Hepatocellular carcinoma
As opposed to benign hepatic tumors, malignant hepatic tumors are cancerous, very severe, and are actually now the third leading cause of cancer deaths worldwide.
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. Now, if the cancer is able to metastasize and gets into the blood stream, it most commonly goes to the lungs as a secondary organ.
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.
The most common risk factor, the one’s that have been linked the most with hepatocellular carcinoma are the hepatitis B and hepatitis C viruses, both of which can become chronic or long-lasting.
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.
A delay in detection of any disease typically means a worse prognosis, and hepatocellular carcinoma is no exception. In general, the cancer may be focal, or limited to one area, but it might also have several areas affected and be multifocal, or it could also spread diffusely through the liver tissue and not really have distinct focal points.
A classic sign of a secondary hepatic tumor, though, are multiple focal points that can even be sometimes felt on the free edge of the liver.
A common place for the tumor to spread is in the portal and hepatic veins, where a mass of tumor cells might lodge and block the veins.
If the hepatic vein is blocked, pressure builds in the portal system, pushing fluid into the peritoneal cavity and leading to abdominal swelling, called ascites, and perhaps hepatomegaly, enlargement of the liver.
This blockage of the hepatic vein is also known as Budd-Chiari syndrome. Because their abdomen’s swollen from ascites and hepatomegaly, patients might present with abdominal pain as well as fever due to the destruction of liver cells.
Having said that, a relatively large proportion of patients though, about one third, are asymptomatic, and as such the cancer is found incidentally.
On histology, it’s common to see bile inside the hepatocytes as well as the smaller cancerous hepatocytes invading the spaces around larger normal hepatocytes.
Also, in the blood, a bigtime indicator is an increase in alpha fetoprotein, or AFP. AFP’s normally found in abundance in fetal plasma, and drops off to smaller amounts in adulthood.
AFP’s also produced by the tumor or proliferating cells, so as the tumor cells proliferate, more AFP than normal can be found in the blood.
Also though, blood ALP and GGT will be increased as well, both of which are enzymes typically found in the liver that can be released after liver cell damage.
Finally, some additional proteins can also be elevated, like erythropoietin, which controls the proliferation of red blood cells, insulin-like growth factor, which promotes cell proliferation, and parathyroid hormone-related protein which can be secreted in higher-than-usual amounts by tumor cells.
Imaging procedures can be helpful in making a diagnosis, like CT scans, ultrasound, and particularly angiography which can help show vascularity.
If the tumor’s found and can be surgically removed, which is about 20% of cases, then the survival rate is improved by quite a bit, but if it’s not able to be removed, then survival is much lower, in the range of months to years.
Typically radiation and chemotherapy have not been shown to be super effective, but certain patients might be candidates for liver transplant.
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