Chapter 18: Malignant Tumors

Question 1

What is the most common liver tumor of early childhood?

Usually occurs before what age?

Answer 1

• Hepatoblastoma
• Rarely occurs >3 yo

Question 2

Which type of hemangioblastoma is composed of small polygonal fetal cells or smaller embryonal cells forming acini, tubules, or papillary structures?

Answer 2

Epithelial type

Question 3

What is the mixed epithelial and mesenchymal type of Hepatoblastoma composed of?

Answer 3

• Foci of mesenchymal differentiation
• May consist of: primitive mesenchyme, osteoid, cartilage, or striated m.

Question 4

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?

Answer 4

• WNT signaling path
• Mutations in APC gene (i.e., Familial Adenomatous Polyposis = higher risk for this tumor)

Question 5

Which regulator of the TGF-β pathway is often highly expressed in Hepatoblastomas?

Answer 5

FOXG1

Question 6

Hepatoblastomas may be associated with what disorder of infancy?

Answer 6

Beckwith-Wiedmann syndrome (i.e., large size at birth, large tongue, red birth mark on forhead or eyelids)

Question 7

A majority of Hepatocellular Carcinoma occurs in area with high rates of which chronic infection?

Answer 7

HBV

Question 8

Which countries have the highest incidences of chronic HBV infection and in turn, high rates of Hepatocellular Carcinoma?

Answer 8

• Asian countries (SE China, Korea, Taiwan)
• sub-Saharan African countries

Question 9

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?

Answer 9

• 20-40 yo
• In the absence of cirrhosis!

Question 10

In Western countries, the incidence of HCC is related to which viral infection?

Typically manifesting between what ages?

Answer 10

• HCV infection (vs. HBV infection in high incidence areas)
• Rarely before the age of 60 (vs. 20-40 yo in high incidence areas)

Question 11

In Western countries, nearly all cases of HCC emerge after what has occurred in the liver?

Answer 11

Cirrhosis has been established (vs. high incidence areas in which many tumors arise in the absence of cirrhosis)

Question 12

Which carinogen is associated w/ an increased risk of HCC?

Answer 12

Alflatoxin

Question 13

Which sex is most often affected by HCC?

Answer 13

Males (3:1 in low incidence and 8:1 in high incidence areas)

Question 14

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?

Answer 14

• Viral infections (HBV and HCV)
• Alcohol and Aflatoxin

*If any of these risk factors co-exist w/ each other they synergize to increase risk

Question 15

Which 2 metabolic diseases increase the risk for HCC?

Of probably greater importance is the metabolic syndrome associated with?

Answer 15

• α-1-antitrypsin deficiency and hereditary hemochromatosis
• Metabolic syndrome assosciated w/: obesity, DM, and NAFLD

Question 16

What are the 2 most common early mutational events associated w/ the development of HCC?

Answer 16

1) Activation of β-catenin
2) Inactivation of p53

Question 17

Which mutation seen in HCC is strongly associated with aflatoxin?

Answer 17

Inactivation of p53

Question 18

What are the 2 cellular dysplasias found in chronic liver disease and what is their relationship to malignancy and progression to HCC?

Answer 18

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

Question 19

High-grade dysplastic nodules are probably the most important primary pathway for emergence of HCC in which associated conditions?

Answer 19

• Viral hepatitis
• Alcoholic liver disease

Question 20

Overall, what 3 ways may HCC appear grossly?

Answer 20

1. Unifocal (usually large) mass
2. Multifocal, widely distributed nodules of various size
3. Diffusely infiltrative cancer

Question 21

HCC can metastasize via what vessels and to what extrahepatic sites?

Which site of metastasis tends to occur late in the disease?

Answer 21

• 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)

Question 22

What is a distinctive variant of HCC that frequently occurs under the age of 35 and w/o gender predilection or underlying disposing conditions?

Answer 22

Fibrolamellar carcinoma

Question 23

Grossly, how does the variant of HCC, Fibrolamellar Carcinoma present?

Microscopically?

Answer 23

- Single + large, hard “scirrhous” tumor w/ fibrous bands coursing thru it

• Nests and cords of well-differentiated cells rich in mitochondria (oncocytes)separated by densecollagen bundles

Question 24

Rising or elevated levels of what in the serum are found in some cases of advanced HCC?

Answer 24

α-fetoprotein

Question 25

What is the most valuable diagnostic method for detection of small HCC tumors?

Which characteristic of these tumors forms the basis of these studies?

Answer 25

• 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

Question 26

What is the prognosis (5-year survival) of large HCC’s?

Answer 26

Majority dying within 2 years

Question 27

Where is Cholangiocarcinoma (CAA) seen more commonly than HCC?

Due to?

Answer 27

• Regions of SE Asia (i.e., NE Thailand, Laos, and Cambodia)
• Places where infestation w/ liver flukes is endemic

Question 28

Globally, are CAA’s most often associated with pre-existing conditions or do they arise sporadically?

Answer 28

Most often sporadically

Question 29

Which liver flukes are most commonly associated w/ CAA?

Answer 29

• Opisthorchis species
• Clonorchis species

Question 30

What are the risk factors associated with developing CAA?

Answer 30

• 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)

Question 31

What are the 2 extrahepatic forms of CAAs and where does each occur?

Answer 31

1. Perihilar (Klatskin) tumors at jct. of right and left hepatic ducts
2. Distal tumors arising in common bile duct where it lies posterior to the duodenum

Question 32

The extrahepatic forms of CAA (i.e., Klatskin and Distal tumors) most often present w/ what symptoms?

Answer 32

• Sx’s of biliary obstruction
• Cholangitis
• RUQ pain

Question 33

What are the most important premalignant lesions for CAA?

How are they graded and which is the highest risk for malignant transformation?

Answer 33

• Biliary epithelial neoplasias (low –> high, Bi1IN-1, -2, or -3)
• BilIN-3 = highest grade and incurs highest risk of malignant transformation

Question 34

Extrahepatic CAA’s generally appear how morphologically and where?

Are typical adenocarinomas so they produce?

Poorly or well differentiated?

Answer 34

• Firm, gray nodules within the bile duct wall
• Are typical adenocarinomas, often produce mucin
• Most are well- to moderately differentiated w/ clearly defined glandular/tubular structures lined by malignant epithelium

Question 35

Although, not as common, intrahepatic CAA’s may tract along the intrahepatic portal system and create what?

Answer 35

A branching tumor within portion of the liver

Question 36

Angiosarcomas of the liver have historical associations with what toxins?

Answer 36

Vinyl Chloride

Arsenic

Thorotrast

Question 37

Hepatic lymphomas are primarily seen in which gender and age group?

Associated with what underlying risk factors?

Take the form of what type of lymphoma usually?

Answer 37

• Middle-aged men
• Usually in association w/ HBV and HCV, HIV and PBC
• Most are diffuse large B-cell lymphomas, followed by MALT lymphomas

Question 38

Hepatosplenic delta-gamma T cell lymphoma are most common in which age group and sex?

Have predilection for what sites?

Answer 38

• Young adult males
• Hepatic and splenic sinusoids as well as the marrow

Question 39

What are the most common sites of cancer that spread to the liver?

What is often the only clinical sign and the telltale sign that metastasis to the liver has occured?

Answer 39

• Colon, breast, lung, and pancreas
• Hepatomegaly