Hi, this is Elliot Fishman and welcome to our latest talk, and this will be a one-parter on the CT appearance of hepatic lymphoma. It's based on an article that literally was just published by Hajra and Satomi and myself, looking at the appearances of lymphoma on CT and seeing what we can learn. Lymphoma, as we know, involves many organs and is often a great mimic. Think about the kidneys, think about the lungs, think about the spleen, differentiating between other malignancies and sarcoid, and the same is true in the liver. The appearance of lymphoma in the liver can be variable, whether we're dealing with primary hepatic lymphoma or secondary hepatic lymphoma. Now, the reality is most cases we do see are secondary hepatic lymphoma, where it's not just the liver involved, but maybe it's liver and spleen, or liver and kidneys, or extensive adenopathy. But let's look at the variable appearances, so you can get a good feel on what you should be thinking about.

So just a few slides I want to go through that are word slides, but just important. Primary hepatic lymphoma (PHL) is defined as lymphoma limited to the liver or perihepatic lymph nodes, without evidence of distant nodal disease, splenomegaly, splenic lesions, or bone marrow/blood involvement for at least six months after diagnosis. It is rare, accounting for less than 0.1% of all non-Hodgkin's lymphoma cases, and typically presents in the fifth decade of life with a male predominance. Lei et al. proposed a diagnostic criteria for PHL comprising: (a) clinical signs and symptoms due to liver involvement, (b) no evidence of distant lymphadenopathy, and (c) absence of leukemic features on peripheral blood smears.

Most common presentation is going to be right upper quadrant abdominal pain, but again that's not very specific. You could see jaundice, weight loss, fever. Depending on the appearance, it can look just like metastatic disease from almost any organ or when solitary can look like an abscess or can look like a cholangiocarcinoma when it's very centrally located. On physical exam, hepatomegaly is present in only about 17% of cases and patients commonly have abnormal liver function studies.

Hepatic lymphoma is a rare malignancy and as I said, primary and secondary, variable and non-specific imaging manifestations. Uh but one of the things we're talking about in this lecture is what are the manifestations? Yes, it may not be totally specific, but what is it that we should be thinking about?

Now, we mentioned that they can be classified as primary or secondary. They can present with CT patterns, and I'll show you every one of them, from a focal lesion to multifocal lesions, a diffuse pattern, or infiltration of the porta hepatis. Primary hepatic lymphoma often presents as solid lesions, while secondary hepatic lymphoma are commonly multifocal, and probably that's not all that surprising. They're typically hypovascular, low central areas, and at times can have a target sign with rim enhancement. They can have an infiltrative growth pattern, they can encase vessels, they can infiltrate the biliary structures, but don't commonly cause dilated ducts. One of the things that when you see an infiltrating tumor in the hilum of the liver and there's dilated ducts present, I'm typically going to think about cholangiocarcinoma because it is more common than primary lymphoma and also uh it causes duct dilatation.

The description of solitary masses, multifocal nodules, or diffuse infiltration, uh we talk about that, but the most common manifestation of primary hepatic lymphoma is a solitary lesion, followed by multiple lesions often with a dominant mass. As we mentioned, lymphoma of the liver, particularly when it's solid, large masses, or multiple masses, can really mimic hepatoma or cholangiocarcinoma. But one thing that helps you is with hepatoma, the liver is often cirrhotic, that's not going to be the case with lymphoma. So that can be very, very helpful. Again, the lesions are hypovascular, hepatoma is often hypervascular. Cholangiocarcinoma is hypovascular and it infiltrates the hilum, encases vessels, encases the duct, so it can be very uh tricky. You can see a scar sometimes which could mimic FNH, but the washout values really don't cause a problem in separating the two.

So here's just a good example of a patient with a single focal lesion in the liver. You can see there are small nodes in the porta hepatis, and the spleen looks enlarged. And again, when we talk about multiple lesions, we then typically talk about uh secondary hepatic lymphoma. Primary hepatic lymphoma would be more like that case with a solitary lesion. You can see in the differential, besides other malignancies, if that's your only finding, it could be TB or sarcoid, it could be a liver abscess, it could be metastasis. So at times, it's not always going to be that uh specific and you may need biopsy for further evaluation.

Now here's an example of multiple lesions involving both lobes of the liver, but you also can see there's involvement of both kidneys as well. So with multifocal disease, it's typically secondary hepatic lymphoma, and those are the patients of course that are going to have other processes: nodes and kidneys, as in this case.

Now, diffuse hepatic involvement is the most challenging to detect on CT, and we know that in general when you have solitary masses or multiple masses, we're pretty good. Infiltration, sometimes it's hard to tell from parenchymal liver disease or congestive changes. Diffuse hepatomegaly, uh there are so many causes for that. So again, something to keep in mind, which can be somewhat tricky.

Here's a large mass infiltrating the right lobe of the liver. And again, you could think about a hepatoma, though it should be more vascular, large metastasis, doesn't look like an abscess, looks like some sort of tumor, and you probably would not have thought about lymphoma as the first possibility because you're looking, the spleen looks good, there's small nodes present in the paraaortic region and aortocaval space, but nothing really substantial.

So again, periportal lymphoma is a rare presentation that may occur as soft tissue cuffing or an ill-defined mass extending into the porta hepatis. And again, you could think about cholangiocarcinoma as one of the differential diagnosis, particularly this hilar cholangiocarcinoma. Hilar cholangiocarcinoma is typically hypovascular, encases vessels, and encases the duct. So it can be somewhat of a challenge.

And here's just a good example of uh that infiltration. You can see in the liver right there, there's the tumor infiltrating, there's duct dilatation, tumor extending into the hilum, encasement of vessels including GDA and hepatic artery here, you can see the tumor infiltration and some nodes. Again, if I saw this with the dilated ducts and the low density infiltration, my first bet would not have been lymphoma, to be honest with you. I would have said cholangiocarcinoma.

Now, primary hepatic lymphoma can mimic hepatoma, we said that, though usually it's hypovascular and most hepatomas are going to be hypervascular, but not all of them. And again, hepatoma is more common in cirrhotic livers, lymphoma is not more common in cirrhotic livers, so it's something to consider. And again, thinking about that whole differential, lymphoma can resemble metastasis, can resemble at times an abscess, theoretically can have a hemangioma-type appearance, though that is exceedingly rare and I've not had any problem with that, but again, thinking about the possibilities.

Another possibility is a target appearance, reflecting central necrosis or degeneration and rim enhancement, which can be seen in up to 15% of hepatic lymphomas. These lesions are often well-defined, and again, differential: intrahepatic cholangiocarcinoma. But again, there's no capsular retraction, there's no significant duct dilatation, or vessel displacement, all that are good findings when you're making the diagnosis of cholangiocarcinoma. CA 19-9 levels are elevated with cholangiocarcinoma, but they're not going to be elevated typically with lymphoma.

And here's a nice example of a large solid mass with some satellite lesions. Again, in this case, you would look at this and say: cirrhosis, multiple lesions, the necrotic dominant mass with that ring sign must be a hepatoma, and the other lesions are just secondary signs of hepatoma. And that would have been my best guess as well, but this ended up being primary lymphoma. So it can be somewhat challenging.

Another comment: in primary hepatic lymphoma, the lesions often surround the intrahepatic ducts or portal vein without compressing or invading them, a finding known as biliary vascular floating sign. In comparison, hepatoma or cholangiocarcinoma will encase the vessels, uh lead to thrombus in the portal vein, be more infiltrating with narrowing and duct dilatation. So again, this idea, this floating sign, is something to think about.

And here's just a good example, this tumor in the porta hepatis. You can see the vessel encasement like the GDA and hepatic artery here. You can see the tumor infiltration and some nodes. Again, you would look at this and say perhaps lymphoma is indeed a good thought. Uh you want to make sure, you know, what could be challenging here is you look at this and you say: what about pancreatic cancer? One thing that pushes you away or makes you think twice about pancreatic cancer not being the diagnosis is the way the nodes or masses settled. If this was pancreatic cancer, you would have had dilated intrahepatic ducts, which you don't see here. But, you know, you could imagine, particularly on the images in the bottom row, that that's a mass coming off the pancreas, there's vessel encasement. But, the correct answer is going to be a vascular floating sign and lymphoma.

So when we talk about it, characteristic CT and MR features: vascular floating sign, multinodular sign, pseudocapsule, double ring sign on delayed imaging, lots of different signs, but it's an infrequent process, and most of the time, the signs don't really help until you know the diagnosis. Okay, the prognosis is relatively better uh with primary than secondary hepatic lymphoma, but survival is variable, there are new immunosuppressive drugs that are being used, so hopefully survival will even get better.

So some just summary statements: hepatic lymphoma is a rare entity that can closely mimic benign and malignant liver lesions. While CT remains the primary modality, it's often challenging, sometimes MR can be helpful. But again, knowing the appearances and recognizing that when you have primary lymphoma, for example, or even secondary lymphoma, uh the tumor appearance is variable in terms of infiltration, in terms of masses. But again, you know, when you think about the solitary and multiple lesions I showed you, there are many tumors that can do that, so it's really hard just looking and making the right call all of the time.

So this article, we spoke about multiple patterns of hepatic lymphoma, and let me go through them one more time. Solitary lesions, common particularly in primary hepatic lymphoma. You can see nodes in the porta hepatis here. Multifocal disease, both kidney and liver, so it's beyond multifocal. But if it was the liver only, you would have said metastatic disease like maybe metastatic colon. When you have the kidney involvement, you know, solid masses in the kidney and liver, I don't see anything obvious in the spleen, maybe tiny lesions, but then it pushes me to saying lymphoma, which this indeed was. That large mass in the right lobe of liver, you would have said cholangiocarcinoma, though they're usually more central, you would have said hepatoma. In a younger patient, hepatocellular, fibrolamellar, are all possibilities. And the porta hepatis, the encasement, the dilated ducts, in this situation, cholangiocarcinoma often is the first thing that comes to your mind and that's reasonable, but think about lymphoma, particularly when you see the images with the vessel encasement, or it's really soft infiltration. And then of course, the ring sign. In this patient, cirrhotic liver, my first and best answer would have been hepatoma. I would not have thought about lymphoma, so it is challenging, though the patient does have a lot of nodes in the porta hepatis, which is obviously more common going to be in lymphoma than in cholangiocarcinoma or hepatocellular carcinoma. And finally, just repeating that vascular floating sign. It's an interesting sign, I have to see if I ever call anything with that sign, and truthfully, I've heard of it but never really followed it. But we are going to take a closer look at it because it has some value, particularly in these challenging liver cases. So with that, my time is up. I hope you now know a little bit more about primary and secondary hepatic lymphoma, the range of appearances, and how indeed it's a great mimic. And with that, have a great day.