Thank you so much, and thank you, Ilchi and Sarah, for the invitation. I'm always happy to talk about pathology, but in particular, esophageal pathology. Welcome everyone. Thank you for the participants for your attention. I'm going to be speaking about the eosinophilic attack in the context of esophageal pathology of EOE, and we're going to cover the key histologic features that I as a gastrointestinal pathologist need to make this diagnosis, and as with any other pathology or ailment that requires a tissue diagnosis, as we all know, there's clinical and there's definitely histological difficulties, pitfalls, and differential diagnoses, so we'll cover those. And lastly, we'll talk about how treatment affects the histologic features and the ultimate diagnosis of EOE. So I always like to start out with definitions. I know that the speakers and the faculty ahead of me have also described the definition of EOE, but what I like about this definition is three things. First of all, it defines that eosinophilic esophagitis is indeed a chronic condition, and then I especially like that it highlights how this has both clinical features and pathologic features, which should alert both the clinician and also their pathology colleagues to certain features, clinical pathologic correlates, that should make you think about EOE. Before we talk about pathology, let's talk about what's normal. I always like to set the bar for what's normal. So when we talk about normal, what or how many eosinophils are considered too many, and how many are just normal in the esophagus? Well, the answer to that question is we don't know. Some studies have said a few, not given a wide range, are okay in some parts of the esophageal epithelium, but then anything deeper or in the superficial layers of the epithelium is not, is pathologic. And unlike the colon, where we do account for seasonal variations, where you can have an increase in the number of eosinophils, we really don't know much about how many are just part and parcel of normal histology of the esophagus. Moreover, this chart here is not entirely comprehensive, but it does cover a whole host of common etiologies for having esophageal eosinophilia. And as you review this, you can tell that there's very, very commonly occurring etiologies such as reflux, and then we have more rare conditions, we have infections, we have systemic conditions. So there's a whole host of reasons why one would have esophageal eosinophilia. The incidence and the prevalence of this disease is rising. As Dr. Nanesky pointed out, a lot of the data that we have currently is from Europe and North America, but it is with more recognition, both clinically and pathologically, we're seeing a rise across the globe, really. And of course, you can see it in both the pediatric and the adult population, but the pediatric or the adult population, the peaks is usually around the 30s and 40s. Allergic conditions tend to travel in groups, and so it is associated with a whole host of other allergic conditions. As Dr. Nanesky pointed out, it can be the first condition that presents, and other times it can present at a later time point with skin or other types of allergies occurring earlier on. When we talk about the pathophysiology of eosinophilic esophagitis, it really is a whole host of different characters that are coming into play, whether it's genomic issues, whether it's molecular, cellular conditions that are at play, or environmental exposures. Let's talk about some of these. When we talk about genetics, we know that there's a higher risk of first-degree relatives of patients with EOE going on to develop eosinophilic esophagitis. Moreover, numerous genome-wide association studies have found certain genetic susceptibility loci. Of these, these four are the most commonly occurring in most of the studies that we have currently. Let's talk about a few of these and see how they interplay with what's going on in the epithelium and how they interact with each other also. We talk about CAPN-14 or CALPANE-14. This is essentially an intracellular calcium-activated, it's a regulatory protease, and it's normally expressed in benign squamous epithelium. You can see here you have squamous epithelium that's benign. This is no pathologic disease going on here. Squamous cells is referred to because squamous refers to high fish scales, and that's how these cells are in the esophagus. They line the portion of our esophagus right above the stomach. There are very, very tight cell junctions that bind them together, almost like a fish scale, and that's why they're referred to as squamous epithelium. CAPN-14 is expressed normally in squamous epithelium. However, we do know that it is highly expressed, or that expression is increased in patients that have EOE. More importantly, what we've noted is that it is also highly expressed in patients that have a diagnosis of EOE before the age of 12 months, so it has some kind of an association with the pediatric population. Moving on to TSLP, this is a cytokine, and it's released not only by squamous epithelial cells, but also activated GI, skin, and lung cells. Interestingly enough, this protein, it has a specific genomic aberration known as a single nucleotide polymorphism, or a SNP as we refer to it, that has been located on the TSLP receptor of the Y-chromosome of male patients. So interestingly enough, it's thought to have, it plays a role in the enrichment of the male population of EOE, as opposed to the female population. And then we have STAT6. This is a DNA-binding transcription factor, and it gets, it undergoes a certain change known as phosphorylation in response to interleukins 13 and interleukins 4, which we know play a role in EOE. And additionally, it also plays a role in the development of Th2 cells, and interestingly enough, we also know that it is associated with the induction of Kappa-N14. So I think you can see here how we have different genomic aberrations that are playing a role individually, but also amongst each other in the pathophysiology of the development of EOE. We know by numerous studies that monozygotic twins are more enriched for the development of EOE than dizygotic twins, and then dizygotic twins, of course, are more than siblings born at different time points, and so we know for sure that there's actually a role of familial genetics as well. But in addition to that, we also have a, many of these studies have also shown that a exposure to early life events, such as the time of birth, the mode of birth, and also the exposure to antibiotics plays a role in the future development of EOE. Now let's talk about the role of the actual epithelium itself, and again, the data on this are evolving, but I want to point out again that this squamous epithelium has, again, it's called squamous because of tight junctions that are very fish scale-like, it's called that because these tight junctions, known as desmosomes, are responsible for the maintenance of the integrity of this epithelium. So this protects the esophagus from food particles, from microbes, from acids that are coming in through, and it provides that first line of defense. These desmosomes are the very, very tight junctions between these cells, and as I move on to show you pathology, I think it'll become more apparent as to the role that they play and how we can kind of observe them. Well, electron microscopy studies have shown that patients with active EOE have decreased desmosomes compared to patients with inactive EOE, compared to patients with reflux, and of course, patients that have no pathology at all. In addition to that, once we have, and we'll discuss this as we move further, active inflammation in the form of eosinophils within the actual mucosa, we also see that there's a separation between these cells, and that's highlighted by these arrows here that you can see. This in turn leads to, this is because of the accumulation of fluid caused by the inflammatory response that you're seeing, this in turn leads to a decrease in mucosal impedance, and again, that's because the barrier is losing its integrity. And so interestingly enough, this mucosal impedance is actually not directly associated with the degree of inflammatory inflammation by the eosinophils, so we know there's other factors at play here, but that decreased mucosal impedance is directly related to the other features that we'll discuss in terms of the whole cascade that occurs once susceptible individuals are exposed to antigens. And so we can highlight that here where, to very briefly describe this, you have an already impaired barrier through which antigens can pass, they meet up with the antigen-presenting cell, that then leads to a whole host of release of certain interleukins, interleukin 4 being the main actor here, which activates the Th2 cells to recruit not only eosinophils, but we will see other cells such as basophils, mast cells, and this cascade over time leads to not only the presence of these inflammatory cells, but then also fibroblasts and myofibroblasts, and what these cells do is they deposit fibrins and fibrotic tissue and fibrotic matrix, which leads to eventually the fibrostenotic complications that you guys see clinically in terms of the decreased caliber of the esophagus, the difficulty in swallowing and all that. So now let's talk about the histologic features that a pathologist would require to make this diagnosis. And of course, first and foremost, I'd like to highlight the normal, and so as you see here, this is a piece of superficial squamous mucosa of the esophagus. It's lined by squamous epithelium up top, as you can see here, with very tight junctions. Towards the bottom of that, you'll notice that it's slightly darker, the bottom portion of the epithelium, and that's because that's the proliferative compartment. So that is where these cells are being regenerated from. So they start from the bottom and when they're immature, they have slightly larger nuclei and that's why they're bluer. And as they move to the surface, they become more pinker because they have more cytoplasm and eventually the stuff towards the lumen, which is away from the glandular stuff, will be sloughed off in daily routine swallowing and ingestion of food. And then towards the bottom half of this sort of micrograph, you'll notice that there's round glandular things. These are just esophageal glands, again, they help in the lubrication and the maintenance of the integrity of the barrier itself. But I want to highlight here that A, this biopsy is slightly pink, B, it doesn't have inflammatory cells, and C, that the area where the glands are have scattered vessels and some submucosal glands, but overall, it's a very light pink, loose character to this. And so this is important for you to realize as we move on and we study the pathology. So before this, I'm going to segue into a little bit about what pathologists do. And so for the most part, we are medical doctors that have differentiated towards laboratory sciences, anatomic pathologists study the tissue findings that lead to certain diagnoses of different features that are associated with different ailments, and then we analyze both biopsy samples and of course, resection samples. So once this tissue is acquired, in this case, it would be a biopsy, it has to undergo immediate fixation to prevent further degradation of the tissue, and then it goes through a whole host of different processes leading ultimately to the embedding of that tissue in wax paraffin, and then those slides being produced for actual review. And so I always like to show this because this is what we in pathology receive as small biopsy samples from the patient. So you can see they're quite tiny and they're quite small. And because they're that small, they need to be wrapped in a certain tissue paper before they go into this cassette where they will fix and formalin for a number of hours before being processed. And after they are processed, you can see the differential in size of this is of course gone a little bit higher to take this picture of the slide, but they become even, even smaller once we process them after they're fixated. And so the two stains that we use that every pathologist uses as a basis to identify basic histology or the pathologic features are the hematoxylin, the eosin stain, shortened, called H and E stains. The hematoxylin component is the purple, and it highlights the nuclear elements of all cells across the body, and then the cytoplasmic elements are highlighted by this pink stain known as eosin. So as we move forward, again, this is a full thickness segment of an esophagus, but for the purposes of this talk, I will be focusing of course on just the mucosa because that is what we receive in esophageal biopsy specimens. So again, I'm going to drive this point home. Let's look at normal. Normal squamous mucosa is slightly pink towards the top, slightly blue towards the bottom because that's where the immature proliferative compartment is. That's where these cells are being replenished form as they move towards the top. And then below that is a supporting structure known as a lamina propria, which has some inflammatory cells. It has some glands, but it's mostly loose, light pink in color and not fibrotic. And so what are the histologic features of eosin? Of course, there are the 15 eosinophils per high power field that is part of both clinical and the pathologic criteria that we use when we correlate between histology and clinical findings. However, there are a whole host of other features that we as pathologists use in combination with both the clinical findings and the other features that we're noticing in addition to the 15 eosinophils per high power field. So let's discuss those. So of course, it's called eosinophilic esophagitis, so you have to have a prominence of intraepithelial eosinophils. And what that means is you have eosinophils within that squamous layer of the epithelium, within that superficial portion of the epithelium. These can be present individually, and there are these very pink granular cells that you see kind of percolating through, so they can be present individually throughout the epithelium, or you can see them as small clusters, which you can notice towards the superficial portion of this photomicrograph, where you see sometimes six or seven of them clustered towards the superficial portion. One thing to note that's important is that because the inflammatory cascade requires not just the presence of the eosinophils themselves, but also the contents of their individual granules, those granules need to be released. And once they're released, we refer to these as degranulated eosinophils. And you'll notice that the yellow stars on this photomicrograph are highlighting those areas of granularity where those eosinophils have released their granules. Now, it's important to note that in our count, in that 15 eosinophils per high power field, and I'll discuss what high power field is moving forward, we do not count degranulated eosinophils. And the common logical explanation is, well, how can I know that these granules that I'm seeing account for one or four or five eosinophils? So because of that, we only count the final count in the diagnosis of actually any esophageal eosinophilia, not just for EOE, includes only intact eosinophils. One thing I like to point out is when I look at this slide under the microscope, I can almost immediately tell that it's an EOE patient. And the reason for that is it looks very blue. And if you jog your memory back to a few slides ago, normal esophagus is rather pink. It's not a very blue. So this is, there's less eosin here and more hematoxylon, that's because the nuclei are very large. And what accounts for that? That is the presence of a thickened basal cell layer. So we know this, regard this as basal cell hyperplasia. So if you recall back, if I go back a few slides, just to jog your memory, the basal cell layer here is not more than two to three cells layers thick. But if we move forward to our basal cell hyperplasia in eosinophilic esophagitis, in addition to there being numerous eosinophils, it's a very blue slide because you have a lot of cells that are proliferating very, very quickly. And they are taking up sometimes six to seven layers thick of the esophageal mucosa. So it appears as a very blue slide. In addition to that, these eosinophils can cluster throughout the entire thickness of the squamous mucosa. They can be in clusters, as I mentioned, or individually, but they can be seen from the top to the bottom. And that phenomenon is known as surface layering. Now that's important to note because reflux, which is a main differential, and we'll discuss this, tends to have esophageal eosinophils that are located towards more of the deeper portion of the epithelium. But in EOE, you can see that throughout the epithelium. In addition to that, I draw your attention to the fact that these eosinophils are also being sloughed off with that superficial portion of the squamous epithelium. So eosinophil layering is also a feature that we know. And again, as I pointed out earlier, because of this inflammatory response, you can see a whole bunch of fluid collecting in between what were once very tightly joined squamous cells. And this phenomenon is known as spongiosis. So now you can see that there's individual white outlines amongst each individual squamous cell. And that should not be the case, because remember, these are like fish scales. They should be very, very tightly joined together. So when you start seeing this kind of spongiotic change, as we call it, again, because it's stretching of those desmosomes. This is a feature of esophageal injury, not very specific to EOE, but more a marker of esophageal injury. But again, taken in this context where you can see easily here, there's lots of intrepid eosinophils. It helps to add to the diagnostic criteria. And again, just to highlight normal, do you see how tightly joined these cells are? Their cell borders are these dark pink lines, and you should not be seeing any white outlines. But that is a nice contrast to what we see in eosinophilic esophagitis. And then moving on to a very, very exuberant display of a collection of eosinophils within the mucosa. You can see here that there's a whole cluster. And this is known as an eosinophilic abscess. So it's hundreds of eosinophils focally clustered in one area. And what I like about this feature is that actually nicely correlates to what the endoscopists are seeing, which are these gray to tan punctate lesions that are present and visually seen endoscopically in the mucosa. But one thing that is a feature that we oftentimes do not see, again, this is just a measure of how deep the biopsy is, or again, how the patient is doing is, and that is the feature of chronicity, which is the presence of lamina propria fibrosis, which you can easily appreciate here. And again, if you jog your memory down to what normal looks like, the normal lamina propria has a submucosal glands, and it's kind of loose and light colored and not as dark pink as you're seeing here, right underneath the epithelium. So this correlates to that chronicity with that fibrosis with the myofibroblast and the fibroblast depositing fibrotic tissue, which over time correlates to the symptomatology of the patient. So now let's discuss, you know, it seems like all these things are straightforward, and there should be no difficulties, but we do have difficulties. Let's talk about them. So there's a list of these, and we'll go through these individually. Well, first of all, as the faculty before me have talked about, we have limited correlation between patient symptoms and what we would see histologically. So severe symptoms don't always mean that the histologic features will be as severe. And we'll talk about why that is. Sometimes that's a feature of just the fact that there wasn't enough sampling. And so we'll talk about that as being a limitation. Next, we have something that's more from the perspective of a pathologist. So you can see here, you have different pieces for the microscope that have different focuses that we use, different fields of view. And so in the past, there was a lot of heterogeneity in the makers of a microscope, and what was determined to be a high power field. So that 15 eosinophils per high power field is based on a 40x field. And different makers of microscopes had different fields of vision. This has now been corrected because we have also limited our count to 60 eosinophils per millimeter squared. So not just that, but also there's actually continuity, and the makers of different microscopes now are all following the same guidelines in terms of what that field of view should be. So this has largely been corrected. But earlier on when we were describing these, the field of view was a big issue. No longer the case anymore. And then as similar to not having a threshold or a number for what is the normal number or what number of eosinophils is not pathologic, we also don't have a defined threshold for what number of eosinophils in a patient that has established eosinophilic esophagitis. So 15 eosinophils per high power field. We don't have an exact number for what defines treatment or what defines resolution of symptoms. Is it less than 10? Is it less than 5? We currently do not know. So that's a big limitation that we have currently also. And then going back to, again, the number of biopsies that is helpful. These two photomicrographs that you're seeing in the top portion of this slide correlate to a single sampling from a patient from a single portion of the proximal esophagus. And I think you can easily note here that between these two, one is bluer, one has more eosinophils, and the other has less. And this tells you how heterogeneous this disease is even within a single portion of the esophagus that is sampled and how having one single sample or having fewer samples can really lead to limitations when it comes to interpretation of features that actually represent what's going on in the patient clinically. So the more samples, the better because this disease is so heterogeneous even amongst a single area of sampling. And again, just to highlight that superficial biopsies of the esophagus do not always account for what is going on clinically with the patient. And that's because they don't always account for the lamina propria fibrosis or the fibrous features that a pathologist needs to pick up to make this diagnosis. So again, if a biopsy is superficial or we don't have as many samples, there's a limitation in that we aren't seeing the true nature of what is going on in the patient histologically. And so next is conquering the age-old question, is this eosinophilic esophagitis or is this reflux? As you all know, reflux is by far the most common compared to EOE. And this chart here kind of highlights the clinical endoscopic and the demographics that may help to differentiate. However, it's important to note that many of the common features, such as heartburn, have also been reported in the majority of EOE patients. So they're not limited to just eosinophilic esophagitis. And also these symptoms can be very, very different in the pediatric population. So it's not the typical symptoms that you would see in adults presenting with classic clinical features of EOE. I've highlighted here many of the histopathologic features that we use to diagnose eosinophilic esophagitis. And I think straight off the bat, you will notice that there's a lot of the words that I've used, basal cell hyperplasia, spongiosis, the presence of eosinophils overlap with reflux. So just as there is clinical overlap, there is also histologic overlap. But again, as I mentioned earlier, we don't take a single feature to make a diagnosis. It's more a combination of what we're seeing. And again, importantly, correlating with what the clinician is seeing also. So the clinical history that we have, the clinical history that you provide us is also very, very helpful. And so in reflux esophagitis, you can easily see here that there is a whole host of features that are overlapping. But then the most obvious is that there's a lot of eosinophils. A high power view here comparing it to EOE will show that, yes, there's definitely more than 15 per high power field. But as you can compare, as I mentioned before, the basal cell hyperplasia, even in robust cases of reflux, compared to EOE is more a feature of EOE as compared to reflux, where you have a lot of the features. But I would argue here that the basal cells still represent about three to five cell layers thick. And so overarchingly, this biopsy looks a lot more pinker because the proliferative compartment is not as expanded as you see in EOE. Again, here, a mild case of reflux esophagitis. Here again, you'll notice that there's mild expansion of the basal cell layer. However, spongiosis and other features are not as robust. And again, on high power, I think you can easily agree that there are more than 15 eosinophils here per high power field. However, the changes tend to be less exuberant. And again, I have to highlight here that this distinction is easy to make when reflux is mild to moderate. When you have extreme robust reflux, it's hard to make a distinction between the two. And we'll talk about that as we go further in the lecture. Again, here, another feature to point out is, of course, chronic longstanding reflux can also lead to fibrosis of the lamina propria. However, in mild to especially chronic moderate cases, the lamina propria does this interesting thing where it tends to move its way into the actual squamous mucosa. So in between, it kind of forms these spikes, if you will. We refer to them as papillae. So when these papillae become more than 3 4ths the length of the actual epithelium, as you can see here, this is a strong feature that we associate with reflux rather than EOE. We don't really see this in EOE. Another thing you'll notice is the squamous epithelium tends to have some squamous cells that are very pale looking. So they're very, very light pink. And this is because of an accumulation of fluid within the cells itself. Again, a feature that is more common with reflux than with EOE. And so that's highlighted here by that black arrow. So you can see that very pale looking cell. And because of the accumulation of intracytoplasmic fluid, it makes it very, very, we refer to as pale bodies. Again, highlighted here that even though there's a decent amount of intrapithelial lymphocytes, reflux biopsies tend to be less blue because of the fact that basal cell hyperplasia is not a prominent finding. It's not as robust as you would see in EOE. There is some spongiosis, but then you will notice here that there's a lot of pale cells also. And then, of course, this spike of lamina propria that is going through almost 3 4ths the length of the actual epithelium itself can help make that distinction. So beyond histologic features, we also use a lot of clinical criteria. Go through the patient's chart to help us see what's going on with the patient. So, of course, if there are any other illnesses, any other reasons for them to have esophageal eosinophilia, so that chart, that orange chart that I mentioned in the beginning of the talk, we have to make sure there's nothing like that going on. If the patient has been on certain medications and if there's been treatment and the patient has actually been compliant. In fact, I would say I would take this opportunity to let you know that if you, when you are submitting these biopsies to the pathologist in your requisition form, if you have information about any of these entities and you can let your pathologist know right from the get-go when you are as part of your requisition form, it's extremely helpful to us to narrow our differential and to make our diagnoses. Another important factor is to compare any past pathology, whether that's a prior biopsy for EOE or whether it's for something else. This is, again, from the same patient that you can see a few months down the line, the disease has progressed. We're seeing a lot more laminar propriofibrosis. It was not present in January. And so prior pathology review is also very, very helpful in figuring out what's, what, which direction this disease is going in and if it is indeed reflux or eosinophilic esophagitis. And then, of course, location. Location is helpful. There's certainly some degree of overlap in the esophagus, but EOE tends to be more robust in its natural form towards the proximal esophagus, whereas reflux is a predilection towards the GE junction area. And, of course, we always correlate. So we always look for the buzzwords like rings, furrows, and exudates. That's important for us to see. Of course, if I'm seeing a biopsy with EOE and the clinical history or the endoscopy note is showing furrowing or rings, you better believe that EOE is the higher on my differential as compared to any other cause that might have intrapitheal eosinophils. And then correlating with radiology. Endoscopic ultrasound and chronic EOE can show expansion of all layers of the esophagus, again, due to that expansion of the wall of the esophagus because of fibrosis. So that's always helpful to correlate for us. And in some instances, again, I will come back that mild to moderate reflux is easier to distinguish from EOE, but robust EOE and very, very marked, severe, robust eosinophilic esophagitis, sorry, reflux is very, very hard to distinguish. These are two cases that you can see here. And I think anyone would be hard pressed to give you a definitive diagnosis, especially in the absence of a clinical history of endoscopic findings to figure out which one is which. And what's really needed in this instance is to see how the disease plays out with serial biopsies, the tincture of time, giving this, whichever entity it is, time to declare itself one way or the other. And so now for the last part of this talk, I'm going to highlight and really just talk about what we see histologically in patients that are undergoing any kind of treatment for eosinophilic esophagitis. So the three main histologic types that we see are patients in complete remission, patients that have a treatment effect, and I'll talk more about what that is, and then those that are progressing despite treatment. And so, of course, complete remission. Here you have someone that is either treatment-naive, an EOE patient, and complete remission is what we all love to see. And that would be a return to a completely normal histologic sample in which there's no inflammation. The basal cell layer is, again, just two to three cell layers thick. It's a very pink biopsy. This is what a normal esophagus looks like. This is what we all love to see. So minimal inflammation, just complete remission. And then moving on to kind of intermediate treatment effects. So again, starting out with a treatment-naive or someone that has very robust eosinophilic esophagitis. So again, a very blue biopsy. And you can see here, again, this is why comparing to the prior is so helpful for us as pathologists, that yes, is there a complete resolution? No. Is it still sort of blue? Yes. Sort of blue? Yes. Is the basal cell layer more than three to five cell layers thick? Definitely. But overall, you can see at this point that the features are much improved compared to the prior sampling that the patient has had. Now, sometimes this is, again, as I highlighted, an intermediary. It can be like in the middle of treatment. And certainly, this can progress to what we all love to see, that is complete remission. But sometimes some patients will hang around just here, even on serial biopsy. So they'll just hang out in that intermediate. And that can be for a whole host of reasons, non-compliance or other features that are going on that the clinical team can then move forward with. But this is also very helpful that you can always, if you have a prior biopsy, it can always help to convey that the symptoms are improved from the prior sampling. So the reason I say that is because the middle photomicrograph that you're seeing here is definitely showing more than 15 eosinophils for high power field, as is the first slide, the first photomicrograph. However, there's a difference in not only the number of eosinophils that are more than 15, but also the overall features that we're seeing here. So there is improvement. The point here is not to get hung up on just the number of 15, but actually the whole count in combination with all the other features that were noted. And then, of course, there is patients that, for whatever reason, just show progression of disease. And that is especially helpful to know when there is, again, a biopsy that is showing that subepithelial tissue, that lamina propria, that degree of fibrosis. So as you can note in the first photomicrograph, although it's very blue, it has eosinophils, there's a little bit of lamina propria, but it's not fibrotic for any means. And then as this disease progresses, this patient, again, went on to need dilatation. It's obvious on the histology that there's advanced fibrosis. And this was contributing to the fibrostenotic changes that we were noting. It's a nice correlate to that. So this is a nice example of when disease progresses and it's refractory to treatment or there's noncompliance. Again, this nicely correlates with the endoscopic findings of rings or furrows or luminal narrowing overall. And so the take-home points are 15 eosinophils is part of the diagnostic criteria. However, it's not entirely defining of the disease. There's many, many other clinical and pathologic features to keep in mind. Keep in mind the features that are present, but also those that are absent. It's also helpful. Correlate with the clinical history that we have. It's important for us to do that. The more samples, the better. It can be a very patchy heterogeneous disease. So more sampling, increased sensitivity. And then, of course, correlating with any prior pathology or any prior clinical history that you could provide. Your pathologist would always be very helpful. And so that ends my session today. And I'm happy to take any questions.

eosinophilic esophagitis

histological features

diagnosis

biopsy sampling

clinical-pathological correlation

treatment effects

disease progression