Thyroid Nodules Sonographic Evaluation and Biopsy Recommendations - SD

Introduction

Hi, my name is Jill Langer.
I'm associate professor of radiology at the University of Pennsylvania, and my topic is Thyroid Nodules, sonographic evaluation and recommendations for biopsy.

Hello, my name is Jill Langer and I'll be talking about thyroid nodules, both from the perspective of sonographic evaluation as well as some recommendation for biopsies.

Now I'd like to overview both the histologic and sonographic appearance of thyroid nodules and also review the recommendations for performing an FNA on nodules that are detected by imaging as developed by the Society of Radiologists and Ultrasound Thyroid Consensus Committee.

Prevalence of Thyroid Nodules

Now, thyroid nodules are very common.
As a matter of fact, if you look at the data from the Framingham study, the incidence of palpable nodules is approximately 6.4% of women and 1.5% of men age 30 to 60 with an annual incidence of about 0.09%.
Certainly, the incidence increases with age, and as we mentioned, there's a gender predominance for women.
We know that approximately 5% of palpable nodules turn out to be cancers.
However, when we look at the incidence of thyroid nodules by more sensitive technique such as microscopic evaluation at the time of autopsy or ultrasonography, we can see that in fact, the incidence of thyroid nodules is much more than expected by palpation, in fact, greater than 50% in some of the older age groups.

Definition of a Sonographic Thyroid Nodule

Now, what is a sonographic thyroid nodule?
A nodule is essentially one or more areas within the thyroid that has a different echo texture than the surrounding parenchyma.
Many nodules that we pick up on ultrasound are very small nodules that are not palpable, but also some large nodules that are non palpable may be detected by ultrasound.
The clinical dilemma is that the vast majority of nodules are in fact benign.
FNA of these nodules is likely not medically necessary in the vast majority of patients.
When we do an ultrasound and we see a focal nodule, what are the possibilities?
The vast majority of these nodules can be benign hyperplastic nodules, which in fact are an area of cells that are proliferating and have no likelihood of becoming a malignancy.
It may be a true tumor such as a benign thyroid adenoma, which comprises approximately 10% of focal abnormalities or a cancer comprising somewhere between five and 10% of the abnormalities.
There are some other less common things that we may see as a focal area in ultrasound such as a focal area of inflammatory disease or thyroiditis, and then some unusual things such as an intra thyroidal parathyroid, a true thyroid cyst, and also rarely metastatic disease.

Histologic and Sonographic Features of Thyroid Nodules

Hyperplastic Nodule

Let's look at some of the histologic features of these nodules and correlate them with the sonographic appearance.
A hyperplastic nodule is essentially an area of the thyroid that is stimulated to undergo follicular hyperplasia with the resultant accumulation of colloid.
If we look at the microscopy slide over here, we can see the normal thyroid in the background down here with areas of colloid and the surrounding follicular cells within the hyperplastic nodule.
We essentially see the same types of cells, but you'll note that the areas of the colloid are much larger and the follicular pattern is much more dispersed.
If we were to sample this, we would see a multiple different types of follicular cells of varying sizes and varying ages as well as colloid the protein matrix that thyroid hormone is made out of and some macrophages.
The characteristic ultrasound appearance is very similar.
We have some areas of solid tissue and some areas of cystic change interspersed among that, you'll note there's often no border around this nodule, yet its margins are somewhat well defined.

Colloid Nodule

Now, a colloid nodule refers to a nodule in which the cellular component is very minimal, and instead we have very large pools of this gelatinous substance.
The colloid, the thyroid hormone is made out of by sonography.
This typically looks like a large hypoechoic area that may have a few echogenic foci within them.
If you look at this echogenic foci, we can see what's called a comet tail or reverberation artifact, and that's a very good sign that we are dealing with colloid and therefore almost certainly a benign colloid cyst.

Spongiform Nodule

Now, another type of nodule that we can describe by sonography is the so-called spongiform nodule.
This is a nodule that's mixed cystic and solid, and it's not as easily recognizable as the colloid cyst because it has more solid elements, but if we look carefully, we can see the same area of increased echogenicity with a small comet tail behind it, representing a smaller island of colloid.
These types of nodules are very common and we want to be careful not to confuse that small echogenic focus with comet tail or reverberation artifact as a small focal calcification.
These are typically benign hyperplastic nodules.

Malignant Thyroid Nodules

Papillary Carcinoma

Now, when we talk about malignant thyroid nodules, the most common type of thyroid malignancy is papillary cancer and that encompasses 70 to 80% of cancers.
These cancers may be pure papillary or they may contain a mixture of follicular cells and papillary cells within them.
The next most common is a pure follicular cancer that comprises 10 to 20% of all thyroid cancers.
The papillary cancers and follicular cancers together are commonly referred to as differentiated thyroid cancer.
Less commonly we have medullary cancer accounting for approximately 10% of all cases.
The rarest is anaplastic carcinoma and also rare is primary thyroid lymphoma.
Under the microscope, papillary carcinoma is characterized by its cellular features and approximately 25 to 50% of tumors will have a psammoma body or a focal calcification.
This is a disease that occurs more commonly in younger patients aged 25 to 30.
It has a female predominance and often there are multiple areas within the thyroid that are affected and approximately one third of cases have bilateral involvement.
There are risk factors for the development of papillary thyroid cancer, including radiation exposure, familial forms, adult polyposis coli syndrome, and Gardner syndrome.
Now on ultrasound, a typical papillary thyroid carcinoma is a solid hypoechoic tumor, often without a capsule and slightly ill-defined margins.
If we look at the ultrasound example here, we can see where as a portion of this large nodule is well defined.
There is an edge here that is very ill-defined and perhaps even infiltrating into the parenchyma.
Calcifications may be seen particularly microcalcifications, which appear as these small echogenic foci often within a solid area of the tumor without shadowing due to their small size and different from the reverberation artifact that we saw earlier.
Some papillary cancers are more sclerosing and infiltrating and are less defined as a mass.
For example. This example here shows an ill-defined somewhat spiculated mass and histology from a different patient.
There are some variants that are predominantly cystic and there are some aggressive cell types that the pathologist can see under the microscope, including tall cell and clear cell variants.
Papillary carcinomas can be a predominantly cystic lesion, but typically they are not a pure cyst.
They contain a solid element that may have calcifications and or vascular flow.
In this example here of a cystic papillary carcinoma, there is a solid component that is heavily calcified and appearing as a crescent.
Within this nodule on gross pathology, we can see a similar finding of a predominantly cystic lesion with a small recess.
These glistening white areas representing calcifications.
Now, mixed follicular and papillary carcinomas may appear slightly different.
There's a tendency for these to be entirely solid and often isoechoic or hyperechoic relative to the thyroid parenchyma.
These lesions may be encapsulated and are typically highly vascular.
They may have a halo, but typically the halo surrounding the nodule is either interrupted or thickened in one area and thin in another.
When we look at the features of papillary carcinoma, there are a variety of things we may see but is nicely summed by this paper by Chan et al in the Journal of Ultrasound of Medicine 2003.
There are some patterns which are the most common in terms of echo texture.
Hypoechoic echogenicity is the most common in terms of consistency.
Solid consistency is the most common, and in terms of margins, there's a slight edge towards a poorly defined margin.
However, we can see that papillary carcinomas, in fact, may have almost every possible sonographic feature.
When we look at the contour, many of them are smoother around a fewer angulated.
The halo is typically absent and just under 50% will have calcifications, and the type of calcification is most commonly microcalcifications.
However, coarse and peripheral calcifications may also be noted.

Follicular Thyroid Tumors

Now, follicular thyroid tumors comprise both the benign adenoma, approximately 80% of the lesions in this category and pure follicular carcinoma approximately 20%.
These tend to be encapsulated tumors and they develop from a monoclonal proliferation of follicular cells.
We cannot differentiate the benign adenoma from the malignant form by using FNA technique, and the reason for this is that the differentiation is not made by the internal architecture or the cellular features, but instead is made by the propensity of the cancers to either invade the capsule of the thyroid or to invade the local blood vessels.
In order to demonstrate this feature, surgical pathology is needed to distinguish these carcinomas.
On the top slide here we can see a follicular carcinoma, colloid proliferation of follicular cells, and we can see this penetrating into the capsule, which is demonstrated here by this pink fibrous tissue.
In the lower slide here we see the fibrous capsule here, the tumor down below, and here we can see the follicular cells invading the adjacent blood vessel.
Now, the follicular adenoma overlaps in appearance with the follicular carcinoma.
It's typically a solid lesion or it may be partially cystic.
If it is undergoing degeneration, it may have variable echogenicity.
It's often quite vascular.
It's less commonly calcified than papillary carcinomas, and it may have a thin halo.
The pure follicular carcinoma is often solid and hyperechoic or isoechoic.
It may have a thick or irregular halo as seen in this particular case, somewhat thicker over here, somewhat thinner or absent in this portion of the tumor, and it may even have calcifications within the rim on gross pathology of a different patient.
We can see this follicular carcinoma portion of the halo and perhaps an infiltrating margin along this side of the lesion.

Medullary Carcinoma

Now, medullary cancers are quite different.
They are typically hypoechoic and unencapsulated.
They're typically smaller when detected about 20 millimeters in size.
Up to 90% of these lesions are in fact calcified.
53% will have coarse often central calcification and 42% will have microcalcifications.
These lesions sometimes come to attention because they have the propensity to produce adenopathy early in their course, and the patients may present with cervical lymphadenopathy not with a palpable thyroid nodule.
Approximately 80% of these are sporadic and 20% occur as hereditary forms often associated with the MEN syndrome.
Type two. Here's an example of a medullary carcinoma and a patient who did present with palpable lymphadenopathy.
There are multiple paracervical lymph nodes identified here, and a 12 millimeter medullary carcinoma was detected on inspection of the thyroid gland.

Anaplastic Carcinoma

The least common type of thyroid cancer is the anaplastic type.
This is typically a very large infiltrating mass with a rapid growth pattern.
These patients come to clinical attention by rapid enlargement of their neck and or airway compromise symptoms.
Here we can see a very large hypoechoic thyroid mass outlined by the yellow arrows and the normal thyroid in the right lobe left behind.
These are more common in elderly patients.

Sonographic Features Indicative of Malignancy

Now, for us as sonographers, one of the questions is can we pick out the cancer using sonographic features from the background of the much more common benign lesions?
So perhaps a thyroid cancer may present itself with some typical features in allowing us to see that this is different and perhaps a bad actor, perhaps the horns in this particular example.
Now, in terms of the sonographic features, we can talk about the size, the sonographic texture.
We can talk about the feature of the margins, the presence or absence of a halo, the presence and type of calcifications, the amount of intralesional, vascularity, and perhaps most importantly, signs of invasion of the adjacent tissue or abnormal lymph nodes at the time of diagnosis.
Here's a 12 millimeter papillary carcinoma.
It's a hypoechoic lesion ill defined.
It has calcifications, but perhaps what's most important that we are able to see that the capsule, the thin white line overlying the surface of the thyroid is interrupted by this lesion, a sign of local invasion.
Additionally, when we look in the lateral compartment of the neck, we can see an abnormal appearing lateral cervical lymph node immediately anterior to the carotid artery, which in fact is a metastasis to the cervical lymph nodes.
Papillary. Thyroid cancer metastasis may be solid and calcified, as in the example I just showed you may be a mixture of cystic and solid areas within a particular lymph node or maybe nearly entirely cystic.
At least 38% of patients have metastasis to the cervical lymph nodes at the time of ultrasound.
Many of these are detectable by sonography.
When patients undergo routine lymphadenectomy at the time of thyroidectomy, the incidence on pathologic review may be quite higher.
In fact, over 80% in some series, the presence of cervical lymphadenopathy will alter the surgery such that at the time of surgery the thyroid will be removed as well as the lateral cervical nodes, but it does not influence the prognosis if only the regional lymph nodes are found to be involved.

Echogenicity

In terms of the sonographic features, let's review some of these and see if they help us to determine which nodules would be more likely to represent a malignancy.
In terms of echogenicity, hypoechoic is a feature that we look for.
The problem however is that although most cancers are hypoechoic, most hypoechoic nodules turn out to be benign because benign nodules far outnumber malignant nodules.
Most hypoechoic nodules are typically benign if they have cystic spaces, but hyperechoic nodules are more likely to be malignant if associated with solid architecture or a thick halo, an isoechoic nodule is indeterminate.
Now here we have two hypoechoic nodules side by side.
On this side of the screen we have a nodule that turned out to be a benign hyperplastic nodule, and on this side a papillary carcinoma.
I think these nodules are very similar in appearance, and in fact it may be hard to just on the basis of hypoechogenicity, predict which one is more likely to be the malignancy.
However, if we look very carefully in the nodule on our right here, we can in fact see some very subtle microcalcifications a feature which would help us other than just the echogenicity of the nodule.
Now, hyperechoic nodules can be thought of as two types.
Those that are uniformly solid such as this one and those that are mixed with small cystic spaces.
The solid and hyperechoic appearance together is more concerning for neoplasm, either a follicular adenoma or a follicular carcinoma, whereas a nodule that has mixed cystic solid elements and or a thin halo is more likely to be benign.

Consistency

In terms of consistency, certainly solid consistency is the most common appearance of thyroid cancer in terms of cystic change, cystic change within a nodule is very common.
Approximately 30% of nodules will have cystic change.
It's a feature more common in benign nodules than malignant nodules.
True cyst of the thyroid are incredibly rare, and most of the lesions that we see that are cystic may have a very, very small solid component difficult to detect by sonography.
However, approximately 6% of papillary cancers are predominantly cystic.
Now, these often have other features other than just cystic composition.
A cystic papillary carcinoma will often have a vascular or calcified solid component.
On the top here we have a very typical hyperplastic nodule that has large islands of colloid.
It has tissue isoechoic to the normal thyroid that is not calcified.
In this lesion down here, which is a mixed solid and cystic papillary carcinoma, we can see that the solid elements of this tumor, in fact have multiple calcifications.
And on color Doppler examination, this nodule was highly vascular.
Now, in predominantly cystic nodules, it may sometimes be difficult to get an adequate FNA.
In fact, the rate of a non-diagnostic FNA can be as high as 50%.
We can use our color doppler analysis here to help us to guide our needle to the areas that are more likely to have cellular tissue in this nodule here that's mixed cystic and solid.
There are a number of gray areas within this nodule potentially representing soft tissue components.
However, when we turn our color doppler on, we can see that this area here does not fill with color.
It may represent hemorrhagic debris, whereas in these areas of the nodule, there is a lot of color flow in the solid elements telling us that this is viable tissue and an area that should be targeted for biopsy.
If there is a consistently, non-diagnostic FNA one should consider the possibility of a cystic neoplasm.
This would be particularly relevant in large cystic nodules, particularly those over three or 3.5 centimeters if we get a bloody aspirate or if the nodule continues to recur after repeated aspirations.
Additionally, the clinical history may be important here, such as a patient with a previous history of radiation may be more suspect than a nodule that is detected incidentally.
Now this particular, slide here will show us how the FNA can be performed when we have a cystic nodule.
Under ultrasound guidance, the needle can be passed into the solid element obtaining cells from that area, avoiding the cystic area, which is typically non-diagnostic.

Calcifications

How about calcifications?
We mentioned before that microcalcifications, these small calcifications less than one millimeter are something that is a high risk for predicting thyroid cancer, but we also know that papillary cancers and medullary cancers, in fact may have coarse calcifications and some follicular and papillary cancers may have rim calcifications.
In general, calcifications are common in both benign and malignant diseases.
They're found in over one third of all thyroids on ultrasound.
However, when we identify calcification in a solitary nodule, that raises the risk to approximately 50 to 70% that that nodule is a malignancy.
Additionally, microcalcifications are a marker of a risk for a malignancy cause that type of calcification is rarely seen in benign nodules.
These microcalcifications are typically very small under two millimeters in size.
They may or may not have distal acoustic shadowing.
They typically are seen in a solid nodule rather than a mixed cystic and solid nodule.
And as we mentioned before, we want to very carefully look for the colloid nodules and these very tiny echogenic foci that have reverberation artifact.
In order to distinguish between the two on our left here, we have a very typical solid hypoechoic infiltrating lesion that has multiple punctate foci without acoustic shadowing, typical of a papillary carcinoma.
On the right here, we have a mixed cystic and solid sort of spongiform nodule that does have an echogenic focus, but we can observe the comet tail artifact indicating that that is most likely a colloid nodule.
We have to be a little bit careful because the presence of colloid does not exclude malignancy.
For example, mixed follicular and papillary and follicular cancers, in fact can have colloid within them.
But rather this point is to distinguish between the presence of a micro calcification versus a small focal echogenic spot within a lesion that may represent colloid.
Now, papillary carcinoma, in fact may be multifocal and it may contain a variety of calcifications.
In this particular patient, we can see two foci of papillary carcinoma.
This with some larger calcifications, this with a mixed population of larger calcifications and microcalcifications.
Sometimes the calcifications may be our only clue this particular patient had underlying chronic lymphocytic thyroiditis or Hashimoto's thyroiditis.
When we look at the gland in cross-section here, we can see that the right lobe of the thyroid has multiple punctate calcifications that are missing on the left.
This is confirmed on the sagittal view of the right lobe as compared with the sagittal view of the left lobe.
This particular patient had an infiltrating type of papillary carcinoma without a discrete lesion.
The presence of asymmetric microcalcifications throughout the right lobe was the clue to the diagnosis.
In this particular case, coarse calcifications larger than two millimeters most commonly with shadowing, as we mentioned before, are common in multinodular glands.
But when seen in a solitary nodule or mixed with microcalcifications is a concerning feature.
This was a solitary nodule that did have microcalcifications as well as large coarse calcifications and was a papillary carcinoma.
This very oddly shaped infiltrating lesion had large coarse calcifications and some small microcalcifications and was also a papillary thyroid carcinoma.
Now, peripheral calcifications may be multiple types.
The thin and regular calcification or so-called eggshell calcification is more commonly seen in benign nodules.
Often these are old hyperplastic nodules that develop dystrophic calcification in the periphery.
However, if we see interrupted peripheral calcification, we want to assess this nodule for other features as this particular feature in fact may be seen in malignancies.
There is a hypoechoic nodule here with interrupted peripheral calcification.
This nodule has an extension through the thyroid capsule to the overlying soft tissue, and this was a papillary thyroid carcinoma.
This is a solid hyperechoic lesion that has interrupted peripheral calcification and an irregular halo and represented a follicular carcinoma.

Margins and Halo

The borders are something we should also look at.
Infiltrating borders are more likely to suggest a cancer than well-defined borders, and again, as we mentioned, the presence or absence of a halo and its characteristics as well as looking at the central vascularity evaluation of the margins is something that is very operator dependent.
The reported sensitivity of this finding in the literature varies from 35 to 86% by nature of trying to use infiltrating margins to detect it underlying carcinoma.
This is an infiltrating carcinoma here with very ill-defined borders, and this is a hypoechoic solid nodule with calcifications with multiple irregular linear extensions into the parenchyma.
Certainly, this type of lesion will be one that would have a very good intra observer variability for the presence of infiltration, but in other cases, this in fact may be quite variable.
Now, a halo may represent one of two things.
A thin and regular halo usually represents compressed blood vessels.
As a nodule is slowly growing and expanding.
It pushes the blood vessels to the side appearing as a hypoechoic thin and regular margin.
This particular feature is noted in between 60 and 86% of benign nodules.
On the other hand, a thick and irregular halo is more suggestive of a neoplasm as it tends to represent a true capsule of the lesion.
Often a follicular lesion, an absent halo has a slight likelihood that the lesion is more likely a malignancy, but does not carry high enough sensitivity or specificity to be used as an independent variable.
Here's an example of a follicular adenoma.
We can see the hypoechoic halo on the side and with color doppler.
In fact, we can see that the halo represents this surrounding rim of vascularity.

Vascularity

Intra nodular flow is something that can be seen in both benign and malignant nodules.
In general, there's a tendency for increased flow within the central aspect of the nodule to correlate with malignancy.
The risk increases to approximately 30 to 40% if a nodule is solid and demonstrates internal vascularity.
However, over 50% of hypervascular nodules will still be benign.

Overall Specificity and Sensitivity of Features

Now, when we look at all of these ultrasound features, how good are we at determining which nodules may or may not be a malignancy of all of the features?
Microcalcifications, as we mentioned before, carries the highest specificity at 90%, but a relatively low sensitivity being present in only 40% of nodules.
The other features such as absence of halo irregular margins, hypoechogenicity at increased nodular flow have varied specificities between 46%, 84%, 49%, and 65% not high enough specificity to differentiate malignant from benign, and similarly, also not high enough sensitivity to capture all malignant nodules.
If we combine features Such as microcalcifications and irregular margins or microcalcifications and hypoechogenicity, in fact, we can increase our specificity, but unfortunately we drop our sensitivity.
This means that if a nodule demonstrates these two features, it increases the likelihood that it is to be a thyroid carcinoma, but unfortunately limits our detection of all carcinomas if we ask for both of those features to be present.

Size Considerations in Thyroid Nodules

Now, the size matter in a nodule, generally nodules over four centimeters in size have a slightly increased risk of being a neoplasm as compared with nodules less small.
This may be, however, a follicular adenoma or a thyroid cancer.
What's more controversial is the lower limits of size.
Most nodules under one centimeter are benign and incidental, particularly when we talk about autopsy series and ultrasound series.
On the other hand, all thyroid cancers at one time arise from a relatively small nodule before growing to a larger detectable size.
So then the question may be for the small size lesion, how clinically significant is it?
Is it likely to have metastasized?
Is it likely to be a clinical problem for that patient?
Well, historically we know that papillary cancers tend to be non-aggressive, one under one centimeter in size, and follicular cancers under 1.5 centimeters in size.
We also know that it's very common to detect very small papillary carcinomas defined as less than one centimeter in size.
These are called micro carcinomas, and these lesions are very commonly incidentally detected in surgical specimens of patients undergoing thyroidectomy or hemithyroidectomy for other nodules.
And in fact, at the time of autopsy, there's been the report in up to 30% of patients may have these small foci of carcinoma in their thyroid gland and likely would not have been of any clinical relevance to that patient.
On the other hand, there have been studies, particularly the study about Papini et al in 2002 that looked at small lesions and the malignant potential in their series.
When they looked at malignant lesions eight to 10 millimeters in size as compared to slightly larger lesions, 11 to 15 millimeters in size, they found an equal likelihood of distant metastasis and invasion, albeit low incidence across both of these groups.
They also very interestingly noted that when they looked at their small nodules, in fact, that the presence of micro calcification, irregular borders and or intranodular vascularity was a much more important predictor of the likelihood of carcinoma than using the nodule size.
They also noted that the likelihood of malignancy was not related to the number of other nodules in the thyroid gland, the ability to palpate the nodule clinically or the echogenicity of the gland.
There were two series which in fact look at these very small thyroid nodules in an effort to see if ultrasound could predict which was more or less likely to be a malignancy.
The first is the Leenhardt paper out of France, which looked at FNA results of approximately 365 nodules in a four to 37 millimeter size.
The median being very small at 12 millimeters detecting 16 cancers.
The other is the Papini paper I just referenced with looked at ultrasound guided FNA of 402 nodules all between eight and 15 millimeters in size, and that group detected 31 carcinomas.
They looked at their data two ways.
The first way was to look that if they had used the size criteria, in other words, of all of the nodules that they had, if they had routinely limited their biopsies to just those bigger or equal to 10 millimeters in the Leenhardt paper or over 10 millimeters in the Papini paper, what have been their yield in the Leenhardt group?
They would've biopsied 286 of the 365 and in the Papini Group 325 out of the 402 patients, they would've detected equal, surprisingly equal numbers of approximately 60% of the cancers and missing approximately 40% of the cancers in their groups.
On the other hand, if they had not used the size criteria but relied only on sonographic features, namely hypoechogenicity and solid echo texture in the first group, and hypoechogenicity combined with either irregular margins increased vascularity or microcalcifications in the second group, they would've in fact limited the number of nodules that they biopsied, however, they would have resulted in a higher yields of carcinoma.
And so both of these authors concluded that in fact, in the small nodule, clearly the sonographic appearance was much more important than any specific size cutoff for the lower threshold of biopsy.

Incidental Detection and Biopsy Recommendations

Now, one of the problems that we as ultrasound physicians come across very commonly is the incidental detection of a thyroid nodule.
In other words, a non palpable nodule that comes to attention because the patient is having imaging ultrasound or perhaps CT MRI of the neck.
It's been a clinical dilemma what to do with these nodules, whereas we know they are very, very common.
We also know that only a small fraction of them will ultimately be a clinically relevant cancer.
So a panel was convened in 2005 to in fact address and come up with some sort of guidelines for this clinical dilemma.
The recommendations were as follows, if a solitary nodule is identified, consider biopsy.
If microcalcifications are present and the nodule is 10 millimeters or larger, consider biopsy if the nodule is solid and or has coarse calcifications if it's 15 millimeters or larger, and consider biopsy if the nodule is cystic and solid or cystic with an identifiable mural nodule a true solid component and over 20 millimeters in size.
So in fact, you can see that these guidelines are based on both our knowledge of the most likely appearance of thyroid carcinoma combined with some clinical relevance in terms of size.
They also mentioned that if a nodule is growing substantially, that nodule should be considered for biopsy, but above all, the group caution that you should apply clinical judgment.
So in other words, if a patient presents with lymphadenopathy or some other feature concerning for malignancy, a biopsy may be indicated regardless of size.

Multinodular Goiter and Multiple Nodules

One other point that I'd like to make is that a multinodular goiter is not the same as a multiple nodule gland.
On the left here we have a true multinodular goiter.
There are multiple sonographically similar mixed cystic and solid nodules without calcifications completely replacing the thyroid parenchyma.
On the right here we have a normal sized thyroid that has more than one nodule, and the multinodular goiter identifying discrete nodules may in fact be difficult and some authors believe a biopsy is not indicated if after sonographic surveillance no nodules with features suspect for malignancy are identified.
Other authors, including the American Thyroid Association guidelines would say to biopsy the largest nodule.
But the issue is that when we have a patient such as this with multiple thyroid nodules, in fact, we have to look in that gland and characterize each nodule reporting its location, its size, and its sonographic features in order to enable the clinical colleagues that work with us to know which nodules, if any within this gland would require a thyroid biopsy.
Now, the risk of cancer is the same for patients with solitary and multiple thyroid nodules.
This particular data has been borne out by a wide variety of papers through the literature.
Early literature seems to indicate that multiplicity of nodules was some way offered a less likelihood of cancer in a particular patient.
Some of those were based on palpable findings, but we know that when we use ultrasound iodine scan or pathology as our arbitrator, we find many, many more nodules when we look.
We can see that when, we subject these patients to FNA by palpation or ultrasound guidance, that there's a similar cancer rate between those patients that have one nodule and those patients that in fact have a multiple, a multinodular gland, across many different studies in the literature.
So the sonographic evaluation of a multinodular gland should be as follows.
We know that the incidence of cancer in patients undergoing FNA is approximately 9.2 to 13%.
We know that it's independent of the number of nodules detected by imaging, and in fact, we know that cancer is present in the non-dominant or not the largest nodule in up to one third of these patients, if not more.
So, our approach to the multinodular gland is somewhat complicated, but in essence what we do is we use the same sonographic criteria that we apply to the solitary nodule gland, to the multinodular gland and biopsy, one or more of those nodules that demonstrate features raising the likelihood for an underlying malignancy.
And although not controversial, and not everyone in the consensus reached the same conclusion, at least in some cases, not a biopsy may not necessarily be needed in patients that have a true multinodular goiter, multiple sonographic similar nodules without any suspicious features.

Selecting Nodules for Biopsy in Multiple Nodule Cases

Now, here's an example of how we can use ultrasound to figure out which nodule to biopsy.
This particular patient was referred for a palpable nodule in the lower pole of the lobe, but on sonographic assessment, a more suspicious nodule, hypoechoic and vascular was seen adjacent to the palpable nodule.
The biopsy strategy was therefore changed to biopsy this nodule first, and in fact, it turned out to be a papillary thyroid carcinoma in a different patient who had a palpable nodule on the left.
Over here, sonographic assessment demonstrated a hypoechoic nodule with ill-defined margins and internal calcifications.
The biopsy was directed not at the palpable abnormality, but at this particular nodule, and that indeed was the papillary thyroid carcinoma.
So if a patient has multiple thyroid nodules that require FNA, we start with the most suspicious nodules first.
We also think that nodules that have sonographic features that are similar to one another can be considered of the same histology and can be followed if not biopsied.
We follow patients with sonography looking for substantial growth.
Substantial growth is another area of somewhat controversial.
We know that benign nodules grow.
We are essentially looking for nodules that have a relatively rapid growth pattern, which can be defined by a variety of patterns.
Most authors use probably at least a 20% increase over a six to 12 month period.

Thank you.