⁶Feusner JH, Ortega J, Haas J, Quinn J, King A, Ablin A, et al. Hepatoblastoma in premature infants. Proceedings of the American Society of Clinical Oncology 1997;16:525a.

⁷Shafford EA, Pritchard J: Extreme thrombocytosis as a diagnostic clue to hepatoblastoma [letter; comment]. Arch Dis Child 69:171, 1993.

⁸von Schweinitz D, Hecker H, Schmidt-von-Arndt G, et al: Prognostic factors and staging systems in childhood hepatoblastoma. Int J Cancer 74:593–599, 1997.

⁹Hamilton SR, Aaltonen LA (Eds): World Health organization Classification of Tumors. Pathology and Genetics of Tumors of the Digestive System. IARC Press: Lyon 2000.