Fibrolamellar hepatocellular carcinoma: Difference between revisions

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{{CMG}}; {{AE}}
{{SK}}
==Overview==
==Historical Perspective==
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
There have been several outbreaks of [disease name], including -----.
In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
==Classification==
There is no established system for the classification of [disease name].
OR
[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].
OR
[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3].
[Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].
OR
Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.
OR
If the staging system involves specific and characteristic findings and features:
According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].
OR
The staging of [malignancy name] is based on the [staging system].
OR
There is no established system for the staging of [malignancy name].
==Pathophysiology==
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
==Causes==
Disease name] may be caused by [cause1], [cause2], or [cause3].
OR
Common causes of [disease] include [cause1], [cause2], and [cause3].
OR
The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
OR
The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].
==Differentiating ((Page name)) from Other Diseases==
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
OR
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
==Epidemiology and Demographics==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
OR
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
OR
In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
Patients of all age groups may develop [disease name].
OR
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
OR
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
OR
[Chronic disease name] is usually first diagnosed among [age group].
OR
[Acute disease name] commonly affects [age group].
There is no racial predilection to [disease name].
OR
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
[Disease name] affects men and women equally.
OR
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
The majority of [disease name] cases are reported in [geographical region].
OR
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
==Risk Factors==
There are no established risk factors for [disease name].
OR
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
OR
According to the [guideline name], screening for [disease name] is not recommended.
OR
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
OR
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
OR
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
==Diagnosis==
===Diagnostic Study of Choice===
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
OR
The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
OR
The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
OR
There are no established criteria for the diagnosis of [disease name].
===History and Symptoms===
The majority of patients with [disease name] are asymptomatic.
OR
The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
===Physical Examination===
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
OR
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
OR
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
OR
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
OR
[Test] is usually normal among patients with [disease name].
OR
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
OR
There are no diagnostic laboratory findings associated with [disease name].
===Electrocardiogram===
There are no ECG findings associated with [disease name].
OR
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
===X-ray===
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [disease name].
OR
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no echocardiography/ultrasound  findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===CT scan===
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===MRI===
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
==Treatment==
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
OR
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
OR
The majority of cases of [disease name] are self-limited and require only supportive care.
OR
[Disease name] is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for [disease name] is [therapy].
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
OR
[Therapy] is recommended among all patients who develop [disease name].
OR
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
OR
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
OR
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
OR
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
OR
Surgery is the mainstay of treatment for [disease or malignancy].
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].
OR
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
OR
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
OR
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
==References==
{{reflist|2}}
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{{SI}}                                                                 
{{SI}}                                                                 
{{CMG}} {{AE}} {{MV}}
{{CMG}} {{AE}} {{MV}}


{{SK}} Fibrolamellar carcinoma; FLC
{{SK}} Fibrolamellar carcinoma; FLC Eosinophilic hepatocellular carcinoma with lamellar fibrosis, Polygonal cell hepatocellular carcinoma with fibrous stroma, Hepatocellular carcinoma with increased stromal fibrosis, Eosinophilic glassy cell hepatoma, and fibrolamellar oncocytic hepatoma.


==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 is most commonly seen 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, [[Liver disease|alcohol-related liver disease]], [[Non-alcoholic fatty liver disease|nonalcoholic fatty liver disease]], and dietary [[Aflatoxin|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]].
'''Fibrolamellar hepatocellular carcinoma''' (''FLC'') is a rare subtype of primary [[Liver mass|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 is most commonly seen 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 [[Hepatitis c|C viral]] infection, [[Liver disease|alcohol-related liver disease]], [[Non-alcoholic fatty liver disease|nonalcoholic fatty liver disease]], and dietary [[Aflatoxin|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 node|lymph nodes]], peritoneum, and lung. Common complications of fibrolamellar hepatocellular carcinoma include: [[hepatic failure]], caval compression syndrome, [[gynecomastia]], and [[cold agglutinin disease]]. Surgical resection or transplantation is the standard of care for fibrolamellar carcinoma (FLC) for eligible patients. [[Embolization|Trans-arterial chemo-embolization]] ([[Therapeutic embolization|TACE]]) may be a useful option in patients who have unresectable disease.


==Historical Perspective==
==Historical Perspective==
*Fibrolamellar hepatocellular carcinoma was first described by 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 was first described by 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>


==Classification==
==Classification==
*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>
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.<ref name="fibrolamelar">Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016 </ref>
*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:  
:*Hard, scirrhous, and well-circumscribed
:*Hard, [[cirrhosis]], and well-circumscribed
:*Tumor bulging
:*Tumor bulging
:* White-brown tumor with fibrous bands throughout and central stellate scar
:* White-brown tumor with fibrous bands throughout and central satellite scar
*On microscopic histopathological analysis, characteristic findings of fibrolamellar hepatocellular carcinoma, include:
*On microscopic histopathological analysis, characteristic findings of fibrolamellar hepatocellular carcinoma, include:
:*Tumor cells growing in sheets
:*Tumor cells growing in sheets
:*[[Trabeculae]] that are separated by collagen bundles (lamellar pattern)
:*[[Trabeculae]] that are separated by collagen bundles (lamellar pattern)
:*Large cells that contain abundant mitochondria
:*Large cells that contain abundant [[mitochondria]]
:*Coarsely granular cytoplasm
:*Coarsely granular cytoplasm
*On immunohistochemistry, characteristic findings of fibrolamellar hepatocellular carcinoma, include:
*On immunohistochemistry, characteristic findings of fibrolamellar hepatocellular carcinoma, include:
:*Positive staining for hepatocyte paraffin 1 (HepPar1)
:*Positive staining for hepatocyte paraffin 1 (HepPar1)
:*Positive staining for glypican-3 (GPC3)
:*Positive staining for [[glypican 3]] ([[Glypican 3|GPC3]])
:*Positive staining polyclonal carcinoembryonic antigen (pCEA)
:*Positive staining polyclonal [[carcinoembryonic antigen]] ([[CEA|pCEA]])
:*CD10 positivity
:*[[CD10]] positivity


==Causes==
==Causes==
* 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>
* 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
:*[[Acute hepatic injury|Active hepatic inflammation]]
:*[[Hepatitis B]] or [[Hepatitis C|C]] viral infection
:*[[Hepatitis B]] or [[Hepatitis C|C]] viral infection
:*Alcohol-related liver disease
:*[[Alcohol]]-related [[liver]] disease
:*Nonalcoholic fatty liver disease  
:*[[Non-alcoholic fatty liver disease|Nonalcoholic fatty liver disease]]
:*Dietary aflatoxin B1
:*Dietary [[Aflatoxin|aflatoxin B1]]


==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:<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 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]]  
:*[[Hepatocellular adenoma|Hepatic adenoma]]
:*[[Hepatocellular adenoma|Hepatic adenoma]]
:*[[Metastasis|Hepatic metastasis]]
:*[[Metastasis|Hepatic metastasis]]
'''Abbreviations:'''
'''[[RUQ]]'''= Right upper quadrant of the abdomen, '''LUQ'''= Left upper quadrant, '''LLQ'''= Left lower quadrant, '''RLQ'''= Right lower quadrant, '''LFT'''= Liver function test, SIRS= [[Systemic inflammatory response syndrome]], '''[[ERCP]]'''= [[Endoscopic retrograde cholangiopancreatography]], '''IV'''= Intravenous, '''N'''= Normal, '''AMA'''= Anti mitochondrial antibodies, '''[[LDH]]'''= [[Lactate dehydrogenase]], '''GI'''= Gastrointestinal, '''CXR'''= Chest X ray, '''IgA'''= [[Immunoglobulin A]], '''IgG'''= [[Immunoglobulin G]], '''IgM'''= [[Immunoglobulin M]], '''CT'''= [[Computed tomography]], '''[[PMN]]'''= Polymorphonuclear cells, '''[[ESR]]'''= [[Erythrocyte sedimentation rate]], '''[[CRP]]'''= [[C-reactive protein]], TS= [[Transferrin saturation]], SF= Serum [[Ferritin]], SMA= [[Superior mesenteric artery]], SMV= [[Superior mesenteric vein]], ECG= [[Electrocardiogram]]
<small>
{| class="wikitable" style="border: 0px; font-size: 90%; margin: 5px;" align="center"
! style="background:#4479BA; color: #FFFFFF;" align="center" rowspan="3" |Disease
| style="background:#4479BA; color: #FFFFFF;" colspan="13" align="center" rowspan="1" |'''Clinical manifestations'''
! style="background:#4479BA; color: #FFFFFF;" colspan="2" align="center" rowspan="2" |Diagnosis
! style="background:#4479BA; color: #FFFFFF;" align="center" rowspan="3" |Comments
|-
| style="background:#4479BA; color: #FFFFFF;" colspan="9" align="center" rowspan="1" |'''Symptoms'''
! style="background:#4479BA; color: #FFFFFF;" colspan="4" align="center" rowspan="1" | Signs
|-
! style="background:#4479BA; color: #FFFFFF;" align="center" |Abdominal Pain
! style="background:#4479BA; color: #FFFFFF;" colspan="1" align="center" rowspan="1" | Fever
! style="background:#4479BA; color: #FFFFFF;" align="center" |Rigors and chills
! style="background:#4479BA; color: #FFFFFF;" align="center" |Nausea or vomiting
! style="background:#4479BA; color: #FFFFFF;" align="center" |Jaundice
! style="background:#4479BA; color: #FFFFFF;" align="center" |Constipation
! style="background:#4479BA; color: #FFFFFF;" align="center" |Diarrhea
! style="background:#4479BA; color: #FFFFFF;" align="center" |Weight loss
! style="background:#4479BA; color: #FFFFFF;" align="center" |GI bleeding
! style="background:#4479BA; color: #FFFFFF;" align="center" |Hypo-
tension
! style="background:#4479BA; color: #FFFFFF;" colspan="1" align="center" rowspan="1" | Guarding
! style="background:#4479BA; color: #FFFFFF;" align="center" |Rebound Tenderness
! style="background:#4479BA; color: #FFFFFF;" align="center" |Bowel sounds
! style="background:#4479BA; color: #FFFFFF;" colspan="1" align="center" rowspan="1" | Lab Findings
! style="background:#4479BA; color: #FFFFFF;" align="center" |Imaging
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Hepatocellular carcinoma]]/[[Metastasis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[RUQ]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Normal
* Hyperactive if obstruction present
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* High levels of [[Alpha-fetoprotein|AFP]] in serum
* Abnormal [[Liver function test|liver function tests]]
*[[Thrombocytopenia]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Ultrasound|US]]
* [[Computed tomography|CT]]
* [[MRI]]
* [[Liver biopsy]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
Other symptoms:
* [[Splenomegaly]]
* [[Variceal bleeding]]
* [[Ascites]]
* [[Spider nevi]]
* [[Asterixis]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan="1" align="center" rowspan="1" |[[Cholangiocarcinoma]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[RUQ]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Elevated [[CA-19-9|CA 19-9]]
* Increased [[amylase]] / [[lipase]]
* Increased [[Steatorrhea|stool fat]] content
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Contrast-enhanced ultrasound]]
*[[Computed tomography|CT scan]]
**[[Calcification]]
**[[Pseudocyst]]
**Dilation of main pancreatic duct
*[[Magnetic resonance imaging|MRI]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Predisposes to pancreatic cancer
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Pancreatic carcinoma]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Mid[[Epigastric]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* ↑ [[Alkaline phosphatase]]
* ↑ [[Bilirubin|serum bilirubin]]
* ↑ [[gamma-glutamyl transpeptidase]]
* ↑ [[CA-19-9|CA 19-9]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Computed tomography|MDCT]] with  [[Positron emission tomography|PET]]/[[Computed tomography|CT]]
* MRI
* [[Endoscopic ultrasound|EUS]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
[[Skin]] manifestations may include:
* [[Bullous pemphigoid]]
* [[Mucous membrane pemphigoid|Cicatricial pemphigoid]]
* [[Thrombophlebitis|Migratory superficial thrombophlebitis]] (classic [[Trousseau's syndrome]])
* [[Panniculitis|Pancreatic panniculitis]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Focal nodular hyperplasia]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Diffuse
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Normal Liver function tests
* Normal AFP
*Minor elevations of
**[[Aspartate]]
**[[Alanine aminotransferase]]
**[[Alkaline phosphatase]]
**[[Gamma glutamyl transpeptidase]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Us
* Multiphasic [[helical CT scan]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Open [[biopsy]] if diagnosis can not be established
|-
! style="background:#4479BA; color: #FFFFFF;" align="center" |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" |Abdominal Pain
! style="background:#4479BA; color: #FFFFFF;" align="center" |Fever
! style="background:#4479BA; color: #FFFFFF;" align="center" |Rigors and chills
! style="background:#4479BA; color: #FFFFFF;" align="center" |Nausea or vomiting
! style="background:#4479BA; color: #FFFFFF;" align="center" |Jaundice
! style="background:#4479BA; color: #FFFFFF;" align="center" |Constipation
! style="background:#4479BA; color: #FFFFFF;" align="center" |Diarrhea
! style="background:#4479BA; color: #FFFFFF;" align="center" |Weight loss
! style="background:#4479BA; color: #FFFFFF;" align="center" |GI bleeding
! style="background:#4479BA; color: #FFFFFF;" align="center" |Hypo-
tension
! style="background:#4479BA; color: #FFFFFF;" align="center" |Guarding
! style="background:#4479BA; color: #FFFFFF;" align="center" |Rebound Tenderness
! style="background:#4479BA; color: #FFFFFF;" align="center" |Bowel sounds
! style="background:#4479BA; color: #FFFFFF;" align="center" |Lab Findings
! style="background:#4479BA; color: #FFFFFF;" align="center" |Imaging
! style="background:#4479BA; color: #FFFFFF;" align="center" |Comments
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Gallbladder cancer]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Mid[[Epigastric|epigastric]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" | Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* ↑ [[Alkaline phosphatase]]
* ↑ [[CA-19-9|CA 19-9]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Ultrasonography|US]]
* CT
* MRI
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Liver hemangioma]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Intermittent [[RUQ]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>−</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Abnormal LFTs
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* US
* [[Single photon emission computed tomography|Single-photon emission computerized tomography(SPECT]])
* MRI
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* US will reveal hypoechoic [[lesions]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Liver abscess]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |RUQ
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Hypoalbuminemia
* Abnormal [[Liver function test|liver function tests]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* US
* CT
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Cirrhosis|Cirrhosis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[RUQ]]+Bloating
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Hypoalbuminemia]]
* Prolonged PT
* Abnormal LFTs
* [[Hyponatremia]]
* [[Thrombocytopenia]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |US
* Nodular, shrunken liver
* [[Ascites]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Stigmata of liver disease
* Cruveilhier- Baumgarten murmur
|- style="padding: 5px 5px; background: #F5F5F5;" align="left" |
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |Inflammatory lesions
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[RUQ]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ±
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | +
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |<nowiki>−</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | −
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |Normal
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* [[Hypoalbuminemia]]
* Prolonged PT
* Abnormal LFTs
* [[Hyponatremia]]
* [[Thrombocytopenia]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |US
* Nodular,shrunken or coarse liver
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
* Stigmata of liver disease
|-
|}
<small>


==Epidemiology and Demographics==
==Epidemiology and Demographics==
Line 474: Line 359:


==Risk Factors==
==Risk Factors==
*There are no risk factors for the development of fibrolamellar hepatocellular carcinoma.
There are no risk factors for the development of fibrolamellar hepatocellular carcinoma.
 
== 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.  
Line 534: Line 418:
:*Single large tumors
:*Single large tumors
:*Central scar (seen in ~75% of cases)
:*Central scar (seen in ~75% of cases)
:*Central scar shows persistent enhancement on delayed contrast enhanced CT.
:*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>
*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
Line 546: Line 430:


== Treatment ==
== Treatment ==
* Surgical resection or transplantation is the standard of care for fibrolamellar carcinoma (FLC) for eligible patients.
* Trans-arterial chemo-embolization (TACE) may be a useful option in patients who have unresectable disease.
* FLC is not typically responsive to chemotherapy.
* In addition to systemic chemotherapy, recent research has focused on taking advantage of the new understanding of the pathogenesis and molecular genetics of FLC.
=== Medical Therapy ===
=== Medical Therapy ===
*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>
* Chemotherapy is recommended for metastatic fibrolamellar carcinoma (FLC).
* Single-agent chemotherapy or combinations of chemotherapeutic drugs give responses of no more than 25%, with questionable benefit for overall survival.
'''<u>Sorafenib</u>'''
* Sorafenib is an orally delivered small molecule that inhibits several different protein kinases, including Raf-1 and B-Raf, platelet-derived growth factor β (PDGFR-β), and vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3.  
* Sorafenib targets both tumor growth (Raf-MEK-ERK pathway) and neoangiogenesis (VEGFRs, PDGFR-β), both of which are thought to be important in the pathogenesis of typical HCC.


=== Surgery ===
=== Surgical Therapy ===
*Surgical resection is the treatment of choice for fibrolamellar hepatocellular carcinoma.
* Optimal management for most hepatic malignancies, including typical hepatocellular carcinoma and fibrolamellar carcinoma, is complete surgical resection
** Wedge Resection
** Anatomic liver resection
** Total hepatectomy with orthotopic liver transplantation.
* There may be occasional utility in treating fibrolamellar carcinoma with neoadjuvant chemotherapy or trans-arterial chemo-embolization (TACE) with the goal of downstaging the tumor to allow resection.
 
{| class="wikitable"
|+
!Procedure
!Description
|-
|Hepatic resection
|
* Cirrhosis often limits the feasibility of liver resection in patients with typical hepatocellular carcinoma (HCC) because cirrhotic patients have increased perioperative risk and require a larger future liver remnant to be left behind to allow adequate liver function.
* In contrast, fibrolamellar carcinoma (FLC) is rarely associated with cirrhosis, and patients are often young and otherwise healthy (For this reason, aggressive liver resections can be more readily undertaken in patients with FLC than in those with typical HCC.)
 
* Several factors are associated with a better prognosis following surgery, including younger age at diagnosis, earlier tumor stage at diagnosis, and absence of large vessel invasion or thrombosis.
* The ability to perform complete resection has been reported to be one of the most important and well-described prognostic factors for FLC.
*  Factors associated with a particularly poor prognosis include lymph node metastasis, multiple tumors, metastatic disease at presentation, and vascular invasion.
* Patients with resected FLC generally have a prognosis similar to that for noncirrhotic patients with resected typical HCC.
* Aggressive surgical approaches, even for recurrent disease, can be undertaken with good results.
|-
|Orthotopic liver transplantation
|
* Total hepatectomy followed by orthotopic liver transplantation (OLT) should be considered in patients with unresectable FLC that is confined to the liver. 
 
* Even among patients who develop tumor recurrence, the time to recurrence is significantly longer in patients with FLC than in those with typical HCC. This may be a result of more indolent behavior by FLC versus typical HCC.
* Alternatively, it may result from the fact that accompanying cirrhosis in typical HCC increases the risk of recurrence (including development of a second primary tumor) via a field effect.
* Orthotopic liver transplantation can result in long-term survival but is a resource-intensive treatment approach.
* In typical HCC, orthotopic liver transplantation confers the advantage of removing the at-risk cirrhotic liver in addition to the tumor itself.
* In FLC, this theoretical advantage is likely not present because no such field effect is present (due to the lack of cirrhosis in most cases).
* As such, it is not clear that the use of donor organs in patients with FLC is an appropriate use of this scarce resource.
* Newer innovative approaches (eg, adult living-related donations, split-liver techniques, and potential use of marginal donor organs) may allow for a future increase in the use of orthotopic liver transplantation for FLC.
|}


=== Prevention ===
=== Prevention ===
Line 558: Line 485:


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
 
[[Category: Oncology]]
[[Category: Oncology]]
[[Category:Up-To-Date]]
 
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Hepatology]]
[[Category:Surgery]]

Latest revision as of 12:54, 2 May 2019

WikiDoc Resources for Fibrolamellar hepatocellular carcinoma

Articles

Most recent articles on Fibrolamellar hepatocellular carcinoma

Most cited articles on Fibrolamellar hepatocellular carcinoma

Review articles on Fibrolamellar hepatocellular carcinoma

Articles on Fibrolamellar hepatocellular carcinoma in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Fibrolamellar hepatocellular carcinoma

Images of Fibrolamellar hepatocellular carcinoma

Photos of Fibrolamellar hepatocellular carcinoma

Podcasts & MP3s on Fibrolamellar hepatocellular carcinoma

Videos on Fibrolamellar hepatocellular carcinoma

Evidence Based Medicine

Cochrane Collaboration on Fibrolamellar hepatocellular carcinoma

Bandolier on Fibrolamellar hepatocellular carcinoma

TRIP on Fibrolamellar hepatocellular carcinoma

Clinical Trials

Ongoing Trials on Fibrolamellar hepatocellular carcinoma at Clinical Trials.gov

Trial results on Fibrolamellar hepatocellular carcinoma

Clinical Trials on Fibrolamellar hepatocellular carcinoma at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Fibrolamellar hepatocellular carcinoma

NICE Guidance on Fibrolamellar hepatocellular carcinoma

NHS PRODIGY Guidance

FDA on Fibrolamellar hepatocellular carcinoma

CDC on Fibrolamellar hepatocellular carcinoma

Books

Books on Fibrolamellar hepatocellular carcinoma

News

Fibrolamellar hepatocellular carcinoma in the news

Be alerted to news on Fibrolamellar hepatocellular carcinoma

News trends on Fibrolamellar hepatocellular carcinoma

Commentary

Blogs on Fibrolamellar hepatocellular carcinoma

Definitions

Definitions of Fibrolamellar hepatocellular carcinoma

Patient Resources / Community

Patient resources on Fibrolamellar hepatocellular carcinoma

Discussion groups on Fibrolamellar hepatocellular carcinoma

Patient Handouts on Fibrolamellar hepatocellular carcinoma

Directions to Hospitals Treating Fibrolamellar hepatocellular carcinoma

Risk calculators and risk factors for Fibrolamellar hepatocellular carcinoma

Healthcare Provider Resources

Symptoms of Fibrolamellar hepatocellular carcinoma

Causes & Risk Factors for Fibrolamellar hepatocellular carcinoma

Diagnostic studies for Fibrolamellar hepatocellular carcinoma

Treatment of Fibrolamellar hepatocellular carcinoma

Continuing Medical Education (CME)

CME Programs on Fibrolamellar hepatocellular carcinoma

International

Fibrolamellar hepatocellular carcinoma en Espanol

Fibrolamellar hepatocellular carcinoma en Francais

Business

Fibrolamellar hepatocellular carcinoma in the Marketplace

Patents on Fibrolamellar hepatocellular carcinoma

Experimental / Informatics

List of terms related to Fibrolamellar hepatocellular carcinoma


WikiDoc Resources for Fibrolamellar hepatocellular carcinoma

Articles

Most recent articles on Fibrolamellar hepatocellular carcinoma

Most cited articles on Fibrolamellar hepatocellular carcinoma

Review articles on Fibrolamellar hepatocellular carcinoma

Articles on Fibrolamellar hepatocellular carcinoma in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Fibrolamellar hepatocellular carcinoma

Images of Fibrolamellar hepatocellular carcinoma

Photos of Fibrolamellar hepatocellular carcinoma

Podcasts & MP3s on Fibrolamellar hepatocellular carcinoma

Videos on Fibrolamellar hepatocellular carcinoma

Evidence Based Medicine

Cochrane Collaboration on Fibrolamellar hepatocellular carcinoma

Bandolier on Fibrolamellar hepatocellular carcinoma

TRIP on Fibrolamellar hepatocellular carcinoma

Clinical Trials

Ongoing Trials on Fibrolamellar hepatocellular carcinoma at Clinical Trials.gov

Trial results on Fibrolamellar hepatocellular carcinoma

Clinical Trials on Fibrolamellar hepatocellular carcinoma at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Fibrolamellar hepatocellular carcinoma

NICE Guidance on Fibrolamellar hepatocellular carcinoma

NHS PRODIGY Guidance

FDA on Fibrolamellar hepatocellular carcinoma

CDC on Fibrolamellar hepatocellular carcinoma

Books

Books on Fibrolamellar hepatocellular carcinoma

News

Fibrolamellar hepatocellular carcinoma in the news

Be alerted to news on Fibrolamellar hepatocellular carcinoma

News trends on Fibrolamellar hepatocellular carcinoma

Commentary

Blogs on Fibrolamellar hepatocellular carcinoma

Definitions

Definitions of Fibrolamellar hepatocellular carcinoma

Patient Resources / Community

Patient resources on Fibrolamellar hepatocellular carcinoma

Discussion groups on Fibrolamellar hepatocellular carcinoma

Patient Handouts on Fibrolamellar hepatocellular carcinoma

Directions to Hospitals Treating Fibrolamellar hepatocellular carcinoma

Risk calculators and risk factors for Fibrolamellar hepatocellular carcinoma

Healthcare Provider Resources

Symptoms of Fibrolamellar hepatocellular carcinoma

Causes & Risk Factors for Fibrolamellar hepatocellular carcinoma

Diagnostic studies for Fibrolamellar hepatocellular carcinoma

Treatment of Fibrolamellar hepatocellular carcinoma

Continuing Medical Education (CME)

CME Programs on Fibrolamellar hepatocellular carcinoma

International

Fibrolamellar hepatocellular carcinoma en Espanol

Fibrolamellar hepatocellular carcinoma en Francais

Business

Fibrolamellar hepatocellular carcinoma in the Marketplace

Patents on Fibrolamellar hepatocellular carcinoma

Experimental / Informatics

List of terms related to Fibrolamellar hepatocellular carcinoma

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 Eosinophilic hepatocellular carcinoma with lamellar fibrosis, Polygonal cell hepatocellular carcinoma with fibrous stroma, Hepatocellular carcinoma with increased stromal fibrosis, Eosinophilic glassy cell hepatoma, and fibrolamellar oncocytic hepatoma.

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 is most commonly seen 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. Surgical resection or transplantation is the standard of care for fibrolamellar carcinoma (FLC) for eligible patients. Trans-arterial chemo-embolization (TACE) may be a useful option in patients who have unresectable disease.

Historical Perspective

Fibrolamellar hepatocellular carcinoma was first described by Edmondson in 1956.[1][2]

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, cirrhosis, and well-circumscribed
  • Tumor bulging
  • White-brown tumor with fibrous bands throughout and central satellite scar
  • On microscopic histopathological analysis, characteristic findings of fibrolamellar hepatocellular carcinoma, include:
  • Tumor cells growing 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:

Causes

  • Common causes of fibrolamellar hepatocellular carcinoma, include:[1]

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]

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease Clinical manifestations Diagnosis Comments
Symptoms Signs
Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo-

tension

Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging
Hepatocellular carcinoma/Metastasis RUQ + − + + + + + + + − +
  • Normal
  • Hyperactive if obstruction present

Other symptoms:

Cholangiocarcinoma RUQ + − + + − − + − − − + Normal
  • Predisposes to pancreatic cancer
Pancreatic carcinoma MidEpigastric − − + + + − + − − − + Normal

Skin manifestations may include:

Focal nodular hyperplasia Diffuse ± − − ± − − + + − − − Normal
  • Open biopsy if diagnosis can not be established
Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo-

tension

Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments
Gallbladder cancer Midepigastric − − + + − + + − − − − Normal
Liver hemangioma Intermittent RUQ − − + + − − − − − − − Normal
  • Abnormal LFTs
Liver abscess RUQ + − + + − − + − − − − Normal
  • US
  • CT
Cirrhosis RUQ+Bloating + − + + − − + − − − − Normal US
  • Stigmata of liver disease
  • Cruveilhier- Baumgarten murmur
Inflammatory lesions RUQ ± − + + − − − − − − − Normal US
  • Nodular,shrunken or coarse liver
  • Stigmata of liver disease

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]
  • FLC is a very rare tumor, although the incidence varies geographically. In the United States and Thailand, less than 1 percent of all primary liver tumors are FLC [3,4], while in Mexico, FLC represents 5.8 percent of all primary liver cancers

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.[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

Laboratory Findings

  • Laboratory findings consistent with the diagnosis of fibrolamellar hepatocellular carcinoma, include:[1]

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 tumors will not accumulate the agent, whereas FNH does.

Treatment

  • Surgical resection or transplantation is the standard of care for fibrolamellar carcinoma (FLC) for eligible patients.
  • Trans-arterial chemo-embolization (TACE) may be a useful option in patients who have unresectable disease.
  • FLC is not typically responsive to chemotherapy.
  • In addition to systemic chemotherapy, recent research has focused on taking advantage of the new understanding of the pathogenesis and molecular genetics of FLC.

Medical Therapy

  • Chemotherapy is recommended for metastatic fibrolamellar carcinoma (FLC).
  • Single-agent chemotherapy or combinations of chemotherapeutic drugs give responses of no more than 25%, with questionable benefit for overall survival.

Sorafenib

  • Sorafenib is an orally delivered small molecule that inhibits several different protein kinases, including Raf-1 and B-Raf, platelet-derived growth factor β (PDGFR-β), and vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3.
  • Sorafenib targets both tumor growth (Raf-MEK-ERK pathway) and neoangiogenesis (VEGFRs, PDGFR-β), both of which are thought to be important in the pathogenesis of typical HCC.

Surgical Therapy

  • Optimal management for most hepatic malignancies, including typical hepatocellular carcinoma and fibrolamellar carcinoma, is complete surgical resection
    • Wedge Resection
    • Anatomic liver resection
    • Total hepatectomy with orthotopic liver transplantation.
  • There may be occasional utility in treating fibrolamellar carcinoma with neoadjuvant chemotherapy or trans-arterial chemo-embolization (TACE) with the goal of downstaging the tumor to allow resection.
Procedure Description
Hepatic resection
  • Cirrhosis often limits the feasibility of liver resection in patients with typical hepatocellular carcinoma (HCC) because cirrhotic patients have increased perioperative risk and require a larger future liver remnant to be left behind to allow adequate liver function.
  • In contrast, fibrolamellar carcinoma (FLC) is rarely associated with cirrhosis, and patients are often young and otherwise healthy (For this reason, aggressive liver resections can be more readily undertaken in patients with FLC than in those with typical HCC.)
  • Several factors are associated with a better prognosis following surgery, including younger age at diagnosis, earlier tumor stage at diagnosis, and absence of large vessel invasion or thrombosis.
  • The ability to perform complete resection has been reported to be one of the most important and well-described prognostic factors for FLC.
  • Factors associated with a particularly poor prognosis include lymph node metastasis, multiple tumors, metastatic disease at presentation, and vascular invasion.
  • Patients with resected FLC generally have a prognosis similar to that for noncirrhotic patients with resected typical HCC.
  • Aggressive surgical approaches, even for recurrent disease, can be undertaken with good results.
Orthotopic liver transplantation
  • Total hepatectomy followed by orthotopic liver transplantation (OLT) should be considered in patients with unresectable FLC that is confined to the liver. 
  • Even among patients who develop tumor recurrence, the time to recurrence is significantly longer in patients with FLC than in those with typical HCC. This may be a result of more indolent behavior by FLC versus typical HCC.
  • Alternatively, it may result from the fact that accompanying cirrhosis in typical HCC increases the risk of recurrence (including development of a second primary tumor) via a field effect.
  • Orthotopic liver transplantation can result in long-term survival but is a resource-intensive treatment approach.
  • In typical HCC, orthotopic liver transplantation confers the advantage of removing the at-risk cirrhotic liver in addition to the tumor itself.
  • In FLC, this theoretical advantage is likely not present because no such field effect is present (due to the lack of cirrhosis in most cases).
  • As such, it is not clear that the use of donor organs in patients with FLC is an appropriate use of this scarce resource.
  • Newer innovative approaches (eg, adult living-related donations, split-liver techniques, and potential use of marginal donor organs) may allow for a future increase in the use of orthotopic liver transplantation for FLC.

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. ↑ 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 Michael Torbenson. Fibrolamellar Carcinoma: 2012 Update. http://www.hindawi.com/journals/scientifica/2012/743790/ Access on April 15, 2016
  2. ↑ 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. ↑ 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.
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