Hepatocellular carcinoma is a cancer associated with , produced most-notably by Aspergillus flavus.
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A 65-year-old man who immigrated from China to the United States 15 years ago comes to the office because of increased abdominal girth, weight loss, and fever. Physical examination shows for right upper quadrant tenderness on palpation and organomegaly. A tissue biopsy is obtained and tests positive for a primary malignancy. Which of the following tumor markers is most likely to be elevated in this patient?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS
With these malignant liver cells or hepatocytes, just like malignant cells in other cancers, they develop some mutation that causes them to replicate at way higher rates and form these masses of cells that continue to grow and potentially spread to other tissues.
This would be a primary hepatic tumor, since it starts in the liver. It’s totally possible, though, for liver tumor to develop as a metastasis from another primary cancer, in which case it would not be hepatocellular carcinoma, but a carcinoma from somewhere else, and this is actually more common than primary liver tumors themselves.
The most common sources of the tumor cells that got to the liver but started somewhere else are the colon, pancreas, lung and breast.
What exactly causes the mutation in the hepatocyte though?
Well the mechanism isn’t fully understood and can probably be caused by a lot of different things, most importantly though, things that put the liver in a constant cycle of damage and repair are the biggest culprits.
If the liver cells are constantly being forced to repair, this raises the chances of genetic mistakes or mutations, potentially leading to carcinogenesis or development of cancer cells.
Examples might be any disease that leads to cirrhosis and scarring of the liver tissue, which can include alcoholic hepatitis and cirrhosis, hereditary hemochromatosis, primary biliary cirrhosis, alpha-1 antitrypsin deficiency, and others.
In this case, these cells are at greater risk because of the constant state of infection and immune cell attack, leading to constant damage and repair.
HBV is particularly problematic because of how the virus replicates; the HBV virus is a DNA virus that integrates into the hepatocyte’s DNA, which, although not completely understood, is thought to either directly disrupt regulation of cell growth and replication, leading to carcinoma, or alternatively cause some indirect effect that later leads to unchecked cell growth and replication.
One interesting risk factor, is exposure to aflatoxins.
Aflatoxins are highly toxic chemicals produced by certain aspergillus molds that can be found in certain foods when they start to decay, like grains, peanuts, and vegetables.
As foods that have this type of mold are eaten, aflatoxins are also eaten, and then they’re absorbed in the small intestine and sent to the liver for metabolizing.
The most potent type of aflatoxin thought to be involved in carcinogenesis is aflatoxin B1, and when it gets to the liver, it’s metabolized to aflatoxin B1 8,9 epoxide.
And now this guy can bind right to DNA, called a DNA adduct.
This interaction leads to mutations in the p53 tumor suppressor gene, which usually when it’s functioning right, stops the formation of tumors, so if it becomes mutated and dysfunctional, tumor formation and carcinogenesis might follow.