Welcome to the master clinician session very creatively entitled thyroid nodule, whack it, zap it, or leave it alone. I'm Mike Tuttle from Memorial Sloan Kettering Cancer Center, where I do thyroid cancer work primarily and then occasionally a thyroid nodule, but you're very fortunate that we have a wonderful panel with us today who actually knows about thyroid nodules. So my job is to ask questions and they will tell us about thyroid nodules. It's going to be an exciting session. We're going to have Dr. Ghaznavi present cases to the panel. And then both Sana and I will ask the panelists questions. We obviously can't cover everything, but we're going to try to cover. Probably the most common questions we get asked if we were actually seeing each other at the endocrine society meeting. So I'm going to ask my panelists just to have a word or two to introduce themselves. So everybody knows who we are. And then we'll get started. Dr. Ghaznavi. Hey, good afternoon, everyone. So my name is Sana Ghaznavi. I'm an endocrinologist at the University of Calgary that treats thyroid nodules and thyroid cancer. And I'm going to be your case presenter today. Yes. And I am Chenning Liu. I'm an endocrinologist at the University of California, San Francisco. My clinical interests are thyroid neoplasia, endocrine neoplasia. It's a great honor and pleasure to be here with my esteemed colleagues. Hi, I'm Mary Fradies. I'm a radiologist at Brigham and Women's Hospital in Boston and Harvard Medical School and a co-author of the ACR Thyrads Classification System. Hello, I'm Mario Stan. I'm a clinical endocrinologist in Rochester, Minnesota at Mayo Clinic. And my interest as it pertains to this session is ablative therapies for thyroid nodules. And I'm Julianne Sosa. I'm an endocrine surgeon at UCSF. And I have the privilege of serving as co-chair of the ATA Guidelines Writing Committee for Adult Patients with Differentiated Thyroid Cancer. Thanks for having me. That's awesome. Fantastic. And we'll try to see if we can sneak some previews of the guidelines out of Dr. Sosa, unless she's sworn to secrecy. But the rest of us will try to get that out of there. All right, Dr. Ghaznavi, let's get started. Show your slides and let's talk about the first case. All right, so it is time to play. Whack it, zap it, or leave it alone. Here's our first case. A 68-year-old man had incidental discovery of a thyroid nodule on carotid ultrasound done for workup of TIA. He denies a personal history of head or neck radiation or a family history of thyroid cancer. And his investigations show a TSH at the low end of normal at 0.22. Here's his neck ultrasound, which we can see shows a 2.7 by 2.0 by 1.2 centimeter left midpole nodule, which is characterized as being solid and hypoechoic. So with that, it's time to play our first round of whack it, zap it, or leave it alone. Okay, Dr. Stan, why did Dr. Ghaznavi put a TSH on there? I thought this was all about nodules and Dr. Frady's telling someone to biopsy or not biopsy. How does that TSH affect how you're thinking about this now? So outside of Memorial Sloan-Kettering, benign nodules, toxic nodules do occur. And I mean, it's interesting that she also gave us an age of 68. And as we know, the TSH doesn't tend to go down, but rather slowly goes up with age. So I'm intrigued when I see a TSH below 0.5, even below one, I would say in six, seven, eight decades, somewhere there, it's got to be a bit suspicious. And Dr. Liu, how does that change how you think about it before we come to the ultrasound here? I mean, in terms of your sort of pathway of how you're going to evaluate this nodule? I mean, when in the evaluation of a thyroid nodule in the setting of a low TSH, and obviously, the first thing come to my mind is, this is autonomously functioning nodule. Especially with the size of the nodule, I think, you know, if it is one centimeter or less, I think that is unlikely, but we're talking about 2.7 centimeter nodule. Yeah. And Dr. Freides, it's always unfair to have a radiologist read a single slide on a PowerPoint. That's impossible. But can you tell us a little bit about when you see a 2.7 centimeter nodule, what are you looking for? I mean, do you really use tirads or do you use something else? Give us a feel for that. Well, I think all of the imaging guidelines or all of the guidelines that look at ultrasound use the same worrisome characteristics for nodules that put our antenna up that this one might be a cancer. And if we look at the ACR tirad system, we'd say this is a solid nodule, and it is hypoechoic, but it has smooth margins. It's not taller than wide, and we don't see any calcification. So we would rank this as four points. So a TR4, that's a moderately suspicious nodule. We recommend a biopsy of anything over 1.5 centimeters in this category. And I think the ATA guidelines would recommend a biopsy for anything over one centimeter in this category. The thing to remember is that this appearance is the most sensitive appearance for a thyroid cancer, but the least specific appearance for a thyroid cancer. And to show you how few nodules I see, hypoechoic means what? Relative to what? I mean, we see that on all the reports. What does it really mean? We look at echogenicity in relationship to the surrounding thyroid gland. So whoever's got control of the pointer can just show the posterior margin of the nodule and compare it to the brighter or whiter or more echogenic normal thyroid gland behind. And then you can look at the echo texture of the nodule itself and compare it to the strap muscles. And if it is darker than the strap muscles, and this is pretty equal to or maybe a little lighter to, again, I only have the one image. If it's darker, that would count as a very hypoechoic nodule, which would increase your suspicion. It would give you one more point, but you'd still land in the same category for biopsy. Gotcha. Dr. Sosa, are we done with this case? I mean, this is a relatively young man, close to my age. TSH is kind of low. It's three centimeters. We're not really going to leave a three centimeter nodule in there, right? You just take him to surgery, right? Is that where we're going? Maybe five or 10 years ago, that might have been the correct answer. You know, I think more and more, we are taking a thoughtful approach and have come to the appreciation that we, A, are over-diagnosing issues, and then as a sequela of that, I think, over-treating them. And I would say that even at high-volume centers where I have the luxury of practicing, we've come to understand that many, in fact, most nodules can remain in. And to take out a nodule, you really have to meet three criteria, suspicion for or diagnosis of cancer, hyperthyroidism, and the patient has expressed preference for a surgical strategy to treat it, or three, symptoms of compression. Very good. Okay, Dr. Gosnell, tell us a little bit more about the case now. Okay, so based on a TIRAD score of TR4, this was biopsied, and the cytology was found to be benign, and so a surveillance approach or a monitoring approach was taken. Twelve months later, the TSH is now 0.12, previously 0.22, so it's drifting down in this 68-year-old gentleman. His neck ultrasound now shows a 3.1 centimeter by 2.4 by 2.0 centimeter nodule, which means there's been an increase in volume greater than 50%. And there's still no other high-risk features like calcifications, for example, or specific extra-thyroidal extensions someone had mentioned in the chat box, whether that was the case or not. So now we're watching this nodule, and what do we want to do with this? It's a growing nodule, and the TSH is drifting downward, so do we need a repeat biopsy? Is there any role for molecular diagnostic testing here or any other diagnostic tests? Let me start with Dr. Freides. Did this really grow, Dr. Freides? We used to talk about 3-centimeter nodules. Now we're talking about volume. How do I know when one of these things grows? Well, this is tough. Some places use volume. Some places use an increase in the longest dimension. I think we don't have a set pattern at the Brigham. I can't say we follow any of those rules. I think that we personally are inclined to repeat the FNA if we think that it's a real increase in size, basically depending on the patient's age. So as you get older and older, we may be more inclined to watch. Oftentimes, we'll ask the patients, are they anxious about the nodule, or will we just watch them again in another six months or nine months and see if it continues to grow? The growth itself is hard to give you a hard and fast rule because there isn't any literature that supports what a correct increase in size is. And then the one thing I would also mention is sometimes if you look at the prior ultrasounds, you can see that the nodule really hasn't grown that much over a year or five years. And sometimes it's technical where the edges of the nodule are measured. So it's not quite as straightforward as we'd like it to be. Right. Dr. Sosa? Yeah, so I'm just picking up on what Dr. Frady said. I think at UCSF, you know, we would want to build in two things. One is understanding the preference of the patient. And I would give the overlay of not only that he is 68, but it's a man. And so in the setting of thyroid nodules in men, there's always a slightly greater index of suspicion for cancer than if it were to be a woman. But the other is, I think this patient probably at UCSF would have another biopsy, and that might be to inform the next decision, which is potentially, are you going to treat with radioactive iodine, ablate, or do surgery? You might want to exclude a diagnosis of a malignancy before offering the portfolio of options. So, Dr. Liu, we've had about 25 out of 24 comments say, why not do a radioactive iodine scan? Where are we keeping down this nodule thing? So let's answer 23 questions all at one time. What do you think, Dr. Liu? Well, I would have done the iodine scan at the very beginning when you presented, and this is also consistent with American Thyroid Association guidelines as well. I would have done that. But now I have time, right? We have time, and this nodule has grown a lot more faster than I expected. And so I will probably stick a needle in there as well, because this is a 68-year-old man growing nodule faster than I would expect it, just to make sure that this nodule has not acquired new mutations or something like that. Okay, Dr. Ghaznavi, because rumor has it you probably did a scan. So let's show the scan, and then we'll ask Dr. Stan what the heck to do with this now. Okay, so this patient actually preferred monitoring, didn't want to have a repeat biopsy. TSH is 0.08. The neck ultrasound shows a nodule which continues to grow, and now complaining of some nonspecific swallowing difficulties. So we've got our thyroid scan, which about 25 people have asked for, flow volume lubes, and a CT of the neck, and lastly, an esophagram. Dr. Stan, where do we go from here? We have a lot of beautiful evidence here to tell us how this nodule is not only changing, but functioning and dealing with the structures around it in a manner that it's quite threatening, even in the short term, not necessarily just long term. So if we start at the bottom left where we see the centigram there, we're seeing a very nice uptake of the iodine left lower part of the thyroid lobe, which fits, if I recall, the ultrasound positioning of this nodule. And then I imagine that the PFTs with that inspiratory flow volume loop were done because there might have been concerns about reduced ventilatory capacity, and it's nice to see. I'm moving my pointer, but I'm sure Sarna can move her pointer as well, to the bottom part of that curve below the X line, and that is a flat inspiratory curve as opposed to a nice dome, which tells us there is very likely an extratoracic compression on the trachea. And that is fitting with what we're seeing on that nice CT slice, and we're seeing the trachea displaced to the right, and actually flattening of the tracheal wall to the left, very nicely abutting the large nodule. And then, needless to say, the esophagogram shows that the esophagus doesn't like this presence, and it's chewed up on that barium column, and it's trickling down, as we can see. And on top of this, the TSH is going into a dangerous territory. We know that TSH is below 0.5, increase the risk of atrial fibrillation. I do think we need to add, and if you want, I can expand on those options, but I'll let you lead, Mike. Yeah, let me pause for just a second. Julia, why is this not a surgical thing? Well, I'm just baffled at how you got all this testing done. At UCSF, we would have never been able to get the esophagram, and we probably wouldn't have gotten those flow volume loops. You have a patient with a hot nodule and symptoms of compression, and that probably would have arrested the diagnostics and moved us to a discussion of what management we want to take. Exactly. So, Julianne, if he was interested in a surgery, and I'll tell you in a second he's not going to be, but if he was interested in a surgery, what would you tell him about the surgery and what would you do? Yeah, so when it comes to surgery, I think a couple things. One is I'd want to understand the clinical presentation of this patient. So he has biochemical evidence for hyperthyroid. Is he clinically hyperthyroid? And obviously here, does he need to be blocked or prepared for surgery? I think secondly, making sure that the contralateral lobe, the right lobe, is bland. If it is, and if he is clinically thyroid, and my endocrinology colleague, because we're managing this patient in a trans-departmental fashion, does or does not believe antithyroid drugs or blockade are needed, we'd be considering a lobe. Possible total, we always consent patients for both, even when the intention is just to do lobectomy. Okay. Let's end this slideshow for just a minute. Dr. Stan, radioactive iodine, ablative therapies, what options do we have if he's not interested in a surgery, or even if he is, what are the alternatives? I think we have now expanded the spectrum of options for this group of patients. And radioactive iodine certainly is a bit more specific in its action than a lobectomy. And we expect many of these patients to remain uteroid after radioactive iodine. But the reality is that we still see probably about a third of them developing hypothyroidism. And it depends on how we handle that TSH around the time of administering radioactive iodine. These last few years, we've been focusing on the idea of being very specific with ablative therapies. And I think there's encouraging data, mainly from outside of the U.S., but our data also suggests that radiofrequency ablation is quite a useful tool for such nodules. And particularly if the ultrasound has a very good visualization, and it's an isolated lesion, and we don't have other concerning elements about anticoagulation status and things alike. So, I think RFA, when I'm talking about ablative therapies, I'm not thinking alcohol here. I'm thinking radiofrequency ablation. So, RFA has a very good outcome, both volume, so addressing compressive symptoms, but also function. And in our cases, we had 90% restoration of normal thyroid function. Okay, very good. Dr. Lu? Yeah, I actually have a question for Dr. Stan. I don't have experience with RFA. Are you not concerned about the initial swelling or edema that can be associated with the procedure causing more mass effects? So, we have not seen in these nodules increased swelling. And in contrast to what we're doing for small papillary thyroid cancers, where we would go outside of the nodule to have a thorough ablation, here we leave a rim of about three to five millimeters at the periphery of the nodule. So, the volume at the end does not end up being a larger volume with RFA for benign nodules. But you are right, if we were to talk about a complete ablation of a malignancy, that leads to an initial increase in size. That doesn't happen as we're looking at a benign lesion. Okay, so there's lots of things we can talk about this case, but we're going to do some highlights on some different cases. So, let's move to another case. I think this is a papillary microcarcinoma case, Dr. Gosnavi. Let's see case number two here. Perfect, okay. So, you're assessing a 35-year-old woman with a left 9-millimeter thyroid nodule. She's got a past history of Hashimoto's and has been on thyroid hormone replacement since age 12. The patient reports increasing fatigue, prompting her primary care doc to order a neck ultrasound. And here are the images. So, we've got a 35-year-old with a 9-millimeter nodule in the left lower pole. And it's time to play whack it, zap it, or leave it alone. Perfect. Dr. Freedes, imagine in your worst nightmare, you were actually working with me. And you know I love to watch lots of these little papillary microcarcinomas. So, knowing my bent is toward observation, when you're looking at these ultrasounds, what are you looking for to sort of help me understand who mainly would not be a good candidate for observation? How do you think about that? Yeah, that was a curveball. I wasn't expecting that. Sorry. You know, it's interesting. We actually have several patients with even biopsy-proven microscopic papillary carcinomas who have chosen to just observe their cancers. And so, we have several of those patients now that we're following as well. And I think I might have been one of them. So, sonographically, when we meet these patients, you're looking for any characteristics that would suggest that this was a more aggressive cancer. That management of observation might not be the best decision. And that would be looking at the surface of the gland, and whether the anterior surface or even is intact, and whether the malignancy has broken through. When you particularly want to pay attention to the relationship with the trachea on that transverse picture, because sometimes you can see that these small cancers are invading the trachea. And then certainly, we do an exam for adenopathy in all patients. So, a patient with extensive adenopathy might color you more towards surgery rather than watching them. But for the most part, we know that patients with subcentimeter thyroid cancers do not have a worse outcome if they are watched than if they go directly to surgery. Dr. Sosa, how do you think about these? Obviously, patients sent to you are sent to get a surgery most of the time. But if they're interested in an observation program, what are the thought process you go through to decide, is this a good person or not a good person? How do you think about that? Yeah. So, as you know, Mike, in the last round of the ETA guidelines, we opened the door for the first time to permit active surveillance for these tiny tumors with the introduction of the word if, if surgery is chosen. Otherwise, a thyroid lobectomy is the prevailing surgical strategy, except in some exceptional circumstances. I've sort of evolved my thinking around these tiny tumors. And the scenario you have presented us with, fortunately, doesn't happen so much anymore because we don't put a needle into tiny nodules like this. And so we follow them without having to know this weighty idea that it's a papillary thyroid cancer. But for me, a big issue is patient preference, but compliance. And when I practiced in North Carolina, where there was a large population of rural indigent and underinsured, a big concern was the patient comes, the patient leaves, and you may never see that patient again. And then you can't truly actively surveil. So one thing I would underline to people considering active surveillance as an option is assurance that not only is the patient comfortable with this, but also can they comply with your recommendations. Let's stop the slide share for me. Dr. Liu, how are we thinking about this in San Francisco? Patients there may be different than North Carolina, than the Upper East Side where I practice. What are you guys thinking about this now? You know, Julianne has joined us, so she's now in San Francisco as well. So we have a wide range of patient populations. We get referrals from many hours away from San Francisco. And I agree with Dr. Jimmy and Sosa that the patient, we have to consider, are they able to follow up in their preference as well? And we do see a wide range of patient population. They're rich, they're educated, they're very socially disadvantaged. Yeah. Dr. Stan, how does this age? I mean, she's 35 years old. How does that sort of play into how you're thinking about this? I think it makes a big difference in that if we're proposing surveillance, I think that we're looking at decades here, potentially. And it troubles me that here I'm a bit of a disagreement with the guidelines. We do agree that even a highly suspicious nodule is not 100% malignancy. So we end up embarking on a road which includes anxiety for at least 20% of patients that probably need zero further monitoring if we could say this is a benign nine millimeter nodule that looks suspicious on ultrasound, granted. But cytology answers that question. So I'm a little bit ambivalent about following without cytology. Particularly in a young person. I like to answer that question. So I'm not that forceful in proposing observation for a nine millimeter if it looks suspicious. I would like to answer it. Gotcha. Dr. Susan? Just want to make sure that folks in the audience know the data. And, you know, probably Dr. Tuttle and his team are assembling data in the United States actively. But probably the largest body still is from Japan. And if you follow over decades patients with these tiny tumors with surveillance, what we know is that young age is an independent predictor of progression. But even then, there is time for rescue in the overwhelming majority of cases without any deleterious effect on survival and outcome. And the numbers are 8% at a decade for enlargement of the tumor and less than 4% with the development of lateral compartment nodal metastasis. So just so you know the data to support whatever stance you take. And if I could add, Mike, just to fill the picture there, as Julianne knows very well, the team in Japan had biopsies on all these individuals that went through their decades long of follow up. So that's skewing probably to a much higher risk. Those are all known PTCs to begin with. Yeah, your point's well taken. Years ago when we started this, I told a patient, based on the ultrasound and everything, there was a 95% chance it was cancer and I wanted to watch. And she looked at me and said, well, that means there's a 5% it's not cancer, right? To which I said, I don't like you very much, but yes, do the biopsy. So, and she was right nonetheless. Julianne, what do you think about following, you know, without these highly suspicious nodules without a biopsy? You know, the issue of missing a medullary and the issue, the Japanese always talk about compliance may not be as good if they don't know it's a thyroid cancer. How do you really do that? Well, you know, it's like, are you going to follow thyroid's recommendations, you know, or not? Like you subscribe or you're not. And it's a slippery slope when you don't. I would say, you know, the patients we see at UCSF being perfectly candid, usually come from outside with a diagnosis. The diagnosis has been made because somebody put a needle in it. And so we're in this scenario. But I think the question is, are we going to be chasing all of these tiny tumors for these exceptional cases? I don't know, you know, I don't know. This is a very interesting and important question. Yeah, I mean, it's certainly an evolving time, right? I think the way Julianne put it, we've opened the door to active surveillance. And now is the tough part. Years ago, I think it was Drew Ridge, a famous surgeon, said he would be in favor of me doing active surveillance if I would agree to eventually do inactive surveillance. At some point, where do we get these guys off the highway? I mean, are we really going to follow them for 100 years? And honestly, even if we do a lobectomy on them, we end up following them for a long time, right? It's a challenge to know how to follow these folks up. Two questions that came in on the things, and this is for anybody. Any role of molecular testing in picking out which nodules to watch or not watch? Julianne, I'll go to you. Any role of molecular testing in that? Well, I mean, if you have a TURK mutation in this tiny tumor, it conceivably might change what we are going to do. And I think ultimately, and here I don't want to riff on a tangent, but I think the way we stage patients today is quite frankly arcane and antiquated. Using tumor nodal metastatic criteria in a time when we can actually elaborately and fastidiously describe the molecular profile of tumors to allow us to personalize what we're doing. I think that's the future of staging. And ultimately, I'd like to see a world where we take AJCC-UICC staging and mold it together with a molecular profile to ultimately say what we should do for this patient versus that patient. So, yeah, I do think that's a good idea. I agree, Julianne. Let me ask two questions and we'll move on. One, first to Dr. Stan. Any role for ablative therapies of any sort for these small tumors now or in the future? And then, Dr. Liu, any role for what TSH goals should be? Would you do suppression or not? Dr. Stan first, then Dr. Liu. Ablative therapy would come if we have obviously evidence that we're dealing with malignancy here. And I think in that setting, if we were to go back to the slide and look at the position of this lesion, it would be easier to decide does it apply or not. Ablative therapy is not for everything. And I should clarify for the broader audience, PTCs treated with RFA are not a routine, even outside of the U.S. But if we select these lesions properly, just recently, I think a couple of months ago, we had a very nice five-year follow-up on RFA for micro PTC with excellent results. And it's typically the lesion that you would consider for surveillance rather than something that sits right on the trachea or stretches the capsule towards posterior, mainly posterior. That's a worrisome location. Yep. Dr. Liu? Yeah. Yes. in terms of TSH suppression, I don't think we have enough data to support TSH suppression. Although physiologically speaking, it makes sense. So I would definitely, if a patient is willing to take some thioforma, I would probably keep TSH on the low side. But again, no data to support what I do. Yeah, so I mean, I think we've brought up a lot of the really difficult issues in this active surveillance. Like most of us agree, there are some patients that would probably benefit from active surveillance. But knowing exactly who they are based on ultrasound, based on their personal characteristics, as Julie mentioned, based on the medical team characteristics and who's doing your ultrasound, I think that's really the challenge to really implementing this widespread right now. But that'll be good information in the future. All right, Dr. Ghaznavi, let's jump to case number three. Take me to number three. All right, okay. So case three, a 54 year old woman had discovery of a large palpable fibroid nodule during a massage. She has no risk factors for thyroid cancer. She works as a university professor in mathematics and her investigations are as follows. So this is her ultrasound. Her TSH is normal at 1.88. The ultrasound shows a left 3.4 by 2.0 by 2.4 centimeters solid hypoechoic nodule. And the cytology shows an indeterminate cytology of Ausflus or Bethesda 3. And now she's wondering what does that mean and what do I do about it? Okay, go back one for me, Sana. Go back one to that last slide. Dr. Freedes, in this space of Bethesda 3, is there anything you guys can do on the ultrasound to kind of help us know which one is risk stratifying more likely or less likely to be cancer or is it just all the same? Any help you can give us? No, I wish I could, but I really don't think that basically sonographically this is a low risk nodule. This fits into the same category as the other ones we've seen so far. It's solid, it's hypoechoic, although it's approaching isoechoic. Again, no calcifications. It looks like a follicular lesion sonographically, and nothing that's highly worrisome about the nodule. But despite the fact that it looks sort of encapsulated as far as we can tell, we still don't know whether it's a benign adenoma, follicular variant, we just can't tell from this, right? Right, capsule doesn't help us. The presence or absence of a capsule will not help you, sonographically will not help you determine what the eventual pathology is gonna be. And in addition, it's interesting, if you put color on this image, you might find that that's not actually a capsule, it's a vessel surrounding the edge of the, or the margin of the lesion. And so there's a lot of overlap between what a vessel looks like and what a true capsule is. And from, I mean, that's interesting. So what would that mean to me as a clinician, if you told me it was a vessel versus a capsule, Dr. Frady, so just a description? It's simply a description, and that's why the presence or absence of a quote unquote capsule in the report is not, has never been shown to be a useful differentiating characteristic. That's great. I'm glad I'm attending this session. Dr. Stan, people come to the Mayo Clinic for an answer. They had this biopsy in New York, and they said those stupid New Yorkers couldn't tell me what it is. I'm flying and driving and taking a mule to the Mayo Clinic. What are you gonna tell them when they get there? As soon as they take their cross-country skis off to make it to us, we talk about where's the specimen. And basically what I'm getting to, whenever we're seeing that, particularly the AUS, I think it's quite important to get those slides reviewed, and there are centers of expertise across the country, but there are many cytopathologists that have to deal with a very broad number of specimens, and they might not have the ability to be very comfortable with the occasional AUS. So I think it's very important before we embark on management to have another pair of eyes, or maybe a few, look at those slides, and if the slides are not to be found, then consider a repeat biopsy. That's where I would start. So if you get two different answers, do you pick the one that you like, or do you do a tiebreaker? But everybody always says have them re-read, but my guys are no... So what do I do? So I think I would take the most expert opinion, but if that happens to be somehow upgrading, obviously I would follow that lead. If that expert opinion downgrades this to say, no, it looks benign, I would probably be in favor of observing this lesion, but with a closer follow-up. Okay, let's stop the slides, Sharon. Let's go back to San Francisco. Dr. Liu, they're now seeing you. They've done a lot of reading on Dr. Google about molecular testing, and they have six different ones they want to do, including next-generation sequencing, because we've never seen a test we think is too expensive at Memorial. What do you tell them about molecular testing in this sort of setting? Well, I think there are only three that are commercially available. There may be research protocols, but there are three available, and I can tell them there's a formal gene sequencing, the Thiraseq V3, and also CyGEN Thiramir. Those are commercially available. Which one to pick is really institutional. At UCSF, in more recent years, we have relied mostly on Thiraseq, and so you can take your pick. The root out, the negative protein value is pretty good for all three of them. Dr. Sosa, you're seeing that this is a 54-year-old person with a three-and-a-half-centimeter nodule. Is the molecular testing going to change what you do? If it comes back saying low suspicion or benign or whatever language they do, are you really going to watch this? And how does that sort of play into whether or not you do molecular testing to help you? I think it's always an interplay, right? And it's not just changing what I'm going to do, and I really have to emphasize this. I think the frame is changing in approach to, in particular, indeterminate thyroid nodules, but also, and I think we're going to come to this, extent of surgery where, if ultimately we have evidential equipoise, patient preference, so what the patient wants to do is more in play, and sort of that's the way I've started to frame it, where you have a discussion where you can continue active surveillance. They have to comply with that and be comfortable with ambiguity, where you can use as an adjunct molecular testing. Personally, I like that, but understand that it is imperfect, versus surgery where you convert the situation to a black and white world. This is what it is, and this is what it isn't. And in the end, I think patient preference is what pushes you down one of the pathways. I do deploy molecular testing. In situations like this, because I think it tells us about the appropriateness of surveillance, and if you choose a surgical strategy, the extensive surgery that you're considering. Yeah, I think that's right. I often frame this discussion by starting saying, we're going to choose between two right answers here. People always want to right no wrong, right? What's the right, what's the wrong thing? But very often, if I start this by saying, we're going to choose between two right answers based on everything that I've seen, and in the next 30 minutes, let's figure out what's the right, best answer for you, right? My opinion, your opinion. Dr. Stan, go ahead. Yeah, I want to add to this conversation that since all these molecular tests are going to set us back, in our experience, it's about two weeks. Maybe you guys are faster, but I have that discussion up front. Do we understand the kind of numbers that we're going to deal with? We're not talking about 100% and 0%. We're talking about moving the needle more towards one end or the other. So I have that conversation, and if they are comfortable with a negative predictive value of 95, 98%, then let's use the test. Granted, it'll be two weeks from now that we'll have that answer. And if they are looking for 100%, then I'm going to explain to them that the test is not going to get us there. And I think that conversation, particularly given cost and delays, in my mind, it's best before we do the test rather than after we have results. Dr. Sosa? And I saw a comment in the chat, which I think was said in the best of intentions, academic physicians don't live in the real world. And I think, and I actually appreciate this point. And I think the other thing at play is the practice setting in which you are working, right? So if you only have access to inexperienced surgeons, and let's face it, more than half of thyroidectomies done in the United States today are done by someone who does one a year, then your threshold for recommending surgery is going to be much higher than if you have seven high volume surgeons to choose from. Similarly, if you have access only to endocrinologists who are very uncomfortable with active surveillance and whose focus of practice is something very different, then you might choose a different pathway. So I do think that's the other thing. What is your practice milieu? And who are the members of this team? And if the members are right to support one of these strategies, then frankly, I think it becomes a less attractive one. So Dr. Liu, help me out here. It turns out Dr. Ghaznavi did do molecular testing and it was negative. So you got negative results back. You've got a 54-year-old with a three and a half centimeter nodule. That patient's comfortable watching because that's why we went down. They're comfortable with knowing it's not perfect, but the molecular testing has made it much less likely to be cancer. What's your follow-up look like now? Well, I think this patient probably can be followed as if they had benign FNA results. I definitely, I mean, you know, molecular testing as we know, they're not 100%, right? Because of the bigger size, I may pick a six months versus a 12 months follow-up. And once I know it's stable, then I can extend out to say, you know, once every one to two years, that kind of protocol. Yeah, and Dr. Freedies, go ahead, please. I was just gonna say that so far, one of the things that's been unique about the cases presented here is that we've been, the presentation has been with a patient with a solitary nodule. And we haven't seen the rest of the gland in any of these cases. But even if we have a nodule that has both a benign FNA or a non-malignant FNA and then negative genetic testing, there's still six nodules on the other side that the patient is gonna end up coming back for and getting relooked at. So it's nice to have a benign testing on one nodule, but you're not really getting them off the hook for most patients. I mean, the majority of patients that come in have more than one nodule. And when you do follow-ups on these, Dr. Freedies, I mean, when you do your report, often it says follow-up suggested. Is there a timeframe for, is it two months? Is it six months? Is it, what do we do? That's so funny because I never tell people when to follow their patients. I, as a consultant, think that you, as the person who's taking care of the patient, has a much better concept of when the correct follow-up time is for you and your relationship with that patient. It's not for me, unless I'm seeing something like a DVT that's a different problem. So I never recommend follow-up with thyroids, but if you are gonna follow them most for, if we're a little concerned or there are a lot of nodules, we'll talk nine to 12 months. Otherwise, certainly after a benign FNA, we talk to 24 months, 18 to 24 months, and then we push them out to 24 to 36 and try to get people sort of off the hook for coming for closer and closer follow-up. Then I'll just add, we have a large pediatric population as well, and we tend to watch them once a year because we're not quite sure what's gonna happen as they go, as kids go through puberty and they often are in because they're high risk or they have a family history. And in folks like that, you might go with the, we go with the one-year follow-up. But in your typical benign older person, we're pushing it to 12 to 18 months and then two years and then longer. Which is good. It's getting us away from this every six months. Dr. Sosa? My computer is rebooting and I cannot make this up right now. What was the question? It's my favorite part about your computer. I think it's software, I can't make this up. Your computer just raised your hand so you wanted to say something, so I'll just. It's amazing, 911, help, I'm upgrading my Firefox. You know, when you're in the operating room and something falls apart, you're not supposed to admit that, Dr. Sosa. You're supposed to, straight face, nothing. This is the way it's supposed to work. This is awesome. We're cool. Perfect. Well, that's a great. I have no question, I'm cool. That's a great segue. So I think on that one, it really was a nice example of these. Bethesda III are still a problem. Understanding with the patient what their values are, what they would tolerate before you do a bunch of fancy testing, to know if that would actually change either their decision-making or your decision-making, which is a great thing. And certainly these molecular testings are helping us in the appropriate patients that would sort of sway them one way or the other. Okay, Dr. Gosnabi, let's go to the last one. And I think we're going to finally get into the argument that will not end. It's 13 hours. Well, awesome. That was good. So in, yes, that had to be Dr. Sosling again. It's my favorite. It's always the surgeons that are getting attention here. So let's talk about the last thing, this argument that will not end. In 1990, when I started my fellowship, every good thyroid cancer meeting was just lobectomy or total thyroidectomy. We've come full circle. So we're back to that now. Let's talk about that. Go ahead, Dr. Gosnabi. Okay, so for our last case, we've got a 42-year-old professional singer presented to her primary care doc with a history of a dry cough for the last two months. On physical exam, she had discovery of a palpable, around three centimeter, thyroid nodule. She's otherwise a healthy woman. She has no risk factors for thyroid cancer. Her TSH is normal, 2.62. On the neck, ultrasound was performed. I'll show you the images on the next slide, and showed a 3.2 centimeter, once again, solid hypoechoic nodule on the left lower pole and no other high-risk features. And the contralateral lobe has two tiny nodules, which are only two and four millimeters. So she undergoes a fine needle aspiration biopsy of the dominant lesion, and malignant cells are present, consistent with papillary thyroid cancer. The last thing I want to point out is a complete sonographic lymph node exam was performed and revealed no lymphadenopathy in the neck. Okay, so no lying to me on this one, because I share patients with every one of you guys, and I know what you do. So, Dr. Freides, Dr. Ghaznavi mentioned about sort of lymph node exam. So a standard thyroid ultrasound that I'd order, neck ultrasound, what does that encompass in your opinion? So there's two different things to remember. One is, what did the guidelines say is the definition of a complete thyroid ultrasound, what did the society guidelines indicate, and what do we do in my practice? So the guidelines currently as written for head and neck ultrasound, and this is the joint guideline supported by the AIUM and the ACR and the SRU, state that evaluation of adenopathy in the neck should be performed when appropriate. At my institution, we perform an evaluation of neck nodes in every patient who comes for a thyroid ultrasound. And by neck nodes, I mean from the clavicle to two thirds of the way up at the neck on both sides, and in the superior mediastinum and the midline upper neck. When we do that for every patient who comes for a thyroid ultrasound, regardless of whether they're coming with a suspicious nodule or with just a palpable mass or with pain, regardless. Other places I know we had an endocrinologist who just arrived who, after her patient got her full thyroid ultrasound, sent her back for the lymph node study because where she came from in a very large academic center in the Southern United States, they did not do lymph node studies as part of their standard ultrasound. So it's really important, as we've said earlier, to know what your imaging centers are doing and not to assume that they've looked unless they specifically tell you there's no adenopathy. Very good. Let's stop the slide sharing and we'll pretend like we don't know who that endocrinologist was. Dr. Liu, 3.2 centimeter final aspiration that's positive. You seriously got to think about a lobectomy? Honestly, come on. Well, it is an option, right? It is an option. And this is, it will take, you know, in the past, it would be total thyroid ducting, radioactive biometry, but now you're spending 30 minutes to discuss options. And because there's no lymph nodes on ultrasound, I think that requires some discussion and I'm comfortable if she were to take lobectomy only. Yes, I think that's an option. Perfect. I think this is a great debate. Dr. Stan, I don't care what you really believe. Make the case that she absolutely has to have a total thyroidectomy. And then we'll come back to Dr. Liu. I don't care what you really believe. Make the case that lobectomy is her only option. Dr. Stan, make the case for total thyroidectomy. Okay. So when she was a child, she had- I just, I don't want to interrupt, but I love this. You just did. We have endocrinologists arguing about extensive surgery. I love this. Yeah, and then we'll give you tips on how to follow the nerve here in just a minute. Give us a second, Julianne. Dr. Stan, make the case. As long as the check is in the mail, then I'll argue in favor of total thyroidectomy. There you go. So this will bring up the history of Hodgkin's lymphoma. Right? And we're all familiar how the radiation is not going to show up just a couple of months later as a side effect on the exposed areas. But obviously, external radiation would change the way I handle such a lesion. Would I say that if she had a family history of colon polyps, familial adenomatous polyposis, when there are a number of, a limited number, fortunately, of genetic syndromes, where those two and four millimeter snippets that we heard about, the contralateral lobe, might mean something or might be a later on development. So basically, there are a limited number of scenarios. 95% of patients, fortunately, are not going to need to consider this. But those scenarios have to be discussed. Dr. Liu, so the patient just came from the Mayo Clinic. They were told they had to have a total thyroidectomy, which the Mayo guys will be yelling at me for. But in my scenario, that's what it was. She's begging you to consider a lobectomy. So what are the arguments to do a lobectomy? Well, first of all, even in best hands, complication rates are higher for total thyroidectomy. And I think, is she a singer? She's a singer, right? Yeah, professional singer. Yeah, so I think that needs to be taken into consideration, even though the risks are small, but there are risks there. So that's one thing. And second thing is, when I think of extensive surgery, I think of, am I going to give this person radioactive eye treatment? Because to have completion or total is to enable radioactive eye treatment. And this is a low risk so far that I am, I can see just on the ultrasound from the size, the no link nerve. So in my mind, I already made up my mind that I'm not going to give her radioactive eye treatment. Therefore, I think lobectomy will be sufficient. And in terms of monitoring, ultrasound will be really the main modality for positive PTC, because recurrences usually are local regional, right? And that can be monitored by ultrasound. You don't need a TG. TG is not very sensitive either. I mean, I think that's what opened the door on the guidelines to lobectomy again. We were rolling back widespread use of radioactive iodine and people began saying, well, if you're not automatically giving radioactive iodine, then which patients should we do with lobectomy? Julianne, obviously this is something that's probably going to see you, professional singer, 3.2 centimeter nodule, thinking about surgery. How do you have that discussion with them about the pros and cons? Yeah, thanks for that. And what I always start by saying is there's actually no right or wrong answer, except there is a right answer for the patient, okay? And I do believe that. And I think the art and science of this to present the options to the patient such that they make the right decision for them. I think a lot of truths have been said and certainly what Dr. Liu said is true is that even in the hands of a high volume surgeon, the risks from total thyroidectomy are twice that compared to the risks of lobectomy. So volume mutes, but does not eliminate that fact. Having said that, there are now data that are emerging. There's been a discrete choice experiment, Dr. Ahmadi, who I think may have been mentioned earlier, but Dr. Ahmadi was the lead author in a discrete choice experiment published in Thyroid. And based on that, you can actually anticipate if we knew more about patients upfront, which way they're gonna go. And the interesting thing in this discrete choice experiment was the thing that mattered the most to patients, 35% of them was what is the risk of recurrence from the cancer? But there were a number of other considerations. So what do I do if the tumor is less than one centimeter, lobe or potentially active surveillance? Over four centimeters, total thyroidectomy. One to four, no extra thyroidal extension, no nodal metastasis, present the options, risks and benefits and allow the patient to drive the decision-making. That is what I try to do. Dr. Sosa, let me keep you on the hotspot there for a second. So how do you explain to the patient that you don't really know whether lobectomy is the right answer or not till two weeks after surgery, right? I mean, you know, based on pre-op, intra-op. Intra-op, I do, remember, I can say, I'm gonna go for lobe, lobe, possible total. And what I say to patients, and this happens in the operating room, you go in, you do not preoperatively in many settings well see the level six lymph nodes that can be disguised by a goiter, an obese patient, a large tumor, and you encounter metastatic disease. You've gotta be able to live in the operating room, amend the strategy to total and central neck, right? Also, if you encounter maybe in the setting of a poorly done ultrasound, a low volume ultrasonographer, extra thyroidal extension, live, you've gotta amend your strategy and move to total. So an important thing is never go to the operating room with the plan absolutely being lobectomy because you'll find yourself handcuffed in an exceptional situation. Yeah, Dr. Stan, there's been a couple of questions come in from the audience. Says, how does this scenario change if the patient's 17 or 18 years old? Three and a half centimeter papillary cancer in a teenager. I think that what we have to account for, and it was in the background but not said, is that most people when they hear the word hypothyroidism are running away with the idea that this is going to change the quality of life forever. So that's where probably our desire to preserve thyroid parenchyma, and particularly when we look at the younger groups, we have to account how a subsequent pregnancy is going to come into the picture, how much more challenging it will be without the possibility at least of preserving your thyroid. So I think that plays into the picture. Now, granted, the younger the cancer is found, the more likely is one to suspect that there might be a genetic abnormality. So I would be really keen on sorting out the family history before I decide that lobectomy is sufficient. And as I said, there are a few rare syndromes that we all read about and we occasionally see them. And that's what I would want to know, and particularly for women, I have in mind the idea of pregnancy, how soon and how that might play. Yeah, and in 17-year-olds, you don't often see a four centimeter with no lymph nodes. I mean, that's sort of not typically how they present. Dr. Liu, there's a great question from the audience that said, thanks for the two right options. I pay you a lot of money, I want to know the answer. I came all the way to San Francisco to see you. So just tell me, should I do a lobectomy or total thyroidectomy? And we've all heard that, right? We get that, that's legit. So what do you tell them? Well, I think being her, being a singer, I say start out with lobectomy, and that would be the good start because as Dr. Sosa goes back in there, I don't think there's increased mortality or mobility associated with second surgery if needed. I would say start out with lobectomy if she cannot make any decision. Dr. Sosa, any role, another question, any role for NEC-CT as you're making this sort of evaluation here or sort of what would be your indications for NEC-CT? Not based on the ultrasound I saw, but there are clear indications for cross-sectional imaging. And I think we are more and more embracing cross-sectional imaging. The settings would be large, bulky tumors, high volume disease, retropharyngeal or intrathoracic extension, a bulky nodal disease with potential aerodigestive, so posterior extension, aerodigestive tract neurovascular involvement. And quite frankly, if I have a tumor over about four centimeters, I have a very low threshold to not be surprised and to get the adjunct of a cross-sectional image. All right, Dr. Stan, we got about one minute left and there are several questions that say, fine, you do a lobectomy. What are the things on the pathology report that would say, bummer, I was wrong, do a completion thyroidectomy and upfront radioactive iodine. Just the top two or three things that would drive you back in one minute. Obviously, we see a lot of classical PTC, but that's not always the case. So a subtype that is displayed as aggressive, a tall cell, columnar, insular, sclerosing, and there are all kinds of names that rarely occur on pathology reports. Those would tell me this is a more aggressive biological behavior. And I would, at that point, discuss the issue and in some case, really strongly recommend the issue of completion thyroidectomy. Beyond that, has the surgeon been able to discern the extrathyroidal extension? Typically, and Julianne can tell us how often it happens that she might be surprised that there was and she didn't see it. But if there is extrathyroidal extension and we're still at a lobectomy stage, then I say we should complete. Have there been lymph nodes in a specimen that were not sorted out? We have frozen section here. So usually Julianne would get that while she's still in the operative field if any of those lymph nodes were positive. But if that happens later, I will bring this back to a discussion. How many, how large the metastatic deposits and so forth. Dr. Liu, 30 seconds. The people obviously choose a lobectomy because many of them don't want to go on thyroid hormone. How high are you comfortable letting their TSH be from their contralateral load before you start thyroid hormone pills? Yeah, I would recommend keeping TSH below two. And I believe there was a recent study, if you use that guideline, more than 80% of people will go on levothyroxine replacement. And that is always a discussion I discuss with my patient. It's not going to take away the levothyroxine replacement and suppression. Dr. Sosa, there's a question here about using thyroglobulin follow-up because some idiot from New York thought this might be a good idea a few years ago. After lobectomy, what do you do with thyroglobulin? That's obviously changed over the last several years. Well, it's very interesting. And we're looking at this in the upcoming guidelines. So I'm whetting people's appetite, but we've actually, it's such an important topic. We are doing a systematic review and meta-analysis. And I anticipate the new guidelines specifically having a recommendation for or against utilizing TG in the post-operative lobectomy setting. Very helpful. Well, thank you very much to our panel. Thank you for Dr. Ghaznavi for these wonderful cases. This concludes our session. And in a few minutes, we have a number of other sessions you may want to join. Have a wonderful thing. Thanks, panel. Thank you.

thyroid nodules

management strategies

repeat biopsy

molecular diagnostic testing

risk of malignancy

surveillance protocol

Hashimoto's disease

indeterminate cytology result

treatment decisions

papillary thyroid cancer