Sonography of Liver Masses - HD

Introduction

Hello, I'm Bill Middleton.

I'm a professor of radiology at the Mallinckrodt Institute
of Radiology in St.
Louis at Washington University School of Medicine.

My lecture is on sonography of liver masses.

The topic of this lecture is sonography of liver masses.

There are six lesions that we're gonna focus on during this lecture, and you can see the list there.

Cysts

We're gonna start with cysts.

Cysts are the most common liver mass,

and unlike in the kidney, where sometimes they can be a little bit tougher to detect
and characterize in the liver, cysts are generally very easy to detect
and are fairly easy to characterize as well.

They usually display the classic sonographic findings
of cyst and that they're anechoic they have posterior acoustic enhancement
and they have a strong reflection from the back wall.

Now, puckering and septations
or partial septations along the wall if hepatic cyst are not
uncommon and shouldn't concern you too much.

This is a typical appearance of a liver cyst.

Anechoic increased through transmission,
strong reflection from the back wall.

Here's a small liver cyst that was scanned
after the patient had an indeterminate lesion seen on CT.

You can see the cyst here.

And even though the cyst is significantly less than a centimeter in size,
it still has strong back wall
and a little bit of increase through transmission.

Small Indeterminate Lesions in Cancer Patients

Now, this case raises an interesting dilemma.

What do you do with liver or with cancer patients
who have small indeterminate lesions seen on CT?

Is sonography helpful in those situations?

And there was a nice study that was published in the Journal
of Ultrasound in Medicine in 2003 that looked at 76 patients
who had 124 lesions, all
of which were less than 15 millimeters.

And the mean size of these lesions was 7.5 millimeters.

So less than a centimeter in size, mean range.

And they had either follow up histology and
or follow up imaging in all of these patients
for a mean of 17 months.

And what they found was, if you looked at all of the lesions
that were being evaluated,
sonography could detect slightly less than half of them,
48%.

If you subcategorize those into the lesions
that had a CT readily available for reference,
then the detection rate increased to 66%.

But if the CT wasn't available to compare
with the ultrasound, then the detection rate was only 32%.

And this was statistically significant difference.

And if you looked at lesion size,
if the lesion was bigger than five millimeters,
the detection rate was 67%.

But if the lesion was less than five millimeters,
then the detection rate was only 19%.

But if you look just at the patients who had lesions
that were bigger than five millimeters
and the CT scan was available for direct comparison,
then the detection rate was 83%.

And these are probably the types of patients
that you're going to see most often.

And hopefully when you do these exams,
you will have the CT available for comparison.

Then of the 60 lesions that were actually identified
and detected sonographically, these are the results
of the lesion characterization.

If you look at this row here, of all lesions
that were characterized, sonography was correct in 93%,
it was correct in 95% of the cysts
and 88% of the solid metastases,
and in a hundred percent of the hemangiomas.

So the bottom line from this study is
that small indeterminate lesions seen on CT in cancer
patients should undergo sonography
for further lesion characterization.

And here's an example of a patient with breast cancer
who is status post partial mastectomy who presented
with chest wall pain and lower extremity swelling.

And on her CT scan on this axial
and coronal reconstruction, you can see on both images
a tiny liver lesion adjacent to the right kidney.

Well on sonography.

If you look closely, you can see that this corresponds
to a very small cyst and notice that that cyst is anechoic
and still has increased
through transmission despite the size that it's probably slightly less than five millimeters in size.

Mimics of Simple Cysts

Now, there are things that can mimic simple cysts,
and vascular lesions are among the most common.

This is an example of a liver transplant patient
who had a simple appearing cyst on gray scale,
but it contains swirling blood flow on color doppler.

And this was a post biopsy pseudo aneurysm
that was subsequently confirmed with angiography.

But in addition to pseudo aneurysms, routine aneurysms can simulate cyst as can arterial venous malformations,
and one particular tumor.

Lymphoma is notorious for being extremely hypoechoic,
and rarely it can be anechoic
and simulate cysts in the liver and elsewhere in the body.

Complex Cysts

Now, what about cysts that aren't simple, that appear complex?

The differential for that includes hemorrhage into cyst
or hematoma, infection in cyst
or abscess metastasis, echinococcal disease, myelomas
and biliary cystic tumors.

And I want to just focus for a minute on infection
and talk about abscesses.

So abscesses can have a fairly typical sonographic
appearance, and that is a complex fluid collection often
with multiple septations.

But it's important to realize
that abscesses can also appear solid
and can simulate neoplasms in the right clinical setting.

A solid lesion should be considered a possible abscess
until proven otherwise.

And small abscesses, micro abscesses in particular,
those caused by candidiasis can have a bull's-eye appearance
as we see here, or can have an appearance
that's called the wheel within a wheel appearance,
where you see multiple layers of varying echogenicity.

Now, if you're dealing with a complex cyst,
the way you confirm the diagnosis is generally
with clinical history and laboratory studies.

That will often allow you to determine now
what it is or at least to determine
what the management should be.

Doppler is obviously helpful
to see if there's internal blood flow or if there is
or if it's a primary vascular lesion to begin with.

In many cases, a follow-up exam in a few weeks will clarify
the situation and if necessary,
ultrasound guided needle aspiration can always be performed.

Hemangiomas

Okay, now I wanna move on to the next
lesion, which is hepatic hemangiomas.

Hemangiomas are solid lesions with multiple
tiny blood filled endothelial lined spaces.

They're like sponges in the liver
that are filled with blood.

It's the most common solid liver lesion
that you'll encounter.

It's present in at least 7% of the population.

More frequently in women than men.

They're usually less than three centimeters in size.

And although most are solitary, up to 10% will occur
in multiple locations.

The sonographic appearance of hepatic hemangioma is typically that
of a solid lesion that's homogeneous
and uniformly echogenic sometimes
with slight scalloping of the margin.

A reverse target appearance that is a lesion
that has a hyperechoic rim is also very typical
of hemangiomas, but seen less often.

Larger lesions are often atypical through transmission
does occur, but it is uncommon.

The majority of hemangiomas are stable over time.

But 20% will change in some way.

And those that change over time usually will go from hyperechoic to hypoechoic.

And rarely they can change typically in
that direction from hyper to hypo over a short period
of time during the course of a single examination.

And although these are lesions that are filled with blood,
they have very slow blood flow,
so you usually don't see much flow, if any, on doppler.

So here's a typical hemangioma,
homogeneous hyperechoic, well-defined lesion in the liver.

On Doppler, they have very little, if any,
detectable blood flow.

This is the reverse target appearance
where you see a hyperechoic rim
surrounding an isoechoic central component.

This is a case that was loaned to me from a former fellow
of mine, and you can see on the initial examination there's
a fairly typical homogeneous hyperechoic liver lesion.

Nine months later, it had converted from hyperechoic
to hypoechoic.

Here's another lesion that comes from another former
Mallinckrodt resident where during the course
of the exam, a lesion typical
of the hemangioma was seen initially here
and later in the examination it had changed to the point
where it was slightly heterogeneous,
but predominantly hypoechoic.

And this occurred over a matter
of several minutes.

Now, atypical hemangiomas do occur
and they have a variety of appearances.

One of the most common is a hypoechoic hemangioma,
and that tends to occur in patients
that have increased liver parenchymal echogenicity,
secondary to fatty infiltration.

As we see in these two cases, large
hemangiomas often are atypical.

And these are two examples
of heterogeneous non-specific liver lesions
that did turn out to be hemangiomas.

And then finally, hemangiomas can occasionally be bull's-eye.

Now, fortunately, this is very rare.

The majority of target lesions
that are encountered on sonography
as we'll hear about later are malignant.

But very rarely a hemangioma can have a target
appearance as in these two cases.

Target appearance is a lesion that has a hypoechoic rim.

Study on Hemangiomas

So how do you deal with hemangiomas?

Well, one of my former fellows did a study
that was published in radiology in 2000
where he looked at 383 patients
that had the word hemangioma in the ultrasound report.

And of those, he eliminated 16 that on review were atypical
95 that occurred in patients who were high risk for malignancy and 59 who had insufficient follow up.

So this group, and that left him with 213 patients
who were at low risk for malignancy
and who had typical hemangiomas on sonography.

Of those two hundred thirteen, a hundred and twenty one had
imaging and or histologic follow up,
and 92 had clinical follow up for a period
of greater than two years.

And of these 213 patients, only one turned out to have
a malignancy.

And that was a patient that had a neuroendocrine met
that was discovered 22 months after the original ultrasound.

So the moral from this study is that
if you have a typical appearing
hemangioma in a patient who's low risk for hepatic malignancy,
the yield of doing any type of follow-up is extremely low
and is really not justified.

Management of Hemangiomas

Now what do we mean by high risk for malignancy?

So if the patient has a prior history
of an extra hepatic malignancy, any current evidence
of an extra hepatic malignancy
or chronic liver disease such as hepatitis
or cirrhosis, then they're put in that high risk category.

Low risk category is basically everybody else.

And notice that this high risk category does not include
anything about liver function tests, patient demographics or number or size of lesions.

So based on all of this, the recommendation for management
of typical hemangiomas
or lesions that have the reverse target
appearance are if the patient is at low risk,
you do no further follow up.

If the patient is at high risk, then follow up is indicated.

And generally, we recommend MRIs.

Now, why do we follow up the patients that are high risk?

Well, that comes from a study that was conducted in Italy
where they looked at hemangioma like lesions in patients
with cirrhotic livers,
and they had a large patient population,
almost 2000 patients with newly diagnosed cirrhosis.

And 44 of those patients had hemangioma appearing lesions.

And ultimately of those 44, 22 were proven to be hemangiomas,
but 22 were proven to be hepatocellular cancer.

Now also they looked at about 1600 patients
who on their initial ultrasound scan had no evidence of a focal lesions.

And of those 26 developed lesions
that looked like hemangiomas on their followup sonograms.

And of those 26, 22 were hepatocellular cancer,
and four were dysplastic, potentially malignant or pre-malignant nodules.

So the bottom line here is if the patient has chronic liver
disease, you clearly need to follow up lesions
that have the appearance of a hemangioma.

And we also add patients with history
of extra hepatic malignancies into that.

Liver Metastases

So we've talked a little bit about liver metastases also.

Now let's focus on that.

The liver and the lung are the most common site
of distant metastases.

Mets are most common malignant liver
lesion in North America.

50% of patients who die of cancer
and have their livers examined at autopsy will
have liver metastases.

Generally, liver metastases are multiple,
that is true in 90%
and they usually involve both lobes of the liver,
but realize that 10% of metastases are solitary.

Signs and symptoms of liver disease are absent in
approximately 50% of patients with liver metastases.

And the liver function tests are notoriously unreliable in detecting liver metastases.

So imaging plays a critical role.

As you all already know on ultrasound, the appearance
of liver metastases is variable.

The two most common patterns are the target appearance
and the hypoechoic solid appearance.

Uncommon appearances occur though
and are not that infrequent.

They can be heterogeneous hyperechoic,
they can be complex cystic, some will contain calcification,
and then occasionally you'll have a diffuse
infiltrated pattern.

But the most common appearance
for liver metastases is the bull's-eye appearance.

So let's look at some of these.

So these are classic target liver lesions that were all liver metastases in four different patients.

The two up above show a thick hypoechoic rim,
and this one shows a thin hypoechoic rim.

The thick hypoechoic rim usually correlates with viable
proliferative tumor.

The thin hypoechoic rim often correlates
with compressed liver parenchyma that produces an area
of sinusoidal dilatation.

Hypoechoic lesions are also fairly common in metastases.

And these are four different examples of patients that have
multiple hypoechoic lesions.

Notice in these cases, the through transmission
behind these solid liver metastases.

And that does occur,
just because you see some through transmission does not
necessarily imply that a lesion is liquified.

Hyperechoic metastases are uncommon.

The tumors that tend to do that most frequently are GI
and particularly colon neuroendocrine tumors and ovary.

And you can see a neuroendocrine tumor here, a carcinoid,
an ovarian tumor here,
and then a patient with osteosarcoma.

Calcified metastases also occur frequently from GI sources such as the colon
and stomach also from the ovary.

And these are three different examples of patients
with partially calcified metastases from colon cancer.

Cystic metastases also occur.

They can occur because the lesion is large
and outgrows its blood supply.

Sarcomas are notoriously cystic
as are squamous cell cancers.

And ovarian cancer can also produce complex cystic lesions.

And you can see a variety of appearances here.

All of which are complex lesions that were metastases.

The diffuse heterogeneous pattern also occurs
here using a standard curved array transducer.

You see that the liver parenchyma looks coarsened.

It's hard to necessarily pick out discrete focal lesions.

When you're faced with this sort of a situation,
you should take a look with a high resolution linear array
and just focus on the near portion
of the liver as we did here.

And in this case, you can see that the pattern actually is due to multiple focal hypoechoic lesions.

Handling Suspected Liver Metastases

So what do you do when you're faced with
what you think may be liver metastases?

Well, you confirm the diagnosis first
with an ultrasound survey of the abdomen looking
for a primary site or looking for other metastases.

And the primary sites that you can diagnose graphically include,
but aren't necessarily limited to the pancreas, the colon,
the stomach, and the kidney.

So at the least you should look at all of those organs.

Most of the patients who have
what you think will be metastasis to the liver will ultimately get a CT of the chest
and abdomen looking for primaries and staging the disease.

And then ultimately many
of them will come back for a liver biopsy.

Or if some other site has been identified
that would be easier to reach than the liver, you can certainly biopsy that as well.

So here's an example of a patient that presented for an abdominal sonogram
and a large liver mass was detected.

Metastatic disease was certainly one of the leading things in the differential diagnosis.

And a survey of the abdomen showed a markedly thickened loop
of colon in the left lower quadrant due
to primary colonic cancer.

Now I mentioned patients coming back
for liver biopsies.

Ultrasound guidance is extremely successful in making the diagnosis of liver metastases.

When we looked at this back in the late 1990s, we collected patients who had lesions
that were less than 1.5 centimeters.

The mean size in this patient population was 1.3 centimeters,
and we had a 96% success rate in making the diagnosis of metastases.

And just to give you a reference,
a 1.3 centimeter lesion is the size of a M&M.

And here's an example of a patient with a history
of melanoma, has a 5.8 millimeter lesion in the liver
that you can see there that was successfully diagnosed
with ultrasound guided biopsy.

Now, one warning to give you is
that when you are thinking of metastatic disease
to the liver, you also need
to include lymphoma in your differential diagnosis.

Lymphoma, as you can see here, can be hypoechoic, it can be bull's-eye,
or it can be diffuse and infiltrative.

And these three patterns closely simulate
metastatic disease.

Unlike metastatic disease,
lymphoma is almost never echogenic, almost never cystic,
and almost never calcified.

Hepatocellular Carcinoma

Now let's move on to hepatocellular cancer.

The third lesion in our list.

As you know, hepatocellular cancer is associated
with chronic liver disease, primarily cirrhosis
and hepatitis B and C,
but the other diseases that can increase the risk
or hemochromatosis and glycogen storage diseases.

Most of the time hepatocellular cancer will either present
as a focal or a multifocal mass,
but it can also be diffuse and infiltrating.

The echogenicity is extremely variable.

They are typically hypervascular lesions.

You generally will be able to detect that
with doppler, but not always.

And venous invasion in unscreened populations is actually quite common, 30
to 60% in the portal vein and 15% in the hepatic veins.

But in screened populations, which is what we tend to deal
with nowadays, the incidence
of venous invasion is much less common.

So I'm gonna show you a series of hepatocellular cancers.

Here is one that is fairly typical appearance.

It's a solid hypoechoic lesion.

This is one that is a typical target lesion,
hyperechoic centrally with a hypoechoic rim.

Here's a heterogeneous lesion that has well-defined areas
of both increased
and decreased echogenicity, which is fairly common
for primary liver tumors, hepatoma
and adenomas.

And here's a lesion that shows a fairly common pattern,
a big primary mass in this case, hyperechoic,
a small satellite lesion in this case hypoechoic,
and then also direct invasion of the adjacent hepatic vein.

If you see this sort of a pattern,
hepatocellular cancer should be your primary diagnosis.

Rarely it'll appear as multifocal lesions, all of which are small like we see in this case.

It's much more common to have a single dominant lesion
and then multiple smaller satellite lesions.

But this patient did have hepatocellular cancer.

And then it can be more diffusely infiltrating
and involve an entire lobe
or an entire hemi liver.

This is a patient that had a history
of cirrhosis on sonography.

You can see that the liver looks heterogeneous,
but you don't actually see a discrete mass any place within
this cirrhotic liver.

We did not detect hepatocellular cancer in this patient,
but his alpha fetoprotein level was extremely high.

He went on to have a MRI
and you can see multiple arterial enhancing lesions
and in areas these were confluent and infiltrating.

As I mentioned, hepatocellular cancer is a hypervascular
lesion most of the time.

You can detect that hyper vascularity on
Doppler as we do here.

And if you do waveform analysis,
the internal vascularity will have an arterial signal.

In some cases, the vascularity will be
extremely disordered looking.

So if you weren't able to appreciate the focal lesion here in the right lobe
of the liver, this disordered vascularity should be your
clue that there is an underlying neoplasm.

Now, I did mention venous invasion.

When it does occur, it is generally isoechoic to the liver.

It expands the lumen of the vessel
and in most cases it will have detectable tumor
vascularity on doppler.

Sometimes you'll see that the tumor thrombus has direct continuity with the primary mass,
but most of the time you won't be able
to appreciate that.

And as you can see in these three different patients,
the isoechogenicity of the tumor thrombus with the rest
of the liver can make it difficult to appreciate.

And what you have to do is look for the vein walls,
which will appear as hyperechoic structures surrounding the tumor.

As we see in all three of these cases,

here's a patient that has a tumor thrombus extending into
the main portal vein on Doppler.

You can see there is some detectable blood flow within
that thrombus and waveform analysis of
that internal flow shows that it's has an arterial signal.

And notice that the arterial signal is
hepatofugal in this case, it's below the baseline,
it's heading as if it was going out of the liver,
and that's a very characteristic of hepatocellular cancer.

Here's a patient who on MRI had tumor thrombus
or had thrombus in the portal vein
that showed no significant enhancement.

After contrast administration, they thought
that this was tumor thrombus,
but hadn't proven it by enhancement patterns.

And the patient came on for a ultrasound.

You can see the thrombus involving the entire portal venous system in
the right hemi liver.

But on doppler, all we could see was flow
around the portal vein thrombus,
but not within the thrombus.

So in this case, we still weren't sure
that this was tumor thrombus, although we suspected it.

In cases like this, you can biopsy the tumor thrombus with sonographic guidance
and you can see that's what we did in this case.

And the result was consistent
with hepatocellular cancer.

Handling Suspected Hepatocellular Carcinoma

So what do you do when you think you're dealing
with hepatocellular cancer?

Well, you confirm the diagnosis initially by doing a survey
of the liver sonographically looking for cirrhosis
and looking for vascular invasion.

If you see either of those, then your diagnosis is gonna be much more firm.

You can get alpha fetoprotein levels
that will help in some cases,
although they are notoriously insensitive, most
of these patients will go on to get a contrast enhanced CT
or nowadays more often an MRI to look at the enhancement pattern.

Contrast enhanced ultrasound is equally
effective in this situation.

And then if necessary,
biopsy can be performed approximately 50% of the time.

We can make the diagnosis using fine needle aspiration.

The other 50% of the time we have to do core biopsies, at least at our institution.

So here's an example of a patient
with a non-specific lesion in the liver.

He did have a history of hepatitis.

We don't really see the cirrhotic changes on this conventional view,
but when you look at high resolution,
you see the coarsening
and the nodularity of the liver parenchyma, which tells you
that this is an abnormal liver parenchyma
and makes the diagnosis
of hepatocellular cancer much more likely.

Focal Nodular Hyperplasia

Now let's move on to focal nodular hyperplasia.

This is the second most common solid benign liver lesion
after hemangiomas.

These lesions are composed of hepatocytes, Kupffer cells
and biliary structures.

They often have a central scar that's seen pathologically.

They're significantly more common in women than in men,
and they're generally asymptomatic symptoms such as pain or bleeding are quite uncommon On sonography.

They have an echogenicity very similar to underlying liver,
which makes sense since they're composed
of all the basic components of liver parenchyma.

They may show mass effect on adjacent structures.

The central scar
that's seen pathologically is rarely seen on non-contrast enhanced sonography,
but they have a typical vascular pattern
that can be detected,
and that's called the spoke wheel pattern,
where a vessel will come from the periphery
of the lesion in towards the center
and then start to branch back out towards
the periphery.

So these are four different patients
with focal nodular hyperplasia.

The two up above, you really don't see a lesion at all on
gray scale sonography
and the two down below have heterogeneous lesions that are relatively nonspecific.

But when doppler was performed on all
of these patients, you can see the typical spoke wheel type pattern on color
and power doppler,
which makes the diagnosis much more likely.

Pulse doppler analysis
of the internal vascularity will show an arterial signal,
similar to what we saw on hepatocellular cancer.

Here's a patient with a slightly hypoechoic lesion seen on grayscale sonography
and fairly non-specific vascularity on power doppler.

In a case like this,
the spoke wheel pattern sometimes is difficult
to appreciate in any single plane of imaging,
but if you reconstruct it in three dimensions,
the spoke wheel pattern will be much more apparent
as it was in this case.

Handling Suspected Focal Nodular Hyperplasia

So what do you do when you think that you're dealing with focal nodular hyperplasia?

Well, at our institution, we confirm the diagnosis
with an MRI and look for the typical pattern of enhancement
and the central scar on contrast enhanced scans.

Now not everybody can undergo MRI examinations,
and if they can't, then a sulfur colloid scan, which is
what we used to do, is also valuable.

Approximately 60% of patients will have the lesion either be hot or warm on a sulfur colloid scan.

And if that's the case, then the diagnosis
of focal nodular hyperplasia is essentially confirmed.

Now, contrast enhanced ultrasound is also very effective in
showing the typical pattern of enhancement
and the central scar
and also often showing a large tortuous feeding vessel biopsy may be necessary in some cases,
but just realize that this is not an easy diagnosis
to make pathologically and the biopsy may be indeterminate.

Hepatic Adenomas

And then finally, I'd like to talk about hepatic adenomas.

These are the least uncommon of all the lesions that we've discussed so far.

It's a rare benign tumor that contains hepatocytes,
but few, if any, Kupffer cells
or bile ducts like FNH, it's more common in women than men
and it's associated with birth control pills,
anabolic steroids and glycogen storage disease.

These patients are at risk for hemorrhage.

So these typically are surgical lesions
and there is a rare
but real risk of malignant degeneration.

Approximately 20% of hepatic adenomas are solitary
and 10% are pedunculated.

They have a variable ultrasound
appearance that I'll show you in a minute.

And generally they're hypervascular,
although you don't always detect that hyper vascularity
with doppler techniques.

Here's a lesion solid hypoechoic on gray scale.

Very nonspecific type lesion,
but has quite abundant
internal vascularity on power doppler.

Here are two different patients with hepatic adenomas.

Patient on the left has solid hyperechoic lesions,
and patient on the right has a solid heterogeneous lesion
with fairly well-defined hyperechoic
and hypoechoic lesions.

This particular pattern is often seen
with primary liver tumors such as adenomas
and hepatocellular cancer.

And in this case, hyper vascularity was detected
on color doppler.

Handling Suspected Hepatic Adenomas

So when you think you're dealing with hepatic adenoma, the diagnosis typically with MRI, clinical history and symptomatology combined with
a suspicious ultrasound appearance.

And a typical MRI appearance is generally all that we do to make the diagnosis.

But sometimes a biopsy will be necessary and in a
and as is in the case with focal nodular hyperplasia.

It's not an easy diagnosis to make.

And sometimes it's difficult
to distinguish an adenoma from a well differentiated
hepatocellular carcinoma.

When an adenoma has been diagnosed,
they generally will ultimately get surgery
because of the potential risk of bleeding.

Summary

So in summary, sonography,
I believe plays a very valuable role in the
evaluation of liver masses.

The combination of ultrasound, clinical history
and laboratory values allows for a diagnosis of what the liver mass is in the majority of cases.

And if you can't determine what the diagnosis is
with sonography, it generally helps in determining
what the next best test will be based on the sonographic findings.

And then finally, when necessary,
ultrasound is an excellent method to use
for guiding biopsies of lesions when tissue confirmation is required.

Thank you very much.