Ultrasound Evaluation of Regional Lymph Nodes as an Extension of the Breast Ultrasound Exam - HD

Introduction

I am Tom Stavros.
I'm a breast imager.
I'm a professor specialist from the University of Texas Health Sciences Center in San Antonio.
And today I'm gonna speak about regional lymph nodes of the breast and evaluating them when you're anticipating biopsy a suspicious lesion in the breast.

Currently in all patients with birads four or five lesions that we are going to biopsy under alt sound guidance, we evaluate the axillary lymph nodes.
We will perform coordin needle biopsy on abnormal lymph nodes that are suspicious for metastatic disease.
We do not wanna biopsy sonographic normal lymph nodes, and we try our best to distinguish reactive, benign nodes from metastatic nodes before we make the decision to biopsy.
Z 11 has only slightly changed our management so far, but it could change it more in the future.
And I'm gonna talk a little bit more about Z 11, at the end of the study.

Sonographic Evaluation of Axillary Lymph Nodes

Sonographic evaluation of axillary lymph nodes in the patient with suspicious breast nodules is really best performed by ultrasound.
Ultrasound I think does a better job than ct, which can really only show a size and not morphology very well, and it's often better than MRI.
Although very high resolution MRI with, sub-millimeter isotropic voxels or if combat X ever gets improved, could change that.
But for now, I think alt sound is the cheapest and best, examination that we have for regional lymph nodes of the breast.

Principles for Evaluating Regional Lymph Nodes

The principles for evaluating regional lymph nodes of the breast are similar to evaluating lymph nodes in any other part of the body, and frankly, we've learned a lot about lymph nodes from our, evaluation in the head and neck and thyroid clinic.
In general it's somewhat easier in terms of differential diagnosis in the EXC because it's usually just lymphoma or metastatic disease or reactive or normal.
There's really only four choices.
Ultrasound will get better.
There is a contrast agent called OID that's, can be ejected, subcutaneously and picked up in lymphatics, and it will, enhance the, sinusoids within the lymph node lighting up the cortex.
And elastography perhaps will help us as well.

Anatomy of Lymph Nodes

Lymph nodes look like miniature kidneys and long axis.
Their reinform in shape with a hypo COA cortex and variable echogenicity in the mediastinum and short axis, they're CS shaped with the hilum opening up on one side.
So this is a long axis, view of a lymph node looking like a miniature kidney.
And this is a short axis view, with the hilum opening on the right side, and a very thin cortex wrapping around the mediastinum.

Now, even though, lymph nodes look like miniature kidneys, they differ in one very important way in a kidney, everything goes in and out of the hilum, the arterial and venous, blood supply and drainage and the collecting system and the lymphatics all go through the hilum.
Virtually nothing comes through the periphery or the capsule, in lymph nodes, however, the afferent lymphatics come through the periphery and, pass through the cortex of lymph node, then the medulla of the lymph node.
And then finally out the hilum.
So we have a, a flow from peripheral to central in lymph nodes, which is different from kidneys.

So this is a, in the top we have a histologic section of a lymph node.
This wavy red line is the capsule of the lymph node.
Just deep to that is the subcapsular sinusoid.
And then between the large pink structures are the cortical sinusoids and then deeper are the medullary sinusoids, with medullary cords between them.
And so the flow is from afferent lymphatics to the subcapsular sinusoids to the cortical sinusoids, to the medullary sinusoids.
And then finally out the ent lymphatics.

Now what we see on the bottom left here is a classical, what I call two zone lymph node.
We have a relatively hypo coic cortex and a hyper coic mediastinum.
I think we have the mistaken idea that most lymph nodes in the axilla look that way.
They really don't. In the breast cancer, screening and diagnostic cohort, usually there are three zone lymph nodes.

So in this two zone lymph nodes, the hypo coic cortex corresponds to these uh, lymphoid follicles and the sub-cortical lymphoid tissue.
And the hyper coic medulla is filled with hyper echogenicity because it's filled with lots of interfaces between medullary sinusoids and medullary cos.

But in the, three zone lymph node, we typically have a much thinner hypo coic cortex that you see between the white arrows that corresponds to the hypo coic, lymphoid follicles and subcortical lymphoid tissue than we have a thin band of hyper echogenicity that represents the medulla that's displaced outward, by a lot of fat that's replacing the central hilum.
So between the white and yellow areas, arrows is the cortex between the two yellow areas is the medulla.
And then we have fatty replacement.
So I call it a three zone lymph node 'cause we have three echogenicity.
We have hypo coic cortex, hyper coic medulla, and iso coic.
Fat that's, infiltrated into the hilum.
The arrows that I'm showing here, the red arrows show the path, the flow, it's from the subcapsular to the cortical to the medullary sinusoids.

Characteristics of Two-Zone and Three-Zone Lymph Nodes

Now typically two zone lymph nodes are smaller, lie more superficially.
They have relatively thicker cortex in relation to the size of the hilum, and they tend to occur in younger, thinner patients.
In the middle, I'm showing an earliest three zone lymph node.
We're beginning to get a little iso coic fatty infiltration into the center of the mediastinum with the, hyper medulla being displaced toward the poles.
And then finally we have a classical three zone lymph node.
And this is the most typical lymph node we see in say, a mid 50 years old and a woman who's slightly heavy.
We have a very thin cortex, a thin layer of hyper coic medulla, and then a very large area, of, iso coic fatty infiltration.
These lymph nodes tend to occur in older, heavier patients.
They tend to line more deeply, typically three, three and a half, sometimes even four centimeters deep.
The cortex is relatively thinner in comparison to the size of the mediastinum, and the overall size of these lymph nodes is larger.
It's not unusual for these fattier placed three zone lymph nodes to be up to four centimeters, five centimeters in size, and yet they're not at all suspicious because the cortex is imperceptively thin in these cases.
And that really explains why size doesn't work.
It's the least reliable of all our, criteria.

The other thing that, makes a difference is what you look for when you're looking for axillary lymph nodes in the younger thinner patient, typically you're gonna look for hypo coic cortex, 'cause that's gonna be the most dominant feature in an older, heavier patient, you'll actually do better switching your mind to looking for the hyper coic medulla.
That's what makes it apparent.

Scanning Techniques for the Axilla

One thing I found my sonographers doing that is sort of destructive to successful evaluation of the axilla is looking from the top down, of the axilla going from superior to inferior.
The reason for that is they often have a preconceived notion of how many lymph nodes they should be able to see.
And if they see two or three lymph nodes, they figure that's about what they should see and they stop and they may not get low enough to actually see the sentinel node.
It's much more, safe and, makes much more sense to begin from inferiorly and work superiorly and even start in the axillary segment because the sentinel node may be intary, it may not even be an axillary node.
So I always like to start in the axillary segment and work my way up.

We have found that we can identify the sentinel node about 95, 90% of cases simply by that being the lowest node that we can identify an ultrasound.
It doesn't always work, but it works about 90% of the time.

Now, this shows the value of harmonics.
On the left is with fundamental imaging.
You can see that the cortex is only minimally hypo coa compared to the surrounding fat, and the lymph node is less conspicuous.
We can see that with harmonics, the cortex becomes blacker, the fat becomes whiter, and the node becomes more conspicuous.
So this really works mostly for two zone lymph nodes in younger patients, but I can find more lymph nodes faster with harmonics on them without harmonics.

This is just a video sweep from high to low, from superior to inferior in a young patient with two zone lymph nodes with harmonics on.
And you can see what's apparent here is the markedly hypo coic cortex, jumping out against the relatively, echogenic, background fat.

These video sweeps on the other hand are bilateral axillary sweeps from high to low.
I'm actually looping them back and forth.
But you can see that the dominant feature here is not hypo coic cortex.
The cortex is extremely thin and it's virtually iso coic with the surrounding fat.
What makes these lymph nodes apparent is the hyper coic medulla.
So I think you need to go in, being prepared to look for both hypo coic cortex.
And if that fails, switch your mindset to looking for the hypo coic me dolla.
And if you're starting, in a pa in a patient who's older and a little bit heavy, you're probably better off just starting looking for the hypo coic medulla, rather than the hypo coic cortex.

Now infiltration of the fatty mediastinum has to start somewhere.
So here we see three lymph nodes lined up side by side.
We have two two zone lymph nodes where we just have hypo coic cortex and hypo coic medulla, but medially, we have a third larger lymph node that's a three zone lymph node.
So what we're seeing is just fatty infiltration to a fairly extensive extent and only one of three lymph nodes.
So you can get mixtures of two and three zone lymph nodes.

Features of Metastatic Disease

Now we know that metastases tend to implant in the subcapsular and cortical sinusoids, and that's why focal cortical thickening is the hallmark of early metastatic disease to lymph nodes.
And the reason for that is the, the flow path.
We, again, flow comes in through the afferent lymphatics, then goes through the subcapsular sinusoids, the cortical sinusoids, the medullary sinusoids, and finally out the eent lymphatics.

If we blow up or magnify the subcapsular and cortical sinusoids, we can see that there are these reticular cells labeled by the RC that span the width of the sinusoids, and they have all these processes that hook into the capsule, anteriorly and the, cortex of lymph node deep.
And we've been taught that lymph nodes aren't just filters, but these certainly do create a, a filtration function.
What they're intended to do is slow down the tumor cells long enough that other immune cells in the area can recognize antigens, and begin building antibodies.
But because of this, filtration effect, and because tumor cells can be relatively large, they are more likely to become entrapped and actually implant in the subcapsular and cortical sinusoids.

Now if, focal cortical thickening is the hallmark of metastatic disease, the appearance of focal cortical thickening can vary greatly depending on, where implantation begins and how extensively it's involved the cortex.
We can have three main implantation sites, from in to out or out to in.
So the most common site would be in the mid cortical sinusoids, but we can see primarily subcapsular implantation sites and we can see deep implantation that's near the junction of the cortical sinusoids with the MedU sinusoids.
And depending on which of these three sites the implantation has occurred, it affects the appearance of the focal cortical thickening.

So in the most common situation, we'd probably have multiple metastases in multiple cortical sinusoids, and as they enlarge, they would tend to cause a focal bulge that's approximately equal, inward and outward.
So it's asymmetric, involvement of the cortex, but symmetric bulging inward and outward, which I'm illustrating in the right lower image.
And here's the image of a real metastatic lymph node.
This one has an equatorial focal cortical thickening that looks like, the lymph node is carrying a backpack, but notice that the bulge outward is approximately equal to the bulge inward.

Now, how thick is too thick for cortex, I don't really like to measure.
I mostly just eyeball it and, look for something that looks vocally thicker than the surrounding tissue.
There's a range of published cutoff numbers for cortex from 2.3 to four millimeters, and I just decided that if I were going to use it, I would use the middle of that range three millimeters as a good compromise.
Since Z 11, I've decided I need to desensitize, ourselves a little bit.
So I actually use the upper end of that range.
But the truth of the matter is I probably use a measurement in 5% of cases.
Most of the time I just eyeball it Enough.

If the implantation site is primarily subcapsular, you might guess that the bulge would be primarily outward in the form of a Mickey mouse here as we're seeing in this lymph node, or perhaps like a dramedy hump on a camel as we're seeing in this lymph node.
And that would be exactly right.
If the implantation is site is primarily external, we're gonna see primarily an external bulge on the lymph node.

Conversely, if the implantation site is primarily, toward the inside of the, cortex near the junction with the medullary sinusoids, we're gonna get a convex inward or rat bite indentation into the hyper coic or iso coic mediastinum.
So we can see that this metastatic lesion is actually bulging extensively internally.
It also has somewhat of an outward bulge, but I'll show you other cases later that have just strictly inward, cortical bulges.

Now, an average lymph node has somewhere between eight and 10 ent lymphatics feeding it.
Typically, there's only two or perhaps three that occur in the equatorial region of the lymph node, and there may be three or four on each pole.
So in terms of sheer numbers, you know, approximately 70 to 80% of all the afferent lymphatics come in in the pole.
So it's more often to see lar cortical thickening than equatorial, lar thickening.
If you get equatorial lar thickening, it looks like a backpack or a dramedy hump.
You can see all of these lymph nodes on the top have focal equatorial, cortical bulges.

If it occurs on the poles, you can get what looked like mickey mouse ears or, long, ovoid have, bulges of the lar cortical thickness.
This we're seeing on the left side, these we're seeing on the lo right side.
And of course, if it involves both sides, then you can get the classical Mickey mouse here hat.
So again, with 80% of the lymphatics coming in on the poles, we far more often see one of these plar cortical thickening than than we do equatorial, cortical thickening.

Now, not everything accumulates in the lymphatic channels, from the outside in like metastasis.
So smaller particles, like foreign bodies that could be silicone, droplets in in a ruptured implant, tend to accumulate from the medullary sinusoids out.
They tend to pass through that filtration system of the subcapsular and cortical sinusoids and be gobbled up by the macrophages lining the medullary sinusoids.
So here's a lymph node with extravasated silicone and, and, snowstorm appearance, but it's affecting only the mediastinum at this point.
It hasn't yet begun to affect the, cortex.
Later on, and more involved nodes, you'll see the whole lymph node affected.
This is a typical metastatic lesion.
On the other hand, with, market involvement of the peripheral aspect of the lymph node.
This is mostly a rat bite indentation affecting lymph node from the outside in.

Distinguishing Reactive from Metastatic Nodes

Now we try to evaluate the, the lymph nodes in, in two layers of assessment layer.
One is, is the lymph node normal or abnormal?
And that's usually relatively easy.
The layer two evaluation is if the lymph node is abnormal, is it more likely reactive or metastatic?
And that's not always so easy and it's a very important distinction because reactive lymph nodes are exceedingly common in breast cancer, breast 'cause breast cancer is a foreign body and we certainly don't achieve anything by biopsying, reactive lymph nodes.
So we wanna try to make that distinction as as much as we possibly can.

Now, when does this occur where we get, cases where we're not sure whether it's reactive or metastatic?
Well, it tends to be when we have mid cortical implantation sites that involve all the mid cortical sinusoids, and we tend to get a symmetrical cortical thickening through the whole lymph node.
That could certainly be fairly extensive metastatic disease, but it could also just be a reactive lymph node.
And what we found is just looking at one lymph node can't help us, but there are many tiebreakers that we can use to help make this distinction and we'll discuss those a little bit later.

So if we summarize all the findings that we can use to evaluate the regional lymph nodes of the breast, in particular the axilla, they probably the most published number is size.
I would suggest you not use that at all if you have to use it, use one centimeter, but only for the minimum diameter.
But I would suggest ignoring it because as I showed you, three zone lymph nodes can have quite large diameters, but have imperceptibly thin cortices and, and not be at all suspicious.
And a little seven millimeter node, might have severe eccentric cortical thickening.
It'd be morphologically grossly abnormal, shape.
Abnormal rounding has been published, and that's definitely a valid finding, but it's a late finding.
Everybody who's got a rounded lymph node has severe cortical thickening market hypo echogenicity, as a valid finding.
But again, it tends to be a late finding and there tends to be severe cortical thickening before that occurs.

More sensitive findings are eccentric cortical thickenings, hilar outward bulges that I, you know, I would call a Mickey mouse here or a roary camel hump, hilar invitation or rat bite, invitation on the mediastinum hilar compression or displacement and hilo obliteration.
These are the most specific and the most sensitive findings for, metastatic disease.

Now, if we have a non-specific abnormal lymph node that could be either reactive or metastatic, that's when we go to our tiebreakers.
And the simplest, fastest tiebreaker simply to rotate your probe until you can bring two or three axillary lymph nodes into view in the same field of view.
If one is involved disproportionately compared to its neighbors, that's far more likely metastatic than reactive.
Reactive, nodes tend to be, more, symmetrically involved.

You can also look at right to left symmetry.
You can look at color doppler flow patterns.
You can look at pulse doppler, spectral waveforms.
You can look at elastography and you can actually look at the location of a primary because in certain sites in the breast, you're far more likely to go metastatic to the lymphatic system at a much earlier phase.

CT really only offers size.
That's our least valuable, parameter.
And I think that's pretty much why, ultrasound is much better than CT for evaluating the lymph nodes.
And again, our best findings are morphologic, various, variants of eccentric cortical thickening.

So if we make a collage of what is a non-specific finding that requires a tie breaker and what is a met till proven otherwise, let's just go through this.
In the center, we have a normal lymph node, slight slight variation in the thickness between the pole and the mid lymph node.
Here we have symmetrical cortical thickening, and I put a white rim around this image indicating that it's non-specific.
I need a tiebreaker, to decide whether or not that's more likely metastatic reactive.

Both of these have focal cortical bulges, in the pole, and it's pretty severe.
It's pretty pronounced. This is gonna be metastatic disease to prove otherwise.
And if we biopsy these, we specifically wanna put the needle in the thickened part of the cortex.
It, it doesn't do any good to put the needle randomly through some other part of the lymph node.

This has both plar, cortical thickening and convex rat bite indentations in the mediastinum.
Again, I've got a pink box around this as I do the focal polar cortical thickening because these are metastatic proven otherwise.

Here we have, symmetric hilar compression.
Certainly the degree of symmetrical cortical thickening is greater.
The hilum has been reduced just to a slit, but this is still non-specific.
You can still see this in reactive lymph nodes.
So we wanna go to our tie breakers.

In this case, we've got displacement of the mediastinum, which is really no different than eccentrical, cortical thickening.
We have thin cortex, deep on the left side of the image and deep on the right side of the image, we have focal cortical thickening involving about 80% of the cortex.
So this is gonna be metastatic to proven otherwise, in this case, the hilum is completely obliterated On a theoretical basis, this could be necrotizing lymphadenitis.
But, nice study from hi AB at the University of Chicago showed that 93% of these were metastatic.
So we're gonna consider complete obliteration of the hilum metastatic.
So proven otherwise. And in this case, we've lost the thin hyper coic, capsule of the lymph node.
We have very irregular margins.
We have some, per nodal edema.
These are findings that suggest a per nodal invasion, and there's a very certain way we wanna biopsy those, and I'll mention that later.

One last thing is that if you see microcalcifications on the mammogram or within the index mass, that we're gonna biopsy on ultrasound, and you also see microcalcifications in the lymph node, this is gonna be metastatic disease, still proven, otherwise it wouldn't fit on the previous, Images.
This is an example of metastatic lymph node with, so-called DCIS in it.
Obviously it has to be metastatic disease, but there are course complications, within that lymph node that we're, we're seeing as punctate calcifications on ultrasound.

Tiebreakers: Comparing Adjacent Nodes

Now, this is our first tiebreaker.
We've simply turned the transducer, so that we can see two lymph nodes in the same field of view.
What we have in the left lymph node is a non-specific abnormal lymph node that could be either reactive or metastatic, but the lymph node right next to it has a normal cortex and a large mediastinum.
So the fact that we have a disproportionate involvement of one lymph node compared to its neighbor strongly favors this being a metastatic lymph node.

On the left side, this is in a more pronounced example, we have a lymph node with a completely obliterated mediastinum on the right and immediately, next to it, its neighbor has a perfectly normal cortex.
This is gonna be metastatic disease all day, every day.
You just wouldn't see that degree of asymmetry with just reactive lymph nodes.

Now here we have two grossly abnormal lymph nodes.
One, we have virtual obliteration of the mediastinum and market hypo and abnormal rounding.
So we have a lot of abnormal findings, perhaps some irregularity, maybe even some, per nodal invasion.
The lymph node next to it has a displaced mediastinum, so it has relatively thin cortex behind, but Foley thick cortex laterally.
In general, we're always gonna consider biopsying the more abnormal of the two lymph nodes.
But in this case, there may be extensive liqui active necrosis in the left lymph node that I would actually target my biopsy to the less abnormal of the two.
But this is gonna be metastatic disease, still proven otherwise.

Now, here's where we have a problem.
We have moderate symmetrical cortical thickening in the left nim flow and the right lymph node right next to it.
Its neighbor has an identical degree of thick thickening.
So this, would favor this being, reactive, but you could still do split screen images with the other side to see if it's asymmetric with the other side, which might change your opinion.
So in this case, we can see that the right sided lymph nodes look perfectly normal as compared to the left.
So even though these nodes were symmetrical, we went ahead and biopsied these and they turned out to be metastatic.

Doppler as a Tiebreaker

Now, if you want to use doppler, it's just important to keep in mind that the histology and the metastatic lesion in the lymph node, it's gonna be identical to the histology.
The primary 85 or 90% of the time at least, that means the biologic behavior is gonna be the same 85 or 90% of the time.
So if you have a very hypervascular primary index lesion with color doppler or power doppler, you can expect that the metastatic lymph node will also be very hypervascular.

If you actually get wave forms in the index lesion, not in the surrounding tissue, but within the center of the index lesion, you'll often see a high peak systolic flow and a high impedance wave form pattern, within the index lesion.
If it's a metastatic lesion, you'll accept, you'll expect to see the same kind of waveform within the metastatic lymph node.

If I compare the waveform inside a metastatic supraclavicular lymph node with that within a reactive node, you can see that the reactive node has a low rounded systolic peak and a low impedance wave form as compared to the metastatic, lymph node that has a high impedance, high resistance wave form.

The truth of the matter is of the tiebreakers that I use, I rarely get down to Doppler, either color doppler or power doppler or pulse doppler spectral analysis.
I can almost always solve my, problem, my dilemma of is it more likely reactive or metastatic using the first tiebreaker, just comparing to adjacent lymph nodes.

Now another thing you can do is look at color doppler, flow patterns.
If I take away all these, the aro lymphatics, so they don't confuse you.
The important thing is that most lymph nodes are fed and drained by vessels that enter and leave through the hilum, and feed the lymph node through the mediastinum.
You don't see any peripheral vessels, feeding or draining this, this lymph node.

On the other hand, in metastatic lesions, that'll be, not the case.
So here's an example of a reactive lymph node with symmetrical cortical thickening and fairly extensive arborization of vessels within the hilar, but no significant non hilar trans capsular feeding or draining vessels.
And that was a reactive lymph node.

On the other hand, this is a small seven millimeter lymph node that's, grossly metastatic.
In addition to the hilar vessel on the left, we see several non hilar trans capsular vessels.
It makes sense that, that would occur because the most common implantation site for these metastases in the subcapsular and cortical sinusoids, and if they implant and stimulate, stimulate their own neovascular, they're gonna stimulate neovascular where they're implanted, which is in the periphery of the lymph node.

So if I compare a classical reactive node on the top, again, it's symmetrical cortical thickening, very extensive arborization of hilar vessels on power doppler.
Can't tell what's feeding and draining, but it's all hilar, flow.
There's no non hilar trans capsular flow.
This on the other hand, is a metastatic lesion.
The mediastinum is all virtually completely displaced down the posterior aspect of the lymph node.
The hilar vessel comes in, but we've got non hilar trans capsular feeding vessels.
This lymph node is also abnormally hypo coic and abnormally rounded.
So it's grossly abnormal and suspicious for metastatic disease based on the gray scale alone.
But it's a good example of how a reactive node looks on gray scale versus a metastatic node.
And on doppler of flow patterns.

Elastography

Now elastography can be helpful, in that reactive nodes are often not stiff and metastatic nodes, can be quite stiff.
This is a very tiny lymph node, but has has a backpack, it has an equatorial lar thickening in the mid later cortex that's, very stiff.

The problem we've had with Elastography is that it tends to, its sensitivity tends to fall off at about three centimeters.
And unfortunately in the breast cancer, screening and diagnostic cohort, the axillary lymph nodes are often in that three, three and a half centimeter depth range.
And so we find that many times the axillary lymph nodes are, too deep for this to work.
Well, we found that elastography seems to work better in the head and neck where we're dealing with lymph nodes that are more typically one and a half to two centimeters in depth.

Also initially we were limited in our ability to change the kilopascal scale.
That would be like buying a doppler with a PRF that you can't change.
Since that the FDA has relented and allowed us to change and use more quantitative stuff.
And the French have found that a lower kilopascal scale, of about a hundred kilopascals as opposed to the 180 that we were, forced to use in the clinical trials was actually more sensitive.

Primary Lesion Characteristics as Tiebreakers

Now the last thing I mentioned is that certain, primary characteristics, primary lesion characteristics tend to be associated with high incidence of lymph node metastasis.
And I can use that as a tiebreaker if I get a non-specific node that could be reactive or metastatic, but I have a high risk, index lesion, then I know that, I'm gonna be more, aggressive about, proving histologically the presence of metastatic disease.

This is a very large invasive lobular cancer growing up, the Cooper's Ligaments, and you can see there's gross lymphatic invasion.
This is actually a different case, but it illustrates a similar problem, a huge lesion, multiple subcutaneous nodules.
You can actually see a grossly distended, enlarged lymphatic, thickening of the skin, edema.
There's almost certainly gonna be lymphatic invasion in the skin.
We could even do a punch biopsy of the skin here, but certainly any, abnormality in the X exhale is gonna make me much more likely to put a needle in it when, when a primary is that extensive.

The important thing about, the lymphatics is that the richest network of the lymphatics lies between the skin and the superficial fascia.
So the superficial fascia is right at this level, and you can see how rich this lymphatic network is.
So any big lesion that grows up cooper's ligament toward the superficial fascia, or even a small lesion that allies at the level of the superficial fascia is more likely to be born on the entrance ramp to the freeway and have early metastatic disease.

So here's an example of two very small lesions that are occurring at the level of superficial fascia.
This white line here is the superficial fascia.
The richest network of lymphatics is between the skin and there.
So any lesion that occurs at that level, even if it's small, is more likely to metastatic meta metastasize at an early, stage.

Subular lesions, same thing.
The, sappies plexus around the arula is extremely rich.
So any superficial, subular lesion is even more likely to go metastatic.
So any of these lesions that are immediately subular, maybe even causing nipple retraction, maybe even growing up the ducked into into the nipple are highly likely to have, metastatic disease in an early stage.
So this would push me more towards biopsy of a nonspecific lymph node.

This is just a, a big birads five lesion.
We core biopsy that this is a me metastatic lymph node that's nonspecific, but the lymph node next to it was perfectly normal, indicating this was more likely metastatic.
And there's a pre-fire in our post-fire.
I use an 18 gauge achieve needle.
Usually, this just illustrates a, focal backpack on a lymph node, very thin cortex, posteriorly, no point in putting a needle there.
Very thin cortex along the right side anteriorly just a focal cortical bulge on the left anor aspect of the lymph node.
So I wanna put my needle specifically through the thickened cortex to make my diagnosis.

Biopsy Techniques for Lymph Nodes

Now people ask, is FNA adequate for biopsy of lymph nodes?
And I would say yes, in most cases it is.
I think FNA is less appropriate for breast lesions themselves, but it works pretty well in lymph nodes.

There are two times when FNA might not be good enough.
One is when we wanna prove that there's per nodal invasion.
And the second time is if we wanna make a specific diagnosis of Hodgkin's disease.
In those cases, we need core biopsy.
And if it's Hodgkin's disease, we need our PMI solution or saline as well as, formin.

Signs of Perinodal Invasion

So what are the signs of perinatal invasion?
Well, one of the early signs is abnormally hyper coic or emus perinatal fat.
If I blow this up, we can see that, there's a normal thin hyper coic, capsule around the anterior and right aspect of this lymph node.
But we can see along the left side the capsule is absent, there are irregular margins and there's peri nodal edema.
So the three findings for peri noal invasion, our loss of thin hyper coic capsule, irregular or angular outer cortical margin and perinatal edema.

When this is present, I think there's a definite advantage to doing core biopsy over FNA because you know, it really changes treatment and it takes Z 11 out of, consideration.
Z 11 is contraindicated if there's per nodal invasion.

So here's an example of two grossly abnormal axillary lymph nodes.
We could certainly make the diagnosis of metastatic disease by putting, FNA needle in lymph node number one on the left, but it would be better.
Looking here along the right side, we have loss of the capsule.
We have angular margins, we have perinatal edema.
I would specifically wanna place a needle that I could fire in two stages where I could preposition my aperture halfway into the lymph node and halfway out of the lymph node and, and then fire only the outer cannula.
And then specifically put on the requisition of the pathologist that I know this is metastatic disease.
I specifically want the question of period nodal invasion answered.

There are several types of needles where you can fire in two stages, achieve the teo, the in rrAD, the sro, there's probably even more by now.
I generally use the 18 gauge achieve for this.

This is an example, of the 18 gauge achieve with the aperture open.
So you can see that I've got about half my aperture in the lymph node and half my aperture outside the lymph node.
And again, it's really critical that you let the pathologist know what the question is because if you don't specifically say, I wanna know yes or no, there's probably nodal invasion, he just gonna give you a diagnosis of metastatic adenocarcinoma of the breast, which you already knew.
You really wanna know about the perinatal invasion.
So you've gotta pose your question in the right way.

Now, do I think that ultrasound is sensitive for peri nodal invasion?
I do not think it's sensitive for periodontal invasion.
I think it's positive predictive value is quite high, but I think its sensitivity is low.
Why is that? Because I think most per nodal invasion does not come from the lymph node, but it comes straight out of the obstructed, distended afferent lymphatics, directly into the fat without ever getting to the lymph node.
So I don't think we're sensitive for it.
Because we don't see signs of it in the lymph node doesn't mean it's not there.
But certainly when we see it, I think it behooves us to document it and it does remove a patient from consideration from Z 11 protocol.

Impact on Sentinel Node Procedure

Now, will core biopsy adversely affect any subsequent sentinel node lymph procedure, by altering flow?
I, I think the answer is no.
And I think in fact it should do the opposite.
It should improve a surgeon sentinel node statistics.
And the reason for that is very simple.
The single most common cause of false negative sentinel node procedure, which is roughly 9% or so, is gross disease that's causing obstruction of lymphatics and collateral flow around the sentinel lymph node.
Those are exactly the cases that we should find and document as positive and remove from the sentinel node population, and therefore remove the, the false negatives from a surgeon's population.

Sentinel Node Procedure Injections

Now what about, sentinel node procedure injections?
You know, I know everybody's gone to the per intradermal injection, but I always thought that that probably wasn't the best thing.
And there was a study done in 2009 in England where they used two different radionuclides.
They injected one intradermally around the reala and then they used a different energy radionuclide in the deep subcutaneous tissues overlying the lesion.
And then they determined where each of those went, and they found that in two thirds of the cases it really didn't matter.
But in one third of patients, drainage from the parenchymal plane is more complex with more than one root to the axilla.
And, I think that's a more accurate representation of what's happening in real life.
So I think a certain percentage of the false negative lymph node, lymph node, sentinel lymph node procedures is likely related to the intradural injection.

So this is just showing that in two thirds of the cases you got identical results.
But in one third of the cases, as I'm showing, on the, right, you got alternative lymph nodes that might not have been lit up by a perrer injection and might not have been removed, remember that a average sentinel node procedure is two or three lymph nodes.

Now we can do alt sound guided sentinel node injections.
I like a a larger volume.
The larger volume opens up the spaces between lymphatic cells, the endothelial cells on lymphatic channels, and allows more fluid to get in faster.
So, we usually use a four ccs and we use ultra filler, ultra filtered, technician sulfur colloid below a hundred angstroms because, that gets taken up faster.
It'll usually get to the lymph nodes within an hour and we get a much higher success rate that works great in an outpatient system where surgery happens close to on time in the hospital, it may be disadvantageous because if you get bumped by an ER case or ICU case, and your surgery goes two or three hours late, the radionuclide may already be at level two or level three.

Now we put in four equal aliquots, generally, one at 12 o'clock, one at three o'clock, one at nine o'clock and one at six o'clock relative to the lesion.
There's always an air bubble in the radionuclide syringe because it's radioactive.
You can't just squirt the air elbow out in the room.
You have to live with the fact that, you know, there's an air bubble there.
So I always come from inferior to superior and I put my first aliquot, superior to the lesion so that the air bubble doesn't obscure the lesion.
And then I back out and go over, to the right side, and inject laterally or immediately, and then go over to the left side and inject laterally immediately, and then finally inject the six o'clock location on the way out.

If a lesion is in the far upper outer quadrant, I'll often just, divide it into two aliquots that are away from the axilla medial and medial and, inferior from the axilla so that, we don't get shined through that.
Interferes with the surgeon's ability to find the sentinel nodes we never inject directly into the lesion or into the cavity.

Lymph Node Levels

Now let's talk about lymph node levels.
The axilla has three lymph node levels.
The pectoralis minor muscle, which is divided here, but I'll draw it in as a, as a trapezoid, determines level two.
So anything that occurs behind the pectoralis minor, and this is the pectoralis minor, not the major, is a level two lymph node.
Lymph nodes inferior and lateral are level one and lymph nodes that are superior medial are level three or infraclavicular nodes.
Those terms can be used interchangeably.

We also have inter, internal mammary nodes, which are most common on the second, third inter spaces, but can occur, more inferiorly.
And then we have internal jugular and supraclavicular nodes All are considered regional lymph nodes of the breast.

The, the breast metastases did, do tend to spread through the lymphatic system in an orderly fashion.
So if we see, negative level one nodes, we don't always look at level two or level three.
And if we, if both, level one and internal mammary nodes are negative, i we hardly ever put the, probe above the clavicle.
We only look where we need to look.
So if level one is positive, we look at level two.
If level two is positive, we look at level three.
If level three is positive, then we go above the clavicle.
So our, our typical exam is usually level one in internal mammary, and if it's negative, we stop.

This is just a, an anti radial view of the pectoralis major and the pectoralis minor.
So the green box, includes level one.
So that's this area between the axillary vein and the pectoralis major muscle behind the pectoralis major even, level two is back behind, pectoralis minor muscle and between the pectoralis muscles are the inner pectoral or rod or lymph nodes.
We always, always wanna look at those.
If we're looking at level two, These are sweeps from high to low and you can see that with the patient having her arm behind her head as we start superiorly, the pectoralis minor stuck out so far that to some extent we didn't even see the pectoralis minor muscle.
And then as we get to about mid axi, they equal and as we get in the lower axi, the pectoralis minor actually sticks out farther than the, farther laterally than the pectoralis major.
So you can't just look and see which, muscle protrudes.
The farthest laterally and say that for sure is internal is pectoralis major or pectoralis minor.
You really need to know how high or low in the axilla you are.

I've had partners call lymph nodes that occur behind the pectoralis minor level two nodes.
These two lymph nodes that you see here are behind the pectoralis major.
They're definitely lateral of the pectoralis minor despite the fact they're behind the pectoralis major.
They are definitely level one lymph nodes.

Now this is a level two lymph node and this is a two zone level two lymph node.
It's directly behind the mid pectoralis minor muscle.
The smaller, deeper, higher level lymph nodes.
In internal mammary nodes, we may see three different appearances.
We may see one zone lymph nodes, small deep nodes may not have a demonstrable, hyper coic medulla.
We may see two zone lymph nodes as this.
So we occasionally, rarely will see a three zone lymph node.
These are less often three zone than the um, level one in, axillary lymph nodes.

This is a one zone, internal mammary lymph node.
We don't see any mediastinal structure in that and that's normal.
That would definitely be abnormal in a level one node.
But in a level two node, sometimes you don't see a mediastinum.

Now this is just a video loop of that two zone, level two node we're sweeping up and then back down, through a level two lymph node right there.

Now we're looking at the left side and this is the pec miner in a pec major in front and the pec miner behind it.
And we can see that there are a couple of level two nodes right at the edge of the pectoralis minor muscle.

Now we can see normal level two nodes in a fair number of automated screening examinations and sometimes they lie right at the edge of the pectoralis minor.
Remember that the pectoralis major and minor are gonna change position, as the arm position changes.
So what appears to be one level, with the arm at the side may be different from where it is with the level abducted at 90 degrees may be different from where it is with the hand behind the head.
So, whether a lesion, whether a lymph node is level one or level two, really only the surgeon can say now because, in, in terms of confirming what we see now, this is the right side and now we're, a medial and superior to the medial edge of the pectoralis miner, which is right where my arrow is.
And we're actually seeing, a, a two zone, level three lymph node there.

I see level three lymph nodes, in normal individuals much less often than I see twos, level two nodes in normals.
So basically we virtually always find level one lymph nodes.
I would say most of the time I can find at least one level two node, certainly not all of the time, and I would say a minority of time can identify normal level three nodes.
But the, the real issue is I don't wanna find normal lymph nodes.
I really only wanna see the abnormal lymph nodes.
It just creates extra consternation to find them.
So, basically again, I don't necessarily go up and look for higher level lymph nodes unless I've got a reason to, unless I've got abnormal level one nodes or unless they've had a previous axillary procedure such as a previous sentinel node procedure or perhaps implants, that were placed from an axillary root.
In those cases, the sentinel node drainage may be abnormal and you may wanna look uh, at higher level lymph nodes, even if level one are normal.

These are, two, lymph nodes that this one is clearly level three.
It's a one zone lymph node.
This one is right in the borderline, so it's about half in zone three and half in zone two.

Now this just shows how much, a lymph node can vary in position with different arm positions.
So I'm pointing to a lymph node right here, which has got some symmetrical cortical thickening and it's about half in and half out of level two with the arm behind the head with the arm at the side.
This was clearly way out lateral, about two centimeters lateral to the PEC minor and clearly in level one.
So again, be aware that, axillary lymph node doubles are arm position dependent.

Now this patient had an abnormal level one node and then when I looked she had a couple abnormal level two nodes.
So because they were abnormal, I went up to level three and I found a node suspicious for prairie nodal invasion there.
So if I draw in, our levels, the lateral inferior edge of the pec miner is the border between level one and level two, and the upper medial border is the border between level three and level two.
So with an extended field of view.
And this by the way is clavicle and you can see why level three is also called infraclavicular.

Um, you can see that an extended field of view can really summarize the extended disease beautifully.
This is a little tricky. It took me two or three times to get it, but I could show on a single view for the surgeon that level one, level two and level three nodes were all positive.

Rotter Nodes

Now these are normal router nodes that were just demonstrated in automated, breast alt sound scans.
They're typically about 10 millimeters in maximum diameter.
They're pretty flat, they're nowhere near round.
This is a two zone, router node, two zone router node, a one zone router node, and a one zone router node.
And I found out it's about equal, about half the cases I can actually see a mediastinum half I can't, again, since this is a higher level lymph node, um, not seeing a mediastinum doesn't mean it's morphologically abnormal, smaller, deeper lymph nodes.
It's much harder to show the mediastinum.
And uh, again, these are typically about 10 millimeters in Maxim band are quite flat and there's a pectoral artery, you'll see they're right along that artery.
So you can use doppler to help find the area that you wanna look at and to help distinguish this from tortuous vessels.

This is a metastatic rotter node.
Here's the pectoralis minor deep, the pectoralis major superficial, and you can see it's bulging the space between the pectoralis major and minor muscles.
This is considered a different level from level two.
Here we can see different view of that same lesion.
Here's the PEC major, in front to the PEC minor behind you can see the inner pectoral AR artery that I told you about.
This is clearly a grossly abnormal lymph node with the hilum replaced.
And there are also two level two lymph nodes posterior to the pectorals minor in the same patient.

I mentioned that I do core biopsy on level one lymph nodes, but anything higher than level one I return to FNA.
So you know, I do FNA of the rotter node or of level two nodes or level three nodes if I need to.
Because that patient had positive level, two and level three nodes, then we went supraclavicular, those nodes were abnormal.
Internal jugular nodes were normal and even the posterior cervical nodes were normal.
So you don't have to biopsy all the levels.
What what I did in this case was I did a core biopsy on the level one node, documented that it was metastatic, and then I chose to do FNA of the highest posterior cervical node and that was positive.
And then I can assume everything in between is positive.
Again, I let what I see determine how high I go.

As long as there hasn't been an axillary surgical procedure, if there's been a previous sentinel node procedure or if implants have been placed through the aela, then I'll look at level one, level two and level three in everybody.
But as long as there's been no axillary procedure, if level one is negative and internal mammaries are negative, I stop.
I don't look at level two or level three.

Internal Mammary Nodes

We can see normal internal mammary nodes.
In most patients with current equipment, they're usually five to seven millimeters in maximum diameter.
They can be anywhere along the second or third interspace, but I find them most commonly just above the costal cartilage in the second and third interspaces.
We can see them pretty well on the transverse fuse too.

The artery, the internal mammary artery tends to be lateral.
The vein tends to be medial and we can usually see these internal mammary lymph nodes, medial and or anterior.
They can lie anywhere. Uh, Along there they can be lateral, anterior or medial, but I find them most often medial.

So these are just, normal internal mammary lymph nodes that are picked up on routine automated breast out sound screens.
Here's the internal mammary artery, the internal mammary vein and a two zone normal internal mammary lymph node.
There's another two zone internal mammary lymph node on the left side, internal mammary artery laterally internal mammary vein, medially and just medial to that is a two zone internal mammary normal lymph node.

This is a one zone internal mammary lymph node and another one zone internal lamie lymph node.
So just like higher level axillary nodes, we often don't see I meine internal lammie nodes.
That doesn't mean they're, abnormal.

This is simply a video sweep, from high to low.
On the right side you can see the internal mammary artery, the internal mammary vein.
And let's just roll this back and see if we can find our, okay, so here's our internal mammary lymph node right here.
So this is the artery, this is the vein.
Here's a normal internal mammary lymph node.

Now there is a tortuous vein, emissary vein that can go from the chest wall along the lateral side of the stern.
I mean, it can be mistaken for an internal amory node.
It's, it's easy just to put on doppler.
I mean, this is just a tortuous vein coming down.
The, internal lam lymph node is actually right here.
And that was just a vein, so don't mistake that.
Emissary vein, for, An enlarged lymph node.

Now an older woman with right heart failure, that can vary large tortuous internal memory veins that can simulate, lymph nodes.
So here we see a combination of some internal memory lymph nodes and a tortuous vein.
But simply turning on color or power doppler can help you sort out what are lymph nodes and what are veins.
So this is just a reflection of the vein off the lung, but we've got a tortuous internal mammary vein and then three, normal sized internal mammary lymph nodes there.

Now it's been said that deep, big medial lesions give rise to internal mammary lymph nodes.
I have not found that to be true.
I found it most commonly occurs with large breast lesions in any location.
This one was actually quite far lateral in the breast grade three invasive ductal cancer, about three centimeters gross axillary adenopathy causing tumor damming obstruction of the normal, lymphatic drainage pattern and collateral flow away from the axilla to the internal mammary lymph nodes with gross internal mammary adenopathy.
And I found that to occur more often than isolated internal mammary adenopathy from deep medial lesions.

But having said that, we can see isolated deep medial lesions that do give rise to gross internal mammary adenopathy.
This is an extended field of view, shown a huge internal mammary lymph node, in the second inner space.
I would never core biopsy this, but you can certainly do careful FNA these under oline guidance.
It's really hard to use the the usual cranial coddle approach.
I find that, by, you know, doing these, it's, it's much easier to come in, in the parallel to the intercostal space.
Usually a little lateral oblique approach.
You can get a flatter course for your needle.
You have to go too steeply to come over the rib in either direction, but if you come in between the ribs, you can get a much flatter approach with your FNA.

Significance of Higher Level Nodes

Now why are these higher level lymph nodes of any significance?
Well, first of all, recognizing per nodal invasion in the X hill is important because we know that there's ary recurrences and we know that they occur higher there and we know that excludes them from the Z 11 protocol.
So they will need a full axillary dissection.

This is an axillary recurrence, but undoubtedly this came from period nodal invasion in the axi that was not recognized.
Right now that's mostly of concern to the radiation oncologist, but also to the surgeon.
If they know it's there, they're gonna do a full axillary dissection and, and they'll also add an axillary field in radiation oncology.

Now here's a so-called chest recurrence that clearly came from per nodal invasion of a level three lymph node.
We can see that there's an adjacent level three lymph node with a nice rat bite.
This one doesn't appear to have per nodal invasion, but this is definitely per nodal invasion from a a level three axillary lymph node.

Here's another so-called chest wall recurrence.
This is clearly arising out of unrecognized untreated rotter nodes because there's the pectoralis me in front and the pectoralis minor behind.
And so again, another so-called chest wall recurrence coming from unrecognized untreated higher axillary lymph node metastasis with per nodal invasion.

And this is a per sternal, lymph node, or chest wall invasion.
Again, we know that these typically arise from per nodal invasion of internal mammary lymph nodes.
So again, I I think it's important for us to recognize these higher level nodes to allow both the radiation oncologist, maybe the medical oncologist than the surgeon to choose the most of treatment to minimize these chest wall recurrences.

Summary of Findings and Z11 Implications

So in summary, positive staging and ultrasound is always more valuable than a negative.
A grossly abnormal ultrasound can lead to diagnosis lymph node metastases positive staging ultrasound with ultrasound guided lymph node biopsy can obviate a sentinel node procedure and allow the surgeon straight to go to axillary dissection.
This is what Z 11 is mostly impacted, and a negative staging ultrasound or negative biopsy of abnormal appearing lymph nodes really can't obviate a sentinel node procedure or an axillary dissection.
And a biopsy of a negative lymph node or a reactive lymph node is just an extra procedure.
So we wanna try to avoid doing, low yield, biopsies.

The Z11 Study

The last thing I wanna show talk about is Z 11.
It was a study designed to see if there's any benefit to doing full axillary dissection, after a sentinel node procedure.
And it was specifically designed to look at whether one or two positive lymph nodes benefited from an axillary dissection versus three or more lymph nodes.

The main role of alt sound has been to obviate SentinelOne procedure, so the surgeon can go straight to full axillary resection.
So if axillary dissection will be needed, less alt sound and alt sound guided biopsy of abnormal lymph nodes may become less important.
Overall, this may make sense since assessment of axillary lymph nodes has always been more about staging and prognosis than treatment.

But despite that, I still see three real reasons that we should put the probe on the axilla.
First of all, we can see cases that would be false negative on sentinel lymph node, approximately 10%, nine or 10%, almost all caused by gross disease tumor damning collateral flow.
These are gonna be obvious on ultrasound, and we should be able to remove these false negatives from the surgical, surgeon's, sentinel node population.

We can see the presence of per nodal invasion, not with high sensitivity, but with pretty good positive predictive value.
And these patients should be excluded from Z 11, and we can document that if we do core biopsy in the right way that I showed you.

If we see three or more nodes that are en large, we enlarged.
We also know this patient is not a candidate for Z 11.
So seeing gross disease can be very helpful.

So there's a subset of patients in which axillary dissection may, still have treatment as well as staging prognostic value.
And I think we can identify those with the sentinel node procedure, but we certainly wanna be very careful about seeing whether something is more likely metastatic than reactive.

A final thing that could help us is a lymphatic contrast agent called oid.
It was actually developed for cardiac.
Somebody must have accidentally extravasated and noticed that it was taken up in lymphatics virtually immediately.
It's certainly not approved for use in humans in the USA.
It's being, researched in animals.
I guess there's a limited supply in the us but they're being more aggressive about looking at it In Japan.
Most of the studies being performed in the US were actually done on melanoma pigs at Thomas Ton University.
1228. Here you're seeing an injection into the, subcutaneous fat of a thigh of a pig, and you can see that immediately it's taken in to the lymphatics addicts and they're gonna follow it superiorly.
And I think you're gonna hear a comment saying it's going so fast, they can't, keep up with it.

There's this spermatic cord, for plexus, so it's a male pig, but you can see where just a few seconds, and now it's already getting up toward the abdomen and now it's disappearing behind bowel gas, but they're gonna use grated compression and push the bowel gas out of the way.
And now you can see that the, sinusoids within the cortex of the lymph nodes are being and, lit up By enhanced contrast, It's been shown, versus blue dye and radionuclide that you know, you can fill the cortex, sinusoids of a lymph node within a couple minutes.

This is a pig and it actually fills from the inside out rather than the outside in like humans.
But you can see within two minutes, you virtually filled all the sinusoids in the lymph node.
So if there's a metastatic lesion, within the sinusoids, what you're gonna get is a filling defect in the contrast agent.
And you can see in this, case here, the only normal, cortex is this pink area.
All the rest is involved by metastatic disease.
But you can see that the contrast enhancement is only occurring in the normal pink tissue.

You really wouldn't need contrast in a lymph node, this grossly involved.
But here's a case where we have a three millimeter metastasis.
That's, you know, two, a micro metastasis defined as two millimeters.
So this is barely bigger than a microme.
But we can clearly see, that there's a metastatic lesion here.

If you were to just blindly stick a needle into the thickened cortex, you could easily get a false negative if you stuck your needle in the anterior part of this lymph node.
But if you specifically put your needle into the area with the filling defect, you're gonna have a lot higher yield on your biopsy, and you're gonna do a lot better job of distinguishing reactive from metastatic lymph nodes.
So I believe this could be very helpful in the future.

Take Home Points

So the take home points here that, lymph nodes in breast cancer screening code are, are more frequently three zone than two zone.
The hyper cook medulla, maybe the key to identifying them.
If you learn to look for the hyper doula, you'll find more lymph nodes faster.

Scan the axilla from inferior to superior because the sentinel node is almost always the lowest node.
If you start from the top down, you may stop before you get to the sentinel node.

Cortical thickening is the hallmark of metastasis and its appearance depends on where the mit, implantation site occurs.

Uniform cortical thickening is nonspecific and requires tie breakers per nodal invasion.
Requires a core biopsy done the right way.

An unrecognized higher lymph node metastasis can give rise to so-called chest wall recurrences.
And it's worth recognizing and documenting these.

Detailed Discussion of the Z11 Study

I'd like to say a little bit about more about the Z 11 study.
It was a multicenter perspective study designed to determine if there's any value in axillary lymph node dissection.
In patients who have positive sentinel lymph node dissection.

Qualified patients were randomized into completion, axillary lymph node dissection and nothing beyond sentinel lymph node, procedure, to see if there was any difference in the recurrence rates or survival rates between the two groups.

In quantifying patients, local and axillary recurrence rates were not significantly different with or without axillary dissection.
In qualifying patients', survival was not significantly different between the groups who did and who did not undergo completion.

So based on this data, it's being recommended that unless a patient has three or more positive lymph nodes, they do not undergo, full axillary dissection.

These are the actual results, and I'm not gonna dwell on that.

We're first gonna ask the question, does it make extent, does, does C 11 make sense?
And to the extent that the rules of inclusion and exclusion apply, I would say yes, it makes sense.
Axillary lymph node, the sections sentinel lymph node procedures have always been about staging and treatment and probably staging more than treatment.
In some populations, their role in staging is greater than the role in treatment.
So we should not ignore it, but I think we should keep strictly in mind the potential limitations and more particularly the subset of patients to whom it applies.

I believe that even though it makes sense, it's being applied to more patients than the inclusion and exclusion criteria would warrant.

So the significance of Z 11 to Xal L sound is that if axillary ultrasound, an ultrasound guided biopsy, whether you do FNA or core of suspicious lymph nodes is being performed to allow surgeons to bypass sentinel load, no, sentinel lymph node procedure and go straight to axillary dissection.
But axillary dissection is no value.
Why perform the axillary lymph node ultrasound?
So that's the dilemma we're faced with.

And so does Z 11 mean that we should no longer put a probe on the X in patients who have suspicious masses in the breast in whom we're going to do alt sound guided biopsy.

So, you know, if you look at different levels of that question, should we completely stop looking at axillary lymph nodes with alt sound because of Z 11?
And if we continue to look at axillary lymph nodes in patients with suspicious breast masses, in whom will we perform ultrasound guided core biopsy in view of the findings of Z 11?
Or should we ever perform a biopsy, under ultrasound guidance because of Z 11?

So to answer this question, we have to examine the subpopulations to whom Z 11 results apply and do not apply.
So we have to examine the inclusion criteria and the exclusion criteria for Z 11 and the limitations of the study.

Inclusion and Exclusion Criteria for Z11

So let's look at the inclusion criteria for Z 11.
The eligible subpopulations, they have to have invasive disease.
It was not designed for pure DCIS.
It should be a T one or T two tumor.
There has to be a planned lumpectomy, not a mastectomy.
There have to be negative lumpectomy margins, and the patient has to undergo whole breast of radiation with high tangential fields that would presumably include the axilla.
And again, most of these patients underwent neoadjuvant chemotherapy as well, which we know can decrease the, rate of lymph node metastases.
And they had to have two or fewer positive sentinel lymph nodes on h and e stains.
They weren't looking for immunohistochemical evidence of micro mets.

Ineligible sub ineligible subpopulations included multicentric disease, bilateral disease, previous axillary surgical procedure, whether it's implants or sentinel node procedure, pregnancy or lactation plan mastectomy, pure DCIS without invasion positive margins after lumpectomy and clinically positive lymph nodes.
And this seems simple to me, clinically positive means palpable, but some surgeons view ultrasound positive lymph nodes as being clinically positive.
So that's in a controversial area.
And then three or more positive h and e uh, lymph nodes and then the presence of per nodal invasion.

Limitations of the Z11 Study

What were the limitations?
Well, it was intended to have 1900 patients enrolled in this for statistical power.
Recruitment was slow and they stopped at 900.
So for some of the things they intended to prove, they really had too few to be sure.

One of the things is they didn't have enough ILCs.
Only 7% of the cancers were invasive lobular.
So this should probably not be applied to invasive lobular.

They didn't have patients under 50, they didn't have enough grade three invasive cancers or HER two positive or triple negatives.
So you're really limited to, grade ones and twos that are ERPR positive.

You can't apply it in multifocality.
They did intend to look at T two lesions, but they had too few T two lesions.
So basically if you're over two centimeters in the two to five centimeter range, you know, they didn't really have enough to say about that, intended to include that, but there weren't enough then 'cause they stopped early partial breast I radiation would exclude you from the criteria because it's intended that the whole breast I radiation with high tangential fields would catch about 90% of the level one lymph nodes.
So if you have partial breast radiation, you're clearly not gonna qualify.
And that doesn't matter whether you have balloon or interstitial or IORT or bios, orb, there's all sorts of different ways they're doing partial breast irradiation now, but progressively larger and larger percentage of the patients are undergoing, partial breast irradiation and then not undergoing new adjuvant therapy.

So you can see that, there are lots of, limitations and under representations of Z 11.
And what concerns me is that people, surgeons are applying Z 11 to all these groups as if there was enough statistical power there.

So again, we asked the question in light of Z 11, can we justify putting an ALT on probe on the ACELA anymore?
Or can we ever justify putting a needle in under ultrasound guidance if the lymph node looks suspicious for metastatic disease?

Remember that Z 11 applies to a subset of breast cancer patients as shown by inclusion and exclusion criteria.
And in the subset of patients that differs from that of Z 11 one can pretty much handle axillary lymph node and ultrasound biopsy just as we used to.

One of the problems we're gonna have as radiologists is that we're gonna not gonna know a lot of those decisions at the time we see the patient.
All those decisions may be made about whether they're gonna get partial breast or radiation or neoadjuvant in tumor board or after tumor board, but we have to make a decision before that.
So we're gonna be somewhat disadvantaged in not having all of that in, information.

Again, partial breast i radiation is being used more frequently these days, whether it's intraoperative or interstitial balloons, hybrid including savvy and ClearPath or bi absorbed markers.
Patients under underlying partial breast irradiation do not qualify for Z 11.

A full breast radiation with high tangential fields gives 90%, 95% of dose to 51% of level one axillary lymph nodes.
And and it really gives that dose to the lower lymph nodes where the sentinel nodes are likely to occur, that a full axillary field does.
And it actually gives, 95% of dose to 26% of level two lymph nodes as well.

Certainly a radiation of lymph nodes was, that was part and parcel of full breast IR radiation likely accounted for at least some of the lack of increased risk in patients with one or two positive lymph nodes.
So if you don't have that, I don't think you can assume that the results would be the same without axillary dissection and with partial breast, I radiation not delivering a high dose of radiation to axillary lymph nodes, we shouldn't expect any protection and I don't think it's safe to assume that not doing an axillary dissection and them is gonna work.

Now, could they prove that it does in the future?
Yes, but they didn't prove that in Z 11.

Now what about adjuvant neo medical, therapy or not?
97% of the patients in Z 11 underwent some form of adjuvant chemotherapy, 58%, when chemo and 46%.
How, how al it's been shown to decrease axillary dis recurrence rates in other studies.
And so this likely also contributed to a lack of benefit to axillary dissection.
So if a patient's not undergoing, chemo or hormonal neoadjuvant therapy, they probably shouldn't qualify for Z 11.

While Z 11 has been widely accepted by breast surgeons, blanket acceptance is not universal.
There's, you know, from my experience it's about half the surgeons accept it and half the surgeons are a little suspicious of it.
Half the surgeons wanna apply it strictly to the subcategories, or subgroups that it applies to and others don't.

Michael Sable is a breast surgeon from Michigan Comprehensive Breast Cancer Center and he had a lot to say about it.
He says that however, one needs to question whether we too quickly abandon axillary lymph node dissection for the entire Z 11 population.
There are two concerning questions whether the axi truly went untreated.
It is suspected that many of the radiation oncologists adjusted their fields in order to cover a larger percentage of the aela.
If this was the case, we should acknowledge that Z 11 was actually a study of radiation therapy compared with axillary surgery.

And the more concerning question is whether we are now applying the results of Z 11 to a group of patients who weren't well represented in the trial.
There was clearly a selection bias on the part of the participating surgeons.

Furthermore, he says that many surgeons have advocated to no longer obtain XL elson and find needle aspiration biopsy of suspicious lymph nodes because this practice identifies women with clinically evident disease who in the absence of Elon would've been sentin a lymph node positive and thus eligible for avoidance of X lary lymph node procedure.
Nodal disease identified by alt sound and FNA is strongly correlated with tumor burden in a number of involved nodes.

So, Dr. Sable is one of the surgeons who believes that seeing grossly abnormal lymph nodes on alt sound should be considered clinically positive and their four should exclude a patient from Z 11.

Further, he says that the difference between normal and abnormal, node on physical examination and an abnormal lymph node on ultrasound has much to do with body habitus and clinical exam skills as it does with tumor biology.
How does it make One makes sense of the argument that a 1.5 centimeter palpable lymph node in a thin individual has a different prognostic implication than a 1.5 centimeter non palpable lymph node in a heavier patient.
Yet by not undergoing ultrasound, the latter patient would be labeled sentinel lymph node positive and offered no xili lymph node, procedure while the former would be labeled clinically positive and undergo, axillary lymph node procedure.

Furthermore, he comments this change in practice takes place, takes a population of patients who are not accrued in the Z 11 study and who clearly were not representative and now labels them as Z 11 eligible.
Thus, we, we may, we may want to be careful about radically altering our approach.

Preoperative ultrasound of the axilla is still extremely useful staging test and patients with large abnormal, albeit non palpable nodes, should still undergo FNA biopsy and be considered for axillary lymph node, dissection if positive.

Selection Bias and Study Limitations

So if we talk about selection bias by the surgeons, the median agents in, sentinel lymph node dissection group was 54 years.
We know that younger women have much higher currents rates and that's why we believe it shouldn't be applied.
Under 50 71% of the sentinel lymph node group had T one tumors only 29% were T two too few to be statistically significant.

83% of the sentinel lymph node, dissection group cancers were er positive.
Only 17% were er negative.
So we believe it shouldn't be applied to er negative 70% were PR positive.

60% had only one positive lymph node on h and e, in the sentinel lymph node only group.
That means that, you know, if, if you have two positive lymph nodes, statistically there weren't enough for power to say that if you had two positive lymph nodes, you shouldn't undergo, axillary dissection.

85% of the lesions were grade one or grade two, so it probably doesn't apply to grade three.
There were insufficient numbers to assess multifocality grade three triple negative HER two positive and there were an insufficient number of invasive lobular cancers.

Why was enrollment less than expected?
We think because some surgeons felt not performing axillary dissection was too radical.
But we still got statistical significance.
It was mostly an older population with small hormonally positive malignant masses.

Another problem was relatively short follow up for the T one hormonally positive lesion six pos six years plus.
Normally we'd wanna follow T one hormone positive lesions for longer, that their recurrences can occur many years afterwards.

And we know that the false negative rate for, for sentinel lymph node procedure nationwide is about 9.8%.
When sentinel lymph node is positive by h and e for macro mets, non sentinel lymph node and LA involvement has been reported in 50 to fif, 58%, but only 25% was reported in Z 11.
That means that they chose a better prognostic subset of patients.
And so again, our average patient may, may not have that good of prognosis.

Other histologic factors that affect lymph node involvement, including grade molecular subtype and lymphovascular invasion weren't really looked at separately.
And again, it doesn't pertain to invasive lobular cancer.

Implications for Radiologists

So in in summary, As a radiologist, you have a difficult decision.
It may depend on your surgeon whether or not you continue to put lymph nodes, under evaluation with the ultrasound probe, during the evaluation of su suspicious breast masses.

If you have just one breast surgeon and that breast surgeon wants to apply Z 11 to pretty much all of his patients, he may ask you not to do it.
You may have more than one surgeon who refers to you and you may have one surgeon who doesn't want you to put the probe on and another surgeon who does.
So you're really gonna have to know your individual surgeons.

In many cases, the decision will be taken out of the radiologist's hands and and it'll be in the hand of the, the surgeon.
But it may be a complex issue because you may have different surgeons with different beliefs.

So in looking at lymph nodes, you'll wanna make a concerted effort to avoid biopsy of reactive nodes, which are very common in breast cancer patients.
And despite all the arguments against axi ultrasound that can be made because of Z 11 one can make several arguments for continual elson evaluation of regional lymph nodes.

I would say number one, identifying grossly abnormal lymph nodes that might cause tumor ing collateral flow around the sentinel lymph node.
And false negative sentinel lymph node procedure is a very good reason to put the probe on, to document the presence of three or more grossly abnormal lymph nodes, which would remove a patient from Z 11 and to document higher level lymph node involvement and to document, document per nodal invasion.
'cause all of these things are exclusion criteria.
And then finally, to look at the internal memory lymph nodes as well.

So theoretically, I, I continue to handle things the same way I used to in patients who are clearly not Z 11 eligible.
On the other hand, if they are Z 11, 11 eligible, I'm, I'm very much more conservative about what I do.

The real problem is, again, at the time I'm seeing the patient, a lot of the decisions, a lot of the information isn't available to let me know whether they are eligible or not eligible.
So I continue to act pretty much the way I did in the past and in fact I've been lucky in that my surgeons really aren't that big advocates for Z 11 and they want us to continue to look at things, the way I used to.

So the bottom line is it's a difficult, problem.
You're gonna have to work with your surgeon many times the surgeon will tell you whether he wants you to do it or not.
And you may have different surgeons who request different things.
But I just give you a whole list of list of reasons why I think we should continue to look at lymph nodes despite Z 11.

Thank you.