Fibrolamellar hepatocellular carcinoma: Difference between revisions
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==Overview== | ==Overview== | ||
Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of primary liver cancer. Fibrolamellar hepatocellular carcinoma was first described Edmondson in 1956.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref><ref name="pmid13282629">{{cite journal |vauthors=EDMONDSON HA |title=Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood |journal=AMA J Dis Child |volume=91 |issue=2 |pages=168–86 |year=1956 |pmid=13282629 |doi= |url=}}</ref> Fibrolamellar hepatocellular carcinoma most commonly in children and young adults. | '''Fibrolamellar hepatocellular carcinoma''' (''FLC'') is a rare subtype of primary liver cancer. Fibrolamellar hepatocellular carcinoma was first described Edmondson in 1956.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref><ref name="pmid13282629">{{cite journal |vauthors=EDMONDSON HA |title=Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood |journal=AMA J Dis Child |volume=91 |issue=2 |pages=168–86 |year=1956 |pmid=13282629 |doi= |url=}}</ref> Fibrolamellar hepatocellular carcinoma most commonly in children and young adults. The pathogenesis of fibrolamellar hepatocellular carcinoma is characterized by the lack of cirrhosis. Common causes of fibrolamellar hepatocellular carcinoma, include: active hepatic inflammation, hepatitis B or C viral infection, alcohol-related liver disease, nonalcoholic fatty liver disease, and dietary aflatoxin B1. The majority of patients with fibrolamellar hepatocellular carcinoma remain asymptomatic for years. Early clinical features include abdominal pain, weight loss, and malaise. If left untreated, the majority of patients with fibrolamellar hepatocellular carcinoma may progress to develop metastasis to abdominal lymph nodes, peritoneum, and lung. Common complications of fibrolamellar hepatocellular carcinoma, include: hepatic failure, caval compression syndrome, gynecomastia, and cold agglutinin disease. | ||
==Historical Perspective== | ==Historical Perspective== | ||
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==Classification== | ==Classification== | ||
*There is no classification for fibrolamellar hepatocellular carcinoma. | *There is no classification for fibrolamellar hepatocellular carcinoma.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
==Pathophysiology== | ==Pathophysiology== | ||
*The pathogenesis of fibrolamellar hepatocellular carcinoma is characterized by the lack of cirrhosis. | *The pathogenesis of fibrolamellar hepatocellular carcinoma is characterized by the lack of cirrhosis.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
*The overexpression of DNAJB1-PRKACA gene has been associated with the development of fibrolamellar hepatocellular carcinoma. | *The overexpression of DNAJB1-PRKACA gene has been associated with the development of fibrolamellar hepatocellular carcinoma. | ||
*On gross pathology characteristic findings of fibrolamellar hepatocellular carcinoma, include: | *On gross pathology characteristic findings of fibrolamellar hepatocellular carcinoma, include: | ||
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==Causes== | ==Causes== | ||
* Common causes of fibrolamellar hepatocellular carcinoma, include: | * Common causes of fibrolamellar hepatocellular carcinoma, include:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
:*Active hepatic inflammation | :*Active hepatic inflammation | ||
:*Hepatitis B or C viral infection | :*Hepatitis B or C viral infection | ||
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==Differentiating Fibrolamellar Hepatocellular Carcinoma from Other Diseases== | ==Differentiating Fibrolamellar Hepatocellular Carcinoma from Other Diseases== | ||
*Fibrolamellar hepatocellular carcinoma must be differentiated from other diseases that cause abdominal pain, weight loss, and malaise such as: | *Fibrolamellar hepatocellular carcinoma must be differentiated from other diseases that cause abdominal pain, weight loss, and malaise such as:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
:*Hepatocellular carcinoma | :*Hepatocellular carcinoma | ||
:*Focal nodular hyperplasia | :*Focal nodular hyperplasia | ||
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==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
* In 2012, the incidence of fibrolamellar hepatocellular carcinoma was estimated to be 0.02 cases per 100,000 individuals in United States. | * In 2012, the incidence of fibrolamellar hepatocellular carcinoma was estimated to be 0.02 cases per 100,000 individuals in United States.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
===Age=== | ===Age=== | ||
*The median age of fibrolamellar hepatocellular carcinoma diagnosis is 33 years | *The median age of fibrolamellar hepatocellular carcinoma diagnosis is 33 years.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
*Fibrolamellar hepatocellular carcinoma is more commonly observed among patients aged 15 to 40 years old.<ref name="pmid16334779">{{cite journal |vauthors=Aramaki M, Kawano K, Sasaki A, Ohno T, Tahara K, Kai S, Iwashita Y, Kitano S |title=Hepatocellular carcinoma in young adults |journal=Hepatogastroenterology |volume=52 |issue=66 |pages=1795–7 |year=2005 |pmid=16334779 |doi= |url=}}</ref> | *Fibrolamellar hepatocellular carcinoma is more commonly observed among patients aged 15 to 40 years old.<ref name="pmid16334779">{{cite journal |vauthors=Aramaki M, Kawano K, Sasaki A, Ohno T, Tahara K, Kai S, Iwashita Y, Kitano S |title=Hepatocellular carcinoma in young adults |journal=Hepatogastroenterology |volume=52 |issue=66 |pages=1795–7 |year=2005 |pmid=16334779 |doi= |url=}}</ref> | ||
*Fibrolamellar hepatocellular carcinoma is more commonly observed among young patients.<ref name="pmid16334779">{{cite journal |vauthors=Aramaki M, Kawano K, Sasaki A, Ohno T, Tahara K, Kai S, Iwashita Y, Kitano S |title=Hepatocellular carcinoma in young adults |journal=Hepatogastroenterology |volume=52 |issue=66 |pages=1795–7 |year=2005 |pmid=16334779 |doi= |url=}}</ref> | *Fibrolamellar hepatocellular carcinoma is more commonly observed among young patients.<ref name="pmid16334779">{{cite journal |vauthors=Aramaki M, Kawano K, Sasaki A, Ohno T, Tahara K, Kai S, Iwashita Y, Kitano S |title=Hepatocellular carcinoma in young adults |journal=Hepatogastroenterology |volume=52 |issue=66 |pages=1795–7 |year=2005 |pmid=16334779 |doi= |url=}}</ref> | ||
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===Race=== | ===Race=== | ||
*There is a racial predilection for Caucasian race in patients with fibrolamellar hepatocellular carcinoma. | *There is a racial predilection for Caucasian race in patients with fibrolamellar hepatocellular carcinoma.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
==Risk Factors== | ==Risk Factors== | ||
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== Natural History, Complications and Prognosis== | == Natural History, Complications and Prognosis== | ||
*The majority of patients with fibrolamellar hepatocellular carcinoma remain asymptomatic for years. | *The majority of patients with fibrolamellar hepatocellular carcinoma remain asymptomatic for years. | ||
*Early clinical features include abdominal pain, weight loss, and malaise. | *Early clinical features include abdominal pain, weight loss, and malaise.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
*If left untreated, the majority of patients with fibrolamellar hepatocellular carcinoma may progress to develop metastasis to abdominal lymph nodes, peritoneum, and lung. | *If left untreated, the majority of patients with fibrolamellar hepatocellular carcinoma may progress to develop metastasis to abdominal lymph nodes, peritoneum, and lung. | ||
*Common complications of fibrolamellar hepatocellular carcinoma, include: | *Common complications of fibrolamellar hepatocellular carcinoma, include: | ||
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== Diagnosis == | == Diagnosis == | ||
===Diagnostic Criteria=== | ===Diagnostic Criteria=== | ||
*The diagnosis of fibrolamellar hepatocellular carcinoma is made with the following diagnostic criteria: | *The diagnosis of fibrolamellar hepatocellular carcinoma is made with the following diagnostic criteria:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
:*Positive imaging findings | :*Positive imaging findings | ||
::*Central scar | ::*Central scar | ||
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=== Symptoms === | === Symptoms === | ||
*Fibrolamellar hepatocellular carcinoma is usually asymptomatic. | *Fibrolamellar hepatocellular carcinoma is usually asymptomatic. | ||
*Symptoms of fibrolamellar hepatocellular carcinoma may include the following: | *Symptoms of fibrolamellar hepatocellular carcinoma may include the following:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
:*Fatigue | :*Fatigue | ||
:*Weight loss | :*Weight loss | ||
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=== Physical Examination === | === Physical Examination === | ||
*Patients with fibrolamellar hepatocellular carcinoma may be well-appearing, or cachectic. | *Patients with fibrolamellar hepatocellular carcinoma may be well-appearing, or cachectic. | ||
*Physical examination of the abdomen may be remarkable for: | *Physical examination of the abdomen may be remarkable for:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
'''Auscultation''' | '''Auscultation''' | ||
*Positive liver scratch test for enlarged liver size. | *Positive liver scratch test for enlarged liver size. | ||
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*Tenderness in right upper quadrant | *Tenderness in right upper quadrant | ||
*[[Hepatomegaly]] | *[[Hepatomegaly]] | ||
*Other physical signs for fibrolamellar hepatocellular carcinoma, may include: | *Other physical signs for fibrolamellar hepatocellular carcinoma, may include:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
*[[Pallor]] | *[[Pallor]] | ||
*[[Jaundice]] | *[[Jaundice]] | ||
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=== Laboratory Findings === | === Laboratory Findings === | ||
*Laboratory findings consistent with the diagnosis of fibrolamellar hepatocellular carcinoma, include | *Laboratory findings consistent with the diagnosis of fibrolamellar hepatocellular carcinoma, include:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
:*Elevated serum levels of aspartate aminotransferase (AST) | :*Elevated serum levels of aspartate aminotransferase (AST) | ||
:*Elevated serum levels of alanine aminotransferase (ALT) | :*Elevated serum levels of alanine aminotransferase (ALT) | ||
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*CT is the imaging modality of choice for fibrolamellar hepatocellular carcinoma | *CT is the imaging modality of choice for fibrolamellar hepatocellular carcinoma | ||
*On CT, findings of fibrolamellar hepatocellular carcinoma, include: | *On CT, findings of fibrolamellar hepatocellular carcinoma, include: | ||
*On MRI, findings of fibrolamellar hepatocellular carcinoma, include: | :*Single large tumors | ||
:*Central scar (seen in ~75% of cases) | |||
:*Central scar shows persistent enhancement on delayed contrast enhanced CT. | |||
*On MRI, findings of fibrolamellar hepatocellular carcinoma, include:<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | |||
:*T1: typically iso to hypointense to the liver | :*T1: typically iso to hypointense to the liver | ||
:*T2: hypo to slightly hyperintense | :*T2: hypo to slightly hyperintense | ||
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=== Other Diagnostic Studies === | === Other Diagnostic Studies === | ||
*Fibrolamellar hepatocellular carcinoma may also be diagnosed using PET. | *Fibrolamellar hepatocellular carcinoma may also be diagnosed using PET.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
*Findings on PET scan, include: | *Findings on PET scan, include: | ||
:*Technetium-99m sulphur colloid scans (taken up by Kupffer cells) are useful as these tumours will not accumulate the agent, whereas FNH does. | :*Technetium-99m sulphur colloid scans (taken up by Kupffer cells) are useful as these tumours will not accumulate the agent, whereas FNH does. | ||
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== Treatment == | == Treatment == | ||
=== Medical Therapy === | === Medical Therapy === | ||
*Chemotherapy is the treatment of choice for fibrolamellar hepatocellular carcinoma. | *Chemotherapy is the treatment of choice for fibrolamellar hepatocellular carcinoma.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
=== Surgery === | === Surgery === | ||
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=== Prevention === | === Prevention === | ||
*There are no primary preventive measures available for fibrolamellar hepatocellular carcinoma. | *There are no primary preventive measures available for fibrolamellar hepatocellular carcinoma. | ||
*Once diagnosed and successfully treated, patients with fibrolamellar hepatocellular carcinoma are followed-up every 3, 6 or 12 months. | *Once diagnosed and successfully treated, patients with fibrolamellar hepatocellular carcinoma are followed-up every 3, 6 or 12 months.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref> | ||
*Follow-up testing include ultrasound, physical exam, and laboratory testing. | *Follow-up testing include ultrasound, physical exam, and laboratory testing. | ||
Revision as of 20:04, 15 April 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Synonyms and keywords: Fibrolamellar carcinoma; FLC
Overview
Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of primary liver cancer. Fibrolamellar hepatocellular carcinoma was first described Edmondson in 1956.[1][2] Fibrolamellar hepatocellular carcinoma most commonly in children and young adults. The pathogenesis of fibrolamellar hepatocellular carcinoma is characterized by the lack of cirrhosis. Common causes of fibrolamellar hepatocellular carcinoma, include: active hepatic inflammation, hepatitis B or C viral infection, alcohol-related liver disease, nonalcoholic fatty liver disease, and dietary aflatoxin B1. The majority of patients with fibrolamellar hepatocellular carcinoma remain asymptomatic for years. Early clinical features include abdominal pain, weight loss, and malaise. If left untreated, the majority of patients with fibrolamellar hepatocellular carcinoma may progress to develop metastasis to abdominal lymph nodes, peritoneum, and lung. Common complications of fibrolamellar hepatocellular carcinoma, include: hepatic failure, caval compression syndrome, gynecomastia, and cold agglutinin disease.
Historical Perspective
Classification
- There is no classification for fibrolamellar hepatocellular carcinoma.[1]
Pathophysiology
- The pathogenesis of fibrolamellar hepatocellular carcinoma is characterized by the lack of cirrhosis.[1]
- The overexpression of DNAJB1-PRKACA gene has been associated with the development of fibrolamellar hepatocellular carcinoma.
- On gross pathology characteristic findings of fibrolamellar hepatocellular carcinoma, include:
- Hard, scirrhous, and well-circumscribed
- Tumor bulging
- white-brown tumor with fibrous bands throughout and central stellate scar
- On microscopic histopathological analysis, characteristic findings of fibrolamellar hepatocellular carcinoma, include:
- Tumor cells grow in sheets
- Trabeculae that are separated by collagen bundles (lamellar pattern)
- Large cells that contain abundant mitochondria
- Coarsely granular cytoplasm
- On immunohistochemistry, characteristic findings of fibrolamellar hepatocellular carcinoma, include:
- Positive staining for hepatocyte paraffin 1 (HepPar1)
- Positive staining for glypican-3 (GPC3)
- Positive staining polyclonal carcinoembryonic antigen (pCEA)
- CD10 positivity
Causes
- Common causes of fibrolamellar hepatocellular carcinoma, include:[1]
- Active hepatic inflammation
- Hepatitis B or C viral infection
- Alcohol-related liver disease
- Nonalcoholic fatty liver disease
- Dietary aflatoxin B1
Differentiating Fibrolamellar Hepatocellular Carcinoma from Other Diseases
- Fibrolamellar hepatocellular carcinoma must be differentiated from other diseases that cause abdominal pain, weight loss, and malaise such as:[1]
- Hepatocellular carcinoma
- Focal nodular hyperplasia
- Hepatic adenoma
- Hepatic metastasis
Epidemiology and Demographics
- In 2012, the incidence of fibrolamellar hepatocellular carcinoma was estimated to be 0.02 cases per 100,000 individuals in United States.[1]
Age
- The median age of fibrolamellar hepatocellular carcinoma diagnosis is 33 years.[1]
- Fibrolamellar hepatocellular carcinoma is more commonly observed among patients aged 15 to 40 years old.[3]
- Fibrolamellar hepatocellular carcinoma is more commonly observed among young patients.[3]
Gender
- Fibrolamellar hepatocellular carcinoma affects men and women equally.
Race
- There is a racial predilection for Caucasian race in patients with fibrolamellar hepatocellular carcinoma.[1]
Risk Factors
- There are no risk factors for the development of fibrolamellar hepatocellular carcinoma.
Natural History, Complications and Prognosis
- The majority of patients with fibrolamellar hepatocellular carcinoma remain asymptomatic for years.
- Early clinical features include abdominal pain, weight loss, and malaise.[1]
- If left untreated, the majority of patients with fibrolamellar hepatocellular carcinoma may progress to develop metastasis to abdominal lymph nodes, peritoneum, and lung.
- Common complications of fibrolamellar hepatocellular carcinoma, include:
- Hepatic failure
- Caval compression syndrome
- Gynecomastia
- Cold agglutinin disease
- Prognosis will depend on stage at diagnosis. The average survival of patients with fibrolamellar carcinoma in the United States is 73% at 1 year and 32% at 5 years.
Diagnosis
Diagnostic Criteria
- The diagnosis of fibrolamellar hepatocellular carcinoma is made with the following diagnostic criteria:[1]
- Positive imaging findings
- Central scar
- Small calcifications
- Single large tumor
- Clinical criteria:
- Young onset
- No previous history of liver disease
Symptoms
- Fibrolamellar hepatocellular carcinoma is usually asymptomatic.
- Symptoms of fibrolamellar hepatocellular carcinoma may include the following:[1]
- Fatigue
- Weight loss
- Abdominal distension
- Nausea
Physical Examination
- Patients with fibrolamellar hepatocellular carcinoma may be well-appearing, or cachectic.
- Physical examination of the abdomen may be remarkable for:[1]
Auscultation
- Positive liver scratch test for enlarged liver size.
Percussion
- Dull percussion
Palpation
- Abdominal mass
- Tenderness in right upper quadrant
- Hepatomegaly
- Other physical signs for fibrolamellar hepatocellular carcinoma, may include:[1]
- Pallor
- Jaundice
- Plantar and palmar erythema
Laboratory Findings
- Laboratory findings consistent with the diagnosis of fibrolamellar hepatocellular carcinoma, include:[1]
- Elevated serum levels of aspartate aminotransferase (AST)
- Elevated serum levels of alanine aminotransferase (ALT)
- Elevated serum levels of alpha-fetoprotein (unspecific)
- Elevated transcobalamin I level
Imaging Findings
- CT is the imaging modality of choice for fibrolamellar hepatocellular carcinoma
- On CT, findings of fibrolamellar hepatocellular carcinoma, include:
- Single large tumors
- Central scar (seen in ~75% of cases)
- Central scar shows persistent enhancement on delayed contrast enhanced CT.
- On MRI, findings of fibrolamellar hepatocellular carcinoma, include:[1]
- T1: typically iso to hypointense to the liver
- T2: hypo to slightly hyperintense
- T1C+: arterial phase: heterogeneous enhancement/ portal delayed phase: iso to hypointense
Other Diagnostic Studies
- Fibrolamellar hepatocellular carcinoma may also be diagnosed using PET.[1]
- Findings on PET scan, include:
- Technetium-99m sulphur colloid scans (taken up by Kupffer cells) are useful as these tumours will not accumulate the agent, whereas FNH does.
Treatment
Medical Therapy
- Chemotherapy is the treatment of choice for fibrolamellar hepatocellular carcinoma.[1]
Surgery
- Surgical resection is the treatment of choice for fibrolamellar hepatocellular carcinoma
Prevention
- There are no primary preventive measures available for fibrolamellar hepatocellular carcinoma.
- Once diagnosed and successfully treated, patients with fibrolamellar hepatocellular carcinoma are followed-up every 3, 6 or 12 months.[1]
- Follow-up testing include ultrasound, physical exam, and laboratory testing.
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016
- ↑ 2.0 2.1 EDMONDSON HA (1956). "Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood". AMA J Dis Child. 91 (2): 168–86. PMID 13282629.
- ↑ 3.0 3.1 Aramaki M, Kawano K, Sasaki A, Ohno T, Tahara K, Kai S, Iwashita Y, Kitano S (2005). "Hepatocellular carcinoma in young adults". Hepatogastroenterology. 52 (66): 1795–7. PMID 16334779.