What is the most common liver tumor of early childhood?
Usually occurs before what age?
- Rarely occurs >3 yo
Which type of hemangioblastoma is composed of small polygonal fetal cells or smaller embryonal cells forming acini, tubules, or papillary structures?
What is the mixed epithelial and mesenchymal type of Hepatoblastoma composed of?
- Foci of mesenchymal differentiation
- May consist of: primitive mesenchyme, osteoid, cartilage, or striated m.
Hepatoblastomas frequently contain activation of which signaling path?
Which downstream gene is also frequently mutated, increasing the risk of the development of this tumor in pts with what disorder?
- WNT signaling path
- Mutations in APC gene (i.e., Familial Adenomatous Polyposis = higher risk for this tumor)
Which regulator of the TGF-β pathway is often highly expressed in Hepatoblastomas?
Hepatoblastomas may be associated with what disorder of infancy?
Beckwith-Wiedmann syndrome (i.e., large size at birth, large tongue, red birth mark on forhead or eyelids)
A majority of Hepatocellular Carcinoma occurs in area with high rates of which chronic infection?
Which countries have the highest incidences of chronic HBV infection and in turn, high rates of Hepatocellular Carcinoma?
- Asian countries (SE China, Korea, Taiwan)
- sub-Saharan African countries
In areas with high incidences of HCC (SE asia and sub-Saharan Africa) the peak incidence occurs between what ages?
Typically in the absence of what finding?
- 20-40 yo
- In the absence of cirrhosis!
In Western countries, the incidence of HCC is related to which viral infection?
Typically manifesting between what ages?
- HCV infection (vs. HBV infection in high incidence areas)
- Rarely before the age of 60 (vs. 20-40 yo in high incidence areas)
In Western countries, nearly all cases of HCC emerge after what has occurred in the liver?
Cirrhosis has been established (vs. high incidence areas in which many tumors arise in the absence of cirrhosis)
Which carinogen is associated w/ an increased risk of HCC?
Which sex is most often affected by HCC?
Males (3:1 in low incidence and 8:1 in high incidence areas)
What are the most important risk factors in hepatocarcinogenesis and the development of HCC?
What occurs if 2 of these risk factors co-exist with one another?
- Viral infections (HBV and HCV)
- Alcohol and Aflatoxin
*If any of these risk factors co-exist w/ each other they synergize to increase risk
Which 2 metabolic diseases increase the risk for HCC?
Of probably greater importance is the metabolic syndrome associated with?
- α-1-antitrypsin deficiency and hereditary hemochromatosis
- Metabolic syndrome assosciated w/: obesity, DM, and NAFLD
What are the 2 most common early mutational events associated w/ the development of HCC?
1) Activation of β-catenin
2) Inactivation of p53
Which mutation seen in HCC is strongly associated with aflatoxin?
Inactivation of p53
What are the 2 cellular dysplasias found in chronic liver disease and what is their relationship to malignancy and progression to HCC?
1. Small cell change - thought to be directly malignant
2. Large cell change - a marker of increased risk for HCC, but in HBV may be directly malignant
High-grade dysplastic nodules are probably the most important primary pathway for emergence of HCC in which associated conditions?
- Viral hepatitis
- Alcoholic liver disease
Overall, what 3 ways may HCC appear grossly?
1. Unifocal (usually large) mass
2. Multifocal, widely distributed nodules of various size
3. Diffusely infiltrative cancer
HCC can metastasize via what vessels and to what extrahepatic sites?
Which site of metastasis tends to occur late in the disease?
- Hepatic venous system to the lungs (late)
- Long, snakelike masses of tumor invade the portal vein (causing portal HTN) or invade IVC (may extend into right side of heart)
What is a distinctive variant of HCC that frequently occurs under the age of 35 and w/o gender predilection or underlying disposing conditions?
Grossly, how does the variant of HCC, Fibrolamellar Carcinoma present?
- Single + large, hard "scirrhous" tumor w/ fibrous bands coursing thru it
- Nests and cords of well-differentiated cells rich in mitochondria (oncocytes) separated by dense collagen bundles
Rising or elevated levels of what in the serum are found in some cases of advanced HCC?
What is the most valuable diagnostic method for detection of small HCC tumors?
Which characteristic of these tumors forms the basis of these studies?
- Ultrasounds to identify nodules
- CT and MRI w/ contrast for vessels
- The increasing vascularization seen in conversion of high grade dysplastic nodules --> early HCC, form the basis for diagnostic imaging
What is the prognosis (5-year survival) of large HCC's?
Majority dying within 2 years
Where is Cholangiocarcinoma (CAA) seen more commonly than HCC?
- Regions of SE Asia (i.e., NE Thailand, Laos, and Cambodia)
- Places where infestation w/ liver flukes is endemic
Globally, are CAA's most often associated with pre-existing conditions or do they arise sporadically?
Most often sporadically
Which liver flukes are most commonly associated w/ CAA?
- Opisthorchis species
- Clonorchis species
What are the risk factors associated with developing CAA?
- Liver flukes
- Chronic inflammatory dz of the large bile ducts (i.e., 1° Sclerosing Cholangitis, hepatolithiasis, and fibropolycystic liver dz)
- Pts w/ HBV and HCV infections + NAFLD (also risk for HCC)