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His primary scientific interests have focused on investigating emerging metabolic and physiologic imaging techniques to evaluate head and neck cancer and to differentiate recurrent tumors from post therapeutic changes. Dr. Mukherjee is a devoted educator and has been an invited speaker on over 500 occasions. We're grateful to him for his support of MRI Online and for serving as our head and neck neuro radiology advisor. At the end of the lecture, please join him in a Q and A session where he'll address questions you may have on today's topic. Please remember to use the Q and A feature to submit your questions so we can get to as many as we can before our time is up. With that, we're ready to begin today's lecture. Dr. Mukherjee, please take it from here. Hey, thanks, Ashley. Thanks again for having me. I love the music too. That was really good. So anyway, thanks a lot for having me for the next hour. So we're gonna spend the time talking about a simplified approach to the lymph nodes of the head and neck. So the lymph nodes are a very interesting part of the whole body as a whole, but especially in the head and neck. So the functions of the lymph nodes are to, first of all, transport lymphatic fluid. And these are the third fluid of the body, if you will, and we'll talk about that later. The lymph nodes filter foreign substances. So I always kind of think of the lymph nodes as almost like the garbage bag or the filtration device of our body and also to initiate the immune response. So those are three primary functions of the lymph nodes. Now, the lymph nodes of the head can be a little bit complicated, but what I wanted to do was at least give you kind of an approach to the lymph nodes because if you don't do a lot of head and neck radiology, the lymph nodes can kind of be a little bit challenging. So I realize most of you probably won't remember me tomorrow and or probably what I say, but if I can just leave you with one concept of the lymph nodes that's gonna maybe give you an approach is just remember the lymph nodes, if you have a dog or a cat or any type of pet, they love to be scratched under their chin like this. So if you've ever done that to your dog, you've been inadvertently palpating their level one lymph nodes. So the level one lymph nodes are gonna be under the chin. Now, the other concept that I wanna leave you with is this string of pearls. So the majority of the lymph nodes involved in the head and neck are in this configuration that look like the string of pearls. So we're primarily gonna be focusing on these groups of lymph nodes, the level one lymph nodes and this group of lymph nodes that are located in this orientation that looks like the string of pearls. Now, there are other lymph nodes in the head and neck area that we're not gonna be covering purely because of time. So there are lymph nodes in the parodic lens or lymph nodes involved in the face. And those don't nearly come into play as much as the regular lymph nodes that we'll be discussing. So just remember the petting your dog, your cat on your chin. And then if you like pearl necklaces, just realize that the orientation of levels two, three, four, five and the supraclavicular lymph nodes just look like a little pearl necklace. And we're gonna go through that in great detail. So this was the classification of how we define the lymph nodes. Now, back when I was a fellow, I hate to say this, but I was born in the last century and I trained in the last century. And when I started my fellowship back in 1992, at that time, we were looking at CT scans and we were trying to separate the level two from the level three lymph nodes. And we were also trying to separate the level three from the level four lymph nodes. So if you look at this diagram right here, you see this little vein right here that's actually draining into the internal jugular vein. This is the facial vein. And this is the separation between level two and level three that the surgeons look for in the operating room. Now, from a CT standpoint, this is what we tried to identify in cross-sectional imaging. And it was really, really painful to do that just on cross-sectional imaging. Remember, this is really before the days of reformats and everything. And if you look at this muscle right here, there's a muscle right here that crosses over the internal jugular vein. And you can't see the internal jugular vein, it's just literally behind here. And this is the omohioid muscle. So again, where the omohioid muscle crosses the internal jugular vein, that separates level three and level four. And we had to look for that on cross-sectional imaging. And that was really, again, really, really difficult. So around that time, radiology was kind of coming into its own, it was pretty well accepted that we could see lymph nodes on CT. And believe me, back when I trained, that was kind of a revelation. So over time, the surgeon started to accept that we could reliably identify lymph nodes on cross-sectional imaging. So what the surgeons did, and they worked with the radiologists, and they actually found out that a good approximator for separating the level two and the level three, i.e. where this facial vein drains into the internal jugular vein could be approximated by the hyoid bone. And then where the omohioid muscle crosses over the internal jugular vein, which separates level three and level four, well, this could be approximated by the bates of the cricoid cartilage. So this is why when we start to look at lymph nodes, why it's important to identify, but to understand where the hyoid bone is and the base of the cricoid cartilage is. So if you've ever wondered why these two things have sort of been so emphasized, that's the reason why. So what I'm gonna do over the next 10 minutes or so is take a deep dive into these various lymph node levels. So we're gonna first start with the level one lymph nodes. So the level one lymph nodes are comprised of the submental and the submandibular lymph nodes. And we'll go over these lymph nodes again and separate these out. But just realize that the level one lymph nodes extend from below the mylohyoid muscle. So when we look at the cross-sectional imaging, this is the mylohyoid muscle here and here's the mylohyoid muscle here. And it goes to above the level of the hyoid bone. So there's our hyoid bone that's located here. And I'm gonna see if this is gonna work. I think it's been working relatively better, but we'll see. So anyway, there's the back of the submandibular gland. So the level one lymph nodes are located anterior to the back of the submandibular glands. So those are the level one lymph nodes. Now the level one lymph nodes are divided into the submental lymph nodes and they're divided up into the submandibular lymph nodes. The submental lymph nodes are the level one A lymph nodes and they're located between the anterior belly, the digastric muscles. So when you look between the digastric muscles, you can see this fat right here. And within this fat right here, we can see this lymph node right here and that's a level one A lymph node. Now, if you do a lot of head and neck radiology and especially oncology, the level one lymph nodes are sometimes resected in the lymph node dissections. Now, sometimes on occasion, the surgeons will go in and they can resect some of the level one lymph nodes, but sometimes if they're not careful, they can inadvertently retain these level one lymph nodes between the anterior belly, the digastric muscles. So from a radiology standpoint, when you're looking at these post-treatment changes, pay close attention between the anterior belly, the digastrics, because I've seen several cases of patients that have undergone dissections in this lymph node group, but there's been recurrences and that's because some of these lymph nodes have been retained. Now the level one B lymph nodes are in the same general location, but they're lateral to the anterior belly of the digastric muscles. So again, the level one A are between the anterior bellies and the level one Bs are posterior lateral. So they're lateral to the anterior belly of the digastric muscles. But remember, these level one lymph nodes are the ones that are right below your chin. So those are the ones that you can occasionally run into if you pet your dog or your cat. Now the level two lymph nodes run from the skull base and they go down to our friend, the highway bone. So we're gonna be coming back to our little friend right here. Now what we do is we take that same line right here and we touch the back of the submandibular glands and the level two lymph nodes are everywhere located behind the submandibular glands. So those are our level two lymph nodes. So they run from the skull base all the way down to the highway bone. But unlike the level one lymph nodes, which are anterior, the level two lymph nodes are gonna be posterior. Now, when you look at these lymph nodes, there's actually a level two A and a two B. And unless you do head and neck radiology, I don't really expect you to remember these. But it is fairly straightforward. The only difference between a two A and a two B is that there is no discernible fat plane between the lymph node here and the internal jugular vein. But on the other hand, when we look at the level two B lymph nodes, we can see a fat plane here between the lymph nodes and the internal jugular vein. So that's the main difference between the level two A and the level two B lymph nodes. So now what we're gonna do is we're gonna continue our journey. So what we did so far is that we talked about the level one lymph nodes which are located below the chin, then we talked about these level two lymph nodes and they run from skull base down to the level of the hyoid bone. Now, we're gonna continue our journey and we're gonna transition from red to green. And this green right here is located between the hyoid bone and the base of the cripoid cartilage. And if you look at the diagram at the top left, there's our little internal, excuse me, the facial vein that goes into the internal jugular vein. There's the Omohyoid muscle right here. But again, these are approximated by the hyoid bone and the base of the cripoid cartilage. So we've just come to continuing our journey. And this is the example of the level three lymph nodes. So when you look at the left-hand side, we'll go from here to here and in red. And these are two examples here of a level three lymph nodes. So here's a lymph node right here. This is at the level of the thyroid hyoid membrane. And there's another lymph node right here, which is metastatic on the right and on the left. But notice how they are at the level of the cripoid cartilage, but they're above the base of the cripoid cartilage. So remember that the transition between three and four has to be the base of the cripoid cartilage. So if you're looking at an XCT and you actually see the cricoaritinoid joint, just realize that this is still a level three lymph node. Now we're going to now talk about the level four lymph nodes. So the level four lymph nodes on the diagram on the upper right go from the green to the purple. And the level four lymph nodes run from the base of the cripoid cartilage down to the level of the clavicles. Now, I kind of joke about this and I say when I talk about the level four lymph nodes, I kind of cheat a little bit. If you read the paper that I referred to before, technically the level four lymph nodes run from the posterior aspect of this muscle, which is the sternocleidomastoid muscle along the anterior portion of this muscle right here, which is the anterior scaling muscle. So the level four lymph nodes are going to be right where my arrow is. So on the opposite side, I'm going to see if I can do this here. I'm sorry about that. I'm going to see if I can do this. There we go. That's it. There's my pen. So I'm going to see if I can draw a line right here from the back of the sternocleidomastoid muscle to the anterior scaling. So the level four lymph nodes are going to be right in here. Now that's technically what you're supposed to do. Now I have to admit when I am doing this, I tend to cheat a little bit. So just to stay with same convention that I use for the other lymph nodes, I tend to draw a line right here that connects the back of both sternocleidomastoid muscles. And in general, that gets me to the right vicinity. So again, if you can't remember all the details about how to draw the level four, I think if you just draw that line connecting the back of the sternocleidomastoid muscles between the cricoid cartilage and the clavicles, I think you should be just fine. And again, just a level set right here, we're dealing with this group of lymph nodes that are identified by the purple. So here's an example of the level four lymph node. So level four lymph node here, and there's another level four lymph node here. And what I did in this particular case, I just drew a line right here that connects the back of the sternocleidomastoid muscle to the anterior scalene. There's that level four lymph node. And this yellow arrow again points at a level four lymph node. So what have we done so far? So just to reiterate, we started here, which was at the level one. Then we were at level two, which runs from the skull base down to the hyoid bone. Level three was hyoid bone down to the base of the cricoid cartilage. And level four was from the cricoid cartilage down to the level of the clavicles. So now what we're gonna do is we're gonna turn our attention to the level five lymph nodes. So when we look at this lymph node group, if we look at the anterior limb of our pearl necklace, remember our pearl necklace, basically we divided that anterior limb of the pearl necklace into three separate levels, level two, level three, level four. The level five lymph nodes is basically the posterior limb of that pearl necklace. So this runs all the way down from the skull base to the clavicle. So technically this is geographically the largest area of that lymph node group all the way from the skull base down to the level of the clavicles. So when we look at this on the axiolimages, here's our skull base, here's our clavicles. If you draw a line right here that connects the back of the sternocleidomastoid muscle, what we talked about with level two, three and four, when we connected this line back here, we were looking at essentially everything here. These constituted two, three and four, but for the level five lymph nodes, we take that same line from the back of the sternocleidomastoid muscle and we extend it all the way back to the trapezius. So from the trapezius to the back of the sternocleidomastoid muscle, this is all part of the level five lymph node. So when again, when you look at that full geographic distribution, the level five lymph nodes is the largest lymph node group. So the level five lymph nodes are fascinating to me. I think all of head and neck is fascinating. So here's an example of a level five lymph node, classic level five lymph node. Here's our sternocleidomastoid muscle. If I drew a line right here, it's connecting the back of it. So unequivocally a level five lymph node. Here's another lymph node right here. This is at the junction of level three and level five because we're at the level of the thyroid cartilage. So the bottom line here is that if you see isolated level five lymph nodes, you have to think of other things besides just the routine head and neck cancers. So first of all, level five lymph nodes that can be associated with nasal pharyngeal carcinoma, no doubt about it. But on the other hand, if you see isolated level five lymph nodes, you have to think of other types of cancers. So specifically we have to think of skin cancers arising from squamous cell carcinoma. So yes, this is squamous cell carcinoma, but it's not arising from the visceral space, but rather it's a skin cancer. And you also have to think of melanoma. So I was just in Australia a few weeks ago and you guys probably know I see patients once a week. And yesterday I was in clinic and we saw a patient that came in with a stout cancer and actually presented with a level five lymph node. So we examined him and he had a big cancer on his skin. It was literally right about the ear, it was about a three centimeter fungating mass there. And we talk about protection, right? We say about from cancers, right? So you don't wanna smoke, you don't wanna drink and those are things that can help you prevent head and neck cancer. But one of the big things is to wear a hat and cover yourself. So this guy, he was a nice guy and he just readily admitted, yeah, I've got a skin cancer, I've got a hat, but I never wear it. And he knows full well, you gotta wear your hat. So especially if you're of light skin, fair skin and you're out in the sun a lot and this guy was out in the sun a lot, he was actually a construction worker, he never wore his hat. It just reiterates the fact that one prevention for head and neck cancers is to wear the hat. So don't not only wear the hat, make sure your ears are covered and make sure the back of your neck is covered as well too, because I can't tell you, other thing too, I've seen a bunch of patients that are wearing a hat, but they don't cover their ears so they have these cancers involved with their pinup. So for peak sake, if you're out in the sun a lot and you really are fair skin, please wear a hat because for me, that's just as important for not smoking and drinking to prevent these types of cancers. And then finally, you can have thyroid carcinomas too that can present with these level five lymph nodes. So again, this is one of these really interesting groups. And if you do see these isolated level five lymph nodes, think of these potential causes. So the level six lymph nodes are again, another interesting group of lymph nodes. So what I'm showing here is a metastatic lymph node that's located at the cricorinoid joint. So this would be a level three lymph node because it's lateral to the carotid artery. The level six lymph nodes are also known as the visceral lymph nodes, and they run from our friend, the hyoid bone, down to the manubrium. But the key thing about the level six lymph nodes is they're actually located between the internal carotid artery. So these are sometimes also referred to as the tracheosophageal groove lymph nodes, the TE groove lymph nodes. So these are the level six lymph nodes. So when we see level six lymph nodes, what do we think about? Well, here's an example of a level six lymph node here. We can see this necrotic mass right here, and we can see a little calcifications. On the opposite side, we see it's other lymph node. In this case, it's not as classic as a one on the right side. You can see the carotids push a little bit anteriorly, but again, we can see a little calcification. So if you understand and you're pretty smart right here, you can figure out what the cause of this is because this type of primary site predisposes you to develop metastatic level six lymph nodes. And in this case, this was from the thyroid gland and this was papillary thyroid carcinoma. So there are certain primary sites that predispose you to developing metastatic level six lymph nodes. They are the thyroid gland, which I just mentioned, the esophagus. Anytime that you have tumors involving the piriform sinus that extend to the apex of the piriform sinus, and if you have a true vocal cord carcinoma with subglottic extension, these all predispose you to developing level six lymph nodes. Another example here, here's a metastatic right lymph node medial to the carotid artery located in the tracheosophageal groove, and this is a TE groove level six lymph nodes. Now, why are they important? They're important for a couple of reasons. Number one, when you are going to an ENT surgeon, what they end up doing is they do a thorough evaluation of your neck. Now, when they palpate your neck, they're pretty good at identifying the levels one, two, three, four, and five, and the supraclavicular lymph nodes, which we'll talk about. But on the other hand, this lymph node is really deep. It's right next to the tracheosophageal groove. So this is a very blind area. They can't see that. The second thing is that the standard neck dissections are performed for the level one through five lymph nodes. In order to surgically resect these level six lymph nodes, they have to do a different type of nodal dissection, and that's referred to a central neck dissection. So when the central neck dissection, the surgeons specifically go in and remove the tracheosophageal groove lymph nodes. So if we see an unexpected central compartment lymph node right this, and the surgeons are gonna have to alter their approach regarding neck dissections and specifically perform a central neck dissection. And this is just a little thing that I learned years ago. This is also a level six lymph node. This was my first exposure to the level six lymph node. This is actually a pre tracheal lymph node. Notice how it's located between the internal carotid arteries. And this is what we lovingly referred to as the Delphian lymph node named after the oracle of Delphi. So rumor has it is that people would travel from far away to meet the oracle. She would palpate your end to your neck. And if she's felt something hard, that usually indicated you weren't gonna live very long. And that's why it was called the Delphian lymph node. Well, the level seven lymph nodes are the mediastinal lymph nodes. Now, I don't necessarily like these lymph nodes. I wish they sort of weren't included in the head neck, but they are. To me, these are lymph nodes that should be covered by our chest radiologists. But on the other hand, what it always makes me do because it is part of our head and neck lymph node classification, it always forces me to look at the mediastinum and to look at the lungs as well too. So the level seven lymph nodes run from the top of the manubrium down to the enameled vein. So remember, all these next CTs always end up clipping the top of the chest. So we are responsible to look for the mediastinal lymph nodes and then also responsible to look for the lung fields as well. Well, the next lymph node group is gonna be the supraclavicular lymph nodes. So if you remember, I began this discussion about talking about the string of pearls. And so the anterior limb of the string of pearls was the level two, the level three, the level four, and the level five lymph nodes. So what connects the level four and the level five? Well, it's this group of supraclavicular lymph nodes. Now the supraclavicular lymph nodes are about the level of the clavicle, the lateral to the carotid artery and they're above and medial to the rib. So when I look at the supraclavicular lymph nodes, what I do is that if I see the clavicle and I look at the fat deep to the clavicle, any lymph nodes in this area, I consider supraclavicular lymph nodes. Now technically it's really hard to separate level four and the supraclav lymph nodes and level five and the supraclav lymph nodes. It's really, really hard to do this. And there have been various ways that it has been done specifically looking at the veins and the thyracervical trunk. But just in a couple of slides, you'll see how I'm not the only one that's had a problem with that. In fact, we've adjusted that in one of the staging systems for the lymph nodes of the head and neck to make it a little bit more consistent. So sometimes if you do have problems separating four from the supraclavs or five from the supraclavs, just realize you're not the only one. Now the supraclavicular lymph nodes are again a very unique group of lymph nodes because when we talk about levels one through five, we're primarily looking at head and neck cancers involving the upper air digestive tract that metastasize to levels one through five. But if you have isolated groups of lymph nodes involving the supraclavicular lymph nodes, this is a transition zone. So realize these lymph nodes can become metastatic from tumors involving the upper air digestive tract. You could have tumors that actually arise in the lymph nodes, but you can also have sometimes it's anti-gravity. You can have tumors below the clavicle metastasizing to the supraclav lymph nodes. So if you see this isolated supraclavicular lymph nodes, think of nasopharynx and hypopharynx. These are a part of the normal upper air digestive tract. They can involve the supraclav lymph nodes. If you have lymphoma, Hodgkin's lymphoma can present as an isolated supraclavicular lymph nodes, or you can have these other lymph nodes that are below the clavicle that have lymph nodes, channels that go to the supraclavicular lymph nodes. So think of lung, think of breast, think of esophagus, think of GI, and think of pancreas. So again, that supraclav lymph nodes is, I always call them transition zone lymph nodes. So we have to think above the clavicles, below the clavicles, and also lymphroproliferative disorders that present right at the supraclav lymph nodes. Now, as I mentioned before, sometimes the supraclav lymph nodes can be hard to specifically identify. So in the eighth edition of the nasopharyngeal cancer staging, we made it a little bit easier so you don't have to kind of have a tussle as to where the level four in the supraclavs begin. So regarding N3 disease, what we now say is that N3 disease for nasopharyngeal lymph nodes are any lymph node groups that are below the caudal border of the cricoid cartilage. So if you actually look at the cricoid cartilage, what we're saying is that if you draw a line through the cricoid cartilage, level four, the inferior portion of five, and also the supraclavicular lymph nodes, if they're involved with NPC will upstage them. So we don't specifically have to look for supraclav lymph nodes and see if where that separation is. So this gives us a little bit more standard approach when we're looking at these lower lymph nodes. Well, this last group of lymph nodes is the retropharyngeal lymph nodes. So I'm not giving a talk on the spaces, but I'll just give you a little bit of a primer. So this little fascial layer right here has numerous names to it. I still call this the visceral fascia. Other people will call it the pharyngeal mucosal fascia. Some people call it the pharyngeal basilar fascia. Doesn't really matter what you say it is, but just realize that there's a fascial layer. Now the other space that's located just anterior to this fascia is called the pharyngeal mucosal space or the visceral space, or just called the pharynx. Well, what do you call the space that's behind the pharynx? Well, that's the retropharyngeal space. And within the retropharyngeal space, you have these lymph nodes. And there's two groups of lymph nodes. You have a medial group and lateral groups, and these are the retropharyngeal lymph nodes. They're also known as the nodes arruviate. So these retropharyngeal lymph nodes are very important group because again, they cannot be palpated by our referring physicians. There are surgeons end up palpating the neck. There's no way that they can feel these lymph nodes. So these are our lymph nodes. So these lymph nodes are located just medial to the internal carotid artery. There's one. And here's another one right here. Here's the carotid artery. And there is a metastatic retropharyngeal lymph node just medial to. In fact, yesterday, we had another patient present with a large nasopharyngeal mass and actually had bilateral retropharyngeal lymph nodes that again, were not palpable on clinical examination. So it's important for us to be aware of these retropharyngeal lymph nodes. So what we've done so far is that we've taken a really deep dive into the anatomy of the lymph nodes of the head and neck. And we talked about the levels of the lymph nodes. We went all the way through one through seven. So that is exactly where these lymph nodes are located. But why do we spend so much time looking at these lymph nodes? Well, the reason is, is that if there is a positive lymph node, this reduces survival by 50%. Now, think of that, 50% is a big, big number. So if we, the radiologists, say that there's a positive lymph node, the survival of that patient is reduced by 50%. Now, when we look at these lymph nodes based on imaging, we have our own imaging criteria. Now, the first point that I want to make is that when we look at the criteria for lymph nodes, there are limitations to this. So I show this image on the right and I specifically want to point out the orientation of the lymph nodes in levels one, two, three, and five. The lymph nodes are like these kidney beans right here. So they're located at one, two, three, and five in a craniocaudate dimension. But on the other hand, look at the lymph nodes in level one and look at the supraclavicular lymph nodes. They're laying on their side. So this kidney bean is on their side. Now, if this patient was having an XET, they'd be on their back and then we would end up forming cross-sectional imaging. And when you do a CT scan, notice how in level two, the plane of that scan is going to be going right through the mid portion of that lymph node. So we're going to have a true axial dimension. But on the other hand, if we use that same plane and we're going through level one, notice we're going through the long axis. We're actually going through the top to bottom. So based on the orientation of the lymph nodes, when we look at the size criteria, they're going to be inherent problems with the size criteria. So these are the standard accepted size criteria. When we look in the head and neck, what we do is that we look at the axial plane and we measure the largest axial dimension. Now this is different than the chest and the abdomen where you would be measuring in this plane. So in the head and neck, we do things different. In fact, if I look at the left-hand side, if I was to measure this based on head and neck, I would draw my plane like this. If this happened to be in the chest or the abdomen, I would draw it like this. So we do our convention differently than compared to anywhere else in the body. Now you have to ask yourself, why do we do it like that? The reason is that there was a paper written back around 2000 that was a perspective study in which we've measured the CT and MRI measurements of these lymph nodes using this orientation and we compared it to pathology. This is where this convention arose from and since then there have been many different types, but the standard accepted size criteria are 10 millimeters for level one, three, four and five and 15 millimeters for level two and the retroferential lymph nodes. Now the retroferential lymph nodes were not included in this study, but levels one through five were included. So these are the standard accepted size criteria and this is why we do it based, it was based on this particular study. Now one thing that oftentimes gets confusing and I wanna point this out right now is that if we as the radiologists say that there is a level three lymph node greater than 10 millimeters or level two lymph nodes greater than 15 millimeters, we're gonna call that a positive lymph node. This is our criteria, but when we look at the staging and upper limit of N1 disease is three centimeters. So there's a little wiggle room for that lymph node to grow between by the time it reaches this upper threshold for us to call metastatic from the time we transition from N1 to N2 disease. So just realize three centimeters is the upper threshold. So again, that can get a little bit confusing sometimes, but I did wanna point that out, that little bit of a wiggle room. Now the size criteria as I mentioned before is kind of fraught with errors. And there are other ways where we can try to look for metastases to improve our diagnostic accuracy. And in order to enter this discussion, I wanted to go over the regular anatomy of the lymph nodes. Now, like every other organ, there is an artery and there is a vein. So we all know this in every organ, there's an artery and a vein. But in a lymph node, we have the third vessel and that third vessel is the lymphatic vessel. Now, unlike the artery in which the artery enters at the hyalum of a lymph node, the afferent lymphatic vessels enter through the periphery of the lymph nodes. So we have this lymph vessels coming in, it enters the periphery, and then eventually it flows centrally and then it leaves this lymph node vessel through the efferent vessels. So this is where the filtration occurs, this is where that immune response occurs. It's this transition of the lymphatic fluid from peripherally to centrally. So if you understand that, then you realize that if you have a squamous l-carcinoma involving a certain area and it invades the lymphatics, the earliest deposition of these lymph nodes are going to be in the periphery of the lymph node. So this is an example of a histologic specimen of a squamous l-carcinoma involving the periphery of a lymph node. This is an example of a lymph node. This was less than 1.5 centimeters and we can see the small peripheral low attenuation deposits within the capsule of the lymph node. So again, early metastases. Now, this is an example of a lymph node that's completely replaced by tumor. In fact, when we start talking about these lymph nodes and they exceed their size criteria, these lymph nodes are already chock-a-block full of tumor. They're already filled with tumors. So the size criteria is actually a late finding. It's not an early finding, it's a late finding. And the earliest findings are gonna be the small little peripheral area of metastases. And the reason is, is because the afferent lymph vessels, these fluid initially drains into the periphery of the lymph nodes. So as a result, we're still unable to detect these small little micro metastases because 40% of metastatic lymph nodes are less than seven millimeters. So the downside is, is that if you look at any of these techniques, including spectral CT and photon counting, the latest thing that's coming out in CT, we still cannot detect micro metastases. We do a pretty good job, our negative predictive value is somewhere between 90 and 95% if we use PET CT or PET MR. But again, we still can't detect these little smaller lymph nodes. But on the other hand, you know, there are certain things that we can do. And I always say there's a difference between science versus art. So the science, if you will, is the size criteria that we use. But what about the art? You know, if you can identify and are comfortable with head and neck lesions, you can use other criteria to help you improve your diagnostic accuracy. So here on the top left, it's a standard size criteria. Now, here's an example of a lymph node that's about one centimeter or so, but is cystic. And if I told you this patient had thyroid carcinoma, well, you can make the diagnosis of metastatic thyroid carcinoma. Here is a patient, a child that has calcifications. Now, this is less than 1.5 centimeters. But on the other hand, if I told you, hey, this patient has a history of neuroblastoma, you can make the diagnosis of neuroblastoma similar with osteosarcoma. This was an example of tumor that extends outside of the lymph nodes. This was extra nodal extension. I'm gonna come back to this because this is a supportive diagnosis, but not a firm diagnosis and we'll see why. But realize you can have these lymph nodes, tumors extending outside of the capsule of the lymph nodes. If you have clumping of lymph nodes, what if I told you this patient had a right side of head and neck cancer? You look real closely and we see multiple clumped lymph nodes. Well, guess what? That's a sign of metastases because look at the opposite side, nothing's there. And this is an example of hypervascular lymph nodes. So if I told you this patient had thyroid carcinoma, again, we can make the diagnosis of a metastatic lesion even though it's less than the size criteria. So these are some other diagnostic size criteria that could help us be a little bit more accurate. And sometimes in lymph nodes, we can make the specific diagnosis. So this was an example, if I told you it was an elderly male and we see the cystic lesion here, we can make the diagnosis of HPV positive oral pharyngeal metastases. If I told you you see this, we can see a cystic hypervascular calcifications. We can make the diagnosis of papillary thyroid metastases. This patient has multiple large lymph nodes involving both neck. We can make the diagnosis in this case of CLL. This could have easily been lymphoma, but in this case it was CLL. And this was an interesting case. I remember I saw this patient in clinic, initially clinically they thought they had lymphoma, but when I saw this, I said, well, here's a clump group of lymph nodes involving the level one lymph nodes. If you look real closely, we can see some reticulation. We ask them if they had cats. And lo and behold, this young man had 11 cats. Don't ask me why the young man had 11 cats. I don't wanna go there, but he loved his cats. And this in fact was cat scratch disease. And this was a young child that ended up having a sore throat, difficulty swallowing, and this was subrative adenitis involving the retrofaring gel lymph nodes. So sometimes we can actually make specific criteria if we're comfortable with these additional differential findings. But occasionally we can't have alligators. And these are some of the things that I've actually missed. I'll tell you the ones that I missed. I missed this one. This was a patient when I was at UNC, we present this patients to the head and neck tumor board. I saw this case and I thought this is a metastatic level two lymph node. You know, I gave a beautiful diagnosis. The biopsy came back negative multiple times and lo and behold, we tested for PPD and this was tuberculosis adenitis. So I completely missed that one. This is one we actually got right. And this was a patient that ended up having melanoma. So this was metastatic melanoma to the right side of the neck. When we look at the opposite side, we see all of these lymph nodes here in the left. This patient also had a history of breast cancer. So the issue was, was this melanoma or was it breast cancer? Well, this was about two and a half years ago. And we also then had to ask where was the COVID vaccine given? This patient had a COVID vaccine three weeks earlier. One of these lymph nodes was resected and it was reactive. So this was path proven reactive lymph adenitis from the COVID vaccine. And this is one where I completely messed up. You know, this was a patient that I was told came in had a glomus tumor and apparently an outside CT was called the glomus tumor. So I remember looking at this next CT and I said, well, it looks like a glomus tumor to me. It looks like it's hypervascular. Then we got the MR and I completely botched it. Anytime that you have a hypervascular lesion, anytime that you have a glomus tumor, greater than two to two and a half centimeters, you should have multiple flow voids. So I had what was called a confirmation bias. I tried to confirm what I was told and I go back and I still kick myself because you can see there are no flow voids and this turned out to be metastatic thyroid carcinoma. So I showed this to warn you about confirmation bias and also warn you anytime that you have a hypervascular lesion in the left neck and if you don't see those flow voids, it's highly unlikely you're gonna have a paraganglioma. And this was an example that you initial thought you may think that it's actually a lymph node, but notice how this is located between the anterior and the middle scalene muscles. This is where the brachial plexus is and these are multiple neurofibromas involving the brachial plexus. So not everything that looks like a lymph node is actually a lymph node. And if you understand the anatomy, you can make the correct diagnosis. So the last thing I'll end up with is, where do I even start? Lymph nodes can be pretty complicated. So what's my approach? So I'm just gonna give you my approach when I'm looking at a head neck CT, especially in patients with cancer. So if I know that the patient has an oral tongue cancer, the first thing that I wanna do is find the cancer and find the side. Once I identify the side, then I know that the majority of the metastatic lymph nodes are gonna be on the ipsilateral lymph nodes and they're going to involve level one, excuse me, level two. So this oral tongue cancer typically involves level two on the ipsilateral side. Here's an example of a floor mouth carcinoma. Again, I find the side it's on, it's in the floor of the mouth. And then when you look at the lymph nodes that are most likely gonna be involved with a lateralized floor mouth cancer, it's gonna be level two and level one. Similarly, this is a tongue-based cancer. Here's a right-sided tongue-based cancer. Now both nodal groups can be involved, but again, a higher likelihood that the ipsilateral level two lymph nodes are gonna be involved. And this is an example of a laryngeal carcinoma and you sort of get where I'm going with this. Right-sided cancer here, the most likely group level that's gonna be involved is level two on the ipsilateral side. So what do we learn from this? If you can understand this, then you can understand the staging system because an N zero disease means that there's no regional metastases. Now, if you have N zero and you go to N one, what do you think N one means? Well, you probably figured out N one disease means that there's a metastases in a single ipsilateral lymph node that's less than three centimeters. Now, if you have an N one, that means you have to have an N two. So what do you think N two means? Well, if this lymph node that's less than three centimeters starts to get larger, well, then that's what's referred to as N two A. You just take that same lymph node and it becomes larger. Now, what if you have this one lymph node and it starts to recruit its friends on the same side of the neck? Well, that is an N two B lymph node. So now we're looking at multiple ipsilateral lymph nodes. Now, what if that lymph node becomes really popular and he goes from one side of the street to the opposite side of the street? So this means that that's the contral lateral neck. So when you look at N two C, this means the contral lateral neck. And then finally, if that lymph node gets really, really big, greater than six centimeters, now it becomes N three disease. Now, if you look real closely right here, I put E and E in yellow. E and E means extra nodal extension. So I think those of you know that I've been on the staging system since the fifth edition. In the eighth edition, for lymph nodes in patients that are HPV negative, this is all HPV negative, we added this classification of extra nodal extension. And what extra nodal extension is, is when the tumor extends outside of the capsule. Now, from a radiologist standpoint, we cannot call extra nodal extension based on imaging alone. Extra nodal extension is a clinical diagnosis. So these lymph nodes tend to be larger and they tend to be fixed, okay? Now, from our standpoint, the radiological findings can be supportive, but they're not definitive. So the reason is, is because if you have over aggressive radiologists like myself that think they're better than they actually are, I may see a lymph node that I think is one centimeter, but with my eyes, I can say, wait a minute, I think I see some extra nodal extension. Well, what we've inadvertently done is that I could potentially upstage a lesion from N zero all the way to N three B disease by calling something by this extra nodal extension. So in order to prevent this stage creep, extra nodal extension is a clinical diagnosis, but on the other hand, radiology is confirmatory. So this lymph node staging is for HPV negative. We all know that in the new staging system, there's actually HPV positive. Now, if you look at this, it's a lot more simpler. So N zero is none, N one is less than six centimeters. Remember back here that N one disease was less than three. Well, this is less than six centimeters. For N two disease, everything's less than six centimeters and there's no separation between if salaral or bilateral disease and N three is less than six centimeters. Now, what this reflects is the better overall prognosis for HPV positive oral pharyngeal carcinomas. So when we look at the overall survival of HPV negative oral pharyngeal carcinomas, if you look at the T stage and the N stage, I wanna point your attention to N two disease and N three disease. Notice for N two disease, it's for A and for N three, it's for B, this is pink and this is red. Red is usually bad, right? So this is for HPV negative, but when we look at HPV positive, look at N two and N three. This is now stage two and this is now stage three. So the reason is, is because overall HPV positive carcinomas tend to be a better prognosis and the reason is based on the staging. So if you look at this example on the bottom left, here's a patient that has a metastatic lymph node to the left neck. And if you look real closely, we can see it's irregular. Clinically, this was fixed to the neck and we can suggest it because we can see this irregular shaggy margin and it's completely invading the muscle. So this was extra capsular penetration. Now, if this was HPV negative, this would be N three B disease, but because this is less than six centimeters and only involving one side of the neck, this is actually N one disease. And this is why this lymph node approach and the overall better prognosis is associated with a better prognosis in HPV positive disease. So in summary, what we've done over the last 50 minutes is that we've gone over the lymph nodes of the head and neck. So for me, the take home message is I know you're not gonna remember everything I say, come back to a medallity and listen to the lecture over and over again, but what I wanna leave you with is this. Remember the level one lymph nodes are these lymph nodes that are below your chin. So remember your dog or your cat or whoever. If you've been palpating their chin, you've been examining their level one lymph nodes. The levels two, three, four and five lymph nodes are like a string of pearls. The next thing is that when you're evaluating patients with head and neck cancer, remember to begin to look at the ipsilateral neck and look at level two. Now you have to look at all of the lymph nodes, but the majority of lymph nodes are gonna metastasize to the level two lymph nodes on the ipsilateral side. And that's exactly where my eye goes to when I'm first evaluating these patients. And finally, remember these retroferential lymph nodes. These are sometimes these hidden lymph nodes. And remember, these are our lymph nodes because there's no way the surgeons will be able to palpate these lymph nodes and they make a huge difference in how these patients are treated. So thank you very much for your attention. I think we have about 10 minutes. I can probably go a few minutes over if we have time, but again, thank you very much for your attention. Thank you so much for your lecture, Dr. McCurgy. At this time, if you'd like to pop open that Q&A feature at the top of your screen, we've got a couple of questions in there. And if anyone else wants to submit questions, please be sure to use that Q&A feature. Okay, the first question I have is, it says, have you seen interglangial lymph nodes in submandibular glands? Why not in reference to parotid nodes? So have not seen specifically metastatic lymph nodes in the submandibular glands? And the reason is the following is that in the parotid glands, there's actually four groups of lymph nodes in the parotid glands and they're located in the pretragal area below the capsule, along the facial nerve, and then also in the tail of the parotid gland. So that's why you can see intraparotid lymph nodes. Now, interglangular submandibular glands, it's very rare, if anything, to see submandibular lymph nodes. So it's very rare. Occasionally what I will see are level one lymph nodes sometimes extend into and involve the submandibular glands. That's also why warthans tumors are very unusual to arise in the submandibular glands because warthans tumors, the other name are cyst adenoma lymphomotosum and they arise within the lymphoid tissues. So that's why we see more warthans tumors in parotid glands and we don't see warthans tumors in general in submandibular glands because the paucity of lymphatic tissues. So hopefully that answered your question. Medial versus lateral retroferential lymph nodes, is there a differentiation? And the answer is yes. Now, I'll tell you that if you, you should be able to, you can see my screen, right, Ashley? I hope you can hear me, is that right? Yeah. So this group of lymph nodes is the lateral retroferential lymph node and this is the medial retroferential lymph node. Now, this is a very important point when it comes to treating patients with head and neck cancer. When we are born, we have direct communications with the lateral and the medial retroferential lymph nodes. In adults, the majority of lymph node metastases are gonna involve the lateral retroferential lymph nodes and the question is why does that happen? Well, some people feel it happens is that as we are kids, we get a lot of throat infections. And one of the theories is, is that because of all the throat infections we get, we tend to fibrose off these lymph channels that go to the medial retroferential lymph nodes. So as we get older, the majority of spread goes to the lateral retroferential lymph nodes and not the medial. On rare occasions, I can see medial retroferential lymph nodes which are gonna be just off midline behind the pharynx. But it's actually important from a clinical standpoint because a lot of the radiation oncologists know as an adult, the majority of lymph nodes are gonna involve the lateral retroferential lymph nodes. So oftentimes they don't treat the medial group. And the reason they don't do that is because if they treat this, then they're going to give a high dose radiation to the superior constrictor muscle and oftentimes these patients will have difficulty swallowing. So your question isn't a very important question because it actually affects how these patients are treated. So in the majority of adults, we're gonna see involvement to the retroferential lymph nodes. The next one is what is the cut-off size for head and neck lymph nodes and head and neck cancer? I think I mentioned that in the talk. It's 10 millimeters for levels one, three, four and five and 1.5 centimeters for level two. So I'll refer you back to the talk again because I think I had a slide on that one. Is it feasible to combine nodal groups in the head and neck to the chest and the lung? So I don't know about how the numbering system in the chest and the lung happened. I can tell you that that level seven lymph node is actually a mediastinal lymph node. So I would say there's that overlap, but I don't know specifically how the numbering system is done in the chest. So I would have to refer to my other colleagues about that. Good question. What about the matted and conglomerate lymph nodes? How to check the size? That's a really, really good question. I can tell you how I do this. If I see matted lymph nodes, I will measure in the axial plane. And if it's greater than 1.5 centimeters, then what I would do is I would then take a different measurement either in the parisagel plane or an oblique plane and take the largest measurement. So for me, what I do is my first measurement is actually in the axial plane. If it's greater than 1.5 centimeters, then I know it's gonna be metastatic. So that takes me to N1 disease. But then what I do is I take a separate measurement in the oblique planes, and then based on that measurement, that will tell me whether I'm dealing with N2 or N3 disease based on that. So that's what I would recommend about the matted or the conglomerate lymph node. That's a very interesting question, but that's kind of my approach. What I'm doing is looking for that largest measurement for the final staging. Can thyroid malignancy present with normal, mildly bunky thyroid or just lymph adenopathy? I just got this as my long exam case in boards in India. Well, I hope you're past your board. So I'm good luck with that. Yeah, so thyroid malignancy can present with bulky thyroid gland. The thing about thyroid malignancy is I think I showed you that one case that I missed that had that big hypervascular thyroid lymph node or that thyroid lymph node. Remember the one that I showed you? That was actually a clinically occult thyroid carcinoma. So I looked at the thyroid gland even in retrospectoscope, I couldn't see anything. So sometimes thyroid cancers can present as clinically occult lesions in the thyroid gland. They just present as bulky lymph nodes. And unfortunately I went down the tubes on that one. So again, anytime that you see metastases that are hypervascular, anytime that you see them that are calcified, anytime that you see cystic, anytime you see anything in the tracheosophageal groove or even the retroferangial node, think of potentially thyroid carcinoma even if you don't see anything in the thyroid gland. So case of parotid lesion with a six millimeter retroferangial lymph node, what would I say? Great question. So in general, I would have to first know what the parotid lesion is. I mean, the majority of parotid lesions are benign. It would be unusual to have primary echelon drainage between the parotid gland and the retroferangial lymph node. So I would probably think that the retroferangial lymph node is an incidental finding in the patient of the parotid lesion even if I would just stop there. I think especially if the parotid lesion was benign, that's why I wanted to say. So I would say that the six millimeter lymph node is probably just incidental finding. Measurement of level one and other levels different as they are oriented. Could you demonstrate how to measure them again? Sure. Let me see if I can go back to that one. Oh, sorry about that. Oops. Hold on for a second. What did I do? Let's see. Oh, okay. Sorry about that. Ashley, can you see my screen still? Yes. Okay. Are we doing okay with time or? Yeah. I would say take maybe three more questions and then we can wrap. Okay. Someone wanted me to ask some measurements. So let me measure that real quick. We should just have a Q and A session on this, Ashley. So many great questions. A lot of questions, yes. So I love the interest. So here's our level one lymph node here and then there's our level two lymph node here. So for the level one lymph nodes, it's basically the same approach. I mean, so if I was measuring this level one lymph node here, so here's a level one lymph node here, I would measure it from here to here, so longest dimension. I think there's one more if I go back really quickly to this level one lymph node, so here, okay. So here's a level one lymph node here, right? So if I was measuring this level one lymph node, I would just make sure you can hear and then go back to there. So again, similar to what we did before, just take the longest axial dimension. Yeah, I'm so glad everyone is still with me too. This is awesome, let's see. Oh, thank you very much for that. Let's see, we're doing Q and A, right, Ashley? Yes. Let's post a check, okay. Thank you, Scott. Let's see, are occipital lymph nodes viewed as level? That's a really good question. No, they're not. They are actually a separate group of lymph nodes or actually referred to as suboccipital or posterior auricular lymph nodes in general. So they're a separate group from that. And I tend to do 10 millimeters for that. So two more. Sometimes we find possibly level five lymph nodes pretty low. Yeah, so to Chinmoy's question, I just call these occipital lymph nodes and I'll probably use a one centimeter cutoff as well too. They haven't been well described, but I will use those as suboccipital lymph nodes. Yeah, significance of larger craniocodad dimension versus AP. Should we report to discrepancy? Great question. I don't, Alex. So what I end up doing is this. If you look at this image on the left, I will measure, let's see, go back here. I will measure my lymph node like this to determine whether it's positive or negative. And then if it's greater than 1.5 centimeters or if I actually think it's metastatic, then I will measure the second plane in a different dimension to see whether it's greater than three centimeters to upstage it to end to disease. I do that because that's the way the surgeons actually palpated. And then one more, Ashley, is that what you want? Let's see. Yeah, that sounds good. So for all level measurements to be done, let's see. For all level measurements we've done in axial and biggest dimension. So yeah, axial plane, largest dimension. If I see a level two lymph node with cutaneous fissure, can I suggest tuberculosis? Yes, if you're in an endemic area and the patient doesn't have a primary tumor, if you're in an endemic area, I think that's very reasonable. And should that sit or should we do one more? Ashley, I'll leave it up to you. How about you find your favorite question? And we'll end on that one. Let's see. Is there a different measurement between lymph nodes between CT and MR? The answer is no to that, that was easy, no to that. Is there a subcategorization for levels four and level five? Yes, there is. Differential between superclav and these, like I say, it's kind of hard. That's probably a lecture unto itself. So why don't you go ahead and stop there, otherwise I'll talk forever on this topic because I love it so much. Well, thank you so much for coming and doing this lecture. Very clearly there is a lot of interest in this. We'll have to do a separate Q and A session or have you back for part two. So thank you so much, Dr. McCurgy. Okay, thank you very much everyone. Yeah, and thank you everyone else for submitting these amazing questions and for participating in today's noon conference. You can access the recording of today's conference and all our previous noon conferences by creating a free MRI online account. You will also get this replay in your email shortly. So be on the lookout for that. Be sure to join us next week on Tuesday, November 21st at 12 p.m. Eastern for a noon conference entitled MRI of the Knee with Dr. Stephen Pomerance. You can register for this free lecture at mrionline.com. Follow us on social media for updates on future noon conferences. Thanks again and have a great day. Thank you.