Pathology, January 31, 2001Landry & Wilson
Dr. Oliver 10 a.m.
Tumors of the Liver
Benign Tumors
- Cavernous Hemangioma
 - Most common tumor of the liver overall
 - Looks like reddish-purple subcapsular nodules
 - It is good that radiologists can easily detect these on CAT scans, because no treatment is required. An unnecessary needle aspiration may cause hemorrhage because the liver is so vascular.
 
Slide: Gross picture of a hemangioma with dark circumscribed lesions and dilated blood vessels
- Focal Nodular Hyperplasia – probably not a true neoplasm
 - Commonly found in young to middle aged patients; more women than men
 - May be associated with oral contraceptives
 - Presents as a single large nodule where a central stellate vascularized scar contains proliferating bile ducts and inflammatory cells.
 
Slide: Gross picture (Robbins, pg. 886) where the central scar is apparent
Slide: Microscopic view of the tumor with a collagen stain that emphasizes the central scar.
Slide: Proliferating ducts and inflammatory cells are seen at a higher power
- Nodular Regenerative Hyperplasia
 - A diffuse lesion with tons of nodules
 - Grossly, it looks like cirrhosis, but there is no fibrosis
 - Less common than cirrhosis
 - It is probably related to focal nodular hyperplasia.
 - Portal hypertension may develop with the nodular regenerative hyperplasia because it is diffuse, UNLIKE focal nodular hyperplasia.
 - (Gross picture in Robbins, pg. 887 and microscopic slide in Curran, pg 194)
 
- Adenomas (No bile ducts – just proliferation of hepatocytes)
 - Liver Cell Adenomas (a.k.a. hepatocellular adenoma) – a benign, true neoplasm of hepatocytes
 - Usually presents in young women on oral contraceptives
 - May spontaneously regress
 - Characterized by yellow-tan nodules with sheets and cords of hepatocyte-like cells. Usually one nodule is seen with no bile ducts. This tumor is hard to differentiate from well-differentiated hepatocellular carcinoma.
 - NO PORTAL TRACTS ARE PRESENT!!
 - Caution! This tumor has a tendency to ruptureleading to intra-peritoneal hemorrhage that may be massive and life threatening. Therefore, it is usually excised.
 
Slide: hepatocellular adenoma with a rupture and hemorrhage (Robbins, pg 887)
Slide: High power view – See lots of hepatocytes and it almost looks normal, except there are no portal tracts. (Curran, pg 206)
- Bile Duct Adenoma
 - Usually single, small subcapsular aggregates of uniform epithelium lined ducts
 
Slide: Bile duct adenoma at high power showing benign bile ducts.
Malignant Tumors of the Liver
Primary Carcinoma of the Liver (o.k. Liver cell carcinoma, hepatoma or hepatocellular carcinoma) KNOW NAMES!!
- More common in countries endemic for viral hepatitis (especially Hepatitis B). It is especially common in China, where vertical transmission of hepatitis B frequently occurs. Nearly all of these children have chronic hepatitis, which leads to carcinoma.
 - Occurs more in older males and blacks
 - α-fetoprotein is a good tumor marker, because it is often made by these tumors.
 - Risk factors:
 - Cirrhosis (almost always precedes this carcinoma)
 - Hepatitis B (especially if vertically transmitted)
 - Hepatitis C
 - Aflatoxins
 - Anything that causes cirrhosis – i.e. alcohol
 - Hereditary tyrosinemia – a rare metabolic disease  40% develop hepatocellular carcinoma
 - Morphology
 - Unifocal, multifocal or can diffusely involve the entire liver
 - Green discolorization from bile
 - Well differentiated and bile secretion is often present (different than cholangiocarcinoma)
 - Similar to renal cell carcinoma, this cancer likes to invade and travel down veins like the portal vein or the inferior vena cava (even into the right atrium!).
 
Slide: Grossly, it looks like a green unifocal, large lesion. (Robbins, pg 889)
Slide: Gross picture showing a tumor and nodules with cirrhosis in the background.
Slide: Gross picture of diffuse hepatocellular carcinoma (hard to differentiate from cirrhosis or nodular hyperplasia). The tiny nodules from the cancer are hard to differentiate from cirrhosis.
Slide: Well differentiated hepatocellular carcinoma – microscopic view. Nuclei are atypical and have prominent nucleoli. Sinusoidal pattern with bile present. This is hard to differentiate from hepatocellular adenoma. Consider who the patient is – older male or young female (adenoma). Also, the plates of liver cells are usually thicker in carcinoma than in adenoma. (Curran, pg 206-207)
Slide: Malignant hepatocellular carcinoma with huge black nucleoli. It is anaplastic, so it is hard to tell if it is hepatocellular.
- Fibrolamellar Variant of hepatocellular carcinoma
 - Young patients
 - No association with HBV or cirrhosis
 - Better prognosis
 
Slide: Cells of this tumor are separated by bands of fibrosis.
Cholangiocarcinoma
- Less common cancer that arises from the bile duct.
 - Risk factors: exposure to Thorotrast (radiographic dye no longer used), liver flukes (Clonorchis)
 - NO bile secretion
 - Mucus secretion may be present
 - Has a lot of fibrosis
 - More commonly metastasize than hepatocellular carcinoma
 
Slide: Gross tumor looks white; it is hard and dense from fibrosis. (Robbins, pg 890)
Slide: Tumor appears to have normal ducts, except there is no bile. It is well differentiated, and some areas have more fibrosis than others. (Curran, pg 207)
Slide: Cholangiocarcinoma with a more papillary form and more fibrosis.
- Clinical Aspects of Primary Liver Carcinoma
 - Nonspecific GI symptoms, hepatomegaly, jaundice, cirrhosis
 - Lab markers
 - Elevated serum AFP (α-fetoprotein)
 - Elevated CEA (carcinoembryonic antigen) – less specific; more likely with cholangiocarcinoma
 - Dismal prognosis  death within 6 months due to liver failure and complications from portal hypertension like esophageal variceal bleeding.
 
- Rare Forms of Primary Liver Cancer
 - Hepatoblastoma
 - Fetal tumor of the liver, so it has immature hepatocytes.
 - Appears in young children and is fatal within a few years
 - Consists of fetal epithelial elements that may be admixed with foci of mesenchymal differentiation like cartilage.
 
Slide: Hepatoblastoma – Embryonic hepatocytes are smaller and are hard to tell that they are hepatocytes. These cells have a clear cytoplasm due to glycogen and lipid in the cytoplasm. Osteoid production is present showing the mesenchymal contribution.
- Angiosarcoma
 - Very aggressive  fatal within 1 year
 - Occurs with exposure to vinyl chloride, arsenic, and thorotrast.
 
Slide: Angiosarcoma composed of endothelial cells (i.e. blood vessels) – several intertwining blood vessels with atypical nuclei
Metastatic Tumors of the Liver
- Most common malignancy of the liver
 - Originate from breast, lung, colon, stomach
 - Presents with hepatomegaly, multiple metastatic nodules, jaundice, and abnormal liver function tests (if massive)
 
Slide: Gross picture with innumerable nodules throughout the liver.
Scribe note: Dr. Oliver then gave a presentation about pathology as a career. If you are interested in pathology, talk to him.
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