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I have one. My name is Thomas. I'm one of the Scotland Reps for assets and so welcome to part three of the mrcs Pathology webinar series. Hope it's been useful for everyone so far. Whether you're sitting the mrcs sooner, sooner or not. So, the same format this evening, we've got to talks both just under an hour with some time for questions as well. Our first talks by Donna Odd were she's ST for pathologist in Glasgow. Give you a wave there on the screen. She's completed mrcs part A and B and C as well worse than this and she'll be doing the colorectal part of the, the evening. Um Second, we have Paris at Tamil Aqueous. He just appeared now and he's ahead and technologist and leads who's also dental trained as well and we'll be doing the head and neck section. Um, so just in the interest of time and we'll pass over to Donna and she'll get the evening kicked off. Ok, fab, thanks very much for that introduction. So I'm just going to get my slides up now. Okay. So, hi, everyone. And I said I'm Donna S T four M pathology in Glasgow, um going to try and use, um, my experience of having done the mrcs many years ago to try and tailor this presentation to what you might need. So, first of all, I just went through and the guide to the Intercollegiate mrcs exam just to re equate myself with how the exam works and the information topics that you need to learn. This is quite a good guide because it shows the layout of the exam for part A and part B. And then when you click on the link, it takes you to I SCP um when you go through the Basic sciences, link and to pathology, it's got some general topics that you need to be aware of. So these are quite general and could and cover quite a wide range of things. And hopefully, in this talk will be able to cover a wee bit about inflammation, neoplasia and genetics. And these are some of the topics that will be covering just for your reference. Um So first office, like, how much do we actually really need to know about pathology? And like, why are we here? Well, actually, like there's quite a lot of pathology in both of the exams. I certainly remember, you know, the PTSD of like my part B and I had a Slavery Gland New possums exam and question, which is like quite common thing that comes up. And another thing where they were asking me about breast cancer and they really were asking me quite in depth questions about the kind of data set items um that the pathologists might use when reporting a breast carcinoma. Um Also, it's important to have just a good grip of pathology for the common conditions because it kind of undermines and overlaps with a lot of other areas that you might come across in your surgical practice. So to get it through all of this um pathology trainees. So I quite like pictures. So there is a lot of theology pictures in here, but that's more for like an aide memoire. Um So don't get too worried about having to memorize all of this. It's just a point of interest for discussing the conditions that we're talking about um to make this quite interactive and keep you engaged and hopefully consolidate some stuff that we're talking about. Um I'm going to be asking some questions again. Don't stress too much because these are questions that I have written kind of based on topics that I've seen come up in like a mrcs past test um and past paper questions. Um So first off, it just be good to get a good idea of where you guys are with regards to doing your exam. So I think the question is going to be coming up in the chat as a pole and you can pick a B R C. So, you know, are you who's pre mrcs A pre part B and people who are maybe nowhere near sitting the exam. Um, so if you could just answer now or? Mhm. Hopefully that working fab okay, seeing some responses come through now. Sorry, that was a moment of terror for me. Okay. So I see a lot of people are pre part a okay. Well, that's good because a lot of the questions that I have in this are kind of your single best answer type questions and the fear of everyone because there can be a couple of things that seem right. But it's the single best answer that you have to try and pick and, and it's really, I just think the more you practice this type of question, just like the easier it becomes. Um, so first of all, to get started, let's start from the top of the gi tract and talk about a pretty big topic. Um So esophagitis. Um So there are many causes of sausage itis. Um, what we see down the microscope really depends on the cause. One of the most prominent cause is, is reflux esophagitis, particularly in the western world. Second, really common causes infections of which candida infections are most common, but you can also get HSV and CNV. And sometimes you can get, if you're unlucky and infected with both at the same time, obviously, um, you know, compromise is a risk factor. Um You can get direct trauma to the esophagus by chemical arrogant irritants such as alcohol, smoking hot drinks. Other causes might be chemoradiotherapy and pill induced esophagitis that you might see in older patient's. And then at the other end of the spectrum in younger patient's, and you might have people presenting with eosinophilic esophagitis. And this is really a clinical pathological diagnosis and that we get the diagnosis to when we've got biopsies from multiple parts of the esophagus. And then histologically, we see a certain number of eosinophils in the esophagus. Um Other types just to be aware of or things like empathetic suffrage itis and GVHD and systemic causes can also cause esophagitis, but they usually um reflect their counterparts and skin. So again, it's just to be aware of these. Um but it's important to have an understanding of the common causes. So as I said, for reflux esophagitis is the foremost cause of esophagitis in the western world. And it's due to reflux of gastric acid which causes a mucosal injury to the lower esophagus. And this is due to decreased lower esophageal tone and increased intraabdominal pressure and which could be secondary to numerous factors. So for example, obesity, pregnancy, alcohol and microscopically in this picture from Wikipedia shows that you might have like edema and erosions um and microscopically. And I just pulled for this from pathology outlines. It shows that we get kind of increase in the number of basal cells of the squamous epithelium and we'll get kind of congested epithelium with lots of chronic inflammatory cells. Um these can be relatively like non specific findings for us. But what's really important with reflux esophagitis is to think about um the sequela of long term reflux esophagitis, which includes ulceration structure and barretts. Uh So, moving on to our next question. So after what we've kind of just said, which of the following statements is true regarding gastroesophageal reflux disease or reflux esophagitis. So hopefully there'll be another um then coming up in the chat for you to answer. So, is it a it's the second most common cause of soft itis be complications include ulceration structure and barrettes. Great. Um I can see a lot of people are going for that. One c mainstay of treatment is behavioral modification d associated with increased lower soft tone and decreased intraabdominal pressure or e so, yeah, be perfect. So that brings us on nicely to the next topic which is Barrett's esophagus. So as I said, this can be a complication of long term reflux. Um So the BSG definition and here is really nice because it highlights that this is kind of a again a clinical pathological diagnosis which depends on what is seen endoscopically, but also what we see microscopically. Um The definition of metaplasia, I seem to remember mrcs loved knowing your definite, you're pathological definitions is the replacement of one differentiated cell type with another. Um And as I said, kind of up to 10% of people with long term re flips can get barracks. So it is very important. And if we see Barrett's esophagus with intestinal metaplasia, that can confer an increased risk of soft deal adenocarcinoma. So, on the left here, we've got a picture of what we might see endoscopically, that kind of red velvety mucosa. Um And the way that this is assessed as using the prag criteria, which describes the circumference and maximum extent of the M barracks that's seen endoscopically. And then on the right, this is what we see down the mic microscopes. So you've kind of got the normal a soft deal squamous epithelium on the left and then transitioning into this glandular mucosa, which is kind of pockmarked with all these like circular gray cells, which I hope he's can see okay. And these are the goblet cells and now metaplasia and barrettes. It's not always intestinal metaplasia, but this is the one that has an increased risk of adenocarcinoma compared to other types of metaplasia. So it is the important one when we're talking about barrettes. Um Also the BSG has guidance on endoscopic surveillance and when a patient is diagnosed with this and that guidance is all centered around like the extent of the Barrett's seen endoscopically and whether intestinal metaplasia is present or not. So, hopefully, this question should be easy to answer. Um So in the context of Barrett's esophagus, what is the pathological process where scream cells are converted to culminate type cells? So hopefully, and that'll be coming up in the chat now for you to answer. I'm just gonna okay, reconnect. So hopefully I can see that fab. So that was an easy question. I'm glad that people are getting that okay. So, um, we've kind of talked about reflux leading to barrettes and then the next equally is esophageal dysplasia. The definition of this is literally disordered growth and, you know, there's significant evidence which doesn't take a genius to work out that dysplasia in the lower esophagus and is a risk factor for the development of carcinoma. All. Um, when we're looking at dysplasia, it ranges from mild to severe. And when we're making a first diagnosis of displays in the lower esophagus and that usually needs to pathologists. Um We can use p 53 staining to help us because this is a mutation that we see in this pathway. Um So on the right, we have kind of a picture showing low grade dysplasia and you can see some normal glands and next to a typical glands and the atypical glands, the cells are more disordered. They're all overlapping on top of each other. They have elongated and look Pence Lee and we can see that they've lost their polarity, they're not sticking to the basement membrane and there's quite a few mitosis popping around there. So that's psychological atypia on the left, that's what high grade dysplasia would look like where we've got the psychological atypia. But we've also got architectural disorder here. Um Now, the reason that the distinction between these two is important is because it has an effect on management. So, for indefinite dysplasia, usually that might require a period of treatment and then re biopsy with low grade dysplasia. This will lead to increased surveillance for the patient. But if there's a diagnosis of high grade dysplasia, this might be a lesion that is amenable to radio frequency ablation, endoscopic mucosal resection or in cases of multifocal high grade dysplasia, even esophagectomy. So it's quite an important diagnosis to make and that we make the right one. So um now we've got a patient who's got weight loss in dysphasia, we've got a mass or G O G and now we've got adenocarcinoma with high grade dysplasia. So we know that this is a risen from the background dysplasia. Now, of all these features here, which actually suggests that the neoplasm is malignant as opposed to just dysplasia. So hopefully, so I will come up in the pools. Okay. So maybe a wee bit of trouble with that one. So, um lympho vascular invasion is the correct answer because you shouldn't really be seeing that in a dysplastic process. So, dysplasia is kind of like you're in situ stage. So all of these things nuclear pleomorphic is um architectural psychological atypia necrosis, dysplasia. That is all just that you can see with dysplasia when something has become cancer. Remember it's invading. So it's gone one step beyond that So, if it's managed to breach the mucosa, if it's managed to get into lymphatics in vessels, dysplasia, doesn't do that. That is a carcinoma process. Um So it is important to know with your definitions, these differences because these, I remember them asking these type of things and me getting confused about it as well. So as I said, dysplasia is a risk factor for developing esophageal adenocarcinoma in the lower esophagus. Um on the left, this is what that looks like. And as we've discussed, it's that kind of progression from barracks to dysplasia to adenocarcinoma with accumulation of mutations that include P 53 Cyclin D one. Um You can also get a diffuse type of vaginal carcinoma, your kind of signature ring cell um adenocarcinoma. Sometimes they ask about that in the context of like limitus plastic cast. So just remember that um now another common carcinoma in the esophagus is squamous cell carcinoma, which looks quite different. We can see that in the picture on the right. Um And this is usually in slightly older patient's than the medicine ah fungus. And it's like multifactorial between genetics and environment. Just a quick thing on how we stage these again, not something to get to hit up into, but to have a good understanding roughly because I remember trying to learn these for MRCS. Um So when it's in the ecoza layer, it's a t want when it's breached beyond this and gone into the muscularis, appropri A, it's T two when we've gone beyond that and we're in the subserosal A, it's T three. And then depending on whether this is a gastric or soft deal cancer when it's gone beyond the serosa and is invading into other structures, we would consider it t four. Um And then obviously, we've got kind of different stages of lymph node metastases as well. And then when we're looking at the important things that we report, um you know, we're talking about the type of tumor, the differentiation of the tumor. So how closely the tremor resembles normal, essentially, uh the depth of invasion, which is t stage. And we've talked about um tremor aggression grade, which can be quite important and particularly in lower soft deal adenocarcinomas might have had chemo radiotherapy. Um So, you know, if there's no regression of the tumor that might influence whether the oncologist wants to give further therapy postoperatively, if there's like lymph nodes involved, um margins are obviously important and are also important, kind of like for surgical audit, particularly circumferential remark, margin status and then obviously other factors that mean that it might be a higher stage tumor. So, as kind of based on what we've just talked about, we've got this older gentleman, um he's got squamous cell carcinoma this time and we've got a tremor that has gone beyond the mucosa, beyond the muscular is appropriate and into the subserosal to and it's gone to two lymph nodes. Um So what is the TNM stage? Hopefully that will be coming up in the pools. Sorry, I think I get a wee bit of a delay. Okay, great. Most of us are getting. Um But yeah, it's A B but like I can understand why you might have said E as well cause like literally just shown you. But you know, these are the type of things. It's a bit of like guesswork. So we know that it's T three cause it's gone in to the subserosal. Uh It's only going to two lymph nodes. So the way that I would kind of approach this question if, if I wasn't sure between the lymph nodes stages because you like, you can't remember everything, but you just have to have a rough idea of like two lymph nodes, doesn't seem very many. So maybe it's N one which it is. So the correct answer is be, but it's just thinking about how to approach questions and using the knowledge that you have to kind of come hopefully to the right answer. And so just x slide really for a bit of reference is obviously there's benign neoplasms that we have in the esophagus. Um A couple of them are associated with a risk of progression to carcinoma. Um for example, squamous papilloma, but it's very rare. And Leo myoma is the most common benign tumor of the esophagus. Um And granular cell tumor is another tumor which we consider benign, but there is a significant proportion of these which actually can be malignant and they have quite a per prognosis. So, based on what I just told you, hopefully should be able to answer this question and which the following neoplasms of these, uh this is the most malignant potential. Um So hopefully you can put your answers in the chat now, Bob Good. Okay. Moving on. So finally, we're away from the esophagus into the stomach. Um gastritis, more inflammation. So, gastritis can be broadly categorized into categories, acute and chronic. Um the causes of these have a lot of like overlap with each other. Um Basically, we get gastritis when precipitating factors, um lead to defects in the stomachs, defense against acid. So these factors might lead the stomach to actually produce more acid, reduced bicarbonate, which should protect the mucosa and reduce mucin and production. You also can get like direct injury. So, again, things like chemo radiotherapy, um it's a direct cause that might cause necrosis. Um Here's kind of a list of the common causes of the different types of gastritis. And as I said, there is a bit of overlap between the two um for exams and kind of remember your stress interest injury. Um and particular women were talking about kind of ulcers particularly in the duodenum. It's knowing the difference between your curling and your Cushing's ulcers. So, you know, your Cushing's ulceration is usually when you've also got an associated um intracranial disease and you're curling ulcers is in the proximal geo Denham, usually associated with burns. So that's a wee bit of a deviation but kind of related. Um, so the most common cause of gastritis world, what chronic gastritis worldwide is H pylori. So, like 50% of people worldwide might have the infection, but that doesn't necessarily mean that everybody has symptoms. Um The reason for this is that it's quite a virulent organism. It's got a flagellum which makes it motile. It has um Cytoxan gene a which helps it to produce cytokines and reactive oxygen species and it produces yuris. And what we see down the microscope is this kind of stomach where the glands are filled with neutrophils and there's lots of neutrophils in the lamina propria and that would trigger us to go looking for h pylori. Um So a reason why this is quite an important type of gastritis is because the complications include intestinal metaplasia, which we've discussed before can be a kind of predisposing um step in the carcinoma pathway, um can lead to ulceration and also mucosal associated lymphoid tissue lymphomas. So, another big cause of chronic gastritis that they ask about the exam is autoimmune gastritis. Um So usually this is in the fungus and body and microscopically, it leads to kind of what we call centralization of the mucosa. And so the specialist cells and bodies start to look like the non specialized glands that we see in the Antrim and it's due to kind of a CD four mediated T cell mediated destruction of the parietal cells alongside your circulating antibodies to the parietal cells. And two intrinsic factor. And this leads to defective gastric acid secretion which then triggers your G cells to actually produce more. So you get hypergastrinemia um and, and then you get the glands, the defect glands regenerating biomet a plastic process. Um So again, the reason that this is important to be aware of is because sick well, include your pernicious anemia because of your antibodies to your intrinsic factor. The fact that you're not absorbing vitamin B 12 and also you get neuroendocrine cell hyperplasia, which then can lead to neuroendocrine tumors. Um So this is just again for reference kind of other um causes of gastritis to be aware of and, and some kind of significant information about them. Um again, for reference, you can also get aside from carcinoma, polyps and benign neoplasms in the stomach. Broadly speaking, these can be categorized as either epithelial or mesenchymal. Um hyperplastic polyps are quite common and associated with H pylori. Another common polyp we see is funded gland polyps which is associated with PPI use and a lot of people are on those. Um and then gastric adenomas, another big one because that's um invariably has dysplasia. So, moving away from talking about gastritis and polyps and other neoplasms that you get in the stomach include gastrointestinal stromal tumors. So these tumor's are most commonly seen in the stomach. And um they're amazing. Kimmel tumor arising from your pacemaker cells in the gi tract. They can arise anywhere in the gi tract. And hess to logically, they look like these kind of blonde spindle cells that we can see here. Um They arise because of activating mutations in the Proco proto oxygen C uh C kit and P D G F R alpha. Um they can be treated by surgical resection, but for high risk tumor's and that have these activating mutations, they can also be treated by tyrosine kinase inhibitors. Um and the way that we decide whether a tumor is high risk is using this kind of lasota mitten in table. So you can see from here that the most important things are location, um the mitotic index and the size of the tumor. So this all contributes to prognosis. Aside from that other things that might contribute to prognosis are local recurrence includes, you know, if the tumor has ruptured. So serosal rupture because obviously in that context, you theoretically have tumor spill into the abdomen um if you've got mucosal invasion, so these tremors are usually in the muscular Aris. So if you've got them going up into the mucosa, that suggests a kind of more advanced behavior and also if the reception margins are involved. So with this in mind, we've got a 50 year old lady who's got a gastro tumor, the tumor is positive for our seek it and CD 34. So it's in keeping with a gastrointestinal stromal tumor. And with what we've just discussed, which feature below is not associated with worse prognosis or local recurrence bob. Great. Um So yeah, small tremor is in the context of the stomach is going to be very, very low risk. And so it's not one. So if we go back and yeah, we can see gastric less than two centimeters, you know, there's literally no risk of per prognosis. So this is not a tumor that would have to be referred for mutational analysis because you're not thinking that they're going to need further treatment. Okay. So, moving on to other lesions that we might see in the stomach gastric lymphoma or this mucosal associated lymphoid tissue lymphoma. So, discussing this because as we said, um H pylori associated gastritis is very, very common and a sequela of this can be mucosa associated lymphoid tissue lymphoma. Um The classic um sign that we see here pathologically is that we get these lympho epithelial lesion's where you see the lymphoma cells actually infiltrating into the glandular epithelium. Um and this is a common extranodal lymphoma of B cells and in the stomach, it is usually marginal zone, lymphoma or large B cell lymphoma, but marginal zone can progress to large B cell lymphoma. Um As I mentioned before, the association with H pylori is extremely important because even patient's with advanced disease can have significant treatment effect when they've had h-pylori um infection eradication. Um So something to be aware of and then again, moving on to other tremors that we see in the stomach. So when we were talking about autoimmune gastritis, remember I was saying that this can lead two neuroendocrine hyperplasia and neuroendocrine tumors or carcinoid gi tumor's. And so nowadays, we call them well differentiated neuroendocrine tumor. Um most commonly, um these are actually seen um in the small bowel, um, as opposed to the stomach and, and also you'll commonly maybe see them in the appendix and large bowel. The most of these tremors are actually non functioning. Um but if they are symptomatic, it's usually secondary to the hormones that they are producing. So, a classical example that you might get as a person who's got a lesion in the terminal ileum, they present with bronchospasm, flushing and diarrhea, a natural carcinoid syndrome. And, and it's secondary to like uh secretion of vasoactive peptides. And you can obviously test for these in the urine. Um, other hormones that can be secreted include um gastroin for proximal duodenal neuroendocrine tumor's. And this can lead to your Zoolander Ellison syndrome and Samata statin again, in proximal duodenal tumor's and this can lead to malabsorption, diabetes and diarrhea. Um, with these trimmers location is really important in terms of uh prognosis. And when we're looking at them, we're grading them via their mitotic in debts keys and they're ki 67. So, with this in mind, we'll try and answer this questions. We've got a lady who's got weight loss, steatorrhea of new onset diabetes. She's recently been diagnosed with Goldstone's and she has a lesion in the duodenal ampulla and we've got a low grade tumour. So like what type of tumor do we think this is um okay. So this is one where the tumor. So it's going to be a well differentiated neuroendocrine tumor and it's producing Samata statin. So it'll be like a somatostatin oma. Again, this is terminology that we don't really use. But again, it's something that comes up on the exams regards um carcinoid. Um it's not neuroendocrine carcinoma because he said it's like a low grade tumor. So there's a different criteria and for assessing that. Um okay. So kind of in the small bowel. Um let's move to celiac disease. Um So this is obviously a very common immune mediated condition affecting up to 1% of the world population. Um And obviously, it's glidden which induces CD eight sales um to like cause entero site a apoptosis, which is why we get the problems. There's also release the site kinds which causes further damage. Um So the top picture shows like normal jodi numb um where you can see the kind of like finger, like projections and that's normal. That's what we want to see. Where is the bottom picture shows you're kind of three pathological hallmarks of celiac disease. Um So we've lost those nice finger like projections. I think that's anyone can kind of see that we've got villous blunting and we've got crypt hyperplasia and then it's difficult to see. Um But the other thing that we would be looking for is an increase in intraepithelial lymphocytes and it's usually CD eight positive websites. Um So those are the kind of three uh pathological Horrell marks that I remember having to learn. Um Now again, just important to always remember the associations that these diseases have. So this is associated with dermatitis, herpetiformis, um but also t cell lymphomas in the gut. So then we'll go into this question where we've got 20 year old who's got abdominal discomfort and bloating. Um So we've done our biopsy. Um And what pathological changes would we expect to see? Um So from what we've just talked about fab cool. So, yeah, that's the pathological hallmarks. Just kind of get that in your head because if it comes up, that's the type of question that is a gift. So staying am in the small bowel, we'll talk about just one of the most common g eye congenital conditions, Meckel's diverticulum. So this is kind of a nice um surgical picture. Um This is due to the persistence of the doctor which connects the yolk sac to the mid got and should regress by like eight weeks gestation. But in some people, it doesn't um the thing to remember about, this was your rule of twos. So it affects roughly about 2% of the population and symptoms before the age of two. It's two inches long and it's 2 ft from the ileocecal valve, um, and affects males twice as commonly as females. Um, another rule of to, to be aware of, um, for us is that you sometimes get gastric or pancreatic tissue within the Meckel's and it's usually having gastric heterotopia which causes um, patient's to present with bleeding. Um, and gastric tissue in the Meckel's is occurs far more commonly um than pancreatic tissue. Okay. So this is kind of a nice picture of what we might see. So on the right, we've got our kind of normal small bowel uh mucosa and then on the left, you've got gastric mucosa that shouldn't be there. Um So with that in mind, we've got two year old boy who's got right lower quadrant pain and rectal bleeding. Um, following imaging, we've decided he's got Meckel's and he's going for surgery and which of the following is false. So excellent. Yeah. So remember it is due to incomplete obliteration of your vital in or and follow means enteric duct. Um And it most commonly contains atopic gastric tissue because remember that's what can cause the bleeding. NPR um seen twice as commonly in males. Um You can actually get lesions arising from within the topic tissue and it occurs in 2% of the population. So rule of twos. Um, we'll just move past this. This was more for interest because obviously it's a common condition and just to kind of highlight different inflammatory pathways that you can get in the gallbladder. Um Another thing again, just moving to the side, it's not really colorectal, but just to be aware of Patil cellular carcinoma seemed to be quite a common question that came up. And so I think because worldwide, it does account for 5% of all tumor's. It's the like fourth most common cause of cancer worldwide and six most common cause of cancer death. Um It's obviously more common in areas where you've got high rate of Hepatitis B and C infection. And the incidents kind of really reflects that by far, the most common cause of it is chronic infection with HEP B or C worldwide and, and HEP B is the leading cause worldwide. However, obviously in the West, we've got vaccination. So we kind of see hepatitis C and take over and then other risk factors such as like alcohol and obesity. Um Here's a list of kind of other risk factors for it. And again, I'm just putting this in because I remember it seemed to come up quite a lot, but it's still important to remember that. Um, actually, you know, if you've got a lesion in the liver most commonly, it's gonna be a metastasis. It's just that this is the most common liver, primary, second, most common liver, primary would be angiosarcoma. So just again, to be aware of that, um and also with the questions um felt sometimes they like you to just have an awareness of what type of infections and risk factors you have for different cancers worldwide versus the West. So I kind of put this question to reflect that. So based on kind of what I've said and what do you think would be the most common cause for HCC um worldwide? Mhm So fab so yeah, the answer is worldwide. It would be hip be and that far, far outstrips HEP C. But yes, and particularly the West Hep C is an important risk factor. So it's just been aware of, has said, knowing kind of common conditions in depth and just having a bit of regional awareness of risk factors. Okay. So finally, we're in the large bowel which means we're near the end. Um So just a quick talk about inflammatory policies. Um So again, it's just really getting in your head. Um the clinical pathological differences between the two. Um and it is important to know this because it is a clinical pathological diagnosis. Um So on the left, we've got a picture of kind of what you might expect to see in ulcerative colitis. You've got uh superficial ulcerations, cryptitis, crypt abscess is an architectural distortion of the glands and lots of information in the lamina propria. And then on the right, we've got some of the futures that you might see in Crohn's disease and so kind of in the center, it's not really coming across very well, but you've got a big granuloma. Um And this slide again, it's just for reference to compare the kind of differences between the two. So, you know, crones anywhere from mouth to anus, you get skip lesions and cobblestoning and you might see endoscopically. So that's where you've got um normal mucosa, which looks raised adjacent to areas of diseased Bell, which is depressed. And the important thing about crone's disease is you're getting like full thickness inflammation. So, from the mucosa through the muscular, it's appropriate also get your granulomas and then because of that full thickness inflammation, that's why you can get things like fibrosis structure and fistula. Whereas all sort of colitis is usually more limited disease but presents a continuous sort of fuse pattern. Um doesn't go usually as deep as crone's disease with its inflammation, you also get pseudo polyps. Um So you can get hundreds of them. And this is usually due to the kind of regenerative process that the bowels going through from continuous damage and ulceration. So, based on this, if we've got a 22 year old man with diarrhea and bleeding, um on colonoscopy, we've taken biopsies and we see loads of pseudo polyps and the biopsy says he's got me cause ulceration, cryptitis and crypt abscess and a diffuse pattern. So like all the way through and know, skip lesion's what would be the most likely diagnosis here. Um So if we can try and answer that. So this is the type of thing that like hopefully you would be a gift. So I see most of you saying ulcerative colitis and that's correct. And the clue here is the fact that there are no skip lesion XYZ continuous pattern of disease. We've got pseudo polyps. Um I'm describing kind of like superficial inflammation. Um by that same token, we should then hopefully be able to answer this next question. So which of the following is not a feature of Crohn's disease? Um So not a feature. So if we think about it. Um Yeah, so most of you've got that and that's one of these kind of um making a question that should be a gift seem, you know, you have to read the question to get it so we can get distillation and crones granulomas we see in crones um inflammation, um it's not confined to the because it goes, it usually goes deep. That's it's hallmark, it's transmural inflammation. Um Of course, not always because they don't always obey the rules. Um You know, that patchy pattern of inflammation is common and um us with everything that is inflammatory, you know, there's always a kind of increased risk with longstanding disease. Um This is just a slide to be aware of other microscopic colitis. So the two are lymphocytic and collagenous. You don't really need to know the specific pathological features. But it's just to be aware in patient's which maybe have symptoms of colitis, but you don't see anything on colonoscopy. So moving on to kind of lower g eye polyps. So this background slide is kind of a picture of the two main pathways to pull up formation formation and then onwards to colorectal carcinoma. So we're all probably aware of the kind of adenoma carcinoma pathway, which is like initiated by your ABC mutation. And then you get further mutations in a step wise progression. Another really important pathway um is the serrated polyp pathway. Um And both of these pathways and can lead to colorectal carcinoma and both can lead to um microsatellite, unstable or microsatellites, stable, tumorous. So what we're kind of more aware of um lower gastro intestinal polyps, adenomatous dysplasia. So this um the adenoma carcinoma pathway is the kind of more common. One accounts for two thirds of um colorectal carcinoma is usually left sided. The initiating mutation is your A P C mutation. Um and we can get low and high grade dysplasia. So, on the right, we kind of got low grade dysplasia and on the left is just a picture of high grade for interest. Um and just an awareness that um depending on the type of dysplasia will obviously depend on colonoscopy surveillance or affect colonoscopy surveillance further down the line. Um This is a picture of Avila's adenoma which is just an adenoma but has a different architecture and then moving on to the serrated polyp pathway. So, serrated polyps can usually be initiated by a bee ralf um mutation. Um And this pathway accounts for up to a third um of colorectal carcinoma and is usually right sided. Um So it's just to be aware of that, usually we see a hyperplastic polyps as kind of a benign lesion, but you can get certain variants of hyperplastic polyp that actually do have this be rough mutation. And then in the kind of proper clinical context, e like size and number of them, you know, if you've got loads of serrated polyp lesion's, then you might have to think is this a patient with them serrated polyp polyposis syndrome? So, as I mentioned before, the reason for distinguishing between all of this is because, you know, depending on what you see and take out a colonoscopy will dictate kind of like further management. You know, whether it's saw serrated lesion or an adenoma with low and high grade dysplasia. And you can access these guidelines on the BSG website. So, um we've got a 44 year old women at colonoscopy, she's had a polyp removed. Um We've got cecil serrated lesion without dysplasia. So, what do we think? What's the, which mutation is most likely implicated in the development of this type of polyp from what we've just talked about. So, um yes, the correct answer is be rough. APC is usually kind of more your adenomatous pathway and the rest are just ignore them. Um So then the other important type of gi polyp is hammertoe metis pull up. Um That's because we see it associated with a lot of polyposis syndromes. Helpfully, these syndromes on this page for your reference for all autosomal dominant. So that should be hopefully easy to remember um associated with different types of mutations. The top two are associated with an increased risk of colorectal cancer and also other cancers. Um Other syndromes that predispose to colorectal carcinoma but um not, don't have Hammertoes. Toes, polyps include are serrated polyposis syndrome, which I kind of just talked about or briefly mentioned when we were talking about are serrated polyps. Um familial adenomatous polyposis, which I'm sure you'll be aware of and are nonpolyposis iss um colorectal cancer syndrome, Lynch syndrome. Um Now, diagnosis of these all leads to slightly different colonoscopic surveillance and they all have slightly different molecular pathways. Lynch syndrome is important because at the minute, we are testing all of our colorectal cancers for mm are deficiency proteins is a way of trying to pick up Lynch syndrome is also associated with an increased risk of endometrial carcinoma. Um And we're also starting to test those two. So it's really important to be aware of this and these kind of new developments. Um So familial adenomatous polyposis iss a really important syndrome because you know, it's a very, very high risk of developing colorectal carcinoma. So if we can try and answer this question, kind of based on the previous slide might be a bit difficult because I've obviously just raced through it. But you can look at the slides for reference later. Okay. So yeah, the correct answer here. And again, it's that difficult question where it's saying which of the features is not associated. So again, it's all about reading question. Um So from F A P is associated with an APC mutation, it's an autism all dominant condition and it results in hundreds of adenomatous polyps. Um And if untreated, we've got our nearly 100% risk of colorectal carcinoma. And other variants include her Cort and Gardner syndrome. Turcotte syndrome is F A P as with um like a medulloblastoma or glioblastoma. And Gardner syndrome is F A P with like osteo HMAS and like multiple skin cysts and desmoid tumors. So, these are kind of common variants and to be aware of. And then this is just kind of um picture of colorectal adenocarcinoma. This is the most common cause of adenocarcinoma in the gi tract. And as I said, usually are initiating mutation is our APC mutation. And the way that we stage these is with the TMM staging RC path does not recommend using Juke stage anymore. Although I've just put it in for reference because I remember when I was doing my exam and they did ask me a question about that, but that was obviously five plus years ago now. So, um, maybe they wouldn't expect you to know that anymore. But roughly, it's kind of all of these staging systems follow very similar, uh kind of rough guidelines, you know, T one and some mucosa t to muscular is appropriate to T three. We're going into the fat and T four, we're onto the serosa and then like T four B would be going into other organs. Okay. We won't do this question. We'll just have a quick look at kind of what we look at um in the colorectal cancer report and perform a really just want to highlight um that nowadays, having a kind of understanding of your molecular pathology is important because as I said before, we are testing, um all these tremors for mmr deficiency. Um and the reason for that is not only to look for Lynch Syndrome and therefore offer genetic counseling and to the families of these patient's is also because there's some evidence that, you know, mmr deficiency has implications for prognosis of the tumor. So some of these tremors have a slightly better prognosis. Um There's not strong evidence but there is some like that suggests they might also have a predictive implications in e like how these patient's are going to respond to different types of therapy. Um Other medications that we commonly test for is K ras mutation. And again, that's a predictive molecular marker assessing how patient's will respond to E G F R therapies. So it is important just to be aware of these things as new developments are coming through. And I'll just go through this question because we did kind of like blitz through those slides. So the incorrect pair would be the bottom one P 10 is associated with Cowden syndrome. Um but otherwise all of these match. So HNPCC is a defect in your DNA mismatch repair genes. Your serrated polyposis syndrome is A B wrath K ras mutation F A P is an APC mutation, juvenile polyposis is mad for. And as I said, it's just important to have a bit of an awareness about these um conditions because they do like to ask about them. Um Okay, so um basically, like, you know, that was a lot of information. Um but don't get too bogged down in it. I think the best advice is just to remember that like common things are common and the reason that I was going into a lot of detail about these things is that I think they want you to know the common things quite well, which you would expect because that's what's going to influence your practice for the future, but also focus on the aspects that are clinically relevant. So, you know, you don't have to, you know, as I said, an awareness of maybe the molecular that's gonna impact on further management for your patient at M D T would be important to know. But do you have to know all the histopathology of every condition? No. Um Yeah, it's a big exam. So you do need to put time aside to revise for it. Um, two weeks of priming won't do it. Um, I know I put in some quite like tough questions in there. But the reason for that is that I just think just constantly, particularly for party doing these questions and just practicing them is really, really useful because it just encourages you to think the way that they want you to in the exam. And you don't want the first time that you're doing these questions to be on the day of the exam because it is single best answer. So they can be a bit tricky and there can be stuff that like seems right. And you've got to narrow it down to like two and then go for the best one and then really just like on the big day, try and relax. I found passing those exams really easy when I decided that I wanted to do pathology because I was only doing it to complete CST. And I didn't care as much. It really helped and that might not be such helpful advice for you, but just kind of try and remember, you know, just keep cool the answers in there. You do know it, you just have to find the knowledge somewhere. Um So, yeah, thanks so much and for listening. To me. I'm sorry if it was a wee bit rushed. No, thanks very much for a great talk. Gonna, uh, some really key topics in there that relevant for, for both exams really and smashed it with the timing as well.