Breast Cancer Staging with Ultrasound - HD

Introduction

Hi, I'm Gary Whitman.
I'm a professor of radiology and radiation oncology at MD Anderson Cancer Center in Houston, Texas.
Today we're going to talk about staging the breast and the regional lymph nodes with ultrasound.
Thank you.

Objectives

The objectives today are to understand the role of ultrasound in staging breast cancer, also to appreciate the role of ultrasound in evaluating the regional lymph node basins.
And in addition, we want to appreciate the role of ultrasound guided biopsy in staging breast malignancies.

Focus of the Talk

In our talk, we're going to focus on tumor size, involvement of the skin, and also involvement of the pectoralis fascia, the pectoralis muscle, and the chest wall structures.

In the second half of the talk, we're gonna focus on looking at the regional lymphatics and how regional lymph node involvement can be detected by sonography.

When we think of staging, we really want to think about the breast as well as the regional lymph nodes.
In addition, an important part of staging is to look at distance sites, such as involvement of the liver or the lung, but we're not gonna focus on that in today's talk.
On today's talk, we're gonna talk about the breast.
Looking for how many lesions are present.
Is there evidence of unifocal disease, disease with more than one lesion in the same quadrant, which we call multifocal disease or multicentric disease where there's more than one quadrant involved.

In addition, we're gonna talk about the regional lymph nodes and how ultrasound can help us in identifying regional lymph node involvement.
So, for example, here, if we look at this lymph node, this is an axial lymph node.
We can see that the hilum is markedly compressed, and there's an enlarged cortex here.
This lymph node was a metastatic lymph node.
We biopsied the enlarged cortex here to show that this patient had involvement of this metastatic axial lymph node.

Evaluating Breast Lesions

When we're looking at breast tumors or breast malignancies, we really wanna determine how many lesions are present.
We want to try to determine if there's evidence of multifocal disease with more than one lesion in the same quadrant, or if there is evidence of multicentric disease with more than one quadrant involved.

So, for example, if we look at this lesion, this is a hypo coic ill-defined mass.
This is an obvious cancer.
This was a large invasive ductal carcinoma, but we're also going to look in other parts of the breast to see if there are other lesions involved.
And notice how in the same quadrant we see two additional lesions.
So this is an example of multifocal disease.

What we would do in this case would be to biopsy the large lesion.
For example, we do a core biopsy here, and then you could biopsy the lesion that's furthest away, such as this one.
If we had good cytology support, we could do a fine needle aspiration.
If not, we would do a core biopsy of this lesion and then place clips in both this lesion as well as the main mass.

Now, regarding biopsy of the second lesion or the satellite lesion, FNA is a good option if you have good cytology support.
If you don't have good cytology support, then you should proceed with core biopsy.

TNM Staging System

When we think of staging, we're going to refer to the TNM system published by the American Joint Committee on Cancer, and that the T stands for tumor and for nodes and m for metastatic disease.

When we think of the tumor size, fairly straightforward that we're giving a t value based on the size.
For example, less than two cm is T one greater than five cm is T three.
And note that T four is any size with direct extension to the skin or the chest wall.
And this is an area where we can identify T four disease, especially involving the skin on ultrasound.

Then when we consider classifying the nodes, we take the nodal station as well as the number of lymph nodes involved.
For example, N two would be metastatic disease to ipsilateral aray and lymph nodes.
And one is metastatic disease to movable aray and lymph nodes.

When we think about N three disease, one area where we can make an impact with ultrasound is looking in the inor as well as the sup calor region.
In both of those areas, if we find involve lymph nodes, metastatic lymph nodes, the patient would be classified as N three.

Examples of N3 Disease

Here's an example of an involved internal memory lymph node.
Notice the lymph node here, somewhat expanded, oval, but irregular heterogeneous echo texture here.
This is evidence of metastatic disease involving an internal mammary lymph node.

Here's an example of involvement of an intraocular lymph node.
We can see that this lymph node, we have very little remaining hilum, a little bit of hilum here.
The borders of the lymph node are irregular.
As you can see here on this side, we're going to do the biopsy of this lymph node here.
Here's our biopsy needle in the node, and we're doing the FNA.
So notice our needle coming through the pectoralis muscle here.
So if we're doing this biopsy, we want to give quite a lot of local anesthesia here.
And then we biopsy this lymph node.
This was positive, so this was evidence of N three disease with involvement of an infra calic or lymph node.

Here's another example of N three disease.
These are multiple matted scalor lymph nodes.
We see multiple lymph nodes that are matted together, and this is an example of N three disease.

Here's the same case with power doppler showing that there is a little bit of flow at the periphery of some of these lymph nodes.

Another case showing several matted SUP lymph nodes.
Some of these rather large, like this lymph node.
Again, an example of N three disease when we think of metastatic disease, MO or M zero is for no distant metastases.
And M1 is evidence of distant metastatic disease that would be involvement of a distant structure such as the lung of the liver, et cetera.

When we compute our staging, then we take the T, the n and the m for example, if we were gonna look at two B, these would be the characteristics of A two B lesion.
It could either be T two N one or T three N zero.

Now when we look for example at stage four, that would be any T or N with metastatic disease.
For example, involvement of liver, bone, or lung.
But note the importance of N three.
This is if in three C disease, that's any NT with N three disease.
So here, a good example of N three as we talked about, would be involvement of the infra or the sup canicular lymph nodes.
And note how, if there's T four disease, that that makes this patient to be staged at stage three B.

Eligibility for Breast Conservation

So what is the eligibility for breast conservation?
Well, we don't want to have any skin edema.
We don't want the surgeon to cut through disease skin in general, we want the tumor size or the extent of disease to be less than five cm, but this is somewhat variable.
We could go more than five cm, for example, in a very large lady.
But it may be five cm may not be a amen for breast conservation in a rather petite woman.

In general, we want no multicentric disease for the patient to be eligible for breast conservation therapy.

Identifying Lesions with Ultrasound

Now, let's see how many lesions we can find and how ultrasound can help us.
Here's an example on this.
Here's the main lesion right here.
Here's a second lesion, A satellite.
Here's an intraoral lymph node.
And we know that if there's intraoral lymph node involvement, that in general, the patients have a worse prognosis compared to those without intraoral lymph node involvement.
And notice at the edge of the film, there's axial lymph node involvement here.

So this is the second lesion or the satellite lesion coming back to it is here.
This is satellite lesion.
Here's our axillary lymph node.
And notice how the hilum is markedly displaced and a greatly expanded cortex here.
And this would be the axillary lymph node involvement here.
And then we looked in the infra region, and we see these lymph nodes here.
These are hypo coic, no visible hilum, infra disease.
This would make it N three.

So when we're documenting evidence of multifocal disease, what we wanna do is sample the main lesion and the lesion farthest from the index lesion.
Again, we would be able to use FNA to sample the satellite.
If we had good cytology support.
I'm quite fortunate at MD Anderson, then I have very good cytology support.
If that was not available, then I would do core biopsy and then I would clip the lesions after showing that there was evidence of metastatic disease.

Here would be an example of multifocal disease.
And the patient has been going for breast conservation.
This is sliced specimen radiography.
We took the specimen and then we sliced it like a salami.
So here's one lesion with the localization wire.
And here's our second lesion with our quip marker.
Here's the wire.
And notice how on the slice specimen radiography, this lesion is close to the margin here.

So let's take this case.
This is a hypo coic mass irregular.
This is an obvious cancer here, invasive ductal carcinoma.
And then we wanna look in the neighborhood to find the satellite.
So if no other satellites were identified, we would measure this distance biopsy.
This one presumably with core biopsy.
This one we would biopsy with FNA if we had good cytology support or with core biopsy.
And then we place a clip in both lesions to document evidence of multifocal disease.

Case: Palpable Mass in Dense Breast

So let's take a case here.
This is a palpable mass in a dense breast.
So we want to ask ourselves, where is the mass?
How many masses are present?
And is the patient a candidate for breast conservation?
So here we're looking in the retro real region.
This triangle marker indicates evidence of a palpable abnormality.
This is the nipple marker.
The nipple is somewhat inverted in this case.
And here's a mass in the retro real region, irregular mass here on this mammogram.
The question is how many masses are present?
So on sonography, we have the main mass, we have a second mass, and then we have a third mass.
But it's very important to keep on looking.
So here was number three.
There's actually a fourth one here.
So we want to biopsy this one.
In this case, I did a core biopsy here, and then I did an FNA on number four and placed clips at both.
And then we documented that there was evidence of multifocal invasive loor carcinoma.

Case: Role of Staging with Preoperative Chemotherapy

Let's take another case to show the role of staging.
In this case, this is an obvious cancer, an irregular speculated mass.
I don't see any additional satellites on this mammogram.
Here we have our ultrasound, the main mass hypo coic with mark shadowing.
And then we did sonographic staging.
We found another lesion, a satellite here.
Note, here's the main mass, and we're measuring the distance from the satellite to the main mass.
And when we go back to our mammogram, I really don't see any additional lesions.
We put a clip in both lesion in the satellite lesion.
And you can see here there is a satellite lesion that we did not identify on mammography in this patient with a rather fatty breast.
Then we gave preoperative chemotherapy.
Notice how the main tumor shrinks down there still is marked shadowing, and the satellite lesion has decreased in size significantly.
Here's the clip marker with a come tail artifact right here.
And this is showing the quip marker, and this is showing the main mass, both decreased in size in a patient undergoing new adjuvant chemotherapy.

Extent of Disease: Ductal Extension

When we're thinking of looking at the extent of disease, we wanna look at prominence of the ducts.
This is somewhat similar to mic, to suspicious microcalcifications in the duct system extending toward the nipple.
So in this particular case, notice how this is a regular mass.
Notice how there's ductal extension here.
And if we look here, there's extension of the ducts really going in both directions here.
And sometimes this can be quite long, quite long as we see here.
The main significance is that we don't want the surgeon to cut through involved ducts.
Sometimes we may localize on either side of the ductal involvement, or sometimes we may even biopsy these areas to prove that there's evidence of involvement.

Again, ductal extension, sometimes rather irregular.
And long as you see here, this is a little bit different, but these are rounded areas.
But notice that they're not purely cystic semi irregularity.
Some internal echoes, and this was an example of DCIS with microinvasion.
And then we biopsied the area.
We picked for an area that was hypo coke with some internal echoes to get to make the diagnosis.

Here's a similar case, calcifications some with shadowing, marked calcifications.
This was an example of DCIS with microinvasion.
Somewhat similar case here.
When we look very carefully, we see some calcifications.
We see some rounded, rounded spaces rather small.
There is some flow with power doppler around some of the rounded spaces.
So this is somewhat suspicious.
I'm gonna try to biopsy the areas of calcifications with a big DI device with a my biggest device or with a vacuum assisted device and take multiple cores and then follow that up with a specimen radiograph.
And that's what we did right here.
And we came up with a diagnosis of DCIS.

Staging the Lymph Node Basins

With microinvasion, we're gonna turn our attention to staging the lymph node basins.
We're gonna focus mainly on the axillary lymph nodes, but a lot of what we say can be applied to the inocular sup lior and the internal mammary regions.
And also the other nodal area that we should think about would be the intra mammary lymph nodes, I-N-T-R-A.
'Cause we know that patients with intra mammary lymph nodes have a worse prognosis compared to those with no intra mammary lymph node involvement.

Intramammary and Other Lymph Nodes

Here's an example of some irregular calcifications in this aary lymph node.
Sometimes we can see calcified lymph nodes in a metastatic setting.
Sometimes we have metastatic disease from a non-breast primary, such as ovarian carcinoma with Sonoma disc calcifications, and we can sometimes make that diagnosis on mammography.

And here we see some involved lymph nodes on MRI, notice how we visualize the lower part of the axilla, but we're not seeing the upper part of the axilla here on MRI.
And notice how on MRI, not only are we sometimes not covering the appropriate area, we probably don't get the upper axilla here, but sometimes some of the lymph nodes can be difficult to identify if there's field in homogeneity, as in this case.

Sentinel Lymph Node Biopsy

I wanna talk a little bit about sentinel lymph node biopsy and just to indicate that this is where we've given the injection in the breast, that we see three areas of uptake in the axilla.
Now this does not necessarily indicate that these lymph nodes are positive, but rather this is indicating that this is where their sentinel lymph node uptake.
And then the surgeon will take out these three lymph nodes and then the sample will go for careful histopathologic evaluation.

Normal vs. Metastatic Lymph Nodes

When we think of involvement of a lymph node, we should note that metastatic disease is coming through the afferent lymphatics coming in this way.
And then it'll expand the cortex sometimes, pushing on the hilum or displacing the hilum.
So our disease should come into the cortex from the periphery of the lymph node.

And here here's looking at the normal lymph node, we have our hyper coic hilum and a ribbon like thin hypo coic cortex.
Here we see the thin cor cortex around our lymph node here.
Again, seeing the thin normal cortex around the anterior aspect of this lymph node.
And sometimes it's very difficult to identify where the lymph node is just as it blends in so well with the surrounding tissues.

Here, x-ray is our lymph node.
Here's our lymph node.
We see a little bit of the outer cortex here.
Basically blending in with the normal structures.

When we're looking for metastatic lymph nodes, we wanna look for absence or deformity of the echogenic hilum and also look for eccentric cortical hypertrophy.
Here would be an example where we have a markedly enlarged cortex as we see here in the calipers.
And the hilum is displaced off to the side.
This is a metastatic axillary lymph node.

So thus it's useful to look at the short axis rather than the long axis or perhaps to look at a ratio of the long to short axis.
For example, if we look at this lymph node, this is the normal side, this is the abnormal side.
And let's take the abnormal side.
Notice how there's marked cortical prominence.
The hilum is markedly compressed and there's increase in the short axis dimension.

Here would be an example just looking at a metastatic lymph node.
Notice how the hilum is markedly compressed with expansion of the cortex here.
So if we were to biopsy this lymph node, we'd biopsy into the area of the prominent cortex.

And here's another example of some malignant lymph nodes.
Notice this is an oval hypoechoic lymph node.
We don't see the hilum.
And as the lymph node moves towards more towards metastatic, it tends to become more rounded as we see here.
The other sign that we can sometimes look for is that the border of the hilum is displaced and sometimes straightened as we see here.

Here would be an example.
Notice that the hilum is displaced and straightened.
So if we were to biopsy this lymph node, we'd biopsy where the yellow arrow is in the region of the cortex here.

Here's another example of some high hilar displacement with a little straightening right here, metastatic axial lymph node.
Another example here, we have this area where the cortex is expanded and the hilum is displaced here, metastatic axial lymph node.

So ultrasound really does provide some added value in determining the morphology.
We can determine if the lymph node is likely benign or malignant.
And also this can help us to guide biopsy.
It would be FNA for example, if you had good cytology support.
If that's lacking, then we could biopsy the lymph nodes with core needle biopsy.

So for example, in this case, we would really go for the greenish cortical bulge as we see here.
And that's where we do our biopsy.
And here's an example, this lo or hypo coic lymph node here.
We're doing our biopsy right here documenting evidence of metastatic axillary disease.

Limitations of Lymph Node Assessment

So when we think about palpable breast cancers, about half of them have al lymph node involvement.
Notable involvement in general is related to tumor size.
There are some limitations.
We know that the sensitivity is not as good as we'd like.
And there are still some limitations on specificity.

Here's an example, just showing in a visual way a limitation.
Here we have in a hypo coic axillary lymph node.
We did the FNA, but there was no evidence of malignancy.
This patient also went on to axillary dissection.
There was no evidence of malignancy.
So occasionally we can have normal lymph nodes with a rather worrisome appearance.

In general, when we think of physical examination of the axilla, if there's palpable suspicious lymph nodes, seven outta 10 of those patients will have metastatic disease.
If there's no suspicious lymph nodes identified on clinical examination, about three out of 10 of those patients will have metastatic disease.

There is our limitations in if we think about patients who've undergone neoadjuvant or preoperative chemotherapy, then we are somewhat limited to in identifying involvement of the lymph nodes on clinical exam and ultrasound.
Although in the cohort, the residual tumor burden is usually minimal.
And in this paper, there were about 55 patients with negative physical examination and ultrasound that had accelerate metastases.
In general, the tumor burden was rather small, ranging in general between one and three positive lymph nodes.

We know that lymph nodes sonography is more sensitive than palpation.
It can identify suspicious non palpable lymph nodes and it can be used to guide biopsy.

Here's an example.
Our expanded cortex biopsy along this pathway here showing evidence of involvement metastatic disease involving this axial lymph node.

And here, here's just another example, just again, pointing out a limitation.
Here's our known tumor in the 10 o'clock region.
On this axial lymph node, we see a little bit of a bulge here.
We're sampling this bulge here.
Here's the needle right in the appropriate area.
FNA came back as negative.
The patient went on to sentinel lymph node biopsy and there was evidence of micrometastatic disease identified on sentinel lymph node biopsy.

So with ultrasound we can identify macro metastatic disease, but a few tumor cells or micrometastatic disease, it'll be very difficult to identify on sonography.

Prognostic Importance of Axillary Lymph Node Status

The aary lymph node status is very important.
As a prognostic indicator, axial lymph node status is associated with relapse-free survival.
Also, it is associated with overall survival and the involvement of the accidental lymph nodes affects local therapy.
For example, if there's axi dissection, and also involvement of systemic therapy.
For example, most patients with OID lymph node involvement will undergo chemotherapy.

So what we're looking for is lobular expanded cortex.
As we see here, the hilum is markedly displaced over here.
Here's just another example.
See the hilum being pushed over markedly expanded cortex.
Here I marked that with a c, in large cortex that we're gonna sample where the C is in this particular case.
And notice on our power doppler, we have quite a lot of flow, but a little bit less flow.
Where the metastatic lesion is really is a space occupying lesion right here in this expanded cortex.

Surgical control of axillary disease is important.
And also knowing what's going on in the axi is important for prognosis for getting prognostic information.

Ultrasound is taking on a role recently in determining if the patient undergoes sentinel lymph node biopsy.
For example, if ultrasound is negative, then the patient will undergo sentinel lymph node biopsy.
If ultrasound is positive, then the patient will undergo axillary lymph node dissection.

Case: Screening Presentation with Multiple Lesions

Let's take a case here to illustrate some of the points we've been talking about.
So this is a patient who presented with screening.
On screening three lesions were identified.
As we see here.
Here's the largest one more posteriorly.
And also there was involvement of this ale that there was en large axial lymph node as we see here.
So this is by screening evaluation.
The patient underwent diagnostic mammography showing that these three lesions were real.
And then the patient presented for ultrasound.
These are all transverse images.
So here we see an irregular hypo coic mass at six o'clock, an oval hypo coic mass, also at six o'clock.
And if somebody irregular hypo coic mass at seven o'clock.
So in this particular area, this particular case, I'm gonna biopsy the six o'clock lesion with core biopsy.
And then I'll biopsy the lesion furthest away, which in this case is the seven o'clock.
And here I did FNA as I have good cytology support, lacking good cytology support, you would go for core biopsy in this particular case.
So both of these were biopsied and then I looked in the axilla.
In the axilla we see markedly expanded cortex.
The hilum is displaced off to the side here, and we biopsied the axial lymph node as well.
Here we see our core needle biopsy here, and this is the FNA in the seven o'clock region.
Ultrasound-guided FNA, here's the needle right in the lesion.
And also we did FNA fine needle aspiration on the axillary lymph node.
Here we have our expanded cortex.
And here's our needle right in the cortex.
Ultrasound guided left axillary FNA.
Then we would look at the results.
We documented multifocal disease.
The left breast six o'clock lesion.
The largest lesion was a triple negative invasive ductal carcinoma.
The seven o'clock lesion was ductal carcinoma.
And in the left axillary region, there was evidence of metastatic adenocarcinoma shown by FNA.
And in all of the lesions that we biopsied, we placed clip markers as well.
As you can see, the clip markers in the breast lesions here, and then a small clip marker identified in this metastatic axillary lymph node here.

Case: 48-Year-Old Woman with Dense Breast

So let's take another case.
This is a 48-year-old woman.
Does she have breast cancer?
Where is the cancer?
What is the stage?
So we'll study the mammogram.
It's a dense mammogram, but if we look above the line, we can see that there's more density above the line than below the line.
Also, if we look here in the outer part of the breast, there's more density than the inner part of the breast.
Furthermore, we know that we probably didn't get as much posterior tissue on the CCC view as we'd like, but we're thinking that probably the lesion is upper outer.
And note this markedly enlarged axial lymph node.
So we're with that large lymph node, we're thinking does either the patient has breast cancer with axial metastasis or perhaps lymphoma.
So we're gonna go looking primarily try to look in the upper outer aspect of the breast.
Here's the upper out of the aspect of the left breast.
Two o'clock region hypo coic mass with indistinct margins.
Here we see it.
And note notice here on the MRI, this, here here's our mass on our T one weighted images and notice how it enhances here.
And then we did the core biopsy of the two o'clock lesion.
Here's our core biopsy orthogonal image with our biopsy device.
Right in the middle of the lesion, we show that this is invasive ductal carcinoma.
Then we go to the axilla notice on the axilla, how we talked about how the disease comes in from the outside, from the afferent as we see it here extending in towards the central region.
But mark cortical enlargement as we see here in this lymph node, left axial lymph node, which was proven to be positive.
Here we see it on MRI on our T one weighted images markedly enlarged and on our T two weighted images here.
But we kept on looking in the left infra clicker region.
We saw this hypoechoic lymph node, very suspicious.
We don't see a hilum.
We biopsied it again, we would give local coming as we come through the pack here, give a lot of local, we biopsied this to show that it was involved and this would be N three disease.

So when we look at this case, this was stage three A, it was T two because there was a 2.2 cm invasive ductal carcinoma and it was N three as there was axillary and infra liquid lymph node involvement.
Eight of 18 axillary lymph nodes were positive.
And this left infra click or lymph node was positive as well, making it N three disease.

Conclusion

So we, when we have a known or suspected cancer, we wanna try to identify how many lesions are present and is there lymph node involvement.
Specifically, is there evidence of involvement of the axillary infra calic or supra calic or internal memory or intra memory lymph node regions and staging can be very helpful at the initial evaluation as well as prior to surgery to assess response to a neoadjuvant chemotherapy.
Or sometimes we may do staging after the patient has had a surgical resection to see if there's additional disease remaining within the breast or the regional lymph nodes.
Thank you very much.