Role of Neck Sonography After Total Thyroidectomy for Differentiated Thyroid Cancer - SD

Introduction

Hello, my name is Sheila.
She and I'm in the radiology department at Johns Hopkins Hospital in Baltimore.
And I'm gonna talk to you today about the role of neck ultrasound in the management of patients with differentiated thyroid cancer.

Paradigm Shift in Management

There has been a paradigm shift for the past 10 years in the management of patients with differentiated thyroid cancer.
Treatment goals have shifted from disease-free survival to recurrence-free survival.
And of course, the optimum treatment for these patients is surgical resection of the primary tumor and any metastasis either at the time of initial diagnosis if they're there, or delayed metastasis at the same time, we want to minimize morbidity.
And there are two recent advantages that have allowed for this paradigm shift.
This is a development of serum tumor markers, for example, thyroid globulin levels for patients with papillary thyroid cancer in high resolution neck ultrasound.

Objectives of the Talk

So the objective of this talk then is to give you a very brief clinical background, and then discuss the role of neck ultrasound in patients with differentiated thyroid cancer.
And I will describe our techniques and protocols.
I will describe the neck compartments as they're relevant for surgical management, and we will discuss sonographic findings that help in differentiated benign cervical nodes from potential metastasis.
Doing this, I will discuss the use of ultrasound in patients after total thyroidectomy first, and then I will also discuss the use of ultrasound at the time of initial diagnosis of differentiated thyroid cancer in preparation for surgery.
As I think we are doing more and more of these.

Clinical Background on Thyroid Cancer

So what are the issues with thyroid cancer?
In 2008, there were over 37,000 new cases diagnosed, and it seems that the incidence is increasing, probably, at least in part, really to the fact that we now have better diagnostic techniques.
And a lot of these cancer are actually detected incidentally, either on a carotid ultrasound or neck ct.
Now, differentiate thyroid cancer account for 90% of these cancer.
And of those papillary cancer or PTC are the most by far and away the most frequent.
The management for these tumors is to perform a total thyroidectomy, followed in many cases by radio ablation with radio iodine 1 31 and also TSH suppression with thyroid with T four levels.
Because this not only treats the hypothyroidism, but also suppresses any cells that would cancer cell that would be dependent on TSH.
Now, while the survival for PTC, which is 98% at 10 years, papillary cancer has a very high propensity for nodal metastasis for at the time of initial diagnosis.
30% of patients diagnosed with PTC have palpable enlarged cervical nodes, and 50 to almost 80% in some series have nodal metastasis that are diagnosed either with ultrasound or when the surgeon perform a lateral jugular node dissection.
In patients who have been treated for PTC, nine to 30% of them will have recurrence at some point in the future, recurrence or metastasis, and the majority will have nodal recurrences.
Now, all of these, the majority of them are really local, regional, so in the neck and 74% will have nodal recurrences.
As you can see on this surgical slide here, 20% will recur in the thyroid bed and 6% will recur in the trachea or the muscle.
So it is very important to have an effective strategy for surveillance and early detection of these recurrences.
And once recurrences have been detected, we need an accurate mapping of nodal metastasis that allows for optimal surgical planning.
And guidelines have been for management and surveillance of these patients have been developed by several societies.
And while there are very minus differences, they're very, very similar overall.
And this is just one reference from the American Thyroid Association down here.
I just want to touch on which stratification.
Basically there are low risk patients, which ages diagnosis is over 16 and less than 45 when the primary tumor is 1.5 centimeter or less, without capsule invasion metastasis.
And there are high risk patients, mostly older patient above 45 male with larger tumors over two centimeters, extra thyroid extension and metastasis.
And depending on the risk stratification, the surveillance protocol will vary.
And again, I wanna stress the important adequate surgical resection, preferably at the time of initial diagnosis to minimize the risk of recurrence.

Surveillance After Total Thyroidectomy

So let's first discuss the detection of recurrences in patients who have had a total thyroidectomy for differentiated thyroid cancer.
Now, most a protocol will recommend an initial follow up at six to 12 months after the surgery, and then yearly follow up thereafter.
Now, the traditional methods of detecting recurrence that were palpation or whole body scans with radioactive iodine really have been abandoned in favor of tumor markers.
And if we talk about papillary cancer, then serum serum thyroglobulin level is the tumor marker.
It is usually done after TSH stimulation.
And we all know that thyroglobulin is a thyroid specific protein, which is a precursor in the biosynthesis of thyroid hormone, and it is only secreted by normal thyroid tissue or functioning thyroid cancer cells such as papillary thyroid cancer.
And of course, after total thyroidectomy this level, the the serum level of thyroglobulin should be fall to zero.
So it is a very good marker if it starts to rise again for the detection of recurrence.
It is also thought that post ablation serum thyroglobulin level at six to 12 months after the initial surgery may be a good prognostic indicator for this patient.
However, approximately 15 to 20% of patients have circulating antithyroglobulin antibodies, and this marker will not be helpful in these patients.
Of course, if we're dealing for a different type of cancer such as medullary cancer, which arise from the C cell of the thyroid, then we'll have to use a different serum tumor marker, which in this case would be serum calcitonin.

Role of High-Resolution Neck Ultrasound in Surveillance

The second arm of the surveillance is high resolution neck ultrasound, which allows for detection of non palpable metastasis and also maps any abnormal node for surgical planning and ultrasound's actually very good.
It has been shown in that it can de has a sensitivity of 94% in detecting recurrence of metastasis that can be as small as four to five millimeters.
Other modalities play an ancillary role, problem solving cases, neck and chest ultrasound and FDZ PET is also increasingly being used.

Challenges in Neck Ultrasound

So when we talk about high resolution al neck ultrasound, there are really four main challenges for the sonographer.
First, it is a tedious examination that requires patients and fortitude.
And for the radiologist interpreting the study, there are three main challenges.
First, to differentiate benign for malignant lesions.
Second, once a malignant or potentially suspicious lesion has been detected, we need to localize them precisely to specific neck compartments.
And finally, we are also often asked to prove malignancy with ultrasound of guided fine needle aspiration.
So really this technique requires meticulous scanning technique following a strict protocol.
And there's definitely a learning curve when we were learning that we made many mistakes, either overlooking some lesions or putting them in the wrong neck compartment.
So definitely there is a learning curve.
Ideally you want to correlate them with the serum tumor markers I talked about, and a physician monitoring the study should really be involved very, very closely, re-scanning any problem cases.
And finally, there needs to be an effective communication with a referring physician.

Neck Compartments

So let's first describe the central compartment of the neck, which is located here, between superiorly, the thyroid, the thyroid cartilage inferiorly, the sternal sternal knot and laterally.
And this is a very important landmark, the common car artery.
So the central compartment is located between the trachea and the common carotid artery, and it contains nodal groups six one A, which is above the thyroid cartilage and is much less commonly involved.
And these level six nodes include pretracheal, para tracheal nodes, which are the most commonly involving, metastasis or recurrence and superior mediastinal nodes.
The lateral compartment, as you can see on this diagram, is located lateral to the common carotid artery.
And the superior band boundary is the, mandible.
And the inferior, boundary is the, the, clavicle.
And again, the important thing is this me, medial boundary, which is the common carotid artery.
So the lateral compartment is lateral to the common carotid artery, and it contains nodal group two A and two B, which are the submandibular slash sub man submental nodes, but also the jugular nodes, which are level three and four and LA more laterally, level five.
And while you know, the distinction between level three and four is not that important, what is really important is that it is lateral again to the common carotid artery.

Scanning Protocol

So this is just brief very briefly, our scanning protocol.
We obtained transverse images from the, mandible all the way down to the external cla, the external notch, and then laterally to the clavicle.
And we also, obtained a sagal measurements to this level.
And without going into detail again in all these, landmarks, the most important thing is again, that your landmark will be the common carotid artery to differentiate the central compartment of the neck from the lateral compartment of the neck.
And while of course we use a high resolution, high frequency linear transducer to em image the neck, it's very important to compliment your, your scanning with a sector or cur in your, transducer and angle below the clavicle as low as we can.
And below the sternal, not as low as we can to try to detect this very low hanging metastasis potentially.
So this is a clip showing the central compartment of the neck.
This is the clavicle. Here we go.
Back up the carotid artery. Here's the central compartment.
And this patient actually has a little, metastasis on that side.
On the left side, of course, you will also see, the esophagus posteriorly, as you can see here.
And then this, clip shows the lateral compartment of the neck.
So again, here mely, you'll see the common carotid artery.
And anything that's in that area is in the lateral compartment of the neck.
And again, we scan from the angle of the mandible all the way to the, subclavian vein and artery.
Now a picture is worth a thousand words, and we always give a referring, clinician endocrinologist s surgeon a diagram which, is composed of a frontal view and two lateral views left and right.
And we mark all the abnormal nodes in their specific compartments as we see them.

Central Neck Recurrence

So let's talk about first central neck recurrence, mostly level six here.
So the normal postoperative appearance of a central compartment of the neck, you see the common carotid artery that's very, very close to the trachea.
There is just, there may be no tissue at all or a little bit of echogenic tissue.
And if we see any mass in this compartment, then, to me it is a suspicious mass until proven otherwise, because since the patient has had a total thyroidectomy, there really should be very little tissue in that compartment.
As you can see in this patient, there is a large mass displacing the common carotid artery away from the trachea.
This mass has microcalcifications within it, it has increased vascularity.
This patient was a patient who had a total thyroidectomy for papillary thyroid cancer to two years prior to this ultrasound.
He came with an elevated serum thyroid globulin level as 131 nanogram per milliliter.
And of course, the, final aspiration confirmed that it was a suspicious, metastasis for follicular variant of PTC and the surgery confirmed this finding.
This is another patient who actually had a total thyroidectomy for presume a papillary thyroid cancer that was done somewhere else 14 months prior to the study.
And he presented with this mass, which is located in between the common carotid artery and the trachea.
Notice that this mass is hypo coic.
It is taller than white, it has increased vascularity.
It is a, on the corresponding neck city, a hypervascular, right para tracheal mass.
And this, was done at final aspiration, and in fact, it was a metastatic medullary carcinoma.
So perhaps the initial surgery was wrong and the surgery confirmed this diagnosis.
Now, this ma recurrence can be very small.
As you can see in this patient.
There are two small somewhat lobulated hypo hypoechoic masses, one on the right level six, one on the left level six.
And despite their small size, they're suspicious because they're somewhat lobulated in shape.
They have perhaps tiny calcifications.
This patient also had positive finding at pet.
And again, this was proven metastatic papillary thyroid cancer.
This recurrence may have a cystic component, which shouldn't really not distribute you from, calling this suspicious.
And this was also a recurrent, papillary thyroid cancer.
Now, there are mimics of recurrence.
Not all tissue in the thyroid bed is going to be metastatic disease.
For example, this patient had a large mass displacing the trachea, the d common carotid artery away from the trachea.
And this was a biopsy residual thyroid tissue.
You can have scar tissue, sutro granuloma, muscle tissue, fat necrosis.
These are all cytologic diagnosis that were found in this series from she NAL published in 2007.
And of their le level six lesion that, underwent FNAA 20 out of 59 were malignant.
And the other one had a variety of, other benign, diagnosis.

Lateral Neck Compartment

Now let's move to the lateral neck compartment.
That includes level 3, 4, 2, and five.
And in this compartment, the challenge is really to differentiate benign cervical nodes that are very, very common from malignant nodes.
So what are the characteristic of a benign cervical nodes?
Well, it should be oblong or oval in shape.
It should have an echogenic hilum.
And this node has a very prominent echogenic hilum, which is a central fat.
But however, this can be difficult to see if the node is very small and if it has vascularity, it should be central and somewhat sparse.
Really, the size of the node is not helpful.
In contrast this to this, malignant, node here, this is a very clearly malignant, it is round and lobulated in shape.
It's long axis to short axis.
If we measured it would be less than two, there is no echogenic hilum.
It echos the echo texture may be hypoechoic or very heterogeneous compared to the surrounding muscle.
And you may see punctate, echogenic foy.
You can see here you can also see cystic changes.
And if you turn the doppler on, this will have irregular vessels.
Here's another example, smaller node, but node is the cystic changes.
And this actually has very high specificity of a hundred percent to diagnose metastatic papillary thyroid cancer.
However, the sensitivity is very low.
And it's interesting to note that while the primary tumor with papillary thyroid cancer is very rarely cystic, their metastasis tend actually to have more cystic changes.
Another, characteristic feature of metastasis would be this hyper echogenic foci, which may represent either micro calcification or oid.
And again, this sign has a specificity of a hundred percent and a sensitivity of 46%.
Same patient, different node, again, hypo echo, very, very hypo eic, partially cystic punctate echogenic foci.
And if we turn the color on, increase disorganized sort of vascularity, again, that is metastatic disease.
Now, does the size matter?
Well, this patient had a thyroidectomy for medullary cancer, and when we scan her, we see this node, which is very small.
It's less than one soter, it's in the lateral compartment, but it's round.
And she also had an elevated, serum calcitonin level.
So we, biopsy this lesion and FNA, this was metastatic MedU cancer.
In fact, nodes as small as four to five millimeters can harbor metastatic disease.
So what's important is the shape of the node and possibly its location.
If you have a a lesion like this in the central compartment of the neck, I definitely would also be very suspicious.

Challenging Cases

Now, let me show you a few challenging cases.
This was a young woman that, which had a history of, pap thyroid cancer when we scanned her left neck, a central compartment here, lateral compartment here with a linear transducer up and down.
We really did not see, very much disease.
It's only when we put the carline transducer and looked very low just above the subclavian vessels here that we found this round mass, which is of course very suspicious.
It has, it is heterogeneous in EQU texture.
And this was metastatic PTC.
So it's very, very important that in all cases we, we remember to change transducer and look low.
Another challenging cases.
So this patient was diagnosed with PTCA year prior to, this, examination.
And we saw this node.
So the first question is when you look at the, transverse, this is the right side.
So the trachea is here. Here's the common carotid artery.
It is anterior to the, to the common carotid artery.
And so it's at level six or four.
It's difficult to see in what I say in these cases is I say it's level six slash four, but I tell the surgeon that it's anterior to the common carotid artery.
And this surgery is usually much less difficult than nodes that are deep in level six.
The other question when we look at it is that it seems like it has a fatty hilum.
However, this node stood out in this patient, it was bigger than the the other ones.
And we also knew that he had an elevated, serum thro globulin level so that he had to have some, metastatic disease.
And when we turn the collar on, you can see that there's only peripheral, but large vascularity here.
And based on that, we recommended that the patient has a final aspiration that confirmed the diagnosis of PTC.
And peripheral vascularity is actually pretty good.
Sign of malignancy, it has a sensitivity of 86% and a specificity of 82% in that study by and out that I quoted earlier.
Another challenging case.
Now, this patient has a lymph node here.
It is in, just anterior to the common carotid artery on the left side and on the transverse through it doesn't look that ominous.
When we look longitudinally here, there is a fatty hilum, but however, there's a portion of the node here that is more lobulated in shape, perhaps a little bit more hypo coic than the rest of the cortex.
And we won't turn the color on.
There is increased vascularity in that area.
So it's a very subtle but real suspicious, recurrence.
And when we did the fine needle aspiration, we made sure that we target this area specifically to prove that this node harbor metastatic papillary thyroid cancer.
Another challenging case, this patient had bilateral lymphadenopathy on the right level four, this node, which is oval in shape, hypo coic, but has no fatty hilum and is actually almost 1.5 centimeter.
He also had a smaller node in left level four.
But if you look at it, there is a fatty hylum, but again, it's very eccentric.
So based on this, we decided to, do final aspiration of both these nodes.
And this turned out to be just a reactive node, but this harbor metastatic, medullary thyroid cancer.
So there are some nodes that I will not be able to put any in any category.
They're not definitely benign.
They're not definitely malignant.
And I will call, call that indeterminate. Here's an example.
This is a patient who has multiple nodes here, the chain of nodes, they're kind of round in shape.
There's some increased vascularity, maybe.
Certainly they have no fatty hilar.
And so I would call this, indeterminate.
And while the patient did have a recurrence in other area in the central neck, on the right side, we biopsy these nodes, which just show proved to be reactive.
So there will be a category of indeterminate nodes.
We also have to keep in mind that level two nodes that are submandibular, tend to be be large, larger, rounder in shape, may not have as clear fatty hilum.
And, these rarely are harbor metastatic disease from papillary thyroid cancer anyway.
So if these are bilateral, I just tend to discard them and, and consider them normal.
We see these kind of plump level two nodes in many, many patients.

Preoperative Neck Ultrasound

So now let me discuss the word of pre thyroidectomy ultrasound.
Now we know that up to 50% or maybe more patients would at the time of initial diagnosis for papillary thyroid cancer have cervical node metastasis at presentation.
And while this noal metastasis rarely affect survival, they are prone to, these patients are prone to recurrence that may occur in up to 30% of the cases.
And so ideally you want to remove that, at the initial surgery because macroscopic nodal metastasis may not be adequately treated with radioactive iodine.
So the current recommendations then is to do a preoperative neck ultrasound in all patients at the time of initial diagnosis prior to their initial surgery to detect potential nodal metastasis and map their location.
And preoperative neck ultrasound will then provide optimal guidance for management.
And the decision from the surgeon to perform a lateral compartment neck dissection will depend on the ultrasound findings.
They will only do a lateral neck dissection if the ultrasound, the preoperative ultrasound is abnormal.
There is a lot of controversy regarding central neck dissection.
Some surgeon do it systematically, some don't.
And that's because when the patient still have a thyroid, thyroid in place, ultrasound has a relatively low sensitivity of only 22.6%.
In this very recent study for detecting central compartment metastasis, nodes that are in the thyroid groove along the recurrent nerve can very oftentimes be obscured by the, when the thyroid is still in place.
So, let me show you a couple of example.
This is a 53-year-old patient who had a very heterogeneous mass replacing almost the entire left thyroid lobe and know how extensive nodal metastasis this is on the left lateral, level three, extensive multiple adenopathy in the lateral neck, very hypervascular.
And of course, these patients will have a lateral radical neck dissection at the time of his total thyroidectomy.
Unfortunately, he also had a small, what I think is an abnormal note on the right side.
It's abnormal because it has cystic changes, tiny bright foci, a little bit of increased vascularity.
And although this is a very recent case, I don't have proof of it, I'm very suspicious that this patient will come back to us to have final aspiration of this node and will at some point require a right neck dissection as well.
Here another patient in which pre, in which preoperative a neck ultrasound changed the management, this patient had a relatively small 1.1 centimeter papillary thyroid cancer in the right lobe of the thyroid.
And when we did the, full neck ultrasound, there is a level three node, which is, it stood out because it looked a little bit more cystic.
We could not really see a fatty hilum.
And while I was not ready to call the suspicious, I definitely called it indeterminate.
And based on this, the patient had a final aspiration that showed metastatic PTC and he ended up having, in addition to his total thyroidectomy, a white radical neck dissection.

Ultrasound-Guided Fine Needle Aspiration

Now, we are often time asked to do final aspiration when we found abnormal nodes.
And I briefly want to show you our setup.
We use a needle guide technique here with an, transducer and the needle guide cover with a sterile cover.
I use local anesthesia in all patients, and we use 25 gauge needle, with capillary technique.
And we are fortunate our institution to have a cytopathologist on site that will give us immediate feedback regarding adequacy of the specimen.
Now these, there are some challenges associated with this technique.
First of all, oftentimes these are recurrences are very small, located adjacent to major vessels.
But I think that since we use very fine, needle such as 25 gauge needle, this is, probably, okay, the, the, the, rate of complication is minimal.
Another perhaps more important question is, how many nodes need need to be biopsied?
And the answer is in every compartment of the neck, if there is an abnormal node, it needs to be biopsy.
So for example, if the patient has bilateral, lateral compartment neck biopsies, our biopsy, the right and the left, if the patient also has central compartment recurrence, this will be biopsy also at the same setting.
So patient may end up having four different biopsies because our surgeons will not go and, undertake these sometimes very challenging.
We operation, there's a lot of scar tissue, a risk of morbidity unless we prove by finding or aspiration there is metastasis in that node.
There has been some, new, development recently in the, final aspiration technique.
Some pathologies suggest that in addition to cytologic evaluation, measurement of thyroglobulin concentration in the needle wash may improve sensitivity and specificity for diagnosis of metastatic node.
And at least in this study, it was suggested that a cutoff of one nanogram per milliliter of thyroglobulin in the wash be used to differentiate, benign for potentially malignant nodes.
And of course, this is only VA valid if the patient does not have any circulating antibodies.

Conclusion

So to conclude, I just want to give you some numbers for ultrasound.
This is from a Mayo Clinic series.
And when they look at the VE patients or patient who had, pt, total thyroidectomy in the past and were coming for potential recurrence, they found that, ultrasound detected non palpable lateral compartment nodes in 64.2% of their, patients and non palpable central compartment nodes in 28.2% of the patients.
And in fact, ultrasound provided add additional information that altered the surgical management in over 40% of their patients.
For the preoperative patient, the patient that came at time of initial diagnosis, again, there were non palpable lateral compartment nodes detected in, slightly over 14% of their patients.
And so there was, ultrasound gave additional information that altered the surgical management in, 40.5 of their patients.
So in conclusion then, the current management of patients with differentiated thyroid cancer has a high emphasis on high quality neck ultrasound.
And this is a quote from that, Mayo Clinic paper, that I just mentioned.
That's an anatomic precision in the dictated report is vital information for the surgeon.
Ideally you really need a multidisciplinary team that, is, comprised of endocrinologist, surgeons, radiologists, sonographers, and cytopathologists.
To handle these patients, communication is incredibly important.
The sonologist need to understand what the surgeon needs, give diagrams to the surgeon depicting the abnormal nodes.
And in difficult cases, we will help the surgeon by doing preoperative marking of the nodes on the skin just prior to surgery.
Or even if the surgeon has trouble difficulty finding, nodes, we will go in the OR and help the surgeon with intraoperative ultrasound.