Hepatoblastoma-a rare liver cancer in children

MD Anderson Cancer Center
Date: 05-12-2014


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Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas: MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. And today our guest is Dr. Susan Abraham. She is a Professor of Pathology here at MD Anderson and our subject is hepatoblastoma, which is a rare liver tumor that occurs in children. Dr. Abraham, how young do children get hepatoblastoma?

Dr. Susan Abraham: Hepatoblastoma is really almost exclusively seen in children. The usual age range is anywhere from six months up to five years but most of them will be in children who are between six months and three years old. About half of them will be under one year and half will be over one year so they say the median age is one year.

Lisa Garvin: So hepato meaning liver and blastoma, usually when I hear that term that involves cells that are not mature. So what is the pathology of hepatoblastoma?

Dr. Susan Abraham: Yes that's exactly right. So hepatoblastomas are primitive tumors that arise in the liver. Like you said, blastoma really refers to how primitive many of these tumors appear under the microscope. There are a wide range of histology's, or appearances, under the microscope that we can see in these tumors. So there's a general classification. About somewhat more than half of the tumors are called epithelial and then somewhat less than half are called mixed epithelial and mesenchymal. The epithelial ones are composed entirely of cells that to varying degrees resemble hepatocytes, the normal cells in the liver, and the mixed tumors have cells that look like hepatocytes as well as what we call stromal elements so that could be cells that recapitulate bone development or chondroid cells that look like cartilage, cells that look like muscle or cells that look like soft tissue. So in terms of their primitive nature in terms of the epithelial cells, most of these tumors look like the type of liver cells that would be seen either in an embryo, and those are called embryonal type hepatoblastomas. And others look like fetal type liver cells that you might see in a fetus anywhere from nine weeks up until birth and those are called fetal type hepatoblastomas. Many of the tumors though aren't really composed of just a single type of cell. And so when the pathologist samples these tumors, and they have to be sampled really carefully, there may be areas that look very undifferentiated and those are called small cell undifferentiated areas. And there may be areas that look almost like adult type liver tumors which are hepatocellular carcinomas. So these areas can be mixed together. Very rarely a patient will have a pure type of tumor.

Lisa Garvin: So diagnosis is very important then since you've got so many factors in play.

Dr. Susan Abraham: It's the diagnosis as well as prognosis so in some cases the histology can give a clue as to how the patient should be best treated with chemotherapy, either before or after surgery and in other cases it will just give some prognostic information, yes.

Lisa Garvin:  I understand there's a genetic connection to hepatoblastoma. There's a gene called FAP. Can you explain that?

Dr. Susan Abraham: Yes, exactly. That stands for Familial Adenomatous Polyposis or FAP. This is a condition that runs in families so most commonly these patients have multiple, multiple polyps in the colon and sometimes in the stomach and small bowel as well. And children that come from these families are at very increased risk for hepatoblastoma in childhood, on the order of about 800 times the risk of the general population.

Lisa Garvin: Does it just have to be one parent that carries the gene?

Dr. Susan Abraham: Exactly so they inherit it from one parent. It's a dominant gene, yes.

Lisa Garvin: And as far as diagnosing and setting a prognoses for hepatoblastoma, I understand that alpha-fetoprotein plays a role.

Dr. Susan Abraham: Exactly. It helps in diagnosis as well as in predicting or helping to determine the best treatment for the patient and giving some prognostic information. So alpha-fetoprotein is a protein that's produced in the fetal liver and it's a bit similar to the protein that's produced in adult livers, which is albumen. So in normal older children and adults, there really is very little AFP that's detected in the bloodstream. In children who have hepatoblastoma, about 90% will have elevated levels of AFP. And sometimes these are really extremely elevated. It's not a 100% diagnostic test because 10% of hepatoblastomas, those patients don't have elevated AFP, and on the other hand, some patients who have adult type liver tumors, called hepatocellular carcinomas, they may also have elevated levels of AFP, but it is helpful. It's also helpful for patients who have been treated for their tumors. They can be monitored for serum levels of AFP. If we know that the tumor is producing AFP and they're treated and their serum level goes to normal and then they're followed up, if that level increases in the future, then that can be a marker of recurrence of the tumor and they may be able to be treated earlier on for recurrence.

Lisa Garvin:  How common is this cancer? Not very, I understand.

Dr. Susan Abraham: Yeah you're exactly right. It's a very rare tumor. It's estimated that in the United States there are about 100 new cases per year so it's very uncommon. It's increasing though over the past few decades so currently each year out of a million children, about 1.5 to 1.6 children will develop hepatoblastoma. But back in the 1970's, it was only about .8 per million children per year who developed hepatoblastoma so the incidence is increasing and even though it is a rare tumor overall, it is the most common primary liver tumor in children. It's about 90% of liver tumors in young children, will be about a blastoma.

Lisa Garvin:  I guess it was hard for me to wrap my head around the fact that young children could have liver tumors. I mean the typical hepatocarcinoma tends to happen in older people. It just seems so odd that young children would have liver cancer.

Dr. Susan Abraham: Yes unfortunately they can develop this. In adults who develop adult type hepatocellular carcinomas, many of those patients will have a background of cirrhosis or an abnormal liver for some reason. They may have hepatitis B or hepatitis C that chronically infects the liver. In children, most who develop hepatoblastoma do not have any underlying condition in their liver. They usually have a normal liver and for some reason they develop this tumor in the background of a normal liver.

Lisa Garvin:  Overall, given all types together, what is the overall prognosis for this cancer?

Dr. Susan Abraham: It's actually much, much better than the adult form of hepatocellular carcinoma. If you take all children who have a hepatoblastoma diagnosis, regardless of any other factor, the five year survival is at least 70%, which is much higher than the five year survival in hepatocellular carcinoma. There are many treatments for hepatoblastoma and even children who have metastatic disease at presentation, meaning that the disease has left their liver and traveled to other organs like the lung, even those children have a very good chance of survival.

Lisa Garvin:  So the basic treatment would be surgery with adjuvant chemotherapy, either before or after surgery, correct?

Dr. Susan Abraham: That's right. There is a sort of a divide in the idea of how to treat these tumors, between how they're treated in Europe and how they're treated in the United States and North America. So in this country, for those patients who are diagnosed with hepatoblastoma and who seem to have limited disease in the liver, that can be taken out by surgery with clean margins, meaning that the surgeon got all of the tumor, many practitioners in the United States will prefer to give those children surgery up front. And then most of them will get chemotherapy after the surgery, so called adjuvant chemotherapy. In Europe the more typical course of action is regardless of how small the tumor is when it's diagnosed and even if it maybe could be taken out by surgery initially, they prefer to treat first with chemotherapy, then do surgery and maybe given more chemotherapy after the surgery.

Lisa Garvin:  Is liver transplantation an option in children this young?

Dr. Susan Abraham: Yes it is. So very young children undergo liver transplantation. And liver transplantations is one of the options in hepatoblastoma. So one unfortunate thing in treating this disease is that only about 1/3 or so of children who are diagnosed with hepatoblastoma will have a tumor that can be surgically resected with clean margins. So for most of these children they really can't go to surgery up front. They're going to require chemotherapy first. And chemotherapy, even in children who have metastatic disease, it can actually render them surgically resectable, and about 75% of the time actually. And so the idea in those children would be that they get chemotherapy and that the tumor in the liver and perhaps the tumor in the lungs shrinks enough that it can be taken out surgically. And at that time the surgeon can remove metastatic disease as well as the primary tumor. There are, unfortunately, some patients who don't respond well to chemotherapy or even if they respond their tumor may not be in a good location of the liver that allows it to be taken out surgically. So perhaps it's in the center of the liver or it's encroaching on major blood vessels, those tumors can't be dealt with surgically and those patients may require a liver transplant.

Lisa Garvin: But livers, of course, are highly sought after. We hear stories about people who are on liver waiting lists for a really long time. Is that a problem in this disease?

Dr. Susan Abraham: Yes it is. Those are called cadaveric livers. The other option is for a relative, usually a parent, to donate a portion of their liver to the child. So of course the adult liver is much bigger than the child's liver. And so only a portion of that adult liver needs to be taken out and it can be transplanted into the child. The entire liver of the child, the native liver, will be taken out along with their tumor, and then a piece of the parent's liver will be transplanted into them. And the liver is really amazing because it regenerates so quickly. So even a small portion of adult liver that's given to a child can grow to a normal size within weeks to months. Sometimes a child who gets a cadaveric liver, if it's from another child they may get the entire liver or even those cadaveric livers, when they're given to children, they may be split into different parts so that they can be given to more than one child.

Lisa Garvin: So what should parents be looking for in regards to symptoms for hepatoblastoma? Are they obvious or vague?

Dr. Susan Abraham: Unfortunately most of the time the tumors present at a relatively advanced stage and they actually present with a mass in the abdomen that's just related to the tumor in the liver, usually on the right side of the liver. So most children are not symptomatic aside from having a mass in their liver. Sometimes they do have symptoms and that can be loss of appetite, weight loss, they may be nauseous or vomiting. There are some very rare symptoms or very rare circumstances that can lead to diagnosis. One very rare condition would be that the tumor bleeds into the abdomen. Another very rare condition is when the tumor produces a hormone that causes precocious puberty in boys. But those are very rare. Mostly it's just an abdominal mass.

Lisa Garvin: So jaundice is not a symptom?

Dr. Susan Abraham: Sometimes they will have jaundice but it's not a common symptom.

Lisa Garvin: So what are we doing with respect to increasing outcomes? Are there certain chemotherapies that can help? Obviously we're using chemo just to debulk the tumor but is there any sort of target that you're looking at with chemotherapy or any other options?

Dr. Susan Abraham: Yeah, a combination of chemotherapy, good surgery by an experienced surgeon and the child being seen at a liver transplant center, all of these things really play into the good prognosis of this tumor. In the 1970's or before the 1980's, the five year prognosis was very poor, about 25% of children with hepatoblastoma live for five years. When viable chemotherapy options became available in the 1980's, mainly based on Cisplatin chemotherapy that really helped to increase the survival in this tumor. And nowadays, as I think we discussed a little bit earlier, the five year survival is at least 70% and sometimes more. So the chemotherapy regimens that they're given play into that as well as the increased option for liver transplantation.

Lisa Garvin: Would genetic testing help in this situation at all?

Dr. Susan Abraham: There are a couple of situations where genetic testing is helpful. So there are a couple major genetic syndromes that are associated with hepatoblastoma in children and the FAP syndrome is one of them and the other is known as beckwith-wiedemann syndrome. Especially in beckwith-wiedemann syndrome the risk of hepatoblastoma is increased probably more than 1,000 times fold the general population. And so it is recommended that children who have beckwith-wiedemann syndrome undergo surveillance for hepatoblastoma and it's a little bit controversial but most people would agree that children who come from families with familial adenomatous polyposis and who have that gene themselves should be monitored for hepatoblastoma.

Lisa Garvin: Due to the rather complicated nature of diagnosis for this disease, is it important for parents to go to a large cancer center or can they just be treated in their community?

Dr. Susan Abraham: Yeah absolutely it's very important for parents to take their children to a center that is experienced in dealing with children's liver tumors. So this disease, like most childhood diseases, really requires a team approach. So you want to take your child to a large center that has experience with diagnosing these tumors, that has experience with treating these tumors, where there are experienced radiologists who look at these tumors and in some cases where the child may need to be referred to a liver transplant center so the parents want to take the child to, again, a large hospital that has access to liver transplantation. This really requires a team approach with the radiologist, the oncologist, the surgeons, maybe liver transplant surgeons and with pathology. So it requires a team approach and that's difficult to find in a small community hospital because these tumors are so rare they really won't develop the experience with treating these type of tumors.

Lisa Garvin: Great, thank you very much. Very informative.

Dr. Susan Abraham: Thank you.

Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline, contact ask MD Anderson at 1-877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.