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OK. Ok. So hello everybody. Um hopefully you can um see myself and, and a couple of my colleagues, um if you can't then feel free to um mention in the chats and we'll see if we can get that sorted out. Um My name is Kyle, I'm one of the um neuropathology registrars, er, based up in Mersey. Um and this is a new webinar series, hopefully looking at all things histopathology. So thank you for joining us over the course of 12 weeks. We're hoping to touch upon er, various histopathology. So, things like um applications interviews, touch upon the training program here in the UK. Um as well as looking at some of these subspecialties such as neuropathology, forensics and Peds and perinatal pathology. Um but we'll also be looking at um actual um histology as well um And trying to apply that er to our clinical practice. So hopefully, um clinicians understand pathologist better and, and likewise, people get a better understanding of pathology as a specialty itself. Um We're lucky enough to be joined today um by Doctor Moore. Um who will, I'll let them, er, introduce themselves um in just a second. Um But just quickly in terms of, er, house rules, um, if we can just remain muted, er, for the purposes of the, um, talk, it is being recorded and will be uploaded to the Man Bleep youtube channel afterwards. Um, if you do have any questions, um, feel free to put them in the, um, chat, Boxer and Doctor Moore will, um, be able to address them either during the, er, presentation or at the end. Er, and yes. Um, so without further ado er, I'll pass over to doctor more to do his instructions and hope you, er, enjoy this first talk. Thank you very much. That was a very lovely introduction. So I've got a dual screen set up. So if I'm not looking directly at the camera, I am still looking at the chat box on my separate screen. I've got my presentation up on here, so I'm gonna share my screen and we may as well get started. You guys have given up some good time out of your evening. I don't want to delay you any further, but let's hope it will be a really fun session for you guys. I've tried to keep it nice and varied and also directed to you guys as foundation doctors and medical students at various different levels. So the talk that I'm going to give is on surgery and pathology relating together because the two overlap quite a lot and both of them provide a lot of information and a lot of input towards the investigative and managerial aspects of overall patient care. But these opportunities are also really good for you guys to get an idea of the different pathways and the different journeys that people go on to get to where they need to be. Obviously, the traditional route that people took was that they would just be on a conveyor belt route to consultancy. But I think it's good to know that options are wide and open. So with that in mind, I'll give you a little bit of background about myself. So that's a picture of me growing up in Yorkshire. I'm from Wakefield originally and that's where I spent the 1st 18 years of my life. And once I've done my mandatory years down in the pits, I end up going to Manchester University from 2012 to 2018. That's where I got my undergraduate degree. I intercalated in anatomical sciences. And then for my foundation training, decided to go down to Cardiff and it was in Cardiff that I started to get a bit more of an exposure to lots of different specialties, surgery, medicine, EDP es and the subspecialties relating to them. One of which that interested me greatly was pediatric surgery that then prompted me to take a few nontraining years out in Manchester Children's Hospital, working in pediatric surgery and neonatology up in the neonatal ICU. Before deciding to go down the surgical route, I completed all of my surgical exams. I did core surgical training across Yorkshire, spent a good amount of time in the Colder Valley before eventually deciding that my lifestyle balance and the things that really interested me about surgery were a little bit more skewed away from surgical practice or a bit more skewed towards the wonderful world of histopathology. So six years after graduating, which to me doesn't feel like a very long time, but I've been told it is a little bit of time ago now, I then embarked on the root of histopathology. And my days look a little bit more like that now, rather than the inside of an operating theater or down in the depths in the bowels of A&E. But I'm very happy with my choices and hopefully I can infuse you guys about the wonderful world of both surgery and histopathology and how they overlap. So, yeah, my journey has taken me all over the UK pretty much on various different courses, various different placements. It's been a bit here there back and forth and everywhere. But I guess the overall point that I want to get across to you guys is that the pathway of your career doesn't necessarily need to be a straight trajectory. You can take time out, you can do other things you can explore and take your time and make sure that whatever avenue you go down is one that you're happy with. No one's ever going to turn around later on in their career and say, you know, I wish I had less experience actually. So everything you do is always going to inform what you do later and will always be a valuable experience. And as long as you take one thing away from it, whether that's personally or professionally, as far as I'm concerned, it's never a waste of time. So with all of that being said, we'll move on to surgery. So surgery in terms of the specialty is a competitive application that you apply for. After your first two years in foundation training, it's a competitive application. So you do need to go through a self assessment process with your portfolio. You need to go to an interview and then you are ranked from there, you have to rank your jobs and then based on your score from the interview you get allocated first come first serve to the most competitive applicant per job. Surgery often gets grouped as one specialty. But there are many, many diverse subspecialties within that, which is very good for us as pathologists because that means that we can associate ourselves with the different subspecialties within it. As Kyle mentioned before, you have pediatric and perinatal pathology. You have neuropathology and within general histopathology, you have gi pathology, head and neck gyne, all of these kinds of things that relate very well to surgical specialties because they are the place where the bulk of the workload for pathology comes from surgical pathology is a massive aspect of the job. And while working in surgery, you get exposed to those diverse subspecialties, a diverse range of pathologies. And along with that, the patients that present in both acute and critical care scenarios, the training pathway is long. So after you've done two years of surgical training, you then do another five years of specialty registrar training. That's if you don't take any time out for fellowships or research or anything like that and you do have on call demands in that time. So nights, days, weekends, long evenings, but it's very rewarding. It's a very hands on specialty. And I absolutely love my time there contrasting that with pathology. It's also a competitive application. And as I've said, there are a number of different diversity specialties within it. Some of those you apply to a little bit later on in the pathology training process, which is five years from start to finish if you were to go straight through. And again, similarly to surgery, you get exposure to the very weird and the very wonderful along with the everyday things. And you get to undertake the really interesting task of the diagnostic process, doing all of the ancillary investigations and getting input into really how that patient is managed after whatever has been excised and sent to you. And the nice thing about pathology compared to surgery, which was what tipped me was that it's a very good work life balance. You generally will do a 9 to 5 Monday to Friday unless you go into something like forensic pathology where you may have some um weekend on calls or you may have some overnight on scene work depending on whereabouts in the UK, you're based. But generally pathology is a good work life balance with a little bit of flexibility. And with the advent of digital pathology, more and more consultants have some time working from home built into their work plan. So for me, there were a lot of attractive things that took me to it. So what is the link between these two specialties apart from surgery, sending things to pathology, pathology, giving an answer. And going back there is a massive knowledge element that the two share as well. So the two images on the screen in front of you are actually part of the syllabus for the membership of the Royal College of Surgery Examinations. And that's the matrix from the MRC SS as well. So all of this information relating to pathological principles, understanding the variety of cancer terminology. The prognosis that various different genetic mutations have on patient outcomes is all surgically assessed knowledge. And similarly with pathology, as I mentioned before, a large bulk of the workload that you can see on the bottom right hand side of the screen is surgical cases, whereby the time you become, become heading towards consultancy, you're expected to see over 1500 surgical pathology cases per year. So the two specialties do lend each other, lend, lend themselves quite well to each other. And the knowledge that you learn is quite nicely transferrable through both as I'm personally starting to find out. So once specimens are removed by a surgeon or a surgically aligned specialty, if you're thinking about something like dermatology where the dermatologists are not traditional surgeons, but they do still excise and remove their own specimens. We will retrieve them. They'll go through the fixating and embedding process, which I'll talk about in a different talk next month. Along with more in depth information about pathology applications. These specimens then undergo the process of diagnostic histopathology where these specimens are looked at under a microscope to see morphologically what they look like. And once we have an idea of what they look like, we can start to grade and see how severe that condition may be if it is, for example, cancer or we can do any extras supplementary tests to prove or better narrow down our differential diagnosis. The MDT plays a really big part of the pathologists workload as well as the surgeon's workload. And as you can see on the image on the right hand side, there's more than just two people in the room. A really good MDT has input from lots of different disciplines. Hence the name multidisciplinary. So you'll have lots of radiology input, you'll have the input from physicians oncologists, even dieticians, physiotherapists to all try and not only diagnose what's going on with the patient to provide the best management in context of that patient holistically and ultimately surgeons, pathologists and everybody else in the room is all focused on the patient outcome and we all contribute a different amount towards that. So with my point being thoroughly made, I think, let's get on to talking a little bit more about some gi pathology. And I'm going to try and do this over the course of cases for you guys so that there's a little bit of interactivity and it takes on a little bit more of the former that you'll be used to in terms of your multiple choice examinations in your exams. So, what I'll do, I've got, I've got the chat box on the other screen, have a little read through this question. I'm just gonna give you a little hint there. I'll give you a few minutes to read this and I'll move on to the next slide. So, got a 67 year old man seen by his GP with a history of increasing fatigue in further questioning. He's had some intermittent diarrhea and he's had to go down a few loops on his belt. So there's an element of weight loss there. Routine bloods show a low hemoglobin and a low M CV. But inflammatory markers and LFT S are normal. What would the next best step be for this gentleman? There's a few options on the screen in front of you pop your answers in the chat box and see what you think this gentleman would need to get the next best diagnosis for him or if you're more comfortable speaking instead, that's absolutely fine. Oh, great. Sander says colonoscopy C and I would be in agreement with that. So essentially we have a gentleman that has weight loss with microcytic anemia and a change of bowel habit and the change of bowel habit along with the microcytic anemia would be massive red flags to earn him a two week wait referral for a colonoscopy, which would be the gold standard investigation to try and look into evidence of any bowel cancer. A ct abdomen and pelvis might be useful in the acute phase. If someone has say a massive bowel obstruction secondary to an obstructing tumor, a serum C ea might be good if you've got someone with very vague histories and constitutional symptoms or weight loss where C ea can be a good marker for any evidence of colorectal cancer, it would then prompt further investigation. Stool might be something worth doing to exclude any sort of viral element and people can protect and it is just getting you to think more about inflammatory bowel diseases and Crohn's disease. But for this gentleman, because of his weight loss and his microcytic anemia, he's earned himself a colonoscopy and on his colonoscopy, this is what is seen. Does anybody know what this is in the most generic name or the most generic sense. So this is an image from the colonoscopy itself. We can see that we have um the bowel wall all around and then we have this little thing right in the center. And this is a really good image of a polyp in the bowel. Now, polyps, the word polyp just essentially means an outgrowth on an epithelialized surface. So you can have polyps on your skin. You can have polyps, Obviously in the bowel, you can have polyps in your stomach, in any respiratory surfaces, nasal surfaces, gynecological surfaces. The polyp is just a generic name for an outgrowth of tissue. Why do we get concerned about polyps because we shouldn't really have outgrowths of tissue wherever there's an outgrowth of tissue. It's a sign that there's a problem with the growth process and we have an over proliferation of cells. And when you think back towards your cancer biology, thinking about you do hit hypothesis oncogenes and tumor suppressor genes. What we know is that cancers are uncontrolled proliferative cells. So, if we have an area where we have unusual proliferation of cells, we have concern that there could be cancer there. Now, when it comes to polyps, in terms of bowel polyps, the general way that we describe them is one by location. So whereabouts in the gi tract? They are obviously this one was found on a colonoscopy. This would be a colonic polyp. And when they say morphology, the word morphology just means how does something look. So when we talk about morphology of cells under a microscope, we literally just have a really fancy way of saying, what does it look like? So when I say morphology of a polyp, what I mean is what does this polyp look like? And we have a few standardized ways of describing how polyps look. You can have a polyp that is essentially a little ball on a stalk. And we would call that pedunculated or you can have a polyp that is quite flat and just a little bit raised evenly from the surface of whichever epithelium it's arising from, we would call that a sessile polyp. Now, certain polyps as they evolve can start to ulcerate into underlying mucosa and certain polyps as you can see on the image right down on the bottom can progress over time into cancer. So, although some polyps are benign, some polyps are precancerous or have malignant potential. So, once we have seen this polyp, the best thing for us to do is to gain a sample of that polyp either by removing it entirely if it's amenable to that or if it's quite big and we're not able to do that in one go safely just by taking a small biopsy sample of the polyp itself, figuring out what it is and whether we actually need to do anything about it or just keep an eye on it. So once you've taken that biopsy we can send it off to the histology lab and we can look at it under a microscope and broadly, the questions that I'm trying to figure out are, is this benign? Is this malignant? And from that, what do I need to do about it? But in order to understand and be able to process exactly what this sample is, I need to know what the anatomy of the gi tract is and what normal histology looks like. So it all comes back to what you've been told about medical school. You can't understand pathology or disease if you don't understand what normal is. So this diagram on the left is something that you will have probably seen a few times in your anatomy textbooks that you probably won't have looked at since you were first assessed on it, which is fine. This is why we go back to things again and again. So if I have a uh a long tube of, of bowel and I cut it and then look at it along on. It's like I'm looking down the center of that cylinder of bowel and these individual layers that I'll see. So the lumen in the middle is gonna be where all of the digestive food sits working from the inside to the outside. We then have our mucosa with all of its specialized epithelial cells that help to facilitate um substance ex exchange across into blood vessels that lie within the submucosa, which is also where all of your glandular tissue lies along with your submucosal nerves that stimulate the gland release, moving outwards. Then you've got your muscularis layer. So we have smooth muscle within our bowel and we have multiple layers of that. So you've got a circular layer and a longitudinal layer that help not only to move um food along, but also to segment it and break it up into smaller boluses to increase the surface area and maximize absorption external to all of that. We have our adventitia slash cirrhosa. And that is a nice surface that is lovely, smooth and shiny and allows the bowel to essentially stay nice and lubricated and not adhere to any of the surfaces. And we can correlate that really nicely with this image on the right hand side where I appreciate none of you are histopathologists and I am exceptionally early on into my histopathology training, but bear with me and we'll talk through it together. So at the very top of this image, this white space is essentially the lumen the inside of the bowel. And then moving down, we have our mucosa. So our mucosa is going to have lots and lots of little cells. It's going to have lots and lots of indentations in vila and crypts depending on whereabouts in the bowel that you are. So if you're in the small intestine, for example, we know that that's going to be where a lot of the absorptive capacity for food comes in. So we're going to expect cells with a lot of microvilli. Whereas in the large bowel, much of the function is about water absorption compacting down that matter into fecal matter and secreting mucus to move it along the bowel. So rather than having vili a vla that are poking out will have crypts that are indenting in. And you can see there are all of these little pale spots on these crypts. These are goblet cells that have got mucus inside of them. So all of these sort of palely white blue circles that you can see in the mucosal layer are little vacuoles of mucus. And what we would expect in the normal mucosa is that you would have crypt cells at the bottom of the crypt, which are essentially a small stem cell population. They will produce new cells that will migrate up towards the surface of the mucosa and just be shed off in time as a natural exfoliative process. You may also be able to see in between these crips along with this sort of pinkish stuff. And these little black spots, these little black spots are some inflammatory cells which are normal to have in the bowel as long as they're nice and even and moving on a lovely gradient where they're maximally concentrated at the bowel surface and less concentrated to the approaches of mucosa, that's all normal. So brief summary mucosa, we have crypts in the large bowel these crypts contain goblet cells that have mucus and they should be more active at the bottom with more inflammatory cells close to the surface inside our submucosa. You can see that this is more horizontally layered and there's a little bit more swirly in terms of its pink color and these are very technical terms. Um this is all just loose connective tissue wherein certain glands will live. And you can also see some blood vessels coming in where you have these little pockets of pink, these little pink dots are red blood cells. So we've got some nice blood vessels in there leading into our muscular layer, our tunica muscularis, you can see that we have two pink layers, one that's nicely horizontally laid and one that's a little bit spotty lower down. Those are your two separate layers of muscularis mucosa, your longitudinal and your circular muscularis because obviously, we're looking at them in two different perspectives. We're seeing two different orientations of them. Another thing to consider in histology is that we're looking at two D images, but these are 3d structures. So you have to sometimes with the eye of faith and trust about who's leading you understand that things are going to look slightly different depending on which way on you're looking at them. So this nice rich pink color is quite typical of muscle cells and these are obviously smooth muscle cells. So if we were to look at this on a little bit higher power, you'd be able to see that these are individual cells rather than nice long striated multinucleate, um skeletal muscle fibers. And then moving down to our last layer, we have our cirrhosa, which is the m the pay list of all of the layers. It just contains a little bit of fatty tissue, some loose connective tissue and a few stray blood cells. So this is normal. This is what you would expect to see in primarily the large bowel. And in terms of how these crypts are lined up, the typical appearance that we call, this is a test tube appearance. So you might say that these crypts are all lined up, they're nice and even and they look like a rack of testes and what we get concerned about with histology, we talk about morphology. We also talk about architecture, which is a really obnoxious way of saying, does this fit with everything else around it? And does this look how I would expect it to look? And does it look like normal tissue? So when I'm looking at a slide, the first thing I want to say is, does this look how I would expect it to, are there normal patches or is this all completely abnormal? What is the architecture of this tissue? And then if I do find abnormal areas, I will zone in and I'll look at those cells and I'll say, what's the morphology of these cells? What do these cells look like, do they look like normal cells or do they look a little bit weird? And if I know how weird they look, can I make a diagnosis from how weird they look and how weird this patch is six. So just reiterating a few things that I've said you will get some variety depending on whereabouts on the gi tract that you are. As I mentioned about inflammatory cells being more common closer to the surface of the colonic mucosa. You may find that in places like the appendix or the cecum, you have quite a large amount of inflammatory cells and that's just normal for that particular bit of tissue. And the two cells on the right hand side are just aiming to reiterate what I mentioned before about looking at things in different orientations. So the image on the bottom is very similar to the image that we've just looked at. We have those cricks that are diving into the mucosa. We've got those white spots. So sometimes they look pale blue or pale pink depending on the staining. And they're the goblet cells that are full of mucus. Now, these are tubes that are going down if we were to cut those tubes across. And we were looking down the column of the tube down a cylinder, we would see the image on the top right hand side. So we've got longitudinal and transverse sections of our crips. So it's important to know that these are both normal. You're just looking at them from a different perspective and what I'm looking for in terms of all of these cells, features of normality or features of malignancy, things that you may be asked about in your exam, things that I'm looking for are to check that all of the nuclei in these cells are all equally sized, making sure that there are equal levels to each other that they're polarized and that they know exactly what they're doing in relation to each other. And then making sure that there is similarity in these crates to each other. That one isn't particularly big and enlarged, that one isn't particularly obscured or distorted. It's literally say what you see and sometimes you might feel like you sound silly saying what you see. But nine times out of 10, if you can see something abnormal, it's because it is abnormal. The caveat to that I would say cos this is something that usually catches me out if we compare this image that we're looking at now to the one that we saw before these images are, are lovely, sort of bright, primarily pink and a little bit purply. This section looks a lot darker. That's just a staining issue. So we use H and E stain as your normal histopathological stain. But sometimes the staining can take in different ways. Different labs may produce different levels of stain. So certain times stains can look slightly different between labs or even within labs, which again is why we are looking at things in relation to each other to check for normality. Because generally if you look at a slide and see that there's quite a lot of dark and quite a lot of purple, it usually makes me a little bit uncomfortable and wonders if there's a level of dysplasia or a level of cancer there. But once I look at this in a lot more detail, I can see that it is pretty much exactly the same as the one on the previous slide. So we've got lovely epithelial cells up at the top, we've got goblet cells full of mucus that are nice and equal with each other between those goblet cells. We've got those little black spots of lymphocytes that are looking normal and all of those layers are actually intact. So again, the variety of normal, much like real people can also transfer into their cells as well. So a large part of histopathology, at least at my stage in particular was understanding what normal is. Once you know what normal is, you can start to then appreciate what abnormal is. So, have a second looking at these pictures and write in the chat box or tell me if there's anything you can see that just looks a little bit weird. Anything that looks a little bit abnormal compared to what we've just looked at, obviously, I will tell you the answers. But by all means give it a go yourself. You'd be surprised how right you can be. So and this image over on the left hand side, if you look at the center of this image, you can see that there are these little circular structures with a little clear lumen in the middle. And there are all these pale cells just sitting around it. Now with the eye of faith, I would say that these nicely spaced, nicely regular circular shaped cells, these are glands or crypts. So they are, excuse me, they're glandular cells, but these are likely to be crypts. And if we go back to two slides, we can appreciate that these are very similar to these structures here on the top right hand side image. So we've got some crypts with some glandular cells forming nice circular formations and the cells around them are not particularly thickened. They're not particularly unusual. But then as we start to progress up towards the top of the image, towards the surface of that image, you can see that in contrast the outlines of those glands, they're just a bit thicker, a little bit more fluffy, a lot more purple and the actual center of those glands themselves is not quite as clear and not quite as big. And none of the words that I've used. There are particularly technical but they describe what I'm looking at and they describe a pathology. In contrast this one over on the right hand side you can see that these white areas with all of these sort of purple cells around them, they look a little bit like the glands that we were looking at, but the center of them is not quite circular. It's a little bit interrupted. It's a little bit jagged, it's not quite clear and the cells around it are a lot more dense. We've got a lot more little black spots, a lot more lymphocytes there. And again, I've not used any technical words there, but I have appropriately described two different pathologies. So, on the left hand side, what we're seeing is a really classical type of polyp. This is a tubular adenoma where an adenoma is something originating from glandular cells like an adenocarcinoma or a cancer from glandular cells, which would be your classical bowel cancer, colorectal carcinoma, colorectal adenocarcinoma. And it's called tubular because essentially, it's got lots of glands that when you put them in different sections look like test tubes like the cricks that we were looking at before. So pathologists much like anatom anatomists, we just describe what we say and we name things after what they look like. They're very simple creatures. We spend lots of our time looking at pictures and naming it after what it looks like. So this is a very classic tubular adenoma, which is a premalignant lesion and the changes that you're seeing at the very surface of this tubular adenoma, these sort of dark purple fluffy bits with these obscure central glands, this is dysplasia. So when we talk about cell changes, obviously, when we talk about neoplasia or production of new cells, which usually end up becoming cancer cells before that happens before these cells become neoplastic or cancerous, they become precancerous. And that's what dysplasia essentially is cells that are not quite normal, that are on a scale of abnormal, but they're not quite cancer. So if we catch them early, then we can prevent that becoming cancer. If we leave it in place, there is a percentage chance that this will go on to form a cancer. On the right hand side, this is a hyperplastic polyp and hyperplasia is just the fancy word that we use for more cells than there should be. So if you think to cardiology, when you have people that have hypertrophic cardiomyopathy or they have cardiomegaly, they muscle hypertrophies, it gets bigger. The number of cells is still the same. But those individual cells are bigger or when people go to the gym and lift weights, their muscles are hypertrophy. Hyperplasia is the increased number of cells. And you might see that in prostate problems, benign prostatic hyperplasia. So under certain influences, organs or tissues will start to produce more cells than they need to. And oftentimes that doesn't cause any problems, but sometimes it can. So hyperplastic polyps are not necessarily a problem in themselves, but it's good to be able to differentiate. But ultimately, it's not a cancer and this is also not precancerous. So it's benign or better out. So, looking at this image on the right hand side and now that you guys are expert pathologists, if you were gonna have your bets, do you think this is a benign thing or a malignant thing? So, pop your answers in the text box and I'll just start to throw out some features that are catching my eye. And again, it doesn't matter if you write or wrong but have a guess and see in your head if your guess is right and why you think it might be. So when I'm looking at this picture, I can see that there are a few shapes that are trying to be like those crypts, like those glands that we saw earlier. Well, I can't really see more than two that look the same. They're all unusual irregular shapes. The actual tissues themselves are not hugely arranged into really clear layers and they're kind of bleeding into each other a little bit. I'm also quite concerned about this really hyper pink area on the left hand side. So sa is putting their money on be malignant and two out of two pal, I would say that this is definitely malignant. So this is a picture of a colorectal adenocarcinoma and why literally the way that I'm processing that is by saying, OK, I know that this is bowel tissue. Does it look like a bowel tissue? That I'm used to seeing. No. Can I make any sense or normality out of this? No. In what way does it look abnormal? Well, there are some things that are trying to be normal things that they're not quite actually achieving that the cells look very different to each other, which really in a tissue shouldn't happen. Everything wants to be nice and coordinated and working together. So, if I've got a tissue that doesn't look normal, doesn't look anything like each other. And it doesn't really have any well organized structures that is really putting red flags up for a malignancy. And even before I knew what kind of malignancy this was, I was, I was at least able to comment on those features. So back yourselves, say what you see and you want me follow up. But ultimately, why am I taking you through this process and why is it important for us to be able to differentiate exactly what these things are? And the answer is because having that diagnosis fits into how we manage the patient after, depending on what the diagnosis is of that polyp, whether it is malignant or benign and what the actual underlying diagnosis is from there. Excuse me, it feeds into whether we do any further testing on that specimen or whether they need to have a further colonoscopy in one year in a few months or three years, which obviously, I don't know if you've ever had a colonoscopy neither have I, but I've seen plenty done. And you, if you can avoid having one, it's probably ideal. If you need to have one done, it's not the end of the world, but it's no one's idea of a fun time. So how we interpret the information that we are given how we reach that diagnosis is really important in feeding back to what actually happens with these patients. And it can be quite a common question in your multiple choice exams to be aware of which polyps are likely to have malignant potential and how that may affect further colonoscopy screening. So I am spoon feeding you is very useful information for your exams. Hopefully. So case number two out of three, we'll go through this one a little bit quicker. Cos obviously, you've had a little bit of time to go through normal mucosa. Now. So this time we have a 47 year old lady referred by her out of hours. That should be out of hours GP to the acute medical unit with a history of nausea and epigastric pain. And the GP is concerned about her having an acute mr her blood tests and her E CG has come back normal. She's tender over the epigastrium and she reports this being worse at night. She's just started a new job and she's been struggling after the sudden passing of her father. So this is not something that this is something that you would fairly commonly see in your medical takes in Ed or in the surgical take. So how would you want to manage this patient? Next. Which things are you thinking about in order to gain a diagnosis from the information that we have someone with epigastric pain, negative cardiac markers, negative amylase and a history of stress with the pain being worse at night. Thank you. No, I will accept any answers. They do not necessarily have to be correct. Um It's three out of three for Sanda. Yes. This person needs an O GD, an esophagogastroduodenoscopy. So this person has their O GD and these are some of the abnormalities that we can see. So on the left hand side, we can see there are some pale patches within the stomach and on the right hand side, we can see that there are some quite freshly inflamed bleeding spots. So given the history and given the imaging that we can see, what kind of diagnosis are we thinking about? I let you guys mull that over. So again, we need to know what normal is in order to understand what abnormal is. So, similarly to to the um large bowel, similarly to the large bowel, the stomach is arranged into the exact same layers. We have our mucosa sitting at the top of the screen, we have our submucosa and our muscularis propria sitting underneath the muscularis mucosa that's labeled here is just that kind of intermediary layer between the mucosa and submucosa, it wasn't mentioned on the first diagram, but it is present. So we have our mucosa submucosa, our muscular is appropriate and we have our cirrhosa exactly the same where things are different in the stomach is that if you think back to your gastric physiology, you know that there's going to be cells there that are secreting hydrochloric acid cells that are secreting pepgen intrinsic factor. And there are going to be glandular cells that are secreting gastrin and ECF cells that are secreting histamine, you're going to have nerves being stimulated as well. And we can see this reflected really nicely in the arrangement of the mucosa, whereby again, we have more gland cells. But the arrangement of these gland cells is different. So in the large bowel, those gland cells were arranged in circular formations that were quite regular and they were arranged in crypts and they were arranged in vili, whereas in the stomach, they're a little bit more haphazard. But you can appreciate that when we look at the lower end of this image compared to the top of the image, all of these glands mature and change shape. So we've got some more tightly packed glands at the bottom, some more loosely packed ones with clearer lumens towards the middle. And then at the top, we again have got some nice white spotty glands that contain mucus and that is our normal gastric mucosa. So the gastric biopsies from our patient, this is how they vary. So we've got our normal slide up on the top left and we have our abnormal slides on the bottom. And again, say what you see, you probably are thinking a similar thing in that. When we look at the lower part of the image, these glands look fairly normal, they're nicely spaced of heart and they look uniform. But as we get towards the surface, everything just looks a little bit more busy. There are a lot more black spots, a lot more lymphocytes, which is what they are. So you've got some inflammation going on there. And when we look at the actual epithelium itself, you can see that some of these cells are a little bit higgledy, piggledy, they're a little bit crowded and they're a little bit uneven. So we've got a lot of inflammatory changes going on here and inflammation in the stomach in the context of our patient will lead us to think about gastritis. But obviously, we then need to think about what is the cause of this gastritis. Now, we could just write this off as our patient being stressed and this contributing significantly to an element of gastritis or with an element of active inflammation, we are obliged to do certain tests and just make sure that it's nothing else. And this leads us on to talk about ancillary testing that we can do in histopathology. So looking at these slides here, I can't see anything abnormal that would be contributing to this patient having gastritis. And there are no abnormal cells here that might point towards what an underlying diagnosis might be. So this could be something, it could be nothing. But I want to be sure. So I'm going to order some extra tests. So we can do immunohistochemistry or use supplementary stains to see if other things show up on our tissues. So we know that certain cells have their own passports and have their own signatures in terms of the proteins they express on their cell surface or the genes that are expressed and readily available in their nuclei. So we can use immunohistochemistry to use colored tags essentially to add on to those receptors and see if they show up on a slide. So we can say if this cell is positive or negative for certain markers that are classical of a cell that we're looking for or a cell that we're hoping is not there. So that's one thing that we can do. And the other thing that we can do because again, you'll probably have some of these questions on your exams is to look at different types of stains. So classically, we use A H and E stain which shows up all our pinks and purples, but we can use lots of different stains to show up with different things. We can use BMC stains Wharf in Starry stains for this particular person. Um We are thinking of getting a stain that we'll talk about in a second. These pictures are just here to show you actually what immunohistochemistry can do and what some of the unique stains are. So, if we have a slide on the top left, which we have used immunohistochemistry on, we would expect if this is positive for it to show up looking a little bit more like a four and B four, a lot more rich in color and a lot more tagged essentially in terms of the cells. So what we're broadly looking for is one, if there is big uptake of the marker that we're wanting to do immunohistochemistry on. But also if we're expecting that in the place where it's showing. So if I'm using immunohistochemistry to look for a cell surface marker and it's showing up nuclei, something's not quite right there. But if I'm looking for a cell surface marker, and I'm seeing lovely outlines of cells, then that tells me that I'm on the right track and they come in a variety of wonderful colors as you can see. So for this particular patient, we were suspicious that they may have had one of the leading causes of gastritis in the western culture and H pylori infection. So H pylori is a spiral or spiro keep bacteria. You can use things like stool antigen testing. You can use a urea breath test if we have a gastric biopsy and we're suspicious of H pylori, then we can do a special thing to show up H pylori. So if we want to look at this slide on the left hand side, knowing what I've just told you about immunohistochemistry and staining. Would we say that this is positive or negative for H pylori? Can we see other things that are staining differently that look a little bit unusual in and around ourselves? Or we wouldn't expect things to be and looking at the time, the short answer of that is yes. All of those orange blobs that you can see are evidence of H pylori colonization. So from this slide, we can diagnostically and conclusively say that this patient has H pylori, which could be exacerbating the symptoms they're having of their gastritis. But this is something that we can treat. So by having this biopsy by doing the testing, we managed to reach critical diagnosis for the patient, which means they can get definitive management and resolve this probability root cause rather than just trying courses and courses of PPI S and seeing if they work. And this is obviously what we look like in the lab when we get a positive stain like that as as Kyle will will tell you. So last quick case, we have a 53 year old man that presents to ed with abdominal pain, fevers and fecal and vomiting after not opening his bowel for seven days and not passing floaters for two CT scan shows free air in his abdomen, a dilated colon with a transition point on the left hand side. And he's taken to theater where a perforation is sound in his colon. There is a concern that this may be resulting from a cancer. So he has an oncological resection of uh of his ascending colon and the specimen is sent to pathology. So as we're looking at this, we receive these samples into pathology, obviously whole and intact where the resection is. So, so being able to understand your macro anatomy or the regular or big anatomy is just as important as being able to figure out what other things look like when they're abnormal under the microscope. So we would receive a specimen on the left hand side into our lab and we would systematically look through it to see if there's any abnormalities there that we need to take any sections of to try and diagnose it. So we may see images like the one in the middle and the right hand side where we can see that there is some abnormal tissue change through this bowel. We can see that there is not a nice even run of um the bowel mucosa on the inside. And we can even see on the right hand side that there's a stricturing or a narrowing of the bowel at a particular point. And this all raises concerns of cancer. What we know about this gentleman is that this obstruction was so bad to the point that his bowel actually perforated. So if you have a completely obstructing cancer, nothing's getting past that. Which is why the bowel then dilates and it perforates. So not only can you see free air on an X ray or a CT scan, which clues you into the diagnosis, but where things are no longer able to pass through that bowel, you can see that bowel as it goes from being nicely big and dilated down to a thin point where nothing can get past it. And that is what we call a transition zone. It's something you may also hear spoken about when looking at bowel, obstruction of other causes on CT scans. But for this particular patient, we're highly concerned about cancer. So we take samples of this cancer and help the Royal College of Pathologists in conjunction with their colleagues in the surgical college, put together data sets that say where we should take our tissue sections from in order to make sure that we are assessing this specimen for cancer appropriately. So as well as making sure that the margins, so where the surgeon has done the resection are clear of cancer at both ends. We also want to make sure that any other surfaces that have been cut away like the knees and toe or the blood supply are clear of any cancer. And we also want to make sure that we're looking at the lymph nodes to make sure there's no evidence of any spread because that will change the staging of this tumor and ultimately change the management for this patient. So again, looking at these slides down at the bottom of the page bearing in mind that this is colonic mucosa, the one that we looked at in our first case, comparing it to the slide up on the upper right hand side, you can see quite clearly that this is not organized tissue. It's not in a nice format that we're used to seeing up on the upper right hand side and all of the cells are differently sized. There's different gradients of really dense black spots of cells and really light areas of spots of cells. There are no clear glands that are forming. So this is consistent with an adenocarcinoma of the bowel. But the thing that we need to be looking at is our lymph nodes. So we have to look at at least 15 lymph nodes. So quite quickly, you become familiar with what a normal lymph node looks like. So, on the left hand side, we have our lymph nodes that has a little pink rim just around the outside of it. And this is the capsule and you have all of our rich lymphoid follicles in the center with some paler germinal centers that are producing all of these cells. And that's a normal lymph node. The questions that we're looking at to see if a lymph node is involved is one is the capsule outside still intact. And two are there just normal lymphoid cells in the center? And if not, what do they look like? Could it give us a clue about where this has come from? So say, for example, that the picture in the middle is from our patient and this is one of their lymph nodes, you can see and appreciate that. On the upper left hand side, there's a little bit of a sort of a capsule or an even border. But as we get towards the bottom and the right hand side, it's just completely eradicated. It's all bubbly and it's very irregular and we're not seeing in the center of this lymph node, anything that looks like the cells on the left hand side. But with the eye of faith, you can see that towards the top of this lymph node, we've got some structures that are trying to form glands. And with the eye of faith, it looks a little bit like the slide on the right hand side. So we can say that this lymph node is positive for metastatic, positive for metastatic spread from our original cancer. So this patient does have nodal involvement in your exams. You'll be asked multiple times about tumor staging. Classically, we use TNM staging where T stands for tumor N that stands for nodes and M that stands for metastases. And we can subdivide that further by having a clinical tumor stage. In other words, how does the tumor look on imaging and how does it look macroscopically and a pathological tumor stage, which is the stage that we get under the microscope, specifically for colorectal cancer, we get very concerned about how much that cancer is spreading through the different layers of the bowel wall because that affects its tumor staging. And we also get concerned about how many lymph nodes are involved and what proximity they are to our cancer. Because if we have local lymph nodes involved, that's one thing. But if you have completely distant lymph nodes or evidence of disease on the opposite side of the body, that is quite significant and impacts their staging. So that our particular patient, our slides were showing an adenocarcinoma that was invading into the muscle layer but not completely through it. And in total, we have two lymph nodes positive out of 15, which is information that I've just given you, we obviously don't know about metastasis because we don't have imaging of the full patient. And that's also not my job. But if we were to try and stage this patient, based on the information that we have how I would look at this is saying that OK, we have got a cancer looking at this tumor staging, it's invading into the muscularis but not through it. So this would be att we have two positive lymph nodes out of 50 lymph nodes taken. So that means we are looking at N one and within the subsection, we have N one B and that is honestly as complex as it gets and literally just matching what I've found onto diagrams so that I can accurately stage cancer for a patient. And again, it matters because this means that we can optimize the testing that we do for these patients. We can do further molecular testing to see what immunotherapies or chemotherapies may be appropriate for them. And all of this is mediated by both surgeons and pathologists. And then ultimately, in our MDT discussion, we have the input from radiologists and oncologists to work with the information that we have so that we can optimize what's happening for our patients. And these three cases were all based on real things that I've dealt with in the last month and a half of pathology training. So having never really looked down a microscope before you learn quite a lot, very quickly, just by having regular input and having the confidence to be able to look at something and say that just looks odd and then having a conversation with someone else who says, yeah, that does look a bit odd. But in what way and do we know how odd it looks? And if this odd matches something that we know about. So, pathology is key knowledge for surgeons, we may surprise you with how much we know about diseases. I've found that there is a lot of transferrable work and a lot of transferrable knowledge the pathology input is a very key part of surgical work. So those of you that are looking to go into procedural or specialties or into surgery, you can't get away from pathology. And for those of you that are wanting to go into pathology, you can't get away from surgery. So knowing about both is really important and appreciating the work that each of them do is really important. The best MDT S have representation from a wide range of specialties and appreciation for what each of these specialties do. So, I think I've done pretty well, finishing one minute to eight and that's been a nice little overview of normal histology of abnormal histology and common pathologies as well as a nice little overview of some of the training aspects and some of the clinical scenarios with a little bit of information that's hopefully going to be really useful for you guys going towards your exams. So if you have any questions, feel free to put them in the chat box, feel free to ask me if there's something you're not confident to ask here by all means, email me whether it's about careers, pathology, surgery, anything you want. I'll do what I can, I think I'll hand it back over to you. Ok, thank you. Um, so yeah, so, um, thank you for Doctor Moore for taking the time to um, do that, um, talk. Um, I thought it was, er, really interesting. Um, I almost wish I'd had that, um, that talk when I started, er, pathology training, to be honest, um, if you've got any questions, feel free to put them in the chat, um I'm also going to just put a quick feedback, er, link in there as well. So those that are attended, if you're happy to fill out the feedback link, that'd be much appreciated. It will give us an idea as well on er, what topics, um you may want us to cover um at future sessions within this webinar series. Um We're fortunate to have um Doctor Moore join us again, er, later on in the series. Um So, er, there'll be another, er, good talk um I think for next month, er, towards the end of next month. Um and between now and then there will be plenty of talks that cover things like histopathology applications, interviews, er, the, and the different specialties and how they work in UK training as well as some more um in depth talks about the actual, er, pathology and the various um organ and tissue systems um within the body. Um So, yes, I'll just reiterate my, thanks for that wonderful talk. Thank you. Any questions. Thank you very much to everyone for your time. I know it's not easy getting enough time out of your evening to come along and do some more learning after a hard day. But thank you for your time and your patience and hopefully you've learned something I appreciate you doing. No problem. So, what I'll do is um, I'll leave the, um, the talk live for just a couple more minutes, er, for people to, er, click the link and provide feedback. However, um, both yourself um, Aidan and um, any of the, um, people who have attended, er, once you've done that, feel free to leave. Um, and then I'll close the session down, er, once everybody's left. So, thank you. Thank you.