'''Hepatoblastoma''' is an uncommon malignant liver neoplasm occurring in infants and children and composed of tissue resembling fetal or mature liver cells or [[bile duct]]s. Hepatoblastoma was first described in 1958 by I. Bartok.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref> It may be classified into two groups based on histology, [[Hepatoblastoma|major category]] and [[Hepatoblastoma|minor category]].<ref name=a>Classification of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia (2015). http://radiopaedia.org/articles/hepatoblastoma-histological-classification. Accessed on November 3, 2015</ref> Development of hepatoblastoma is the result of multiple genetic mutations. On gross pathology, it is characterized by well circumscribed large masses, usually single, with heterogeneous cut surface.<ref name=differential>Pathology of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 3, 2015</ref> There are no established causes for hepatoblastoma.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref> Hepatoblastoma is a common tumor that tends to affect children aged less than five years.<ref name="AllanParikh2013">{{cite journal|last1=Allan|first1=Bassan J.|last2=Parikh|first2=Punam P.|last3=Diaz|first3=Sofia|last4=Perez|first4=Eduardo A.|last5=Neville|first5=Holly L.|last6=Sola|first6=Juan E.|title=Predictors of survival and incidence of hepatoblastoma in the paediatric population|journal=HPB|volume=15|issue=10|year=2013|pages=741–746|issn=1365182X|doi=10.1111/hpb.12112}}</ref> 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.<ref name=risk>Incidence. National Cancer Institute 2015. http://www.cancer.gov/types/liver/hp/child-liver-treatment-pdq#link/_570_toc. Accessed on October 28, 2015</ref> To view a comprehensive list of risk factors that increase the risk of hepatoblastoma, click [[Hepatoblastoma risk factors|here]].<ref name=risk>Risk factors. National Cancer Institute 2015. http://www.cancer.gov/types/liver/hp/child-liver-treatment-pdq#link/_570_toc. Accessed on October 28, 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.<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> 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> If left untreated, patients with hepatoblastoma may progress to develop [[failure to thrive]], [[weight loss]], [[Abdominal mass|rapidly enlarging abdominal mass]], spontaneous rupture, hemorrhage, and death.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref> The staging of hepatoblastoma is based on the Intergroup staging system.<ref name=staging>Intergroup staging system of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma-staging-2. Accessed on November 3, 2015</ref> Symptoms of hepatoblastoma include [[Abdominal mass|painless lump in the abdomen]], [[abdominal pain]], and [[weight loss]].<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref><ref name=differential>Clinical presentation of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 5, 2015</ref> Common physical examination findings of hepatoblastoma include [[hepatomegaly]], [[Abdominal mass|asymptomatic palpable abdominal mass]], [[hemihypertrophy]], [[jaundice]], [[pyrexia]], and [[anemia]].<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref><ref name=differential>Clinical presentation of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 5, 2015</ref> Laboratory tests for liver function are usually normal. 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 chunkycdense calcifications.<ref name=differential>CT scan of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 4, 2015</ref> Other diagnostic studies for hepatoblastoma include [[biopsy]]. The predominant therapy for hepatoblastoma is surgical resection. [[Neoadjuvant]] and [[adjuvant chemotherapy]] may be required.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref> [[Surgery]] is the mainstay of treatment for hepatoblastoma.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref>
'''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|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 (pathology)|staging]], and recurrence of the [[tumor]]. The mainstay of treatment is [[surgery]], but the [[adjuvant]] [[Chemotherapeutic agent|chemotherapeutic]] agents and [[liver transplantation]] also are helpful.
==Historical Perspective==
==Historical Perspective==
Hepatoblastoma was first described in 1958 by I. Bartok.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</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 may be classified into two groups based on histology, [[Hepatoblastoma|major category]] and [[Hepatoblastoma|minor category]].<ref name=a>Classification of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia (2015). http://radiopaedia.org/articles/hepatoblastoma-histological-classification. Accessed on November 3, 2015</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.
*
==Pathophysiology==
==Pathophysiology==
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.<ref name=differrential>Pathology of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 3, 2015</ref> On microscopic histopathological analysis, hepatoblastoma is characterized by small round cell tumor, fetal hepatocytes ~ 1:3 NC ratio, eosinophilic cytoplasm (mesenchymal component), and immature fibrous tissue osteoid or cartilage.<ref name=microscopy>Microscopic features of hepatoblastoma. Librepathology (2015). Accessed on http://librepathology.org/wiki/index.php/Liver_neoplasms#Hepatoblastoma. November 3, 2015</ref> Hepatoblastoma is demonstrated by positivity to [[alpha-fetoprotein]], hepatocyte specific antigen (especially in fetal component), and ''[[beta-catenin]]'' (cytoplasmic and nuclear).<ref name=microscopy>IHC of hepatoblastoma. Librepathology (2015). Accessed on http://librepathology.org/wiki/index.php/Liver_neoplasms#Hepatoblastoma. November 4, 2015</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" />
==Causes==
==Causes==
There are no established causes for hepatoblastoma.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</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]]).
==Epidemiology and Demographics==
==Epidemiology and Demographics==
Hepatoblastoma is a common tumor that tends to affect children aged less than five years.<ref name="AllanParikh2013">{{cite journal|last1=Allan|first1=Bassan J.|last2=Parikh|first2=Punam P.|last3=Diaz|first3=Sofia|last4=Perez|first4=Eduardo A.|last5=Neville|first5=Holly L.|last6=Sola|first6=Juan E.|title=Predictors of survival and incidence of hepatoblastoma in the paediatric population|journal=HPB|volume=15|issue=10|year=2013|pages=741–746|issn=1365182X|doi=10.1111/hpb.12112}}</ref> Males are more commonly affected with hepatoblastoma than females.<ref name=differential>Epidemiology of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 6, 2015</ref> 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.<ref name=risk>Incidence. National Cancer Institute 2015. http://www.cancer.gov/types/liver/hp/child-liver-treatment-pdq#link/_570_toc. Accessed on October 28, 2015</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.
==Risk factors==
==Risk factors==
To view a comprehensive list of risk factors that increase the risk of hepatoblastoma, click [[Hepatoblastoma risk factors|here]].<ref name=risk>Risk factors. National Cancer Institute 2015. http://www.cancer.gov/types/liver/hp/child-liver-treatment-pdq#link/_570_toc. Accessed on October 28, 2015</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]]).
==Screening==
==Screening==
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.<ref name=abc>Hepatoblastoma. USPSTF. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=hepatoblastoma</ref><ref>Hepatoblastoma. AASLD. https://www.aasld.org/search/node/hepatoblastoma%20screening</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.<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>
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==
==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==
If left untreated, patients with hepatoblastoma may progress to develop [[failure to thrive]], [[weight loss]], [[Abdominal mass|rapidly enlarging abdominal mass]], spontaneous rupture, hemorrhage and death.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref> Common complications of hepatoblastoma include paraneoplastic features, [[erythrocytosis]], [[thrombocytosis]], [[hypocalcemia]], [[Precocious puberty|isosexual precocious puberty]], [[hypoglycemia]].<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref> The 5-year survival rate of children with hepatoblastoma is approximately 70%.<ref name=risk>Prognosis and Prognostic Factors. National Cancer Institute 2015. http://www.cancer.gov/types/liver/hp/child-liver-treatment-pdq#link/_570_toc. Accessed on October 28, 2015</ref>
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%.
==Diagnosis==
==Diagnosis==
===Staging===
===Diagnostic study of choice===
The staging of hepatoblastoma is based on the Intergroup staging system.<ref name=staging>Intergroup staging system of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma-staging-2. Accessed on November 3, 2015</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===
Symptoms of hepatoblastoma include [[Abdominal mass|painless lump in the abdomen]], [[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]].<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref><ref name=differential>Clinical presentation of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 5, 2015</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]].
===Physical examination===
===Physical examination===
Common physical examination findings of hepatoblastoma include [[hepatomegaly]], [[abdominal distension]], [[Abdominal mass|asymptomatic palpable abdominal mass]], [[hemihypertrophy]], [[jaundice]], [[pyrexia]], and [[anemia]].<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref><ref name=differential>Clinical presentation of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 5, 2015</ref>
Common physical examination findings of hepatoblastoma include [[hepatomegaly]], [[abdominal distension]], [[Abdominal mass|asymptomatic palpable abdominal mass]], [[hemihypertrophy]], [[jaundice]], [[pyrexia]], and [[anemia]].
===Laboratory Findings===
===Laboratory Findings===
Laboratory tests for liver function are usually normal. An elevated concentration of [[alpha-fetoprotein]] is present in patients with hepatoblastoma.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref>
Laboratory tests for liver function are usually normal among patients. An elevated concentration of [[alpha-fetoprotein]] is present in patients with hepatoblastoma.
===Xray===
===Xray===
Findings on abdominal xray are nonspecific for hepatoblastoma and include [[Abdominal mass|right upper quadrant abdominal mass]] and/or calcifications in 10% of cases.<ref name=differential>Ultrasound scan of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia (2015). http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 4, 2015</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===
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.<ref name=differential>CT scan of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 4, 2015</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.
===MRI===
===MRI===
Abdominal [[MRI]] is helpful in the diagnosis of hepatoblastoma. On MRI, hepatoblastoma is characterized by hypointensity on T1-weighted imaging and hyperintensity compared to liver with areas of necrosis and hemorrhage on T2-weighted imaging.<ref name=differential>Radiographic features MRI of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 4, 2015</ref>
[[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.
===Ultrasound===
===Ultrasound===
[[Ultrasound]] may be helpful in the diagnosis of hepatoblastoma. Findings on ultrasound suggestive of hepatoblastoma include echogenic soft tissue mass, well defined lesion, and areas of shadowing due to intralesional calcifications.<ref name=differential>Ultrasound of hepatoblastoma. Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hepatoblastoma. Accessed on November 4, 2015</ref>
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.
===Other Diagnostic Studies===
Other diagnostic studies for hepatoblastoma include [[biopsy]]. Histopathological findings on biopsy can be found [[Hepatoblastoma pathophysiology|here]].<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</ref>
===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==
==Treatment==
===Medical Therapy===
===Medical Therapy===
The predominant therapy for hepatoblastoma is surgical resection. [[Neoadjuvant]] and [[adjuvant chemotherapy]] may be required.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</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.
===Surgery===
===Surgery===
Surgery is the mainstay of treatment for hepatoblastoma.<ref name="MadabhaviPatel2014">{{cite journal|last1=Madabhavi|first1=Irappa|last2=Patel|first2=Apurva|last3=Choudhary|first3=Mukesh|last4=Aagre|first4=Suhas|last5=Revannasiddaiah|first5=Swaroop|last6=Modi|first6=Gaurang|last7=Anand|first7=Asha|last8=Panchal|first8=Harsha|last9=Parikh|first9=Sonia|last10=Raut|first10=Shreeniwas|title=Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity|journal=Case Reports in Pediatrics|volume=2014|year=2014|pages=1–5|issn=2090-6803|doi=10.1155/2014/104543}}</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.
===Primary Prevention===
===Primary Prevention===
There are no primary preventive measures available for hepatoblastoma.
There are no primary preventive measures available for hepatoblastoma.
===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.