A lump on the thyroid is a common finding in both physical exams and imaging studies, but the significance varies greatly. This talk from endocrinologist Myat Han Soe, MD, MS, lays out the process of evaluation, covering essentials of the patient history, lab tests, elements of a comprehensive ultrasound exam, and how to know whether a fine needle aspirate – the most accurate way to check malignancy – is warranted. He also decodes the classification systems used in pathology reports and offers guidance on monitoring, including for lumps considered benign.
Good morning, everyone. Uh, this is Meet. I'm an assistant clinical professor of medicine at UCSF endocrinology. I, uh, pretty much, uh, focus on, uh, endocrine neoplasia, uh, in my, uh, current practice. So essentially thyroid, uh, parathyroid, you know, uh, adrenal, different types of, you know, adrenal nodules, pheochromocytoma, paraganglioma, or rare, you know, endocrine tumors. So, uh, it's my great pleasure, uh, to be with the group today, and I'm going to present the topic, uh, management of incidental direct nodules. So I will start with, um, Disclosure. 01 minute. OK. So I don't have anything to, uh, disclose. OK. So I will start with some background information. So, uh, what is the thyroid nodule? So it's a discrete lesion, uh, within the thyroid gland that is radiologically distant from the surrounding thyroid parenchyma. It's a very common clinical problem because thyroid nodules are usually incidentally identified either during a physical exam or imaging studies such as carotid Dopplers, CT MRI, or PET CT. Uh, when we do a physical exam, you know, about 5% of women and 1% of men can have a palpable thyroid nodule during physical exam. Uh, if we do an ultrasound, uh, ultrasound can detect, you know, thyroid nodules in 19 to 68% of the randomly selected individuals. And why do we care about thyroid nodules? Because up to 15% of those thyroid nodules, you know, can be thyroid cancer. So then uh when we see a thyroid nodules, then what is the appropriate evaluation for patients with either clinically detected or incidentally discovered thyroid nodules? So it's a stepwise approach and my presentation, you know, here is mainly based on the American Dir Association, Association guideline from 2015. Uh, some of this might change maybe later today, uh, because they're going to publish a new guideline later this year. Uh, but the first, uh, for now, the first step would be state of the history and physical exam, and then we will do, uh, lab evaluation, and then the comprehensive thyroid ultrasound. Then we'll look at the nodules, you know, features in the thyroid ultrasound to decide if FNA is a fine needle aspiration, uh, biopsy is indicated or not. Uh, if we end up doing the fine needle aspirations, then we'll have to interpret the, uh, FNA, uh, results. And then the management of the nodules, you know, will depend on the uh FNA results. And, and, and, you know, lastly, I will talk about, you know, what do we do about those nodules not meeting the FNA criteria. So the first step is the history and physical exam. Um, there are a few things in the history, you know, that can predict, uh, malignancy. For example, uh, you know, childhood, head and neck, uh, radiation. Um, total body radiation for the bone marrow transplantation, uh, exposure to ionizing radiation, you know, from out in childhood or adolescence, uh, usually the radiation is associated with, you know, certain type of, uh, gene fusions, you know, causing, um, thyroid cancer, especially in the younger individual. When we see a thyroid cancer, we always ask about, you know, radiation, um, history. Or there could be a family of thyroid cancer syndrome. It usually accounts for less than 5 to 10% of all thyroid cancer. Uh, usually the, you know, these syndromes are like, you know, um, Warner syndrome or like Hamattomata syndrome, like Hawden syndrome, uh, also have other systemic, you know, manifestation of, you know, uh, the, the, the underlying mutations. Or if, you know, that, uh, there is a family history of, you know, thyroid cancer, especially in the first-degree relative. So one study looked at it and found that, you know, there is a tenfold increased risk of thyroid cancer in relatives of thyroid cancer patients. Uh, another study actually, you know, like give us more detailed information about the incidence ratio of the thyroid cancer. I didn't put it here, but I can talk about it a little bit. If, uh, you know, uh, patients have, you know, for example, oh, my father or my mother, you know, have, uh, uh, thyroid cancer, then that individual is about 3 times higher risk of having a thyroid cancer. If a sibling has a thyroid cancer, Uh, about sixfold, you know, increased risk of having a thyroid cancer. If that sibling is a sister with thyroid cancer, then, you know, the incidence ratio increased to about 11, you know, so it's like much higher. And then another thing we can tell from the history is, you know, rapid nodular growth, and the patient might tell that, you know, oh, you know, a few years ago, it was just about a small egg size, and now I feel like, you know, it's getting bigger, um, over time. And the worst thing is the hoarseness of voice. If the patient has, you know, persistent hoarseness of voice, uh, that could be, uh, indication of, you know, thyroid cancer invading into, uh, recurrent laryngeal nerve. And from physical exam, you know, we always, uh, look for cervical lymphadenopathy. Uh, because, you know, majority of the thyroid cancer are papillary thyroid cancer and usually spread to the, you know, cervical lymph nodes in the neck or the physicians of the nodule to the surrounding tissue or vocal cord paralysis. So these are the warning signs of the, um, of thyroid cancer. And the next step, uh, we will, um, do lab evaluation, uh, mainly measuring the thyroid stimulating hormone TSH. Uh, why we measure the TSH, uh, because, you know, so far the evidence, you know, point out that the higher the TSH, the higher the risk of malignancy in a thyroid nodule. Uh, for example, you know, in this, uh, meta-analysis, uh, if the TSH is less than 0.4, the prevalence of thyroid cancer is 2.8. But if, you know, that individual with the thyroid nodule have a TSH of more than 5.5, the prevalence of malignancy increased to about almost 30%. Uh, but one, the TSH is subnormal, which is low, uh, it could be a clinical or subclinical hyperthyroidism, and we usually do the, uh, iodine scan, you know, to check out if that thyroid nodule is hyperfunctioning or toxic. Um, here, you know, the, the, uh, you know, the, the essence here is if the thyroid nodule is hot or toxic. It is very rarely, you know, cancerous. Uh, Usually those core nodules are, you know, uh, cancer, uh, and then if the TSH is normal or elevated, then iodine scan is usually not needed. Uh, American Thyroid Association guideline, um, does not, you know, recommend, uh, checking thyroglobulin or calcitonin in the assessment of the thyroid nodule. And then the next step after the lab is, you know, yes, we probably, we will need to do a comprehensive, uh, neck ultrasound to, uh, better characterize the, uh, nodule. So it should be performed in all patients with, you know, thyroid nodule either discovered uh by physical exam or any incidentalloma, you know, noted in any form of, uh, other exam. And the comprehensive neck ultrasound in the report, it should describe The following. Number 1 is the thyroid gland size. Uh, number 2 is thyroid tissue architecture, um, you know, whether it is uh homogeneous or heterogeneous. Uh, and then all the, uh, above the thyroid nodule, it should describe, you know, uh, uh, several things. Number 1 is 3-dimensional size of the nodule. Uh, location, where it is located, uh, you know, not just only like, oh, right side, left side, you know, is it located close to the trachea? Is it located close to the esophagus, or is it located, you know, uh, near the posterior capsule of the thyroid where, you know, recurrent laryngeal nerve is around there? And then the composition of the nodule, is that solid nodule, is a cystic nodule, echogenicity of the nodule, is it the nodule looks a little bit darker, does the nodule look kind of the same like the surrounding thyroid parenchymer, you know, all the margins of the nodule, is it smooth, regular, irregular, you know, lobulated. Uh, do we see any calcifications, uh, inside the nodule? Usually, calcification is, uh, indicative of, uh, papillary thyroid cancer. Uh, shape of the nodule, vascularity of the nodule, and then finally, the cervical lymph node status, you know, do you also see any suspicious lymph nodes, you know, in the neck? So, the figure here is just essentially showing, you know, the upper one is the normal thyroid gland, you know, I just want to show here the homogeneous. Uh, architecture. When we see a homogeneous architecture, uh, in the thyroid gland, this is normal thyroid gland. When we see a heterogeneous architecture, as you can see here, you know, you can, uh, uh, compare with the normal, uh, homogeneous architecture and heterogeneous architecture. Heterogeneous architecture is the best evidence of autoimmune thyroid disease or Hashimoto's thyroiditis. Sometimes you might say, you know, uh, patient has a negative thyroid peroxidase antibodies, but if the ultrasound is showing the heterogeneous architecture, this patient has autoimmune thyroiditis, you know, even though, uh, the TPO antibody, TG antibodies are negative. Oh, next, uh, this is the, uh, you know, I just also want to mention about the pseudonodules in Hashimoto thyroiditis. As you can see here, the thyroid architecture is so heterogeneous, and the heterogeneity is heterogeneous, uh, you know, architecture is mainly due to the lymphocytic infiltrate, you know, uh, uh, inside the thyroid gland in those autoimmune thyroiditis patients. So because of those lymphocytic infiltrates, you know, the architecture become heterogeneous, sometimes they can assume the appearance of a nodule, and we call it, you know, pseudonodule. Uh, the best way to know whether it is a pseudonodules or not is to repeat another ultrasound in. A couple of months because those lymphocytic infiltrates, you know, they don't always stay the same. So if you repeat an ultrasound in a couple of months and the appearance, you know, changes, oh, you know, those things that we feel like they are nodules, they're no longer there, you know, that, those are pseudonodules. And then the, uh, before going to the next step, I want to um talk about the uh FN uh the FDG ABI nodule. I'm not sure if you guys can see, see my title. Like the FNA. Sorry, the fine needle, uh, aspiration, no, I I need aspiration, FDG. I'll put my screen here. OK. So FDG avid thyroid incidentalloma. So, uh, it is, uh, you know, it can be detected in about 1 to 2% of the patients, uh, having, uh, uh, FDG PET CT. Um, you know, why do we care about the FDG avid thyroid incidentalloma? Because approximately 1 in 3 or 35% of those FDG avid thyroid nodules are cancer. Um, usually they have higher, uh, SUV max, you know, compared to the benign nodule. So American Thyroid Association guidelines suggest fine needle aspiration should be done in those FDG avid nodules bigger than 1 centimeter. Um, if we see a diffuse FDG uptake inside the thyroid gland, and if we know that, you know, uh, ultrasound appearance is quite heterogeneous and that, you know, autoimmune thyroiditis and diffuse FDG uptake usually do not require, um, uh, fine needle aspiration unless we're suspecting, you know, thyroid lymphoma. Uh, here is the, uh, figure just showing the, you know, the FDGFI, you know, thyroid nodules on both lobes of the thyroid gland, and this is the CT, uh, correlate. If we do the ultrasound, you know, looking at the, uh, right, uh, nodule, this is the ultrasound appearance. It looks a little bit darker compared to the, uh, surrounding, you know, thyroid parenchyma. So I would essentially call this, you know, hypoechoic nodule. And you might be able to see some, you know, a little bit of uh bright spots, uh, inside the, uh, thyroid, you know, uh, uh, nodule, and those are microcalcifications. So it is a little bit, you know, uh, on the high suspicion side, you know, for thyroid cancer and definitely need to have needle aspiration done. OK, so the next step is um ultrasound-guided uh fine needle aspiration. Uh, this is the most accurate and cost-effective method for evaluating thyroid nodule, one clinically indicated. So, uh, you know, we decide if FNA is needed, uh, based on ultrasound features of the nodule. Um, here, there are two scoring systems available to score the thyroid nodules to see how suspicious they are and do they really need a fine needle aspiration, uh, biopsy. And then American Thyroid Association guideline usually has a lower size threshold for fine needle aspiration. But these days, most of the, you know, uh, radiologists, they prefer to use the, uh, TED scoring system, you know, to score the thyroid nodule when they report the ultrasound, uh, results. So TRAD stands for thyroid imaging, Reporting and Data System. So it does look at uh different aspects of the thyroid nodule. Uh, first, is it solid? Uh, you know, uh, it is, uh, if it is solid, it's 2 points. If it is mixed solid and cystic, it's 1 point, you know, kind of something like that here, echogenicity, uh, if the nodule architecture is similar to the surrounding thyroid tissue, it's isoechoic, hyper is a little bit, you know, uh, uh, brighter than the normal thyroid tissue. Uh, usually, we worry more about the hypoechoic, uh, nodules, and it usually they score higher here. Shape, taller than wider. Uh, I, I will show an example, you know, in the, uh, later slide, taller than white. Uh, has, uh, you know, more likely to be thyroid cancer margins, you know, whether it is smooth, ill-defined, lobulated, you know, or sometimes you can see that the nodule's border is not well defined and you can see that hypoechoic tissue, you know, going outside the nodule invading the thyroid, and that's the extrathyroidal extension. Uh, echogenic foci essentially implies calcifications, and there are different types of calcification with, you know, different scoring, and the one we worry more is the one I just shared in previous slide, Ponte cal echogenic foci. It, you know, scored 3 points, and then if we add all these points together, then we'll have the total, you know, TED score. So 10 points, Tyret 1 is nothing, 2 points, not suspicious, and neither aspiration is not needed. If the Pyret score, uh, you know, 3 points, it's Pyret 3, mildly suspicious. We do need an aspiration if it is more than, uh, bigger than 2.5 centimeters. If the nodule score 4 to 6 points, it's yret 4, then we will do need an aspiration if it is bigger than uh 1.5 centimeter. Uh, if the nodule scores more than 7 points, it's tyre 5. It's very suspicious and we do need an aspiration when it is bigger than 1 centimeter. Sometimes when, you know, the, uh, uh, the ultrasound, you know, the radiologist report the, uh, uh, the, the nodule description or the scoring. Uh, there could be some, you know, interpersonal, uh, you know, variability or variation reporting. So that's why, you know, when we see the patients here in our clinic, you know, we always, uh, review the ultrasound images, you know, ourselves. If it is the outside referral, we always request the ultrasound images, you know, to send. To us, not just only the report so that we can take a look at it ourselves. If we cannot decide ourselves, we bring it to our radiology, you know, like we have, uh, uh, you know, very good, uh, radiologist, you know, uh, looking at the thyroid ultrasound and usually we ask, you know, advice for them like, hey, can you take a look and let us know, you know, what you think. Uh, this is the American Thyroid Association, um, you know, the thyroid nodule risk stratification. Um, it is a little bit different than the, uh, thyroid, as you can see, highly suspicious chance of malignancy, 70 to 90%. As you can see here, this is a very hypoechoic nodule with a lot of, uh, puntate, you know, uh, ecogenic foci inside the nodules. Uh, this is the hypoechoic nodule. The margin is kind of a little bit irregular. Uh, this is taller than wider nodule, and you can see the border is less clear here. It might, you know, start invading into the nearby structure. This is again, you know, um, taller than a wider thyroid nodule, suspicious, and it's like growing here, here, here, right? And intermediate suspicion is essentially hypoechoic um solid thyroid nodule. So American Thyroid Association guideline, if we use those ATA guidelines, you know, if we see a solid. Hypoechoic nodule, bigger than 1 centimeter, you can biopsy. You know, but if you go by the pirates, you know, pirates might say, uh, you probably need to wait till 1.5 centimeter, you know, to biopsy. It depends on like what other clinical risk factors, you know, uh, does the patient have like family history. You know, I recently had a patient, a very strong family history of thyroid cancer in different, you know, members. Um, the nodule size is 99 millimeter. It's not 1 centimeter yet. It looks suspicious, you know. Do we biopsy? I did. You know, it's 9 millimeter. It's almost 1 centimeter. Family history is very strong and the patient is going to get pregnant soon, so she wants to get things, you know, figured out before planning for the pregnancy. So, um, low here, low suspicion, isoechoic nodules, you know, risk of malignancy, 10% ATHA biopsy if it is bigger than 1.5 centimeter, you know, uh, spongy form and the benign, uh, biopsy is, you know, rarely needed. Here ATH they say, you know, maybe 2 centimeter biopsy, but in real clinical practice. Uh, when we see a spongiform nodule, you know, we don't usually, uh, biopsy because the chance of malignancy is less than, you know, 3%. And then we look at the, uh, if we do the needle aspiration, then we have to report the FNA results, right? We use Badesta reporting system to report FNA results. So essentially it's 6 category, Badesta 1, non-diagnostic. Badesta 2, it's benign nodule, Badesta 3 and 4, we see some, you know, atypical cells, but we're not able to tell whether it is benign or malignant, so it's indeterminate. Uh, Badesta 5, very suspicious for malignancy. Uh, Badesta 6, we're sure it is malignant. So then the, uh, management, you know, depends on, uh, what is the FNA result. So I will start with, uh, Podesta 1, non-diagnostic or unsatisfactory. So it usually we can see this in up to 15 or 16% of all FNA sample. It's just that, you know, we don't get the representative sample and there is not enough cellular materials, you know, in the cytology specimen to give the diagnosis. So if that's the scenario, then we should repeat, um, you know, FNA as the next step. Let's say we do it again. Uh, if it is still non-diagnostic, what do we do? Then it depends on the ultrasound features of the nodule. So if the nodule is very suspicious looking, uh, FNA 2 times, uh, non-diagnostic, uh, then, you know, yeah, we can discuss about surgery, you know, for diagnostic lopectomy. Or if the patients already have, you know, other risk factors. Or, you know, when you repeat the ultrasound, the nodule increase in size. Here, the point is, uh, the, the, you know, essence is increase in size in two dimensions. You know, when we report the ultrasound, the, the nodule is given as three dimensional, like for example, 1.5 into 1.2 into 1.1 centimeter. We need to see the increase in size in at least two dimensions or at least 20%. Um, if the patient does not have any, you know, high-risk ultrasound features, then we may just continue the, um, um, you know, surveillance. Uh, this is, you know, usually the type of, you know, FNA result we end up reviewing with the radiologist, uh, not the pathologist. Sometimes the pathologist might say that, you know, yes, the, you know, if we look at the cells, we don't have enough cellular material in the specimen, so, you know, probably we might say it's, uh, but there's that one non-diagnostic, but we see a lot of colloid materials in the slide. Even though we don't see a lot of cells, co-like material is, um, you know, uh, indicator of benign nodule. So then they might just report it as benign even though they don't see enough, you know, cells, and these are the cases that we usually bring up to our cytopathologists, you know, to, uh, review. Uh, the second step is, the 2nd 1 is the benign nodule. So if the FNA result is benign, then what do we do? Uh, if it is benign, then, you know, uh, the next step depends on the, uh, you know, how suspicious it is. If it is quite suspicious, then repeat the FNA and the ultrasound and the FNA in 1 year. If it is not that suspicious, then we repeat the ultrasound in 1 to 2 years. Again, if size increases by more than 20% in two dimensions, uh, with a minimal increase of at least 2 millimeters or 50% increase in the volume, then that's the time we repeat another FNA. Sometimes we But, you know, the scenario we see is we have a, a patient's benign nodule proven by FNA. 5 years later, the nodule grow a little bit. We always look at the three-dimensional size. Is that just in one dimension or more than one dimension, you know, the size increase. If it is, you know, uh, uh, in two dimensions, at least 2 millimeter increase in size, then we should do another needle, uh, aspiration. Uh, if the nodules are very low suspicion in the ultrasound pattern, then we might just do the FNA, uh, the needle aspirate, um, ultrasound again, you know, in over 2 years. Uh, if the nodule is already benign twice, we're done, you know, no ultrasound surveillance is needed to assess malignancy risk. Uh, if the nodules are, uh, yes, they are benign, but they are growing slowly, then, yeah, we should still do the, you know, uh, uh, ultrasound, you know, serially, maybe like every 1, every 1 to 2 years, you know, something like that. Uh, do we do surgery for the benign nodule? Uh, the answer is yes. If the benign nodules are big, uh, for example, bigger than 4 centimeters, or if they're already causing the, uh, compressive symptoms. For example, closer to the trachea with breathing difficulties, closer to the esophagus with, you know, the swallowing difficulties, um, stuff like that, then we can suggest, you know, surgery in those, uh, cases. I would jump to Bethesda 5 and 6. Uh, malignant cytology, what do we do? Surgery. But if those tumors are less than 1 centimeter, probably we can do the active surveillance, you know, in selected, you know, cases. For example, yeah, it is a small thyroid cancer, less than 1 centimeter, no nodal involvement, no other risk factors. Uh, we can safely do the surveillance, and I can just share this one here. So this is the um study published last year by Memorial Sloan Group, you know, in New York. They look at those um small thyroid cancer, less than 1 centimeter, we call it papillary thyroid microcarcinoma, surveillance um over 5 years of, uh, 5 year period, and as you can see, 80% of them. are still stable with the surveillance and only a minority of, you know, patients uh require, you know, surgery and they identified 6 different growth patterns, but here I do, I want to point out that, you know, majority of the patients are quite stable, uh, um, during the ultrasound, uh, follow-up. And then Baster 3 and 4 in determining cytology, uh, we don't know what they are. We're not able to say whether it is benign or malignant. Then the next step is, you know, uh, molecular tests, uh, which are widely available, um, these days, uh, you know, um, the, the most commonly used tests are a farmer thyrosik. Here at UCSF we use, um, thyrosik, uh, you know, to predict the uh malignant risk. Uh, if molecular testing is not available, what do we do? We probably have to repeat FNA again and to see if we can get a more diagnostic, you know, results. Um, PET CT is not recommended. This is just the results of the molecular testing, how it is reported. If nothing is found, no mutations, nothing, you know, found in the molecular test, then those indeterminate nodules are likely benign and their risk of cancer is very low and we can safely monitor them, you know, over time. If the molecular testing come back with some mutations like NRAS mutation, TARD mutations, then here they will predict the risk of malignancy, uh, it's 90%, then we should, you know, um, do surgery in those cases. Uh, how about those nodules not meeting the FNA criteria? Uh, if they are suspicious looking, then we repeat ultrasound in 6 to 12 months. If they're not that suspicious looking, then repeat ultrasound in 1 to 2 years. Um, you know, here this is the ATA say, but we don't necessarily do it, you know, in the real practice. They say, oh, it's a very suspicious ultrasound pattern, including the spongy bo nodule cyst. You might want to do ultrasound in, you know, over 2 years. But this is also like depends on the patients, you know, if the patient is uh anxious about the nodules, then yeah, we might repeat ultrasound in 2 years, but essentially, spongy bone nodule and cyst, you know, they are rarely, rarely cancer. Uh, the chance of being cancer is less than 3%, so we don't, if you don't offer ultrasound, that's also OK. Nodule less than 1 centimeter, spongy form or cyst, no follow-up is needed. Um, our practice here at UCSF, uh, we're, you know, a, a big group. Uh, we have thyroidologists, us, radiologists, dedicated ultrasound technician, we have dedicated thyroid psychopathologists and endocrine surgeons. We usually walk in the multidisciplinary approach, you know, reviewing those, uh, complicated or complex, you know, case to come to a collaborative, you know, decision making. We have our thyroid tumor board to discuss the case, thyroid path conference to review the cytopathology. Uh, we also have the, you know, post-clinic thyroid conference, and then nuclear medicine conference, you know, to review different, uh, imaging. Um, So, uh, if you have a thyroid nodule patient, uh, please, uh, feel free to, uh, refer to us for further, um, evaluations, and I will take, uh, questions.
