For patient information, click here
Hepatoblastoma On the Web
American Roentgen Ray Society Images of Hepatoblastoma
Synonyms and Keywords: Epithelial hepatoblastoma; Fetal hepatoblastoma; Embryonal hepatoblatoma; Macrotrabecular hepatoblastoma; Mixed hepatoblastoma; Rhabdoid hepatoblastoma; Small cell hepatoblastoma; Undifferentiated hepatoblastoma; Cholangioblastic hepatoblastoma; Teratoid hepatoblastoma; Chondroid hepatoblastoma; Osteoid hepatoblastoma; Rhabdomyoblastic hepatoblastoma; Neuroid-melanocytic hepatoblastoma; Well differentiated hepatoblastoma; HB
Hepatoblastoma is the most common primary liver tumor occurs in infant and children, usually less than 3 years old, more frequently in male, and accounting for over 1% of pediatric cancers. The etiology is unknown and not well understood, but it has been associated with Beckwith-Weidemann syndrome, familial adenomatous polyposis, and other factors such as low birth weight, preeclampsia, hemihypertrophy. The primary treatment is surgical resection, however, chemotherapy plays an important role by increasing the number of tumors that are respectable, chemotherapeutic agents helps in shrinkage of the tumor and make it easier to be resected by surgery. Prognosis of the tumor depends on various criteria such as resectability of the tumor, distant metastasis, tumor size, PRETEXT staging, and recurrence of the tumor. The mainstay of treatment is surgery, but the adjuvant chemotherapeutic agents and liver transplantation also are helpful.
In 1898, the first case of hepatoblastoma was published in English literature, the tumor was diagnosed in a 6-week old boy in Prague, by a physician named Misick, who found a large tumor on the autopsy of his liver. Decades later on 1962 Willis used the term, hepatoblastoma for this type of liver tumor because of it's embryonal origin 
- Hepatoblastoma are divided into two broad categories:
- Epithelial type (E-HB)
- Mixed epithelial and mesenchymal type (MEM-HB). The mixed type is subdivided into:
- The exact pathogenesis of hepatoblastoma is not fully understood. 
- Loss of function mutations in APC leads to intracellular accumulation of the protooncogene beta-catenin, which leads to germline mutation of Wnt signal transduction and pathway.
- Hepatoblastomas originate from primitive hepatic stem cells.
- B-catenin mutations have been shown to be common in the majority of sporadic hepatoblastomas.
- Studies revealed that tumor occurs more often in families affected by familial adenomatous polyposis(FAP), which is caused by inactivation of the adenomatous polyposis coli (APC), a tumor-suppressor gene that down-regulate the amount of beta-catenin.
- Immunohistochemical markers such as expression of CK19, beta-catenin and EpCAM were correlated with tumor behaviour, response to chemotherapy and survival.
- Underlying causes of hepatoblastoma poorly understood and most tumors are sporadic but there are some risk factors and conditions that have a strong association with this tumor such as:
- Beckwith-Weidemann syndrome
- Familial adenomatous polyposis (FAP)
- Down syndrome
- Edward syndrome (trisomy 18)
- Low birth weight infants are at higher risk of developing a hepatoblastoma
- Parental tobacco smoking
- Oxygen therapy
- Certain medication (furosemide)
- Total parenteral nutrition (TPN)
- The most common genetic mutation which plays role in etiology of sporadic cases include:
Differentiating hepatoblastoma from Other Diseases
- Hepatoblastoma must be differentiated from other diseases that cause rapidly enlarging abdominal mass in pediatrics such as:
Epidemiology and Demographics
- Hepatoblastoma is the most common primary liver cancer in infants and children, tumor involves right lobe of liver more often.
- The incidence/prevalence of hepatoblastoma is approximately 0.05–0.15 patients per 100000 population in children younger than 15 years.
- Peak incidence means of 18 months, mostly in infants and children younger than 3 years old, with a male predilection.
- Hepatoblastoma accounts for one percent of all primary malignancies in pediatrics.
- Common risk factors in the development of hepatoblastoma include:
- There is no screening method for detecting hepatoblastoma.
- Ultrasound is the main tool for suspected hepatic lesions in children.
- Serum alpha-fetoprotein (AFP) is the most important clinical marker of hepatoblastoma and helps to estimate malignant change, response to the treatment, and relapse. 
Natural History, Complications, and Prognosis
- Prognosis is based on different factors including:
- Age of diagnosis, younger children have a better prognosis.
- Alpha-fetoprotein (AFP) levels, drop in AFP level after chemotherapy means better response to treatment.
- Histologic subtype, the well-differentiated fetal subtype has a better prognosis compared with small cell undifferentiated ones.
- Pretreatment extent of disease (PRETEXT) which was developed to stage the tumor before surgical removal and compare the efficacy of varous adjuvant chemotherapeutic agents. It is based on anatomy of liver and depending on tumor free sectors of liver.
- Complications of hepatoblastoma includes:
Diagnostic Study of Choice
- The diagnosis of hepatoblastoma is made when abdominal mass is detected on ultrasound or spiral CT scan, but a definitive diagnosis requires the histological evaluation of biopsy specimen after surgery.
History and Symptoms
- The majority of patients with hepatoblastoma have an abdominal mass or abdominal distension. 
- Other symptoms of hepatoblastoma include:
- Ruptured tumor can cause symptoms of peritoneal irritation due to intraperitoneal bleeding such as severe abdominal pain, nausea, vomiting, and severe anemia.
- Physical examination of patients with hepatoblastoma is usually remarkable for single, mildly painful, rapidly enlarging abdominal mass that is found in the right lobe of the liver.
- Most tumors are solitary; but can be multifocal as well.
- Laboratory findings that help with the diagnosis of hepatoblastoma includes:
- There are no ECG findings associated with hepatoblastoma.
- Chest x-rays can be useful especially since this tumor has the affinity to metastasize to lungs.
- Imaging studies play an important role in the diagnosis, staging, and treatment of disease, most tumors can be resected surgically and ultrasound is often used in order to detect tumor size, also the initial diagnosis is made by abdominal ultrasound.
- CT scan is very helpful to diagnose the disease, children with hepatoblastoma undergo either a CT or MRI scan at diagnosis. 
- Surgeons prefer an angiographic or biphasic CT scan because of better depiction of the hepatic arterial, portal venous and hepatic vein and other liver structures.
- Concerns about radiation exposures in pediatrics has changed this modality in favor of MRI, although MRI is much lengthy exam than CT has the advantage of multiplanar soft-tissue characterization, and when diffusion-weighted imaging techniques are used, MRI is exquisitely sensitive for detecting tiny liver lesions.
- Spiral CT scan findings of hypervascular lesions in the liver with delayed contrast excretion are highly suggestive of a malignant liver tumor.
- MRI has the advantage of multiplanar soft-tissue characterization, lack of harmful ionizing radiation and when diffusion-weighted imaging techniques are used, MRI is exquisitely sensitive for detecting tiny liver lesions.
Other Imaging Findings
- Other imaging studies such as PET scan or even bone scan when there is evidence of metastasis to bone may be helpful in the diagnosis of hepatoblastoma. PET scan can be helpful in localizing recurrent hepatoblastoma.
Other Diagnostic Studies
- Other diagnostic studies for hepatoblastoma include evaluation of serum level of alpha-fetoprotein, serum hCG level in rare cases of precocious puberty.
- The mainstay of therapy for hepatoblastoma is surgery, however, the vast majority of the tumors cannot be completely resected because of their large size or metastasis.
- Liver transplantation can be considered for tumors that cannot be removed by surgery.
- Chemotherapy is an important adjuvant therapy, and cisplatin is the most commonly used chemotherapeutic agent, it can reduce the volume of tumors that are too big for surgical removal.
- Surgery is the mainstay of treatment for hepatoblastoma.
- The feasibility of surgery depends on the resectability of tumor at diagnosis.
- There are no established measures for the primary prevention of hepatoblastoma.
- There are no established measures for the secondary prevention of hepatoblastoma.
- Aronson DC, Czauderna P, Maibach R, Perilongo G, Morland B (October 2014). "The treatment of hepatoblastoma: Its evolution and the current status as per the SIOPEL trials". J Indian Assoc Pediatr Surg. 19 (4): 201–7. doi:10.4103/0971-9261.142001. PMC 4204244. PMID 25336801.
- Rowland JM (November 2002). "Hepatoblastoma: assessment of criteria for histologic classification". Med. Pediatr. Oncol. 39 (5): 478–83. doi:10.1002/mpo.10171. PMID 12228903.
- Czauderna P, Lopez-Terrada D, Hiyama E, Häberle B, Malogolowkin MH, Meyers RL (February 2014). "Hepatoblastoma state of the art: pathology, genetics, risk stratification, and chemotherapy". Curr. Opin. Pediatr. 26 (1): 19–28. doi:10.1097/MOP.0000000000000046. PMID 24322718.
- MacDonald BT, Tamai K, He X (July 2009). "Wnt/beta-catenin signaling: components, mechanisms, and diseases". Dev. Cell. 17 (1): 9–26. doi:10.1016/j.devcel.2009.06.016. PMC 2861485. PMID 19619488.
- Kiruthiga KG, Ramakrishna B, Saha S, Sen S (April 2018). "Histological and immunohistochemical study of hepatoblastoma: correlation with tumour behaviour and survival". J Gastrointest Oncol. 9 (2): 326–337. doi:10.21037/jgo.2018.01.08. PMC 5934143. PMID 29755772.
- Heck JE, Meyers TJ, Lombardi C, Park AS, Cockburn M, Reynolds P, Ritz B (August 2013). "Case-control study of birth characteristics and the risk of hepatoblastoma". Cancer Epidemiol. 37 (4): 390–5. doi:10.1016/j.canep.2013.03.004. PMC 3679264. PMID 23558166.
- Finegold MJ, Lopez-Terrada DH, Bowen J, Washington MK, Qualman SJ (April 2007). "Protocol for the examination of specimens from pediatric patients with hepatoblastoma". Arch. Pathol. Lab. Med. 131 (4): 520–9. doi:10.1043/1543-2165(2007)131[520:PFTEOS]2.0.CO;2. PMID 17425379.
- Mussa A, Duffy KA, Carli D, Ferrero GB, Kalish JM (January 2019). "Defining an optimal time window to screen for hepatoblastoma in children with Beckwith-Wiedemann syndrome". Pediatr Blood Cancer. 66 (1): e27492. doi:10.1002/pbc.27492. PMID 30270492.
- Curia MC, Zuckermann M, De Lellis L, Catalano T, Lattanzio R, Aceto G, Veschi S, Cama A, Otte JB, Piantelli M, Mariani-Costantini R, Cetta F, Battista P (January 2008). "Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 mutations". Mod. Pathol. 21 (1): 7–14. doi:10.1038/modpathol.3800977. PMID 17962810.
- Hiyama E (October 2014). "Pediatric hepatoblastoma: diagnosis and treatment". Transl Pediatr. 3 (4): 293–9. doi:10.3978/j.issn.2224-4336.2014.09.01. PMC 4728840. PMID 26835349.
- Darbari A, Sabin KM, Shapiro CN, Schwarz KB (September 2003). "Epidemiology of primary hepatic malignancies in U.S. children". Hepatology. 38 (3): 560–6. doi:10.1053/jhep.2003.50375. PMID 12939582.
- Allan BJ, Parikh PP, Diaz S, Perez EA, Neville HL, Sola JE (October 2013). "Predictors of survival and incidence of hepatoblastoma in the paediatric population". HPB (Oxford). 15 (10): 741–6. doi:10.1111/hpb.12112. PMC 3791112. PMID 23600968.
- Shelmerdine SC, Roebuck DJ, Towbin AJ, McHugh K (August 2016). "MRI of paediatric liver tumours: How we review and report". Cancer Imaging. 16 (1): 21. doi:10.1186/s40644-016-0083-3. PMC 4986178. PMID 27526937.
- Musick SR, Babiker HM. PMID 30521216. Missing or empty
- Aronson DC, Schnater JM, Staalman CR, Weverling GJ, Plaschkes J, Perilongo G, Brown J, Phillips A, Otte JB, Czauderna P, MacKinlay G, Vos A (February 2005). "Predictive value of the pretreatment extent of disease system in hepatoblastoma: results from the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 study". J. Clin. Oncol. 23 (6): 1245–52. doi:10.1200/JCO.2005.07.145. PMID 15718322.
- Becker K, Furch C, Schmid I, von Schweinitz D, Häberle B (January 2015). "Impact of postoperative complications on overall survival of patients with hepatoblastoma". Pediatr Blood Cancer. 62 (1): 24–8. doi:10.1002/pbc.25240. PMID 25251521.
- Ke HY, Chen JH, Jen YM, Yu JC, Hsieh CB, Chen CJ, Liu YC, Chen TW, Chan DC (October 2005). "Ruptured hepatoblastoma with massive internal bleeding in an adult". World J. Gastroenterol. 11 (39): 6235–7. PMC 4436650. PMID 16273660.
- Zhang Q, Ming J, Zhang S, Guo D, Qiu X (2013). "A rare case of adult hepatoblastoma with neuroendocrine differentiation misdiagnosed as neuroendocrine tumor". Int J Clin Exp Pathol. 6 (2): 308–13. PMC 3544231. PMID 23330017.
- Exelby PR, Filler RM, Grosfeld JL (June 1975). "Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey--1974". J. Pediatr. Surg. 10 (3): 329–37. PMID 49416.
- Nickerson HJ, Silberman TL, McDonald TP (January 1980). "Hepatoblastoma, thrombocytosis, and increased thrombopoietin". Cancer. 45 (2): 315–7. PMID 6153151.
- Perilongo G, Brown J, Shafford E, Brock P, De Camargo B, Keeling JW, Vos A, Philips A, Pritchard J, Plaschkes J (October 2000). "Hepatoblastoma presenting with lung metastases: treatment results of the first cooperative, prospective study of the International Society of Paediatric Oncology on childhood liver tumors". Cancer. 89 (8): 1845–53. PMID 11042582.
- Aronson DC, Meyers RL (October 2016). "Malignant tumors of the liver in children". Semin. Pediatr. Surg. 25 (5): 265–275. doi:10.1053/j.sempedsurg.2016.09.002. PMID 27955729.
- Figarola MS, McQuiston SA, Wilson F, Powell R (December 2005). "Recurrent hepatoblastoma with localization by PET-CT". Pediatr Radiol. 35 (12): 1254–8. doi:10.1007/s00247-005-1568-6. PMID 16170514.
- Archer D, Babyn P, Gilday D, Greenberg MA (December 1993). "Potentially misleading bone scan findings in patients with hepatoblastoma". Clin Nucl Med. 18 (12): 1026–31. PMID 8293620.
- Nakagawara A, Ikeda K, Tsuneyoshi M, Daimaru Y, Enjoji M, Watanabe I, Iwafuchi M, Sawada T (October 1985). "Hepatoblastoma producing both alpha-fetoprotein and human chorionic gonadotropin. Clinicopathologic analysis of four cases and a review of the literature". Cancer. 56 (7): 1636–42. PMID 2411379.
- Morinaga S, Yamaguchi M, Watanabe I, Kasai M, Ojima M, Sasano N (May 1983). "An immunohistochemical study of hepatoblastoma producing human chorionic gonadotropin". Cancer. 51 (9): 1647–52. PMID 6187430.
- Pham TA, Gallo AM, Concepcion W, Esquivel CO, Bonham CA (December 2015). "Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer". JAMA Surg. 150 (12): 1150–8. doi:10.1001/jamasurg.2015.1847. PMID 26308249.
- Reyes JD, Carr B, Dvorchik I, Kocoshis S, Jaffe R, Gerber D, Mazariegos GV, Bueno J, Selby R (June 2000). "Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence". J. Pediatr. 136 (6): 795–804. PMID 10839879.
- Häberle B, Bode U, von Schweinitz D (2003). "[Differentiated treatment protocols for high- and standard-risk hepatoblastoma--an interim report of the German Liver Tumor Study HB99]". Klin Padiatr (in German). 215 (3): 159–65. doi:10.1055/s-2003-39375. PMID 12778356.
- Uchida H, Sakamoto S, Sasaki K, Takeda M, Hirata Y, Fukuda A, Hishiki T, Irie R, Nakazawa A, Miyazaki O, Nosaka S, Kasahara M (December 2018). "Surgical treatment strategy for advanced hepatoblastoma: Resection versus transplantation". Pediatr Blood Cancer. 65 (12): e27383. doi:10.1002/pbc.27383. PMID 30084209.