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==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
*Hepatoblastoma is the most common primary liver cancer in infants and children, tumor involves right lobe of liver more often.<ref name="pmid12939582">{{cite journal |vauthors=Darbari A, Sabin KM, Shapiro CN, Schwarz KB |title=Epidemiology of primary hepatic malignancies in U.S. children |journal=Hepatology |volume=38 |issue=3 |pages=560–6 |date=September 2003 |pmid=12939582 |doi=10.1053/jhep.2003.50375 |url=}}</ref> | |||
*The incidence/prevalence of hepatoblastoma is approximately 0.05–0.15 patients per 100 000 population in children younger than 15 years.<ref name="pmid23600968">{{cite journal |vauthors=Allan BJ, Parikh PP, Diaz S, Perez EA, Neville HL, Sola JE |title=Predictors of survival and incidence of hepatoblastoma in the paediatric population |journal=HPB (Oxford) |volume=15 |issue=10 |pages=741–6 |date=October 2013 |pmid=23600968 |pmc=3791112 |doi=10.1111/hpb.12112 |url=}}</ref> | *The incidence/prevalence of hepatoblastoma is approximately 0.05–0.15 patients per 100 000 population in children younger than 15 years.<ref name="pmid23600968">{{cite journal |vauthors=Allan BJ, Parikh PP, Diaz S, Perez EA, Neville HL, Sola JE |title=Predictors of survival and incidence of hepatoblastoma in the paediatric population |journal=HPB (Oxford) |volume=15 |issue=10 |pages=741–6 |date=October 2013 |pmid=23600968 |pmc=3791112 |doi=10.1111/hpb.12112 |url=}}</ref> | ||
*Peak incidence means of 18 months, mostly in infants and children younger than 3 years old, with a male predilection. | *Peak incidence means of 18 months, mostly in infants and children younger than 3 years old, with a male predilection. | ||
*Hepatoblastoma | *Hepatoblastoma accounts for one percent of all primary malignancies in pediatrics. | ||
==Risk Factors== | ==Risk Factors== | ||
Revision as of 19:17, 26 December 2018
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American Roentgen Ray Society Images of Hepatoblastoma |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2] Nawal Muazam M.D.[3]
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
Overview
Hepatoblastoma is the most common primary liver tumor in young children, usually less than 3 years old, accounting for over 1% of pediatric cancers. The etiology is unknown, but it has been associated with Beckwith-Weidemann syndrome, familial adenomatosis polypi, and low birth weight. The primary treatment is surgical resection, however, chemotherapy plays an important role by increasing the number of tumors that are respectable. The prognosis for patients with resectable tumors is fairly good, however, the outcome for those with nonresectable or recurrent disease is poor.
PMID: 11110595
Historical Perspective
- In 1898, the first case of a child with HB was published in the English literature. A 6-week-old boy was described whose autopsy showed a large tumor that occupied the lower half of the right liver lobe.[1]
Classification
- Hepatoblastoma are divided into 2 broad categories:[2][3]
- Epithelial type (E-HB)
- Fetal, which has four subtypes:
- Well differentiated
- Crowded or mitotically active
- Pleomorphic
- Poorly differentiated
- Anaplastic
- Embryonal
- Macrotubular small cell undifferentiated (SCU)
- Cholangioblastic
- Fetal, which has four subtypes:
- Mixed epithelial and mesenchymal type (MEM-HB). while the mixed type is subdivided into
- Stromal derivatives
- Teratoid variants
- Epithelial type (E-HB)
Pathophysiology
- The exact pathogenesis of hepatoblastoma is not fully understood. [4]
- Loss of function mutations in APC leads to intracellular accumulation of the protooncogene b-catenin, an effector of Wnt signal transduction.
- 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 b-catenin.
- Immunohistochemical markers such as expression of CK19, beta-catenin and EpCAM were correlated with tumour behaviour, response to chemotherapy and survival.[5]
Causes
- 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:[6][7][8]
- Beckwith-Weidemann syndrome
- Familial adenomatous polyposis (FAP)
- Down syndrome
- Edward syndrome (trisomy 18)
- Nephroblastoma,
- Low birth weight infants are at higher risk of developing a hepatoblastoma
- Preeclampsia
- Parental tobacco smoking
- Oxygen therapy
- Certain medication (furosemide)
- Radiation
- Total parenteral nutrition (TPN)
- The most common genetic mutation which plays role in etiology of sporadic cases include:[9]
- The Wnt signaling pathway which results in the accumulation of beta-catenin
Differentiating hepatoblastoma from Other Diseases
- Hepatoblastoma must be differentiated from other diseases that cause rapidly enlarging abdominal mass in pediatrics such as:[10]
- Hepatocellular carcinoma (HCC),
- Focal nodular hyperplasia
- Hepatic adenoma
- Lymphoma, and metastases
Epidemiology and Demographics
- Hepatoblastoma is the most common primary liver cancer in infants and children, tumor involves right lobe of liver more often.[11]
- The incidence/prevalence of hepatoblastoma is approximately 0.05–0.15 patients per 100 000 population in children younger than 15 years.[12]
- 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.
Risk Factors
- Common risk factors in the development of hepatoblastoma include:[6]
- Low birth weight infants
- Preeclampsia
- Fetal distress
- Premature labor
- Chromosomal anomalies such as Down syndrome, Edward syndrome.
- Parental tobacco smoking before and during pregnancy
- Oxygen therapy,
- Certain medication (furosemide)
- Total parenteral nutrition (TPN)
Screening
- Ultrasound is the main screening tool for suspected hepatic lesions in children.[13]
- Serum alpha-fetoprotein (AFP) is the most important clinical marker of hepatoblastoma and helps to estimate malignant change, response to the treatment, and relapse. [10]
Natural History, Complications, and Prognosis
- Prognosis is based on different factors including:[14][5]
- Age of diagnosis, younger children have a better prognosis.
- Metastases,
- Alfa-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.[15]
- Complications of hepatoblastoma includes:
Diagnosis
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.[10]
History and Symptoms
- The majority of patients with hepatoblastoma have an abdominal mass or abdominal distension. [10]
- Other symptoms of hepatoblastoma include:
- Abdominal discomfort,
- Generalized fatigue,
- Loss of appetite (Anorexia)
- Nausea and vomiting
- Ruptured tumor can cause symptoms of peritoneal irritation due to intraperitoneal bleeding such as severe abdominal pain, nausea, vomiting, and severe anemia.[17]
Physical Examination
- 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.[18][10]
- Most tumors are solitary; but can be multifocal as well.
Laboratory Findings
- Laboratory findings that help with the diagnosis of hepatoblastoma includes:[19]
- Anemia on complete blood count
- Thrombocytosis(more frequent because of the effect of thrombopoietin)[20]
- Thrombocytopenia(less common)
- High levels of Alpha fetoprotein(AFP)
- Mild liver function disturbances
Electrocardiogram
- There are no ECG findings associated with hepatoblastoma.
X-ray
- Chest X-Rays can be useful especially since this tumor has the affinity to metastasize to lungs.[21]
Echocardiography or Ultrasound
- 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
- CT scan is very helpful to diagnose the disease, children with hepatoblastoma undergo either a CT or MRI scan at diagnosis. [22]
- 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 findings of hypervascular lesions in the liver with delayed contrast excretion are highly suggestive of a malignant liver tumor.
MRI
- 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.[13]
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.[23][24]
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.[25][26]
Treatment
Medical Therapy
- 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.[27]
- Liver transplantation can be considered for tumors that cannot be removed by surgery.[28]
- 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.[29]
Surgery
- Surgery is the mainstay of treatment for hepatoblastoma.[30]
- The feasibility of surgery depends on the resectability of tumor at diagnosis.
Primary Prevention
- There are no established measures for the primary prevention of hepatoblastoma.
Secondary Prevention
- There are no established measures for the secondary prevention of hepatoblastoma.
References
- ↑ 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.
- ↑ 5.0 5.1 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.
- ↑ 6.0 6.1 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.
- ↑ 10.0 10.1 10.2 10.3 10.4 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.
- ↑ 13.0 13.1 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
|title=(help) - ↑ 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.