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Fine Needle Aspiration Biopsy in Thyroid Nodules: Patient Selection, Cytology & Indeterminate Results

Author Taylor Spurgeon-Hess covers Fine Needle Aspiration Biopsy in Thyroid Nodules: Patient Selection, Cytology & Indeterminate Results on BackTable ENT

Taylor Spurgeon-Hess • Nov 27, 2021 • 69 hits

While fine needle aspiration (FNA) biopsies provide insight when performing a thyroid nodule workup, understanding the best times to utilize them and what to look for can increase their value tenfold. This article discusses the criteria for which an FNA is indicated, what exactly the cytologist is looking for, and how to proceed if the results come back indeterminate.

This article features excerpts from the BackTable ENT Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.

The BackTable ENT Brief

• As a rule of thumb, Dr. Goldenberg recommends biopsying any suspicious thyroid nodule that is larger than one centimeter.

• Dr. Goldenberg also contends that, despite the potential for indeterminate results, nodules larger than four centimeters should still be biopsied, as the procedure can often provide insight.

• Cytopathologists most often look for papillary thyroid cancer when examining a fine needle aspiration biopsy. To determine the presence of this cancer, a cytopathologist focuses on identifying nuclear inclusions, nuclear grooves, and nuclear enlargement.

• The two common thyroid cancers that fine needle aspiration biopsy cannot diagnose include follicular thyroid cancer and Herthel cell cancer.

• Molecular testing, such as ThyroSeq or Afirma, can provide additional clarity if a biopsy returns with indeterminate results.

Fine needle aspiration biopsy smear showing a papillary carcinoma

Table of Contents

(1) Criteria for Performing a Fine Needle Aspiration Biopsy

(2) Fine Needle Aspiration Cytology

(3) Addressing Indeterminant Fine Needle Aspiration Biopsies

Criteria for Performing a Fine Needle Aspiration Biopsy

Despite its utility, fine needle aspiration cannot be applied to every thyroid nodule case that a physician sees in the clinic. For complicated nodules, members of the care team, including the otolaryngologist, pathologist, and radiologist, often converse on a case-by-case basis to determine whether that specific case warrants an FNA. Dr. Goldenberg recommends biopsying any nodule larger than one centimeter that also presents with suspicious features. While an FNA on larger nodules (4+ cm) may not produce an accurate picture, the procedure’s success depends on the operator.

[Ashley Agan MD]
So, moving on to FNA. What's your criteria for FNA? Does every nodule get an FNA? Is there a size where it maybe it's too small to get? And then how does the work-up proceed from there?

[David Goldenberg MD]
So, no, not everything gets an FNA, and not every nodule is FNA-able. And often we have a conversation with the radiologist, if they're doing the FNA as to whether this is justified or not. And I absolutely encourage a very good working relationship between the otolaryngologist, the pathologist, and the radiologist.
And we have that here, open dialogue, you know, is it why, why not et cetera? So certainly anything larger than a centimeter that has suspicious features, we'll get a fine needle aspiration biopsy. The issue of below centimeters, which is a microcarcinoma. And remember a centimeter is relatively arbitrary.
0.9 is not a centimeter. Is it a microcarcinoma? If there are highly suspicious features, I will have this, undergo fine needle aspiration biopsy. And I know that there is some discrepancy amongst those who say, well, if it's very small, it's not going to do anything anyway. That being said, I'm old enough to have seen many, a microcarcinoma send cervical metastases. So I also, in my neck of the woods, and this is just where I, where I practice, patients are not willing to hear, “Yes, it may be a cancer, but let's just watch it.” They're just not. So typically a centimeter, I guess we have to ask ourselves, what about the opposite side?
Are you going to get a biopsy if it's larger than four centimeters? Because there are those who say that larger than four centimeters, the fine needle aspiration biopsy is, and I quote, “wildly inaccurate.” And I don't agree with that. First of all, your fine needle aspiration biopsies are typically as good as the person doing them.
They are operator dependent and my institution, they're excellent doing this and they can get a nice diagnosis. You throw in molecular testing, it already becomes more accurate. So, I do not believe that the size of a nodule in and of itself is a criteria for surgery, unless it's bothering the patient.
So if you say to me, I feel fullness when I lie down or I have a swallowing difficulty that I believe is attributable to this thyroid nodule, then maybe. If the patient doesn't know about it and it's four and a half centimeters, I'm still gonna send her for a fine needle aspiration biopsy.

[Gopi Shah MD]
And you just made the point of it's operator dependent. So that is why a radiologist, IR, whoever, that does a lot of these, is doing these FNAs. This is not, is this something that ENTs are doing in their clinics?

[David Goldenberg]
Absolutely.

[Gopi Shah MD]
Okay.

[David Goldenberg MD]
And when I had more time, I was doing these in my clinic and, you know, we'd have to do smears and, in my institution it just flows better for them to do, they do pathology and radiology together. And what they have that I don't have is they can take the aspirate and look for adequacy of cells.
And I, I can't do that myself. So in my institution, we found it to be the best in the patient's best interest to do it that way. Certainly, if it's urgent, I have no problem putting a probe on, making smears in clinic, et cetera, et cetera.

Listen to the Full Podcast

Thyroid Nodules with Dr. David Goldenberg on the BackTable ENT Podcast)
Ep 35 Thyroid Nodules with Dr. David Goldenberg
00:00 / 01:04

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Fine Needle Aspiration Cytology

When a cytopathologist analyzes a fine needle aspiration biopsy, they primarily look for papillary thyroid cancer. Other common malignancies include follicular thyroid cancer and Herthel cell cancer, but neither can be diagnosed with FNA biopsy. Generally, if a thyroid nodule is malignant, it is later identified as papillary thyroid cancer. Nuclear enlargement, inclusions, and grooves can lead a cytopathologist to this diagnosis.

[Gopi Shah MD]
And then talking about cytology FNA, what are we looking for?

[David Goldenberg MD]
Typically what the cytopathologist is looking for is papillary thyroid cancer. Now, why do I say that? First of all, the overwhelming majority of these are going to be papillary thyroid cancer, if they're going to be a cancer. Okay? The second, most common follicular thyroid cancer, as well as its cousin Herthel cell cancer, you cannot make the diagnosis by fine needle aspiration biopsy because the criteria that differentiates malignant from benign are invasion of the thyroid capsule, the capsule of the tumor and invasion or invasion of vasculature. And neither of those things can be seen on FNA.
Medullary thyroid cancer. Very rare. I recently had a lady who, you know, she had a biopsy, which was indeterminate and it turned out to be medullary thyroid cancer, so that certainly can happen. And, you know, usually obviously, the more horrific thyroid cancers such as anaplastic and lymphoma are not subtle in their presentation.
But, you know, if we're looking for papillary thyroid cancer, they look for a nuclear inclusions, and nuclear grooves, and nuclear enlargement, that kind of thing.

Addressing Indeterminant Fine Needle Aspiration Biopsies

When a biopsy comes back and the results fall short of a definitive “benign” or “malignant,” a number of possibilities could underlie the root cause. In some instances, the nodule simply may not give up cells to examine, while in other scenarios, the operator may have extracted an insufficient sample. These situations indicate the need for a repeated FNA or a six month follow-up. Conversely, some results return labeled indeterminate, but the physician possesses suspicion for follicular neoplasm. Here, molecular testing often follows as the best course of action.

[Ashley Agan MD]
… When you get your FNA report back, you're going to see, the more straightforward results are usually going to be your benign or malignant, right? And we know that if it's malignant, we start talking about treatment. If it's benign then, you know, and the characteristics fit, then we say, okay, maybe we don't need it.
… It's the indeterminate, the atypia of undetermined significance, you know, things that are in the middle that can be more nuanced in the further management. Can we talk about that a little bit?

[David Goldenberg MD]
That's a really good point because that's a concept that is a little bit more complex to explain to patients. Patients want to know, is it good? Is it bad? Is it cancer? Is it not cancer? So what happens is really interesting. Patients are often referred by an outside physician with a diagnosis of cancer that they don't have.
So I get to tell them, hold on. It's not the chance of this being cancerous 30%. Let's talk about it. Sometimes patients will be sent in and they understand it as “well, it's not cancer, but it's not right anyway.” So I have to go and this is really important to explain to patients. And what I typically say is, “There's about six categories that this could be, two of them are very straightforward. If it's cancer, we'll talk about treatment and you'll be fine. If it's benign, then depending on what it is, you'll either go home and we say goodbye to you or, you'll be watched every year, every two years, or referred to endo or something like that.”
And then we talk about other things. So nondiagnostic, what I tell the patient is sometimes the nodule doesn't give up cells. Okay. And again, it could be operator-dependent, but sometimes it's actually the nodule that doesn't give up.
It happens. And our choices to either watch it or to repeat it, depending on the patient, the specific points of this patient or their ability or inability to sleep at night. Then you come in with the atypia and follicular neoplasm or suspicious for follicular neoplasm. And for the last, ooh, it's gotta be almost a decade, maybe a little less, we've been sending these out for molecular testing.
We use ThyroSeq, and another one is Afirma. Those are the two big boys in town. And what this does is it helps us rule in or out cancer, more accurately than cytopathology alone. And I explained that to the patients. Bethesda V is called suspicious for malignancy.
And theoretically, you can send that out for molecular testing too. In my experience, I have never seen a case that was suspicious for malignancy that was not in fact malignant. And I treat it as such, and I explain this to the patients. We see a lot of thyroids, a lot of thyroid nodules, and we send out a lot of these for molecular testing.
And, in the vast majority of cases, it saves the patient an unnecessary surgery. So before molecular testing, if someone came in with a Hurthle cell neoplasm, the implied risk of malignancy, right, is up to 30%. And I tell the patient, we recommend that you take out half the thyroid gland just to make sure, it's a grand biopsy.
Nowadays, we're doing a lot less than a lot, a lot less than those. Another interesting thing that we've been learning, you know, if someone has a BRAF mutation, we know that they have a thyroid cancer. But now we're learning about co-mutation. So if someone comes in and they have a BRAF mutation together with a TERT mutation, well, you know, not only do they have thyroid cancer, but there's a good chance they have a very aggressive thyroid cancer and you have to speak to them about that and let them know. So, that's a conversation that has to be, you know, like you said, I think Ashley, it is nuanced. It's, you know, it's in the patient's best interest.

[Ashley Agan MD]
Yeah. And I think, you know, another one that I find that can be difficult are, a larger size nodule. So, you know, maybe two to three centimeters and you, you get a benign FNA, and maybe there's some radi, the radiology features for the ultrasound are not perfectly cystic. You know, there's some suspicious features. And then having that conversation with the patient about, you know, are we, do we feel like we got a good enough biopsy to really say this has benign and not worry about it?

Podcast Contributors

Dr. David Goldenberg discusses Thyroid Nodules on the BackTable 35 Podcast

Dr. David Goldenberg

Dr. David Goldenberg is a professor and the chair of the department of otolaryngology - head and neck surgery at Penn State in Hershey, Pennsylvania.

Dr. Ashley Agan discusses Thyroid Nodules on the BackTable 35 Podcast

Dr. Ashley Agan

Dr. Ashley Agan is a practicing ENT and assistant professor at UT Southwestern Medical Center in Dallas, TX.

Dr. Gopi Shah discusses Thyroid Nodules on the BackTable 35 Podcast

Dr. Gopi Shah

Dr. Gopi Shah is a practicing ENT at UT Southwestern Medical Center in Dallas, TX.

Cite This Podcast

BackTable, LLC (Producer). (2021, November 2). Ep. 35 – Thyroid Nodules [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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