Liver Path 8

Question 1

Focal Nodular Hyperplasia

Answer 1

Most commonly found in adult women (20-30 yo)

Can be large occupying an entire lobe of the liver, but over 85% are under 5 cm in diameter

Composed of hyperplastic nodules of hepatocytes, separated by fibrous septa which often form typical stellate scars

Absence of true bile ducts and a connection to the biliary outflow tract

(central scar is classic)

Question 2

Nodular Regenerative Hyperplasia

Answer 2

Liver is entirely transformed into nodules grossly similar to micronodular cirrhosis but without fibrosis

Can be associated with the development of portal hypertension

Most patients are asymptomatic

Thought to be a regenerative response to vascular injury (small vessel vasculitis??)

Liver biochemical tests are usually normal or nearly normal

Question 3

NRH vs cirrhosis

Answer 3

may resemble each other grossly

at cut surface, NRH nodules less well defined, parenchyma softer than in cirrhosis, fibrous septa are lacking

Question 4

NRH histology

Answer 4

There is sinusoidal dilation present. There are no inflammatory infiltrates, fibrosis and no areas of necrosis.

Question 5

NRH leads to

Answer 5

non-cirrhotic portal hypertension

Question 6

Hepatic adenoma

Answer 6

Benign tumor of hepatocytes in young women taking oral contraceptives (increased 30-40 fold)
If in males, associated with anabolic steroids

Subcapsular location prone to rupture especially in pregnancy. Resect if > 5cm or symptomatic, cessation of sex hormones can lead to full regression

Three different subtypes of adenoma

Question 7

types of Hepatic adenoma

Answer 7

HNF1-α Inactivated hepatocellular adenoma
Most commonly found in women
(most common one)

β-Catenin Activated Hepatocellular Adenomas (minority of adenomas)
Very high risk for malignant transformation
Often have a high degree of cytologic or architectural dysplasia

Inflammatory hepatocellular adenoma:
Found in both men and women

Associated with non-alcoholic fatty liver disease

**Small but definite risk of malignant transformation

Question 8

gross appearance of hepatic adenoma

Answer 8

rounded smooth borders and no central scar

Question 9

Cavernous hemangioma

Answer 9

H & E: typical hemangioma with vascular channels

Diagnosis can be reliably made by several imaging modalities
(CT, e.g.)

Cavernous hemangiomas are the most common benign liver tumors

Question 10

Key Concepts: Liver Adenoma

Answer 10

The liver is the most common site ofmetastatic cancersfrom primary tumors of the colon, lung, and breast.

Hepatocellular adenomasare benign tumors of neoplastic hepatocytes. Most can be subclassified on the basis of molecular changes:

HNF1-α inactivated adenomas,with virtually no risk of malignant transformation, often associated with oral contraceptive pill use or in individuals with MODY-3

β-Catenin activated adenoma,with mutations in the β-catenin gene leading to marked atypia and associated with a very high risk for malignant transformation

Inflammatory adenomas,the hallmark of which is up-regulation of C-reactive protein and serum amyloid A (often derived from gp130 mutations); 10% of these have concomitant β-catenin activating mutations. Risk for malignant transformation is intermediate.

Question 11

Malignant tumors

Answer 11

Hepatoblastoma

Hepatocellular carcinoma

Cholangiocarcinoma

Angiosarcoma

Metastatic tumors

Question 12

Hepatoblastoma

Answer 12

Most common liver tumor of young childhood 90% before age of 5 years

Usually fatal within first few years if not treated

Pathologic variants
Epithelial type composed of polygonal epithelial cells or embryonal cells growing in patterns recapitulating liver development

Mixed epithelial-mesenchymal type contains mesenchymal elements, osteoid, cartilage, or striated muscle

Question 13

Hepatocellular carcinoma

Answer 13

Most common primary hepatic malignancy of adults worldwide

Hepatocellular carcinogenesis secondary to viral infections (HBV, HCV) and toxic injury

**Majority of cases in the world are due to hepatitis B virus

Number of hepatitis C -associated cases increasing in the Western world.

Question 14

Hepatocellular carcinoma- initiation

Answer 14

Toxins
Aflatoxin (Aspergillus mycotoxin moldy peanuts & grains)

Activation of β-catenin and inactivation of p53 are the two most common early mutational events.

Significant male predominance

Question 15

Hepatocellular CarcinomaClinical Features

Answer 15

Hepatocellular carcinoma is clinically silent and most patients present with advanced disease

Upper abdominal pain, weight loss and signs of decompensated liver disease such as jaundice or ascites are frequent at presentation

Elevated serum alpha-fetoprotein in 50% of patients (low sensitivity and specificity, not useful for screening

Question 16

Precursor Lesions of Hepatocellular Carcinoma

Answer 16

Hepatocellular adenoma

Chronic liver disease hepatocellular dysplasias:

• Small cell change
• Large cell change

Dysplastic nodules associated with cirrhosis

Question 17

what can the tumor nodules of Metastatic
hepatocellular
carcinoma
look like?

Answer 17

Production of bile by the tumor accounts for the yellowish color of the tumor nodules
still have to work it up

Question 18

Hepatocellular Carcinoma Fibrolamellar Variant

Answer 18

85% occur under the age of 35 without gender predilection

Has no association with HBV, HCV or cirrhosis

Tumors are slow-growing and frequently surgically resectable

Five-year survival rates range from 30 to 75%

Fibrolamellar hepatocellular carcinoma seems to be a different biological entity from other types of HCC.

Question 19

Hepatocellular Carcinoma Fibrolamellar Variant- histology

Answer 19

Fibrolamellar tumours are typically hard, due to the presence of fibrous stroma

Tumour cells are larger than normal liver cells and have a deeply eosinophilic coarsely granular cytoplasm (large number of mitochondria in cytoplasm)

Question 20

hepatocellular carcinoma Key Concepts

Answer 20

The mainprimary malignancies are Hepatocellular carcinomas (HCCs) and cholangiocarcinomas
HCCs are by far the most common.
HCC is a common tumor in regions of Asia and Africa, and its incidence is increasing in the United States.

The main etiologic agents for HCC are chronic hepatitis B and C, alcoholic cirrhosis, non-alcoholic fatty liver disease, and hemochromatosis. In the Western population, about 90% of HCCs develop in cirrhotic livers; in Asia, almost 50% of cases develop in noncirrhotic livers.

The chronic inflammation and cellular regeneration associated with viral hepatitis or the activation of IL-6/JAK STAT pathway may be predisposing factors for the development of carcinomas.

HCCs may be unifocal or multifocal, tend to invade blood vessels, and recapitulate normal liver architecture to varying degrees.

Question 21

Cholangiocarcinoma

Answer 21

Second most common hepatic malignant tumor

Arises from bile duct epithelium and resembles other adenocarcinomas
60% are perihilar (Klatskin tumor)

Question 22

Cholangiocarcinoma - risk factors

Answer 22

primary sclerosing cholangitis, congenital biliary cystic diseases, thorotrast exposure, parasites (liver fluke)

Question 23

Cholangiocarcinoma metastasis and prognosis

Answer 23

Hematogenous route of metastasis in ~50%

Frequently difficult to differentiate from metastatic carcinoma from breast or pancreas

Lethal tumor (median survival 6 months)

Question 24

Cholangiocarcinoma- extra stuff

Answer 24

Premalignant lesions for cholangiocarcinoma include biliary intraepithelial neoplasias (low to high grade)

Typical adenocarcinoma that often produce mucin (Most are well-differentiated)

Lymphovascular invasion and perineural invasion are common with frequent intrahepatic an extrahepatic metastases

Question 25

Cholangiocarcinoma on ERCP

Answer 25

will produce a filling defect or area of narrowing with irregular borders at teh level of occlusion. Samples of tissue from the tumor can be obtained durin the procedure by brush or biopsy to confirm the diagnosis. In cases of complete occlusion, ERCP may not be able to evaluate the biliary tree proximal to the tumor. These patients would benefit from percutaneous transhepatic cholangiography

Question 26

Gerald Klatskin MD

Answer 26

Pioneered the use and development of the liver biopsy

Demonstrated that hepatitis B is associated with chronic hepatitis

Alcohol withdrawal could lead to the clinical improvement of patients with alcohol-induced liver disease

Among the first to recognize the occurrence of the full histologic spectrum of “alcoholic liver injury” in patients who did not use alcohol to excess (NALFD)

Question 27

Key Concepts- Cholangiocarcinomas

Answer 27

Is endemic in areas where liver flukes such asOpisthorchisand Clonorchis species are endemic.

Chronic inflammatory diseases of bile ducts are also risk factors.

The tumors may arise from extra hepatic or intrahepatic bile ducts.

They have uniformly poor prognosis.

Question 28

Angiosarcoma

Answer 28

Rare tumor (10-20 cases / year in US)
Most common primary sarcoma of the liver
Vascular origin
25% of cases are associated with
Vinyl chloride monomer
Thorotrast (radiographic contrast medium from 1930s)
Arsenic
Anabolic steroids
Predominantly older patients (60-70s)

Question 29

Metastatic Tumors

Answer 29

Metastatic neoplasms are the most common tumors in the non-cirrhotic liver and uncommon in the cirrhotic liver

Immunohistochemistry for tumor specific antigens is frequently critical for diagnosis of metastasis

Can be from nearly any primary site, but most common in adults are: lung, breast, colon, pancreas