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. This is my assistant Clinical Professor of Medicine at UCSF Endocrinology. I pretty much focused on endocrine no pleasure in my current practice. So essentially thyroid, parathyroid, adrenal, different types of, you know, adrenaline, ah deus glioma or rare, you know, endocrine tumors. So, it's my great pleasure to be with the group today and I'm going to present a topic, management of incidental direct nodules. So I will start with disclosure one minute. Okay. So I don't have anything to disclose. Okay. So I will start with some background information. So what is the direct nodule? So it's a discrete lesion within the direct land that is radiological lee distant from the surrounding direct parent heimer. It's a very common clinical problem because direct knowledge is are usually incidentally identify either during a physical exam or imaging studies such as Karadic Dobler's CTMRI or pet CT. When we do a physical exam, you know, about 5% of women and 1% of men can have a probable direct knowledge of during physical exam. Uh if we do ultrasound, ultrasound can detect, you know, direct knowledge is in 19-68% of the randomly selected individuals. And why do we care about direct knowledge als because up to 15% of those direct knowledge is, you know, can be a direct cancer. So then when we see a direct knowledge als, then what is the appropriate evaluation for patients with either clinically detected or incidentally discovered direct nodules? So it's a step boys approach and my presentation, you know, here is mainly based on the American Direct Association Association guideline from 2015. Uh some of this might change maybe later today because they're going to publish a new guideline later this year. But the first for now, the first step would be state of the history and physical exam and then we will do a lab evaluations and then the Comprehensive Direct Ultrasound, then we'll look at the nodules, you know, features in the direct ultrasound to decide if is finally the aspiration biopsy is indicated or not. If we end up doing the finding the aspirations, then we'll have to interpret the f any results. And then the management of the nodules, you know, will depend on the f any results and, and, and, you know, lastly, I will talk about, you know, what do we do about those nodules not meeting the criteria. So the first step is history and physical exam. Um There are a few things in the history, you know, that can predict malignancy, for example, uh you know, childhood had a neck radiation, um total body radiation for the bone marrow transplantation, exposure to organizing radiation, you know, from board out in childhood or adolescence. Usually the radiations it's associated with, you know, certain type of gene fusions, you know, causing direct cancer, especially in the younger individual. When we see a direct cancer, we always ask about, you know, radiation history Or there could be a family or direct cancer syndrome. It's usually accounts for less than 5-10% of all direct cancer. Usually the, you know, these syndromes are like, you know, um one or syndrome or like homage to media syndrome, like Cowden syndrome also have other systemic, you know, manifestation of, you know, the underlying mutations or if you know that there is a history, family history of, you know, direct cancer, especially in the first degree relative. So once 30 look at it and found that, you know, there is a 10-fold increased risk of direct cancer in relatives of direct cancer patients. Another study actually, you know, like give us more detailed information about the incidents ratio of the direct cancer. I didn't put it here, but I can talk about it a little bit if you know, patients have, you know, for example, oh my father or my mother, you know, have uh direct cancer than that individual is about three times higher risk of having authorized cancer. If a sibling has a direct cancer About six fold, you know, increased risk of having a direct cancer. If that sibling is a sister with direct cancer, then, you know, the incidents 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 growth and the patient might tell that, you know, you know, a few years ago, it was just about a small exercise. And now I feel like, you know, it's getting bigger 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 an indication of, you know, barrett cancer invading into recurrent laryngeal nerve. And from physical exam, you know, we always look for cervical lymph latino. But the because, you know, majority of the direct cancer are popularly direct cancer and usually spread to the, you know, survival 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 direct cancer. And the next step, we will um do lab evaluation mainly measuring the direct stimulating hormone TSH. Why we measure the TSH? Because, you know, so far the evidence, you know, point out that the higher the TSH, the higher the risk of malignancy in the direct nodule. Uh For example, you know, in this matter analysis, uh if the TSH is less than 0.4, the prevalence of direct cancer is 2.8. But if you know that individual with a direct knowledge, Ooh have a TSH of more than 5.5, the prevalence of malignancy increased to about almost 30%. But one, the PSH is subnormal which is low, it could be clinical or subclinical hyperthyroidism. And we usually do the iodine scan, you know, to check out if that direct knowledge is hyper functioning or toxic. Um Here, you know, the, you know, the accents here is if the direct nodule is hot or toxic, it is very rarely, you know, cancerous, usually those cold nodules are, you know, cancer. Uh And then if the TSH is normal or elevated, then iodine scan is usually not needed. American Thyroid Association guideline um does not, you know, recommend checking thorough global in or calcitonin in the assessment of the thyroid nodule. And then the next step after the lab is, you know, yes, we probably will need to do a comprehensive neck ultrasound to better characterize the nodule. So it should be performed in all patients with, you know, direct nodule, either discover by physical exam or any incidental lomas, you know, noted in any form of other exam. And the comprehensive neck ultrasound. In the report, it should describe the following. Number one is the direct land size. Uh Number two is direct tissue architecture. Um you know whether it is a homogeneous or heterogeneous. Uh and then all the about the direct nodule, it should describe, you know, uh several things. Number one is three dimensional size of the nodule uh location where it is located. Uh you know, not just only like 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, near the posterior capsule of the far? Right where, you know, recurrent laryngeal nerve is around there and then the composition of the nodule is that solid nodule is a cystic nodule echo Jenness city of the nodule. Is it the nodule looks a little bit darker? Uh does the nodule looks kind of the same like the surrounding direct parent timer? You know all the margins of the nodule is a smooth, regular, irregular, you know, low populated. Uh Do we see any calcifications inside the nodule? Usually calcifications is indicative of the popularity direct cancer shape of the nodule vascular charity of the nodule. And then finally, the cervical lymph node status, you know, do you also see any suspicious lymph nodes in the neck? So the figure here is just essentially showing you the upper one is the normal thyroid gland. You know, I just want to show here the homogeneous architecture when we see a homogeneous architecture in the direct land, this is normal direct land. When we see a heterogeneous architecture. As you can see here, you know, you can uh compare with the normal homogeneous architecture and heterogeneous architecture heterogeneous architecture is the best evidence of autoimmune direct disease or hashimoto direct itis. Sometimes you might say, you know, patient has a negative velocities antibodies. But if the ultrasound is showing the heterogeneous architecture, this patient has autoimmune thyroid itis, you know, even though uh T P O antibody T G antibodies are negative. Next. Uh this is the uh you know, I just also want to mention about the pseudo nodules in hashimoto direct ideas. As you can see here, the direct architecture is so heterogeneous and the heterogeneity is heterogeneous. You know, architecture is mainly due to the lymphocytic infiltrates, you know, uh inside the direct land in those autoimmune disease 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, pseudo nor do the best way to know whether it is a pseudo nodules or not, is to repeat another ultrasound a couple of months because those lymphocytic infiltrates, you know, they don't always stay the same. So if you repeat the ultrasound in a couple of months and the appearance, you know, changes, oh those you know, those things that we feel like they're not real, they're no longer there, you know that those are pseudo nodules. And then the before going to the next step, I want to talk about the F and the F D G Abbott. Now do I'm not sure if you guys can stay see my title like the F N A. Sorry to find me. The aspiration, not finding aspiration F D G, I'll put my screen here. Okay. So F D G added direct incidental Loma. So, uh it is, you know, it can be detected in about 1 to 2% of the patients having uh F D G pet CT. You know, why do we care about the F D G Avid direct incident Aloma? Because approximately one in three or 35% of those FDG avid Foreknowledge Jews are cancer. Um Usually they have higher SUV max, you know, compared to the benign nodule. So, American Direct Association guidelines suggest finally, the aspiration should be done in those F D G avid nodules bigger than one centimeter. Um If we see a diffused F D G uptake inside the direct land, and if we know that, you know, ultrasound appearance is quite heterogeneous and that, you know, autoimmune direct itis and diffuse F D G uptake usually do not require um finding the aspiration unless we're suspecting, you know, direct lymphoma. Here is the figure just showing the, you know, the F D G avid, you know, direct nodules on both lobes of the direct land. And this is the C T correlate if we do the ultrasound, you know, looking at the right nodule, this is the ultrasound appearance. It looks a little bit darker compared to the surrounding, you know, direct baron climber. So I would essentially call this, you know, hypo echoing nodule. And you might be able to see some, you know, a little bit of bright spots inside the direct, you know, uh nodule and those are micro calcification. So it is a little bit, you know, on the high suspicion sites, you know, for direct cancer and definitely need to have needle aspiration done. No, Okay. So the next step is ultrasound, guided, fine needle aspiration. This is the most accurate and cost effective methods for evaluating direct knowledge e1 clinically indicated. So, you know, we decide if F N A is needed based on ultrasound features of the nodule. Here, there are two scoring system available to score the direct nodule to see how suspicious they are. And do they really need fine needle aspiration biopsy. And then American Direct Association guidelines usually has a lower size threshold for fine needle aspiration. But these days, most of the you know, radiologists, they prefer to use the tire its scoring system, you know, to score the direct knowledge e when they report the ultrasound results. So tire it stand for direct imaging reporting and data system. So it does look at different aspects of the direct knowledge. Ooh first is that solid, you know, it is, if it is solid, it's two points. If it is mixed solid and cystic, it's one point you know, kind of something like that here. Echo Jenness City. Uh if the nodule architecture is similar to the surrounding direct tissue. It's so echoing hyper is a little bit, you know, brighter than the normal direct tissue. Usually, we worry more about the hypo eco ick nodules and it usually does go higher here shape taller than wider. I will show an example, you know, in the latest, like taller than white has, you know, more likely to be direct cancer margins. You know, whether it is smooth, ill defined low belated, you know, or sometimes you can see that the nodules border is not well defined and you can see that hypo echoing tissue, you know, going outside the nodule invading the direct and that's the extra direct extension. Eca genic foresight 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 share in previous like contact estrogenic foresee it, you know, scored three points and then we add all these points together that will have the total, you know tyra score. So 10 point tyrants, one is nothing to point, not suspicious. Needle aspiration is not needed. If the the pirates score, you know three points, its tire, it's three mildly suspicious. We do need an aspiration if it is more than bigger than 2.5 centimeter. If the nodules score 4 to 6 points, it's Pirates four, then we will do need an aspiration. If it is bigger than 1.5 centimeter. If the nodule scores more than seven points, its tire, it's five, it's very suspicious and we do need an aspiration when it is bigger than one centimeter. Sometimes one, you know, the the the ultrasound, you know, the radiologist report, the uh the nodule description or the scoring, there could be some, you know, inter personal 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 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, you know, very good radiologist, you know, looking at the 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 this is the American Thyroid Association. Um you know, the direct knowledge ooh risk stratification. Um It is a little bit different than the tyrants as you can see highly suspicious chance of malignancy 70 to 90%. As you can see here, this is a very hypo echo, acknowledge you with a lot of contact, you know, eco genic cozy inside the nodules. Uh This is the hippo echo, acknowledge you the margin is kind of a little bit irregular. Uh This is taller than wider knowledge you 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 wider direct nodule suspicious and it's like growing here here here, right? And intermediate suspicion is essentially Hippo eco Ick solid direct nodule. So, American Thyroid Association guideline, if we use those 88 guidelines, you know, if we see a solid hypo echo, acknowledge you bigger than one centimeter, you can biopsy, you know, but if you go by the tire, it's, you know, pirates might say you probably need to wait til 1.5 centimeter, you know, to biopsy. It depends on like what other clinical risk factors, you know, does the patient have like family history? You know, I recently had the patients very strong family history of thyroid cancer in different, you know, members. Um the nodule size is 99 millimeter. It's not one centimeter yet it looks suspicious, you know, do we biopsy? I did, you know it's nine millimeter, it's almost one centimeter. Family history is very strong and patient is going to get pregnant soon. So she wants to get things, you know, figure out before planning for the pregnancy. So low here, low suspicions. I so eco ick nodules, you know, risk of malignancy 10% 80 S A biopsy if it is bigger than 1.5 centimeter, you know, spongy form and the benign biopsy is, you know, rarely needed here, 80 S D say, you know, maybe two centimeter biopsy. But in real clinical practice, When we see a spongy form, nor do you know, we don't usually 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 epiphany results, right? We use protest a reporting system to report if any results. So essentially it's six category but as the one non diagnostic test to it's benign, no Jew. But as the three and four, we see some, you know, atypical cells but were not able to tell whether it is benign or malignant. So it's indeterminate but there's the five very suspicious for malignancy. But esta six, we're sure it is malignant. So then the management, you know, depends on what is the f any results. So I will start with batista, one non diagnostic or unsatisfactory. So it's usually we can see this in up to 15 or 16% of all F ed a sample. It's just that, you know, we don't get a representative sample and there is no enough cellular materials, you know, in the psychology specimen to give the diagnosis. So if that's the scenario, then we should repeat, you know, FNA as the next step. Let's say we do it again. 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 f any two times non diagnostic, then you know, yeah, we can discuss about surgery, you know, for diagnostic lumpectomy or if the patients already have you no other risk factors. Or you know, when you repeat the ultrasound, the nodule increase in size here, the point is the, you know, excellence is increase in size in two dimensions. You know, when we report the ultrasound that 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 you know, surveillance. This is, you know, usually the type of, you know, f and a result we end up reviewing with the radiologist, 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, but as that one non diagnostic, but we see a lot of core Lloyd materials in the slide, even though we don't see a lot of cells called like material is um you know, 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 case that we usually bring up to our psycho pathologists, you know, to review. The second step is the second one is the benign nodule. So if the, if any result is benign, then what do we do? If it is benign, then you know, the next step depends on the, you know how suspicious it is. If it is quite suspicious, then repeat the F N A and the ultra ultrasound and the F in a in a 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 with a minimal increase of at least two millimeter or 50% increase in the volume, then that's the time we repeat another F and A. Sometimes we, you know the scenario we see is we have a patient benign nodule proven by F and a five 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 dimensions, you know the size increase. If it is, you know, in two dimensions, at least two millimeter increase in size, then we should do another needle aspiration. If the nodules are very low suspicions in the ultrasound pattern, then we might just do the f in a needle. Um, ultrasound again, you know, in over two years, if the nodule is already benign twice, we're done, you know, no ultrasound surveillance is needed to assess malignancy risk if the nodules, yes, they are benign, but they are growing slowly then. Yeah, we should still do the, you know, uh, ultrasound, you know, serially, maybe like everyone, everyone to two 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, for example, bigger than four centimeter or if they're already causing the compressive symptoms, for example, close, closer to the trickier 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 cases, I would jump to better stuff. Five and six malignant psychology. What do we do surgery? But if those tumors are less than one centimeter, probably we can do the active surveillance, you know, in selected, you know, cases, for example, yeah, it is a small direct cancer less than one centimeter, no nodal involvement, no other risk factors. We can safely do the surveillance and I can just share the this one here. So this is the study published last year by Memorial Sloan Group, you know, in New York, they look at those um small direct cancer less than one centimeter. We call popularity direct micro carcinoma surveillance over five years of a five years period. And as you can see, 80% of them, our stay stable with the surveillance and only a minority of, you know, patients require, you know, surgery and they identified six different growth patterns. But here I, I want to point out that, you know, majority of the patients are quite stable um during the ultrasound follow up. And then because there were three and four indeterminate psychology, 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, molecular tests which are widely available these days. You know, the most commonly used tests are a farmer Diro seek here at UCSF. We use um tiro sick, you know, to predict the malignant risk. Uh if molecular testing is not available, what do we do? We probably have to repeat after me 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 in determining nodules are likely benign and the 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 and and rust mutations, mutations, then here they will predict the risk of malignancy, it's 90%. Then we should, you know, do surgery in those cases. How about those nodules not meeting the f any 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 A T A 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 bomb. No, Jew cyst, you might want to do ultrasound in, you know, over two years. But this has been also like depends on the patients. You know, if patient is anxious about the nodules, then yeah, we might repeat ultrasound in two years, but essentially spongiform nodule insist, you know, they are rarely, rarely cancer. The chance of being cancer is less than 3%. So we don't, if you don't offer ultrasound, that's also okay, not do less than one centimeter spongiform or says no follow up is needed. Um Our practice here at UCSF, we're, you know, a big group. We have parapsychologist, us, radiologists, dedicated ultrasound technician. We have dedicated my rights to bust cycle pathologists 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 decision making. We have our thyroid tumor board to discuss the case direct path conference to review the psychopathology. We also have the, you know, post clinic direct conference and then Nuclear Medicine conference, you know, to review different imaging. Um So if you have a direct knowledge of patients, please feel free to refer to us for further evaluation. And I will take questions.