Hello, my name is Ada Sola, I'm one of the second year GI fellows at Vanderbilt. My name is Sophia Saleria, I'm a gastrointestinal, liver and pancreas pathologist. I believe for most pathology or diseases that we study, it's important to have a reference point of what that part of the body looks like when there's no significant histopathologic change or any kind of disease process going on. For pathologies, it's especially important because once you have a frame of reference of what normal looks like, it helps you identify visually the features that are contributing to the actual disease process that the endoscopist is seeing. So first of all, we divide these really based on how severe the process is. So as the name indicates, a hallmark of the disease is the presence of exuberant intraepithelial eosinophils, which means that there's eosinophils present within the superficial layer of the mucosa. These are in numbers of 15 or higher, and they're present either as clusters, known as microabstances, or individual cells percolating throughout the esophageal mucosa. Along with this, one of the features of chronic EOE is the presence of lamina propria fibrosis, which is fibrosis underneath the superficial layers of the epithelium. And that correlates with the fibrostenotic findings that you see in the clinic. Correct. So that when we do endoscopy, you know, sometimes we appreciate strictures or areas of narrowing of the esophagus. And when we biopsy these areas underneath the microscope, Dr. Salera can appreciate this lamina propria fibrosis, and we see when the disease state has been present for quite a number of years. So a lot of these findings can show a direct correlation to what the endoscopist is seeing visually and what we see under the microscope histologically. Endoscopically, when we see changes involving the esophagus as concerning for us, for eosinophilic esophagitis, we're trying to get at least six biopsies from the distal end of the esophagus. And then we also are trying to get six biopsies from the proximal part of the esophagus as well. Obtaining these biopsies sometimes can be challenging, but we have really good recommendations or guidelines on how to best obtain these samples. And hopefully in getting more samples, we increase the diagnostic yield of making this diagnosis. So that correlates nicely to what we see histologically and why it's important to really get a higher number of samples. What you see endoscopically as a provider can vary because it's not every single portion of the esophagus that you're seeing. That correlates to what I see histologically in that the histopathologic findings of the prominent eosinophils will vary based on the area sampled and how that looked endoscopically. A more accurate diagnosis can be provided when there's an increase in sampling and this overcomes the patchy and the variable nature of the disease. So eosinophils in the esophagus is a hallmark of a disease process, especially when they're there more prominently than you expect, but in itself is not diagnostic of eosinophilic esophagitis. You know, we really need to take into account the symptoms that patients are having or we're seeing endoscopically and ultimately what our pathologists see underneath the microscope. So one of the things that we most commonly have to make sure that we're ruling out is gastroesophageal reflux disease or GERD for short, because that can also have some changes involving eosinophils under the microscope too. One important clinical distinction is the symptoms that people coming with and such that acid reflux, people can present with heartburn and all those sort of symptoms, but sometimes they can also have the sensation that things are getting stuck in their esophagus too called dysphagia, such that endoscopically we can also appreciate strictures, but it tends to be further down in the esophagus, in the distal part of the esophagus than we see with eosinophilic esophagitis. So it's very important to take into account, again, the clinical picture, what we're seeing, but also making sure that, again, we're obtaining accurate biopsies to help our pathologists help us make that diagnosis. Similar to clinical overlap, there's also a huge histopathologic overlap with reflux and eosinophilic esophagitis. We have to keep in mind that reflux is one of the most frequently occurring causes of esophagitis here in the United States. However, having said that, there are certain features, especially when the disease is mild to moderate, that can help distinguish between EOE and reflux, and we talk about that in our module, different features that can help differentiate. Some of those involve the way that the eosinophils are present within the epithelium itself, and also the number of eosinophils can help, especially in mild to moderate disease. It is important to note that when both eosinophilic esophagitis and reflux are untreated and robust, and also presenting that way, it is difficult for a pathologist to make that distinction on the basis of a one single time point biopsy, similarly as it would be difficult for the clinician. And in that instance, it really does require waiting and seeing the response to treatment followed by serial biopsies to see how this disease is progressing to figure out what really is going on with the patient. It's very important for the pathologist to first and foremost very basically know where these samples are taken from. So were they taken from the mid, the proximal, or the distal portion of the esophagus? So location is key and important. After that, especially if this is a patient that is treatment naive or has been undergoing different forms of treatment, it's important to know what kinds of treatment and how compliant the patient has been. Similar to that, adding into your requisition form the fact that the patient currently is still exhibiting a lot of the symptoms that they came in maybe six months ago is important for us to know because then we can correlate symptomatology to the histologic findings that we're seeing. I think that from my perspective as an endoscopist, gastroenterologist, it's very important to really take into account the clinical symptoms that someone is presenting with, being as detailed as I can in doing this endoscopy and obtaining biopsies that are great samples so that I can empower my pathologist to also help in making that diagnosis and also understanding that acid reflux, gastroesophageal reflux disease, is a more prevalent disease process in the United States, but we also understand that the incidence and prevalence of EOE is rising and to always keep that in mind with these patients. Additionally, I'd say from the pathology perspective, it's important for the trainer to understand that increasing the number of samples obtained not only helps the pathologist make a more accurate diagnosis, but this ultimately helps in patient management in the long run. I think one other thing that I wanted to add as well is that, again, the presence of eosinophils in the esophagus, even when we read the biopsy or the pathology report, doesn't in itself confer diagnosis of eosinophilic esophagitis. You really want to, again, keep it relevant to the clinical case and to just keep in mind that there are other things that can cause eosinophils to be present within the esophagus. I wish you all good luck with this module. I hope it has provided you with a better understanding of the underlying pathophysiology, histopathology of eosinophilic esophagitis and will lead you to making better diagnosis for your patients. If you have any questions or suggestions, we welcome your feedback.

eosinophilic esophagitis

gastrointestinal conditions

histology

biopsy

gastroesophageal reflux disease