*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 [[Embryo|embryonal]] origin <ref name="pmid25336801">{{cite journal |vauthors=Aronson DC, Czauderna P, Maibach R, Perilongo G, Morland B |title=The treatment of hepatoblastoma: Its evolution and the current status as per the SIOPEL trials |journal=J Indian Assoc Pediatr Surg |volume=19 |issue=4 |pages=201–7 |date=October 2014 |pmid=25336801 |pmc=4204244 |doi=10.4103/0971-9261.142001 |url=}}</ref>
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 [[Embryo|embryonal]] origin
==Classification==
==Classification==
*Hepatoblastoma are divided into two broad categories:<ref name="pmid12228903">{{cite journal |vauthors=Rowland JM |title=Hepatoblastoma: assessment of criteria for histologic classification |journal=Med. Pediatr. Oncol. |volume=39 |issue=5 |pages=478–83 |date=November 2002 |pmid=12228903 |doi=10.1002/mpo.10171 |url=}}</ref><ref name="pmid24322718">{{cite journal |vauthors=Czauderna P, Lopez-Terrada D, Hiyama E, Häberle B, Malogolowkin MH, Meyers RL |title=Hepatoblastoma state of the art: pathology, genetics, risk stratification, and chemotherapy |journal=Curr. Opin. Pediatr. |volume=26 |issue=1 |pages=19–28 |date=February 2014 |pmid=24322718 |doi=10.1097/MOP.0000000000000046 |url=}}</ref>
Hepatoblastoma can be divided into major and minor categories based on histology. Major categories constitutes epithelial, small cell undifferentiated and rhabdoid while minor constitutes cholangioblastic (ductal), keratinising squamous epithelium, intestinal glandular epithelium, teratoid (neuroid-melanocytic), rhabdomyoblastic, chondroid, and osteoid.
**[[Epithelial]] type (E-HB)
*
***[[Fetal]], which has four subtypes:
****Well differentiated
****Crowded or [[mitotic]]<nowiki/>ally active
****[[Pleomorphic]]
****Poorly differentiated
****[[Anaplastic]]
***[[Embryo]]<nowiki/>nal
***Macrotubular small cell [[undifferentiated]] (SCU)
***Cholangioblastic
**Mixed [[epithelial]] and [[mesenchymal]] type (MEM-HB). The mixed type is subdivided into:
***[[Stromal]] derivatives
***[[Teratoma|Teratoid]] variants
==Pathophysiology==
==Pathophysiology==
*The exact [[pathogenesis]] of hepatoblastoma is not fully understood. <ref name="pmid19619488">{{cite journal |vauthors=MacDonald BT, Tamai K, He X |title=Wnt/beta-catenin signaling: components, mechanisms, and diseases |journal=Dev. Cell |volume=17 |issue=1 |pages=9–26 |date=July 2009 |pmid=19619488 |pmc=2861485 |doi=10.1016/j.devcel.2009.06.016 |url=}}</ref>
Development of hepatoblastoma is the result of multiple genetic mutations. Genes involved in the pathogenesis of hepatoblastoma include ''[[Beta-catenin|CTNNB1]]'', ''CAPRIN2'', ''[[SPOP]]'', ''[[OR5I1]]'', and ''CDC20B''. On gross pathology, hepatoblastoma is characterized by a solitary, large, well circumscribed mass with heterogeneous cut surface. On microscopic histopathological analysis, hepatoblastoma is characterized by small round cell tumor, fetal hepatocytes ~ 1:3 nuclear-cytoplasmic ratio, eosinophilic cytoplasm (mesenchymal component), and immature fibrous tissue osteoid or cartilage. Hepatoblastoma is demonstrated by positivity to [[alpha-fetoprotein]], hepatocyte specific antigen (especially in fetal component), and beta-catenin (cytoplasmic and nuclear).[[File:Hepatoblastoma.jpg|300x300px|thumb|Hepatoblastoma H&E[https://commons.wikimedia.org/wiki source:wikipedia]|center]]<br style="clear:left" />
*Loss of function [[mutations]] in [[APC]] leads to [[intracellular]] accumulation of the [[protooncogene]] [[beta-catenin]], which leads to [[germline]] [[mutation]] of [[Wnt signalling pathway|Wnt signal]] [[transduction]] and pathway.
*Hepatoblastomas originate from primitive [[hepatic]] [[stem cells]].
*[[Beta-catenin|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.<ref name="pmid29755772">{{cite journal |vauthors=Kiruthiga KG, Ramakrishna B, Saha S, Sen S |title=Histological and immunohistochemical study of hepatoblastoma: correlation with tumour behaviour and survival |journal=J Gastrointest Oncol |volume=9 |issue=2 |pages=326–337 |date=April 2018 |pmid=29755772 |pmc=5934143 |doi=10.21037/jgo.2018.01.08 |url=}}</ref>
*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:<ref name="pmid23558166">{{cite journal |vauthors=Heck JE, Meyers TJ, Lombardi C, Park AS, Cockburn M, Reynolds P, Ritz B |title=Case-control study of birth characteristics and the risk of hepatoblastoma |journal=Cancer Epidemiol |volume=37 |issue=4 |pages=390–5 |date=August 2013 |pmid=23558166 |pmc=3679264 |doi=10.1016/j.canep.2013.03.004 |url=}}</ref><ref name="pmid17425379">{{cite journal |vauthors=Finegold MJ, Lopez-Terrada DH, Bowen J, Washington MK, Qualman SJ |title=Protocol for the examination of specimens from pediatric patients with hepatoblastoma |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=4 |pages=520–9 |date=April 2007 |pmid=17425379 |doi=10.1043/1543-2165(2007)131[520:PFTEOS]2.0.CO;2 |url=}}</ref><ref name="pmid30270492">{{cite journal |vauthors=Mussa A, Duffy KA, Carli D, Ferrero GB, Kalish JM |title=Defining an optimal time window to screen for hepatoblastoma in children with Beckwith-Wiedemann syndrome |journal=Pediatr Blood Cancer |volume=66 |issue=1 |pages=e27492 |date=January 2019 |pmid=30270492 |doi=10.1002/pbc.27492 |url=}}</ref>
There are no specific causes of hepatoblastoma and most tumors are sporadic but there are some [[Hepatoblastoma risk factors|risk factors]] and conditions that have a strong association with this [[tumor]] such as [[Beckwith-Weidemann Syndrome|beckwith-Weidemann syndrome]], [[familial adenomatous polyposis]] (FAP), [[down syndrome]], [[Edward's syndrome|edward syndrome]] ([[trisomy 18]]).
**[[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:<ref name="pmid17962810">{{cite journal |vauthors=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 |title=Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 mutations |journal=Mod. Pathol. |volume=21 |issue=1 |pages=7–14 |date=January 2008 |pmid=17962810 |doi=10.1038/modpathol.3800977 |url=}}</ref>
**The [[Wnt signaling pathway]] which results in the accumulation of [[beta-catenin]].
==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>
Hepatoblastoma is a common tumor that tends to affect children aged less than five years. Males are more commonly affected with hepatoblastoma than females. The annual [[incidence]] of hepatoblastoma in the United States appears to have doubled from 8 (1975-1983) to 16 (2002-2009) per 100,000 children aged 19 years and younger.
*The incidence/[[prevalence]] of hepatoblastoma is approximately 0.05–0.15 patients per 100000 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.
*Hepatoblastoma accounts for one percent of all primary [[malignancies]] in [[pediatrics]].
==Risk factors==
==Risk factors==
*Common risk factors in the development of hepatoblastoma include:<ref name="pmid23558166">{{cite journal |vauthors=Heck JE, Meyers TJ, Lombardi C, Park AS, Cockburn M, Reynolds P, Ritz B |title=Case-control study of birth characteristics and the risk of hepatoblastoma |journal=Cancer Epidemiol |volume=37 |issue=4 |pages=390–5 |date=August 2013 |pmid=23558166 |pmc=3679264 |doi=10.1016/j.canep.2013.03.004 |url=}}</ref>
Common risk factors in the development of hepatoblastoma include [[Low birth weight]] infants, [[Preeclampsia]], [[Fetal distress]], [[Premature labor]], [[Chromosomal anomalies]] such as [[Down syndrome]], [[Edwards syndrome]]. parental [[tobacco]] [[smoking]] before and during [[pregnancy]], [[Oxygen therapy]], certain medication ([[furosemide]]), [[Total parenteral nutrition]] ([[TPN]]).
**[[Low birth weight]] infants
**[[Preeclampsia]]
**[[Fetal distress]]
**[[Premature labor]]
**[[Chromosomal anomalies]] such as [[Down syndrome]], [[Edwards syndrome]].
**Parental [[tobacco]] [[smoking]] before and during [[pregnancy]]
**[[Oxygen therapy]]
**Certain medication ([[furosemide]])
**[[Total parenteral nutrition]] ([[TPN]])
==Screening==
==Screening==
*[[Ultrasound]] is the main screening tool for suspected [[hepatic]] lesions in children.<ref name="pmid27526937">{{cite journal |vauthors=Shelmerdine SC, Roebuck DJ, Towbin AJ, McHugh K |title=MRI of paediatric liver tumours: How we review and report |journal=Cancer Imaging |volume=16 |issue=1 |pages=21 |date=August 2016 |pmid=27526937 |pmc=4986178 |doi=10.1186/s40644-016-0083-3 |url=}}</ref>
According to the American Association for the Study of Liver Diseases and United States Preventive Services Task Force, there is insufficient evidence to recommend routine screening for hepatoblastoma. However, [[ultrasound]] is the recommended 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]]. <ref name="pmid26835349">{{cite journal |vauthors=Hiyama E |title=Pediatric hepatoblastoma: diagnosis and treatment |journal=Transl Pediatr |volume=3 |issue=4 |pages=293–9 |date=October 2014 |pmid=26835349 |pmc=4728840 |doi=10.3978/j.issn.2224-4336.2014.09.01 |url=}}</ref>
==Differentiating Hepatoblastoma from other diseases==
==Differentiating Hepatoblastoma from other diseases==
Hepatoblastoma must be differentiated from other diseases such as [[Hamartoma|hepatic mesenchymal hamartoma]], [[hepatocellular carcinoma]], [[Hepatocellular carcinoma|hepatic metastases]], [[infantile hemangioendothelioma]], and [[Rhabdomyosarcoma|rhabdomyosarcoma of biliary tract]].<ref name=differential>Differential diagnosis of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 3, 2015</ref>
Hepatoblastoma must be differentiated from other diseases such as [[Hamartoma|hepatic mesenchymal hamartoma]], [[hepatocellular carcinoma]], [[Hepatocellular carcinoma|hepatic metastases]], [[infantile hemangioendothelioma]], and [[Rhabdomyosarcoma|rhabdomyosarcoma of biliary tract]].
==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
*Prognosis is based on different factors including:<ref name="pmid30521216">{{cite journal |vauthors=Musick SR, Babiker HM |title= |journal= |volume= |issue= |pages= |date= |pmid=30521216 |doi= |url=}}</ref><ref name="pmid29755772">{{cite journal |vauthors=Kiruthiga KG, Ramakrishna B, Saha S, Sen S |title=Histological and immunohistochemical study of hepatoblastoma: correlation with tumour behaviour and survival |journal=J Gastrointest Oncol |volume=9 |issue=2 |pages=326–337 |date=April 2018 |pmid=29755772 |pmc=5934143 |doi=10.21037/jgo.2018.01.08 |url=}}</ref>
**Age of diagnosis, younger children have a better prognosis.
If left untreated, patients with hepatoblastoma may progress to develop [[failure to thrive]], [[weight loss]], [[Abdominal mass|rapidly enlarging abdominal mass]], spontaneous rupture, [[hemorrhage]]. Common complications of hepatoblastoma include paraneoplastic features, [[erythrocytosis]], [[thrombocytosis]], [[hypocalcemia]], [[Precocious puberty|isosexual precocious puberty]], and [[hypoglycemia]]. The 5-year survival rate of children with hepatoblastoma is approximately 70%.
**[[Metastases]],
**[[Alpha-fetoprotein]] ([[AFP]]) levels, drop in [[Alpha-fetoprotein|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]].<ref name="pmid15718322">{{cite journal |vauthors=Aronson DC, Schnater JM, Staalman CR, Weverling GJ, Plaschkes J, Perilongo G, Brown J, Phillips A, Otte JB, Czauderna P, MacKinlay G, Vos A |title=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 |journal=J. Clin. Oncol. |volume=23 |issue=6 |pages=1245–52 |date=February 2005 |pmid=15718322 |doi=10.1200/JCO.2005.07.145 |url=}}</ref>
**Complications related to [[chemotherapy]] such as [[renal failure]]
**Post-[[transplant]] complications such as [[hepatic]] ductal [[obstruction]], [[biliary]] leakage, [[thrombosis]].<ref name="pmid25251521">{{cite journal |vauthors=Becker K, Furch C, Schmid I, von Schweinitz D, Häberle B |title=Impact of postoperative complications on overall survival of patients with hepatoblastoma |journal=Pediatr Blood Cancer |volume=62 |issue=1 |pages=24–8 |date=January 2015 |pmid=25251521 |doi=10.1002/pbc.25240 |url=}}</ref>
**[[Psychosocial]] effects of treatment and painful procedures
==Diagnosis==
==Diagnosis==
===Diagnostic study of choice===
===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.<ref name="pmid26835349">{{cite journal |vauthors=Hiyama E |title=Pediatric hepatoblastoma: diagnosis and treatment |journal=Transl Pediatr |volume=3 |issue=4 |pages=293–9 |date=October 2014 |pmid=26835349 |pmc=4728840 |doi=10.3978/j.issn.2224-4336.2014.09.01 |url=}}</ref>
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.
=== Screening ===
The staging of hepatoblastoma is based on the Intergroup staging system.
===History and Symptoms===
===History and Symptoms===
*The majority of patients with hepatoblastoma have an [[abdominal mass]] or [[abdominal distension]]. <ref name="pmid26835349">{{cite journal |vauthors=Hiyama E |title=Pediatric hepatoblastoma: diagnosis and treatment |journal=Transl Pediatr |volume=3 |issue=4 |pages=293–9 |date=October 2014 |pmid=26835349 |pmc=4728840 |doi=10.3978/j.issn.2224-4336.2014.09.01 |url=}}</ref>
The majority of patients with hepatoblastoma have an [[abdominal mass]] or [[abdominal distension]]. Other symptoms include [[abdominal pain]], [[weight loss]], [[loss of appetite]], early [[puberty]] in boys, [[jaundice]], [[nausea]], [[vomiting]], [[back pain]], [[failure to thrive]], and [[Abdominal mass|rapidly enlarging abdominal mass]].
*Other symptoms of hepatoblastoma include:
**[[Abdominal discomfort]]
**Generalized [[Fatigue (medical)|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]].<ref name="pmid16273660">{{cite journal |vauthors=Ke HY, Chen JH, Jen YM, Yu JC, Hsieh CB, Chen CJ, Liu YC, Chen TW, Chan DC |title=Ruptured hepatoblastoma with massive internal bleeding in an adult |journal=World J. Gastroenterol. |volume=11 |issue=39 |pages=6235–7 |date=October 2005 |pmid=16273660 |pmc=4436650 |doi= |url=}}</ref>
===Physical examination===
===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]].<ref name="pmid23330017">{{cite journal |vauthors=Zhang Q, Ming J, Zhang S, Guo D, Qiu X |title=A rare case of adult hepatoblastoma with neuroendocrine differentiation misdiagnosed as neuroendocrine tumor |journal=Int J Clin Exp Pathol |volume=6 |issue=2 |pages=308–13 |date=2013 |pmid=23330017 |pmc=3544231 |doi= |url=}}</ref><ref name="pmid26835349">{{cite journal |vauthors=Hiyama E |title=Pediatric hepatoblastoma: diagnosis and treatment |journal=Transl Pediatr |volume=3 |issue=4 |pages=293–9 |date=October 2014 |pmid=26835349 |pmc=4728840 |doi=10.3978/j.issn.2224-4336.2014.09.01 |url=}}</ref>
Common physical examination findings of hepatoblastoma include [[hepatomegaly]], [[abdominal distension]], [[Abdominal mass|asymptomatic palpable abdominal mass]], [[hemihypertrophy]], [[jaundice]], [[pyrexia]], and [[anemia]].
*Most tumors are [[solitary]]; but can be multifocal as well.
===Laboratory Findings===
===Laboratory Findings===
*Laboratory findings that help with the diagnosis of hepatoblastoma includes:<ref name="pmid49416">{{cite journal |vauthors=Exelby PR, Filler RM, Grosfeld JL |title=Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey--1974 |journal=J. Pediatr. Surg. |volume=10 |issue=3 |pages=329–37 |date=June 1975 |pmid=49416 |doi= |url=}}</ref>
Laboratory tests for liver function are usually normal among patients. An elevated concentration of [[alpha-fetoprotein]] is present in patients with hepatoblastoma.
**[[Anemia]] on [[Complete blood counts|complete blood count]]
**[[Thrombocytosis]] (more frequent because of the effect of [[thrombopoietin]])<ref name="pmid6153151">{{cite journal |vauthors=Nickerson HJ, Silberman TL, McDonald TP |title=Hepatoblastoma, thrombocytosis, and increased thrombopoietin |journal=Cancer |volume=45 |issue=2 |pages=315–7 |date=January 1980 |pmid=6153151 |doi= |url=}}</ref>
**[[Thrombocytopenia]] (less common)
**High levels of [[Alpha-fetoprotein]] ([[AFP]])
**Mild [[liver]] function disturbances
===Xray===
===Xray===
*[[Chest-X-Ray|Chest]] [[Chest X-ray|x-rays]] can be useful especially since this [[tumor]] has the affinity to [[metastasize]] to [[lungs]].<ref name="pmid11042582">{{cite journal |vauthors=Perilongo G, Brown J, Shafford E, Brock P, De Camargo B, Keeling JW, Vos A, Philips A, Pritchard J, Plaschkes J |title=Hepatoblastoma presenting with lung metastases: treatment results of the first cooperative, prospective study of the International Society of Paediatric Oncology on childhood liver tumors |journal=Cancer |volume=89 |issue=8 |pages=1845–53 |date=October 2000 |pmid=11042582 |doi= |url=}}</ref>
Findings on abdominal xray are nonspecific for hepatoblastoma and include [[Abdominal mass|right upper quadrant abdominal mass]] and/or calcifications in 10% of cases. [[Chest-X-Ray|Chest]] [[Chest X-ray|x-rays]] can be useful especially since this [[tumor]] has the affinity to [[metastasize]] to [[lungs]].
===CT===
===CT===
*[[CT scan]] is very helpful to diagnose the disease, children with hepatoblastoma undergo either a CT or [[MRI]] scan at diagnosis. <ref name="pmid27955729">{{cite journal |vauthors=Aronson DC, Meyers RL |title=Malignant tumors of the liver in children |journal=Semin. Pediatr. Surg. |volume=25 |issue=5 |pages=265–275 |date=October 2016 |pmid=27955729 |doi=10.1053/j.sempedsurg.2016.09.002 |url=}}</ref>
Abdominal CT scan may be helpful in the diagnosis of hepatoblastoma. Findings on CT scan suggestive of hepatoblastoma include well defined heterogeneous mass, frequent areas of necrosis and hemorrhage, and chunky dense calcifications.
*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===
[[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.
===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.<ref name="pmid27526937">{{cite journal |vauthors=Shelmerdine SC, Roebuck DJ, Towbin AJ, McHugh K |title=MRI of paediatric liver tumours: How we review and report |journal=Cancer Imaging |volume=16 |issue=1 |pages=21 |date=August 2016 |pmid=27526937 |pmc=4986178 |doi=10.1186/s40644-016-0083-3 |url=}}</ref>
===Ultrasound===
===Ultrasound===
*Imaging studies play an important role in the diagnosis, [[Staging (pathology)|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]].
Imaging studies play an important role in the diagnosis, [[Staging (pathology)|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]]. Findings on ultrasound suggestive of hepatoblastoma include echogenic soft tissue mass, well defined lesion, and areas of shadowing due to intralesional calcifications.
===Biopsy===
===Biopsy===
Biopsy is the gold standard for the diagnosis of hepatoblastoma.
Biopsy is the gold standard for the diagnosis of hepatoblastoma.
===Other Imaging Findings===
===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.<ref name="pmid16170514">{{cite journal |vauthors=Figarola MS, McQuiston SA, Wilson F, Powell R |title=Recurrent hepatoblastoma with localization by PET-CT |journal=Pediatr Radiol |volume=35 |issue=12 |pages=1254–8 |date=December 2005 |pmid=16170514 |doi=10.1007/s00247-005-1568-6 |url=}}</ref><ref name="pmid8293620">{{cite journal |vauthors=Archer D, Babyn P, Gilday D, Greenberg MA |title=Potentially misleading bone scan findings in patients with hepatoblastoma |journal=Clin Nucl Med |volume=18 |issue=12 |pages=1026–31 |date=December 1993 |pmid=8293620 |doi= |url=}}</ref>
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.
==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
*The mainstay of therapy for hepatoblastoma is [[Surgery|surger]]<nowiki/>y, however, the vast majority of the tumors cannot be completely resected because of their large size or [[metastasis]].<ref name="pmid26308249">{{cite journal |vauthors=Pham TA, Gallo AM, Concepcion W, Esquivel CO, Bonham CA |title=Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer |journal=JAMA Surg |volume=150 |issue=12 |pages=1150–8 |date=December 2015 |pmid=26308249 |doi=10.1001/jamasurg.2015.1847 |url=}}</ref>
The mainstay of therapy for hepatoblastoma is [[Surgery|surger]]<nowiki/>y. However, the vast majority of the tumors cannot be completely resected because of their large size or [[metastasis]]. [[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.
*Liver [[transplantation]] can be considered for [[tumors]] that cannot be removed by surgery.<ref name="pmid10839879">{{cite journal |vauthors=Reyes JD, Carr B, Dvorchik I, Kocoshis S, Jaffe R, Gerber D, Mazariegos GV, Bueno J, Selby R |title=Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence |journal=J. Pediatr. |volume=136 |issue=6 |pages=795–804 |date=June 2000 |pmid=10839879 |doi= |url=}}</ref>
*[[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.<ref name="pmid12778356">{{cite journal |vauthors=Häberle B, Bode U, von Schweinitz D |title=[Differentiated treatment protocols for high- and standard-risk hepatoblastoma--an interim report of the German Liver Tumor Study HB99] |language=German |journal=Klin Padiatr |volume=215 |issue=3 |pages=159–65 |date=2003 |pmid=12778356 |doi=10.1055/s-2003-39375 |url=}}</ref>
===Surgery===
===Surgery===
*[[Surgery]] is the mainstay of treatment for hepatoblastoma.<ref name="pmid30084209">{{cite journal |vauthors=Uchida H, Sakamoto S, Sasaki K, Takeda M, Hirata Y, Fukuda A, Hishiki T, Irie R, Nakazawa A, Miyazaki O, Nosaka S, Kasahara M |title=Surgical treatment strategy for advanced hepatoblastoma: Resection versus transplantation |journal=Pediatr Blood Cancer |volume=65 |issue=12 |pages=e27383 |date=December 2018 |pmid=30084209 |doi=10.1002/pbc.27383 |url=}}</ref>
[[Surgery]] is the mainstay of treatment for hepatoblastoma. Liver [[transplantation]] can be considered for [[tumors]] that cannot be removed by surgery. The feasibility of [[surgery]] depends on the resectability of [[tumor]] at diagnosis.
*The feasibility of [[surgery]] depends on the resectability of [[tumor]] at diagnosis.
===Primary Prevention===
===Primary Prevention===
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===Secondary Prevention===
===Secondary Prevention===
Effective measures for the secondary prevention of hepatoblastoma include use of abdominal ultrasound and alpha-fetoprotein levels in patients with [[Beckwith-Wiedemann syndrome]] or isolated hemihyperplasia.<ref name=risk>Beckwith-Wiedemann syndrome and hemihyperplasia. National Cancer Institute (2015). http://www.cancer.gov/types/liver/hp/child-liver-treatment-pdq#link/_509_toc Accessed on November 4, 2015</ref>
Effective measures for the secondary prevention of hepatoblastoma include use of abdominal [[ultrasound]] and [[alpha-fetoprotein]] levels in patients with [[Beckwith-Wiedemann syndrome]] or isolated hemihyperplasia.
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 livertumor because of it's embryonal origin
Classification
Hepatoblastoma can be divided into major and minor categories based on histology. Major categories constitutes epithelial, small cell undifferentiated and rhabdoid while minor constitutes cholangioblastic (ductal), keratinising squamous epithelium, intestinal glandular epithelium, teratoid (neuroid-melanocytic), rhabdomyoblastic, chondroid, and osteoid.
Pathophysiology
Development of hepatoblastoma is the result of multiple genetic mutations. Genes involved in the pathogenesis of hepatoblastoma include CTNNB1, CAPRIN2, SPOP, OR5I1, and CDC20B. On gross pathology, hepatoblastoma is characterized by a solitary, large, well circumscribed mass with heterogeneous cut surface. On microscopic histopathological analysis, hepatoblastoma is characterized by small round cell tumor, fetal hepatocytes ~ 1:3 nuclear-cytoplasmic ratio, eosinophilic cytoplasm (mesenchymal component), and immature fibrous tissue osteoid or cartilage. Hepatoblastoma is demonstrated by positivity to alpha-fetoprotein, hepatocyte specific antigen (especially in fetal component), and beta-catenin (cytoplasmic and nuclear).
Hepatoblastoma is a common tumor that tends to affect children aged less than five years. Males are more commonly affected with hepatoblastoma than females. The annual incidence of hepatoblastoma in the United States appears to have doubled from 8 (1975-1983) to 16 (2002-2009) per 100,000 children aged 19 years and younger.
According to the American Association for the Study of Liver Diseases and United States Preventive Services Task Force, there is insufficient evidence to recommend routine screening for hepatoblastoma. However, ultrasound is the recommended for suspected hepatic lesions in children.
Differentiating Hepatoblastoma from other diseases
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.
Screening
The staging of hepatoblastoma is based on the Intergroup staging system.
Laboratory tests for liver function are usually normal among patients. An elevated concentration of alpha-fetoprotein is present in patients with hepatoblastoma.
Abdominal CT scan may be helpful in the diagnosis of hepatoblastoma. Findings on CT scan suggestive of hepatoblastoma include well defined heterogeneous mass, frequent areas of necrosis and hemorrhage, and chunky dense calcifications.
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 abdominalultrasound. Findings on ultrasound suggestive of hepatoblastoma include echogenic soft tissue mass, well defined lesion, and areas of shadowing due to intralesional calcifications.
Biopsy
Biopsy is the gold standard for the diagnosis of hepatoblastoma.
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.
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. 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
Surgery is the mainstay of treatment for hepatoblastoma. Liver transplantation can be considered for tumors that cannot be removed by surgery. The feasibility of surgery depends on the resectability of tumor at diagnosis.
Primary Prevention
There are no primary preventive measures available for hepatoblastoma.
