Liver Path 8 Flashcards
Focal Nodular Hyperplasia
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)
Nodular Regenerative Hyperplasia
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
NRH vs cirrhosis
may resemble each other grossly
at cut surface, NRH nodules less well defined, parenchyma softer than in cirrhosis, fibrous septa are lacking
NRH histology
There is sinusoidal dilation present. There are no inflammatory infiltrates, fibrosis and no areas of necrosis.
NRH leads to
non-cirrhotic portal hypertension
Hepatic adenoma
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
types of Hepatic adenoma
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
gross appearance of hepatic adenoma
rounded smooth borders and no central scar
Cavernous hemangioma
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
Key Concepts: Liver Adenoma
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.
Malignant tumors
Hepatoblastoma
Hepatocellular carcinoma
Cholangiocarcinoma
Angiosarcoma
Metastatic tumors
Hepatoblastoma
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
Hepatocellular carcinoma
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.
Hepatocellular carcinoma- initiation
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
Hepatocellular CarcinomaClinical Features
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
Precursor Lesions of Hepatocellular Carcinoma
Hepatocellular adenoma
Chronic liver disease hepatocellular dysplasias:
- Small cell change
- Large cell change
Dysplastic nodules associated with cirrhosis
what can the tumor nodules of Metastatic
hepatocellular
carcinoma
look like?
Production of bile by the tumor accounts for the yellowish color of the tumor nodules
still have to work it up
Hepatocellular Carcinoma Fibrolamellar Variant
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.
Hepatocellular Carcinoma Fibrolamellar Variant- histology
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)
hepatocellular carcinoma Key Concepts
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.
Cholangiocarcinoma
Second most common hepatic malignant tumor
Arises from bile duct epithelium and resembles other adenocarcinomas
60% are perihilar (Klatskin tumor)
Cholangiocarcinoma - risk factors
primary sclerosing cholangitis, congenital biliary cystic diseases, thorotrast exposure, parasites (liver fluke)
Cholangiocarcinoma metastasis and prognosis
Hematogenous route of metastasis in ~50%
Frequently difficult to differentiate from metastatic carcinoma from breast or pancreas
Lethal tumor (median survival 6 months)
Cholangiocarcinoma- extra stuff
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
Cholangiocarcinoma on ERCP
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
Gerald Klatskin MD
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)
Key Concepts- Cholangiocarcinomas
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.
Angiosarcoma
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)
Metastatic Tumors
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
