 Okay, so just continuing our little tour of Edinburgh. So I don't know if you guys realize that Scotland is part of the United Kingdom, but it's continually threatening to break away. So what the Royal Family did is this is the Britannia, the Royal Yacht. When they retired it, they put it in Edinburgh as a sign of solidarity with Scotland. And then in another way that you show solidarity, they built a huge mall right next to it. So this is interesting. It's on an inlet from the bay and the boat's parked there and you can go through it. But there's this massive mall you have to walk through to get to it. So it was an era, it was a redevelopment project to redevelop the downtrodden parts of Edinburgh. So I figured what the heck, you don't get to go on the Queen's Yacht very often. So this is the Britannia and it was the Queen's Yacht starting in 1953. And this is it. I mean, it's kind of a nice little boat, you know, it's got a crew of about 250. And I mean, it's important for the Queen to get away from her duties in the palace. I mean, it's a really tough life. And so it's important to get away on occasion on your yacht. And so this is the yacht, really nice, you know, wood decks, beautiful yacht. And this is the rest of it on the side. And I mean, this is a chip. I mean, this isn't just, you know, even Trump doesn't have one this big. And so this is a nice shot. This is the formal dining room, which is nice because it's important when you are on your yacht going around to, you know, parts of the empire that you do have to have formal dinners. And so this is the formal dining room that's there. This is a little taxpayer fund. And this is, of course, I mean, England, the taxpayers always fund the monarchy. This is the sitting room, very, very nice. What was amazing to me, though, is the bedrooms. So you've got this palatial yacht. So I said, wow, this is going to be really spectacular. And then the bedrooms where the queen sleeps is about the size of two of these desks. And it's got a little queen bed, a little twin bed, not even a queen bed, a little twin bed, and a little desk with the chair next to it. That's it. That's it. No, no, not even a queen bed. It's like a little twin bed. I was just stunned. It was like, maybe that was her, you know, her little pitch toward austerity to show that she's with the people. And so this is the sitting area, of course, with its fireplace, and it's got the windows all over. Now, my favorite is you have to have an operating room on there in case something happens with the queen. So this is the OR, you know, circa 1950s. And so, or the VA, you know, this is the VA OR. And so this is the OR, and you've got your anesthesia machine there. And there's a surgeon on board. And so, you know, just in case, you know, you're out to sea. I mean, you know, the queen has a problem. And so she's got her own OR here on the yacht. OK, let's get back to real work here. So our final real path lecture today is going to be on tumors. And when I'm starting on tumors, you can't really just talk about childhood tumors without talking about the differential diagnosis of leukocorea. So first of all, Rhys, what does leukocorea mean? White. White pupil, literally, for much language? Degree. From the Greek, of course, from the Greek. So luco, white, you know, like luco, white blood cells, you know, luco is white in Korea, pupil, white pupil. So you've got a young child with a white pupil. What's your differential diagnosis? What's the first thing you want to worry about? Retinoblastoma. Retinoblastoma, OK. Cataract. Cataract. Coats. Asymmetric refracting. Oh, OK. On a list of 10, that would be 15. No. OK. Albinism. Again, that would be 14 on a list of 10. Astrocytocamartoma, that'd be like 10, maybe. Exactly. We used to call it PHPV. Now it's called, you may see that written in place. Now it's called persistent fetal vasculature. ROP. Retinopathy prematurity. Yeah, well, that was, we already said that, yeah? Well, yeah, you always want to, exactly. End up the Midas. Always keep that on the list. All right, we cover them up. There are a few little obscure things we'll go to. OK, so, all right, so, yeah, exactly. Toxoposmosis, that's infectious, so good. All right, so back to Rhys. So you're looking at a young child, say this child's like two and a half years old, and you die at the pupil, and you see this. What do you see in here? So elevation of the retina, just behind the lens. Oh, sorry, wrong button. All right, I'll figure out where we get to, here we go. OK, so you've got, it looks like there's, these are retinal vessels, and so that tells you maybe something's behind the retina, pushing it forward, because if you look, you see that the retina looks like it's pushed right behind the lens. And so if you look inside, and now you see this. What are you seeing when you look in here? Calcium. All right, so you see the little white. The little white areas here. So you see this fluffy white lesion, but you see these little white specks on here. So does calcium help you when you're looking at your differential diagnosis? Indeed it does, because if you're looking for a retinoblastoma, retinoblastoma is calcify, whereas the other lesions that cause bucochlorida do not. And so one way you can tell the difference is you can do a B-scan ultrasound. And remember, the ultrasound, when it hits calcium, will bounce back real strong, so you get these strong spikes. Now, problem is, is two-year-olds don't let you do ultrasounds. So you have to do all this while they're asleep. But if you do an ultrasound, and then slowly turn down the gain, where the calcium is, it'll be all lit up, and then the rest of the aisle disappear. And so retinoblastomas calcify, whereas other potential causes of bucochlorida usually do not. Now here we see an eye that has been cut in half sagittally. And this is a large retinoblastoma. And again, if you look, it looks white. And you can see it's coming underneath the retina. Now, Eileen, what are the two growth patterns that you can see with retinoblastomas? And no fitting with exophytics. Okay, and what are those, how are they defined? Exactly. So if you look right here, you can see that the retina is draped over the top of that and pushed forward and the tumor is growing underneath. So this would be an exophytics. Exophytic means exo outside. It means it's growing outside the retina or underneath it, if you will. Endo is in, so endophytic means it's growing into the vitreous. And so you can see a large tumor here. Again, see the chunks of calcium all through this tumor. Again, a good way to tell that it's a retinoblastoma. And then here's another one, same thing. You can see it growing under the retina and then this is all exudate right here. So this is some exudate that you get from the tumor itself. All right, so Adam, this is showing you a tumor at lower power. And what can we make out on this tumor lower power? What are some of the things we can see when we look at low power? Exactly. So these little right kind of magenta colored areas are calcium on an H&E state. What's the growth pattern here? So it's mostly endophytic, but if you look, there's a couple of areas here that are growing under the retina. So you can have both. You can have both endophytic and exophytic. And this is mainly endophytic. It's growing into the vitreous. And then you can see a little bit growing exophytic. All right, so what is the characteristic findings that you see here at Medium Power? We'll go to Chris, right? Chris, okay. What am I pointing out here? What's the difference in these areas here as opposed to those areas there? A lot of areas kind of more global or I think it's very much about the same. Gosh, I was gonna see if I could get you, maybe a third of that is right. So if you were a baseball player, you'd be worth $10 million now because that means you're successful a third of the time. Okay, so what this denotes here is the darker cells are viable cells. These are cells that are still viable. But if you look, each one of these clusters of viable cells has a blood vessel in the middle of it. So there's a blood vessel here in the middle of each of these clusters and then there's some cells around it. This is actually not stromal connective tissue. This is dead tissue. And so the thing about retinoblastomas is they grow so rapidly they outgrow their blood supply and then they die off. And so basically what you're seeing here is viable tumor cells around the blood vessel. And then you're seeing areas here where it's just necrotic. These pink areas are necrotic. And what happens when this necrotic tissue dies off, it can become secondarily calcified. They call this dystrophic calcification. So that's why you see calcification in here. The cells grow so fast they outgrow their blood supply and then basically they die off and they become calcified. And here's a close up showing you that. Here's some viable tumor cells here in these clusters. And then in between this pink area this is dead tumor cells they've outgrown their blood supply and they've secondarily calcified. So dystrophic calcification. All right Ashley, what feature is this that's commonly seen in these tumors? Okay, so home or right rosettes you can see in neuroblastomas. But in retinoblastomas there's a more specific rosette that you see. Julian? They're winter steiner. Exactly, flexner wintersteiner rosettes. There's the Germans that say flexner wintersteiner. So flexner wintersteiner rosettes. And these are rosettes that are characteristic of differentiation of retinoblastoma. So when you see these it means the tumors differentiated. And you see it's got these round clusters of cells. And the reason that that happens is that these tumors arise from primitive retinoblasts, primitive retinal tumors. And so when primitive retina goes bad it starts to make round structures instead of flat structures. And so these little rosettes, it's funny if you look at them, you could almost get a hint that it's trying to make little rods and cones out here. I mean, if you really hallucinate with me sometimes you can even see a little outer limiting membrane here. And so these are attempting to form retin except retina usually doesn't have one of these structures. Ashley, what is that? Mytotic. Mytotic figures. They usually don't have that in normal retina. So, and there's a nice mytotic figure there. So these are the flexner wintersteiner rosettes. These are what we see as a sign of differentiation in these tumors. Now for bonus points, let's see that kind of counted. It's all right, you get a count on that. Renee, what kind of stain is this and why would I be showing you this? Okay. And you're trying to stain for mucopolysaccharides. Very good, extra brownie points for that one. So this is an ocean blue stain which if you remember from your corneal dystrophy stains form mucopolysaccharide. And if you look inside here you can see the mucopolysaccharide usually the stuff that's underneath the retina, you know where the rod and cones actually are between the RPE. Now I used to think that that's what kept it stuck down there, but it's not. It's negative pressure pulling from the coroid. It doesn't really get stuck down to the RPE. And so there is mucopolysaccharide in the center of these flexner wintersteiner rosettes. All right, Jack, what are we showing here? I mean, here's some rosettes here. That is this thing. Okay, so they're kind of palisading. You see they haven't shown a circle here. They're almost like a C-shaped. They're almost like a circle that's becoming unzippered. What is that called? Nick. All right, this is called a floret. And it is a sign of even more differentiation. So when you see florets, that means that the tumor is even more differentiated than a rosette. So it's like a rosette unzipping. And so that's a sign that the tumor's really well differentiated when you see this nice, pretty floret. I guess back to Rhys. What are we showing right here? What part of the eye are we in? And why would I show you this? So it looks like iris and lens on the left side of the screen. Okay, iris, lens here. And then the vitreous behind that, all the way to the right, just filled with tumor cells. Okay. What is this right here? I mean, I think I would call that vitreous seeding. Exactly, this is vitreous seeding. And so this is kind of a funny cut. It's way in the periphery. So it's almost like a flat section. These are little ciliary processes. And so you can see tumor cells are broken off into the anterior vitreous. They're behind the lens. They're even in between the ciliary processes here, all the way up behind the iris. And so this is vitreous seeding. Is that important? It is. Why? In terms of treatment, you know, you either have to do the vitreal chemo or take the eye. Okay, yeah. So that is important because it's tough to get treatment into there. And so when you do the intra-arterial chemo, it works pretty well nowadays. But sometimes if you've got vitreous seeding, it doesn't work too well. People are even advocating, injecting chemo directly into the vitreous itself to try to get rid of these vitreous seeds. And so this is a sign that the tumor is spreading. You don't like to see cells in the anterior vitreous because that's a poorer prognostic factor. All right, what are we looking at right here, Eileen? What's wrong with this picture? Blue cells, what else? Well, there's definitely tumor cells in the angle, which is a bad sign, but this picture is upside down. I do this every once in a while just to see if you're paying attention. So I'll throw in an upside down one every couple of lectures. So this is upside down. This is corny up here. This is iris back here. This is tumor seeding into the angle. And so when you get a retinoblastoma where the tumor cells have broken off, you can often get seeding in the angle. And if it's a lot, you can even get what's called a pseudohypopion. We've even seen severe retinoblastomas where it's been misdiagnosed as an endothelitis because you'll see these kids with these white, fluffy cells actually layering out in the anterior chamber angle. And it's just seeding of the retinoblastoma cells. So here you can see these retinoblastoma cells have gone into the anterior chamber. They're even in the angle and in the trabecular mesh work. Is that a bad thing prognostically? Yeah, because it can spread. And so that's a bad place for tumor cells to be. So you can get not only seeding of the vitreous, but seeding in the anterior chamber and even pseudohypopions from this. All right, Adam, what's the worst prognostic factor when you look for retinoblastoma? Exactly. So when these tumors spread, they spread by direct invasion into the optic nerve. So here you see tumor here and look, there's tumor into the optic nerve. And so this is an old, old slide I borrowed from the AFIP. This was probably, this slide's probably from the 60s sometime. And this is actually the, you know, percent of kids that die depending on where the tumor is. So this is before we had, you know, chemotherapy, intra arterial and intra vitriol and all that. And so the bottom line is, is if you have tumor just inside the eye, this was at that point, you had like an 8% chance of dying. But if it goes through the, I'm gonna crybrosa, it doubles. If it goes into the nerve itself, but not at the cut end of the nerve, it goes up even higher. And the worst prognosis is at that distal end of the nerve, if there is still tumor there, that means the tumor can get into the orbit and even go back to the brain. And so the worst prognostic factor is tumor at the distal end of the nerve. And so when we get a retinoblastoma specimen in our lab, when boopy or whoever's taking these out takes them out to take, cause a lot of a piece of nerve as they possibly can, first of all. And the first thing we do is we cut the distal end of the nerve and make sure that the distal nerve is free of tumor. Cause that's important prognostically. So if you still have tumor at the distal end of the nerve, you know, they had a 65% chance of dying 50 years ago. All right, and this is what happens when you don't treat it. And so this is a child from Nigeria. And unfortunately retinoblastoma is very aggressive. And so if you don't treat it, you know, in the third world, sometimes these kids are not, you know, have any access to medical care. This tumor can take over an entire orbit. So this was a retinoblastoma. And unfortunately this is, you know, prognostically by this time, you know, this kid is gonna die very rapidly. All right, so we're looking at other possible entities now that, first off, any questions on retinoblastomas? Now realize that on OCAPs, OCAPs have a lag time of a few years because treatments have to become widespread before they can quiz you on them. And so I don't know if there's gonna be any questions on intra arterial or intra vitriol chemotherapy cause I don't know if it's accepted enough and the greater communities show up on OCAPs. So I'm not sure, you know, if you need to know the specifics of that or not. Sometimes it's a lag time. So questions? All right, so now we're gonna look at other entities that can cause leukocorrhea. Chris, what do we see in right here? What's funny about this picture? Okay, what makes you say it would be Coates disease? Some areas are normal retinoblastoma. So you see those funny, beady, dilated, telangiectatic vessels, that's a little tip-off. But if you look right here, those are actually, it's not even like, this almost looks like when people get carotid attachments, you know, when you get the carotid pushing in, you get kind of those kissing carotidals. This is actually a kissing exudative retinal detachment, if you will. Believe it or not, this little cavity here, that's what's left of the vitriol. And there's so much exudate under the retina that it's pushed it forward. So you got a total exudative detachment of the retina. The reason it's yellow in color is it's the lipid-rich exudate underneath there. And these are all these bizarre, tealangiectatic vessels. All right, so tell me, what's the usual age range in the Coates? Yeah, so older than a retinoblastoma, certainly. So six to 10, six to 12, unilateral or bilateral? Unilateral, good. Okay, so again, I'll tell you what I told all these guys. If you're making a guess, you say it with conviction. So if you say unilateral, you let your voice go up, you're guessing, you get no credit for that on board. So they'll look at it while you're guessing. You say unilateral. So even if you're wrong, you still, at least, you get credit if you were right. So just guess with conviction. So unilateral, excellent. And male or female? Male. Yeah, so more male. More males. All right, so here again, this is another view we're looking inside. You've got a little normal-looking retina here. Here, this retina is elevated because there's all this yellow lipid-rich exudate under the retina. Here's all these telangiectatic, bulbous-looking vessels that cause this. When you look, here's an eye that was actually nucleated due to Coates disease. This lipid-rich exudate, when the fellows will cut these eyes in the lab, I mean, this stuff is like gelatin. And so it's like, you know, the state food of Utah, you know, jello. The only difference is it's not green, but it's very gelatinous. If it were green, it would be Utah's state food. And so it's very, very gelatinous. When you cut these in the lab, it literally feels like jello in there because it's a lipid-rich exudate. And here is a retina. Here is one of these telangiectatic vessels and these little empty vacuoles here are dissolved lipid. And so these little telangiectatic vessels leak this lipid-rich exudate and eventually it can gather under the retina and give you that total RD. All right, so actually, you know, Ashley, we'll save that for you. Anybody? What are these banana-shaped white areas here underneath the retina? What do they signify? Very good cholesterol. And so for some reason, cholesterol, when it gathers in an exudative detachment, it'll form little banana shapes. I don't know why, but sometimes they'll be straight and long for another time. Look at that, forms a perfect banana there. And so the cholesterol will gather in clumps and then it'll dissolve on our tissues process. So this is lipid-rich. These are little macrophages all over the place, stuffed with this lipid, trying to chew it up, but they get overwhelmed. They just can't keep up with it. So Coates disease. Ashley, what are we seeing right here? Persistence. Okay, and what makes you say that? Good, so you see this whitish mass, and if you look carefully, there's what's left of the crystalline lens right there. So this mass is either behind the lens or maybe even invading into the lens. And then you see all these little tiny blood vessels here. So this would be consistent with persistent fetal vasculature. We used to call it PHPV. Primary hyper-persistent, primary hyperplastic vitreous. All right, so if you see the term PHPV, that's what it's referring to. So again, age, actually, no, no. So older than retinoblastoma. So it's not usually recognized until a little bit older, but not as old as Coates, so kind of in between. Unilateral or bilateral? Unilateral. Unilateral, exactly. And I don't think there's a sex predisposition. Not that I recall. All right, so this is an eye that's been cut, you know, cut kind of tangentially from behind, and this shows you that when this lesion grows into the lens or behind the lens, it tends to pull the ciliary processes in. So it almost pulls them to the center when you look at it. All right, and Julia, what is this showing? So this is the persistent high load artery coming in, and you can see this mass taking over almost half of the crystalline lens, and so oftentimes they'll grow behind the lens, but sometimes they'll actually grow into the lens, and you can see right here where you've got that high load artery there, and then going here, and look, here's the ciliary processes being pulled to that. So this is actually the same eye that we took that picture of at the very first, showing you that it's invading half of the lens and then pulling the ciliary processes in. So it's there when they're warm, but it doesn't get white. It doesn't get white until, I don't know why, it let's proliferates, and you almost get connective tissue growing in there, and blood growing in there, and so it takes time for it to grow on. All right, so this is an eye that's been removed, and you can see the problem here is you have a complete stock of that high load system coming from the optic nerve head, back behind the lens, and then involving them. But you look right here, the retina just isn't well developed in that in general. These are tough to treat because you think, oh, you just go ahead and take out the lens and do a vitrectomy, and you can, but the problem is the retina's just not well developed, and so these kids just don't do well, even if you do a heroic surgery. So here we have a crystalline lens. Here's the stock of the persistent high load artery, and here you can see multiple little vessels here, and then this is growing into the lens, causing scarring and opacity of the lens. All right, here you see a nice view. Look at that ciliary process. It's like somebody grabbed it and just yanked it in. So there's that so-called elongated ciliary process growing in here. Now, this is a kid. This just shows how our legal system works in this country. This family was really concerned. Dr. Harry did an ultrasound on this kid, about three different people looked at him. They said, man, this looks really scary. We think maybe this is retinoblastoma. There was some iffy changes on there. It wasn't clear what it was. And so the decision was made to enucleate the kid. And so we looked at the path and we said, wow, this is just really nasty persistent fetal vascular, not retinoblastoma. And so the doctors involved went to the family and said, you know, we've got great news for you. This turned out not to be a tumor. This was something else. So the kid doesn't have a chance of dying down the road. This is great news, at which time the family sued them. Wow, you removed an eye that didn't have a tumor in it. So this is our legal system here. That's how it works. And so you take a news and say, great news, no tumor. Oh, well, we're suing you then. And so they wouldn't have sued it, there really been a tumor there. But they're suing because they removed the eye that didn't have a tumor, even though the eye had no visual potential. So welcome to the legal system you're going into in this country. So this is that kid. And you can see they had this fibrin reaction in here. They had a kind of a pseudo-hypopion. And they had this big growth back here. The scleric process is yanked forward. And there again, you can see that this is the aurasirata. Even the peripheral retina is being yanked into that. So it just pulls everything to the center when you've got the PHVV. All right, Renee, what is this? Okay, so this is a less significant remnant of the hyalurid artery. So instead of having a full-blown persistent fetal vasculature, this is just the posterior remnant of that hyalurid artery. So you'll often see a corkscrew vessel. Any clinical significance to that? Absolutely not. So you just tell the patient, yeah, you've got a curiosity in the eye. It's not gonna cause you any problems. Don't worry about it. So that's just the posterior hyalurid that hasn't quite regressed. What's the equivalent of the anterior hyalurid that hasn't quite regressed? Okay, so this is that little remnant hyalurid artery. Sometimes you can see that in the vitreous. You'll see a cloquage canal where it runs. And oftentimes where it attaches here, you'll see a little dot on the posterior surface of the lens. I'm sorry, I don't have a good picture of a mitendorf dot. You see them all the time. We just don't think about taking pictures of them. And here's that posterior corkscrew vessel coming up here. And that really has no visual significance. It really doesn't cause any problems. All right, Jack, what are we seeing here? All right, so does that change your kind of thinking on a differential if you see leukocorrhea bilateral? Okay, so you can't have bilateral Arbis. So don't forget that. How about Coates disease or persistent fetal vasculature? So short-term memory, we just said that. They're unilateral usually. They're usually unilateral. So what's a bilateral if it's not a retinoblastoma? What are other causes of bilateral leukocorrhea? Okay, those are usually unilateral. What's the cause of a bilateral? Cataracts, good. That's one that could cause you bilateral leukocorrhea. What's another that could cause you bilateral? Something we still see a little bit nowadays, retinopathy of prematurity. So retinopathy of prematurity can give you bilateral leukocorrhea. And this is what it looks like when it's resolved. This is called a drag-to-disc. So what happens is when kids are born prematurely, that temporal retina hasn't finished vascularizing yet. You take these kids, you chuck them in an incubator, give them a whole bunch of oxygen. Basically, then you'll get all kinds of vessels starting to grow in that non-perfused peripheral retina. Those will eventually start to contract. You can get attraction, retinal detachment, and all kinds of problems. It was interesting in the 1950s and early 60s, they discovered that when kids were born prematurely, if you gave them oxygen, you could save them. Except one of the side effects of too much oxygen is you would get retinopathy of prematurity. And there was a huge epidemic of ROP at that time. And then as people got better at treating these kids and realizing you don't give them too much oxygen, you monitor it very carefully. The incidence of retinopathy of prematurity dropped. But now, in the last couple of decades, it's creeped up again. And the reason for that is now we are saving kids who would die previously. I mean, these kids are coming out now. These kids that are like this big, they're like little fetuses, and we find a way to save them. And so the more premature a child is, the more chance they could develop retinopathy of prematurity, even with our modern technology of following their oxygen level. So this is a so-called drag disc that we see in this resolve retinopathy of prematurity. Now, if we don't treat retinopathy of prematurity, then you can get a total exudative type retinal detachment. And they used to call this retrolental fibroplasia because it just means you just get this kind of white mass behind the lens, and it's a total RD. So again, these are really difficult to treat once they get to this stage. And so we can prevent them. You guys do need to know this for O-caps. You know, we used to do cryotherapy in that non-previews peripheral retina in these little neonates, but now people started to do indirect laser. And there's less side effects, less inflammation with that. So I think now that pretty much the party line, I think most people here just do the laser rather than the cryo. But if you can laser or cryo that area of non-prefuse retina, you could prevent those abnormal blood vessels from growing and prevent these total retinal detachments, so-called retrolental fibroplasia. Okay, so for a bonus point here, Nick, this is a kid that had eye removed for severe retrolental fibroplasia. What kind of surgery has he had to try to save the sign? Sclerobuckle, exactly. So you see, there's the buckle. There's the buckle. So they did a sclerobuckle to try to save the sign. You do have a trachomy, sclerobuckle. Again, these are very difficult to treat once you get that stage five closed funnel. Extremely difficult to treat. All right. What do we got here? Kind of a weird-looking eye. We're kind of going pretty far down on our list of causes of leukocorina now. I mean, so there's kind of an exudative retinal detachment. Yeah, so an exudative detachment, kind of a white mass right here, so kind of a focal white mass. What could give you a focal mass, causing a white pupil and an RD-like look in a kit? This is the path. Toxocara, so there's actually a beast in there that's been broken down. I mean, this is a broken down beastie. So toxocara, which unfortunately comes from puppy poop, basically, and what do puppies do? They lick their poop? Then what do they do? They lick your face. And so little kids are always down there by the puppies, getting their face licked. And so what happens is the toxocara gets into the system that goes through the intestinal wall, then it can spread to end organs. And one of the end organs is the eye. So if you get toxocara in the eye, you're really stuck because if you treat it with antiparasitic drugs, it'll kill the beast in the eye and then the inflammation will kill the eye from killing the beast. And so if you can find a focal area, you may want to try to go in there and do a trick to me and get it out of there, but these are, again, difficult to treat. Okay, Eileen, boy, extra bonus points. Now we're really going down to obscure causes of leukocoria. What part of the eye are we looking at here and what the heck are we looking at? Ciliary body, there's the iris, ciliary body. What kind of tissue is this? Actually, it's a normal tissue in an abnormal place. This would almost be like a chorostoma. They love this stuff on board. It's just really obscure my new show like this. Believe it or not, this is Highland Cartilage. So you need to remember that. What entity gives you Highland Cartilage in the ciliary body? Well, actually it could. That's a good answer, but what they look for in these is trisomy 13. So trisomy 13 can give you Highland Cartilage in the ciliary body and can give you leukocoria. And this is the other thing that occurs with trisomy 13. Now this is not a retinoblastoma, but you see those rosettes? Malformed retina can form rosettes. And so in trisomy 13, you get in the ciliary body Highland Cartilage and you get these dysplastic looking rosettes in the retina. Now trisomy 13 is even in this era is pretty fail. I mean, these kids don't live very long and so not a good thing to have. So trisomy 13, obscure cause of leukocoria, but if you see Highland Cartilage in the ciliary body, jump all over that. All right, so now we're gonna go to more tumors of adults. And of course when we're talking about tumors in adults, the one thing we always talk about is pigmented lesions. So Adam, what do we see in here? Okay, are there any features of that that are alarming? All right, so it's big, it's kind of thick. Looks elevated, good. Now fortunately it's not going into the angle. You can still see a clear iris there. It's not quite pulling that pupil, but this is a non-dilated look. So it is kind of pulling that pupil over there a little bit, a little ovelling of the pupil. So you would be concerned. And so whenever we see pigmented lesions like this, our concern is, is this a nevus versus a melanoma? Now is this more concerning? It is, so look at the slit beam. Here's the beam on the cornea. Here's the beam on the iris. Look, that's almost touching the cornea. It's markedly elevated and it's going into the angle. So you would be very concerned about this particular lesion for melanoma. So when we spent time in the lab, what you guys will do is you guys will read up on the diagnoses, the various causes of pigmented lesions of the iris. And when I was a resident, it was taught that iris melanomas were different than melanomas elsewhere. They have a very good prognosis, you know, 90% prognosis because you can see them and you treat them earlier. Well, Fred Jacobiak, at that time he was in New York, he looked at about 180 of these at the AFIP and said, wait a minute, let's look at these. So he took 180 quote iris melanomas from the AFIP, the Armed Forces Institute of Pathology which doesn't even exist anymore but was the repository of tens of thousands of tumor cells for 100 years. So I think you can still get ahold of the tissue if you want to do studies. But he looked at these and what he found is the reason that the prognosis is so good is that 80% of these are really just nevi, not melanomas. And so he came up with a classification of iris pigmented lesions and it's real important that you know that. So Adam, this is the first one that we look at. What do you see in here? Mostly spindle cells. And no, there's no nucleolionin, there's no pleomorphism, they look really benign. So what do we call this? Spindle nevus. So the first benign lesion that you want to know about in these quote iris melanomas, spindle nevus. Chris, what do we see in here that's different than that previous one we showed? Man, you've got good eyes if you can call those mitotic because I can't from here. But what I wanted to show you is look, there's tumor cells in the iris stroma but look, there's like a whole bunch of them on the surface of the iris. That's a plaque. So you can also get spindle nevus with a plaque and those can look pretty scary when you look at them clinically. So spindle nevus, spindle nevus with plaque. All right, Ashley? There's still a lot of these little spindle cells here. Look at all of them. But if you look next to them, some of these cells are now becoming rounder or more oval. Not quite epithelioid but more round or almost cigar-shaped starting to show a little bit of features that would concern you. But there's still areas in here where it's these benign spindle-y guys here. Okay, so it's called a borderline spindle nevus. And so these are where they're starting to look a little bit more malignant, starting to become more oval, more cigar-shaped. So borderline spindle nevus. How about this, Renee? So this is actually a spindle melanoma. This would be the equivalent of a spindle-B melanoma of the coroid. So this is actually spindle melanoma. So even just with spindle cells, you've got a couple of benign, a borderline, and then finally, this is a spindle melanoma. So the equivalent of like a spindle-B melanoma of the coroid. All right, Jack, what are we seeing here? I'll give you a hint. This was bleached because this was so heavily pigmented you couldn't even see the cell details. So we actually had Mary bleach these. I've got a ton of melanoma. So this is what's called an epithelioid nevus. These are rare as hence to. So I think I've seen one of these in my whole career. But you can also have epithelioid nevi. Just remember that. And then finally, Nick. What's going on here? Look at that cell right there. Is that where you? That one there, that one there, that one there. Place here. You don't have to do it too much though, right? You don't have to do that. All right, absolutely. Look at that huge nucleolus in there. Giant nucleus. Actually, outline of the cell border right there. Oh, okay. Outline of the cell border here. So what kind of cells are these? These are epithelioid cells. And so just like a melanoma elsewhere in the coroid, you can get spindle melanomas. You can get mixed spindle and epithelioid. You can actually even get epithelioid-type melanomas of the iris. So those are the ones that we think of as really tumors. And then last but not least, you can get melanocytomas, which are huge, benign-looking pigment itself. So the key thing you wanna remember is, in iris tumors, you can get similar to coroidal tumors. You can get spindle B. You can get mixed and get epithelioid. This is an epithelioid melanoma. Nucleoli in there, large cells, pleomorphism. These, if you look, we bleached them. You look at the nuclei. The nuclei are small and round. And you don't see activity in there. You just see a bigger cell stuffed with pigment, but you get a smaller on nucleus. This would be an epithelioid nevus. But even a melanocytoma looks like this too. It's kind of a benign, big epithelioid-looking cell. So they can look like this. Epithelioid nevi are, as I said, I've seen one in 28 years. It's very, very rare. But again, something that shows up on there. And so there's, you don't differentiate between spindle A and spindle B, melanoma is on iris. Not on iris. Only in the coroid and the ciliary body. Okay. Rhys, what's going on here? So in the face of the picture, I can tell if that's just where the iris, there's just a clot in the iris. Only the way, or if it's a mass down here. All right, now there's something that tells me this is a mass. So you see this right here. Look at this, right? Oh. Look at that peeking out. So it probably could be like a ciliary body. Exactly. So probably a pigment, a tumor rising from the ciliary body. This is one of my favorite patients, really nice guy. He drives up from Champaign, Illinois to Chicago to see us. And he's a University of Illinois football fan. And he has season tickets. And he could see the scoreboard out of the side the first game, and then it started getting blurry by the third game. And then the final home game, he couldn't see the scoreboard. Not quite. And so he came up because of that. And we looked at him and he did have a central PSC cataract, but he had this tumor pushing from the ciliary body onto the lens and peeking through into the angle here. So those are a couple of factors you really don't like to see. Tumors that are that big, because indeed they're growing from the ciliary body. And here's another one showing you the same thing. Here's a tumor poking through from the ciliary body behind into the anterior chamber angle and pushing out from the ciliary body into the lens. And so these people, because these tumors grow behind the iris, they can grow pretty big before you have symptoms. And then they'll push on the lens and they will eventually cause a cataract and the patient will come in. So here's a Goni overview. Look at the tumor back here in the ciliary body. And there it is pushing up into the angle. All right, now Eileen, what is this thing right here? Why would I be showing you this? Sentinel vessel, what does that mean? Exactly, so these are great. You know, a Sentinel is something that's out on the edge there. And so what this does is this points to the tumor. So whenever you see a single isolated solitary vessel right there, you wanna dilate that person real carefully and look behind there because this is a hint that hey, something's going on here in the ciliary body. And sure enough, here's a tumor in the ciliary body, heavily pigmented, pushing against the iris, I mean against the lens, and causing that lens to push over a little bit and then again can cause a cataract. No, this is a different patient. Yeah, I wish I would. I should have said it was. Yeah, yeah, it is, yeah, yeah, it's that patient. These are all melanomas. And so when you look at the ciliary body and the coroid, those are all treated the same and we'll go over the cell types of those. Just remember the iris is a little different. Ciliary body and coroid are the same when we classify these. So here you see a tumor, here's the iris root, here's the trabecular mesh work, and here's the tumor growing from the ciliary body into the trabecular mesh work. And so this again is a bad place because what do you have coming out of the trabecular mesh work? You've got slump's canal, you've got aqueous veins. Tumors can get out of the eye in this area. So this is a poor prognostic factor in having a tumor in the ciliary body just by definition. And here you see another one, pretty big one here, growing right here. And Adam, why would I be showing you this picture? Look up here. So sure enough, this is a closeup of that. If you look carefully, here's the tumor in the ciliary body. There's that first vessel we looked at. This is out on the epi-sclera. So indeed, when you get tumors inside the eye that are melanomas, how do they spread? Through like veins or emissarial channels. Through anywhere you've got something coming into or going out of the sclera, i.e. a vein going out, an artery and nerve coming in, tumors, the melanomas get out that way. So retinoblastomas go out from the optic nerve, melanomas go out from emissarial channels. And so here you can see, this is one of these aqueous veins and here's the tumor. And sure enough, there's tumor right up there. So this is spread out of the eye and under the epi-sclera space. So again, a very bad prognostic sign. All right, so now we're gonna look at coroidal lesions. Chris, we're looking at one right here. What do we see here? So how would you tell? What are things you look for that would make you alarmed for melanoma rather than anivis? Okay. Well, you can look, but if this is probably not gonna show any, because it's gotta be at least a millimeter and a half, two millimeters raised to show up. What you look for raised, that's good. You look for fluid, you look for lipofucin, orange dye on the surface of these guys. And then of course, size, size and diameter. So this is consistent with anivis. So you just take a picture of it and watch it. Now, would you be more concerned about this? Yeah, because here's the optic nerve. And there, and that's not a focus because this growth is coming from under the retina, pushing the retina forward. And so this is a big growth coming out from the coral, right? And now here's those little lipofucin dots I told you about. Little orangish gatherings here. You can see there's some fluid around this. You can see it's elevated. So you would be concerned that this would be more than just anivis, that this would be a melanoma. So Ashley, what is the particular pattern of growth of these coroidal melanomas that we often see? Mushroom shade. And so if you look right here, brooks membrane has got the elastic layer in it, a couple collagen layers. So those tumors will grow in the coroid. Eventually, they'll stretch brooks, and then it'll break through. But now brooks will still tether, almost like a lasso. And then the tumor cells will grow underneath the retina. So it'll form a mushroom shape still tethered at the base. So very common for coroidal melanomas to form this mushroom shape. Now, this is just a classic appearance of a coroidal melanoma. Now, in terms of the cellularity, now there was a man named Calendron in the 1930s who classified melanomas. Renee, what type is this? This is a spindle-A pattern. So spindle-A pattern, spindle-shaped nucleus, no nucleolus, indistinct cytoplasm. Some people would argue this is just anivis. This may not even be considered a melanoma. So spindle-A, Jack, oh, I already said, all right, spindle-B is the next one. So spindle-B, they tend to get a little bit more oval with a single nucleolus in them, cigar shape, but still indistinct cytoplasm, spindle-B. Jack, what are these? All right, these are epithelioid. So spindle-A, spindle-B, you can have a mixed type, mixed epithelioid and spindle, and then lastly epithelioid. These are the worst pregnancies. Look at these. Bizarre-looking, compchromatin, big nucleoli. You can actually see the cellular borders around these. So these are epithelioid, and the further you go toward the epithelioid side, the worse the prognosis. So these epithelioid tumors are bad prognosis. And again, here you can see mostly epithelioid in here, and then there are a few little spindle ones mixed in here. So this is the mixed tumor. So spindle-A, spindle-B, mixed epithelioid. Calinger had another classification. He called it fascicular, which is just a funny-looking spindle-B. And then his last one was necrotic, where at that time they didn't have ultrasound. They didn't have ways of looking at eyes. By the time they'd removed these tumors, it would just be necrotic. But the key you want to remember spindle-A, spindle-B, mixed epithelioid. All right, what are we showing right here? Are those the mesterial vessels? Exactly. This is a vortex vein draining the chloride. And sure enough, there's tumors right there. And where do these tumors metastasize when they do get out of the eye? What organ? The liver. Okay, so how do you remember that? The old saying, beware the yellow man with the glass eye. Think about it. Beware the yellow man. And that almost sounds like something out of Pirates of the Caribbean. So you say, argh at that, argh. Beware the yellow man with the glass eye. So here we see this is a vortex vein. And look, there's the tumor. There's the vein pushed to the side. There's the tumors going through it. And again, it can get out of the eye via the vortex veins. I don't know why they go to the liver, but here's a piece of liver with tumor in it. And they can even go years later. There've been documented cases more than 20 years later. Someone who had a melanoma of the eye and then they die of a metastatic melanoma to the liver. I don't know if they're just quiescent and then suddenly they grow or what, but for some reason they go to the liver. And so very important that you remember that. All right, a couple of other things we can cover in one minute here, okay? So we are back to Reese. What do we see in here? How is this different from the other ones we've shown? Whatever it is, it's a melanotic. Yeah, so it's kind of a melanotic. It's elevated. It is elevated. It's under, you know, in the chloride. It's kind of whitish looking and you don't have that distinct edges. It's almost feathery around there. What if I say it's a 75 year old woman? It could be a man. Okay, what kind of man? Breast cancer. Exactly, so this is easy to remember. You know, breast carcinoma is the most common cause of metastasis to the core aid in women. But as I mentioned previously, lung is catching up because you know, women are now smoking like men. They've come a long way and so they can die like men do too, lung cancer. But still it's breast lung catching up rapidly. So this is an adenocarcinoma of the breast metastatic and those tend to be less distinct, kind of fluffy looking and they can even be multiple because they are metastatic. And so metastatic tumors can occur in the coroid. Breast most common in women. And in men, this is another tumor and in men, lung is most common. Other ones are more rare like, you know, prostate and things like that are much more rare. So remember, breast, lung in women, lung in men, most common. And this is what I love. This is in the mall at the Britannia in Edinburgh. And sure enough, Mr. Nix, home of the Yiddos. All right, so no matter where you are in the world, there's always some Greek guy with a restaurant somewhere. So Mr. Nix. All right, so we wanted to put the quick review of path for the OCAPs as close to OCAPs as we can. So next Tuesday is an OCAP path review. I've got a two hour lecture that I give to medical students and we're just gonna show them in one hour. So please kind of review this stuff so you're ready. It's gonna be show the picture. You got five seconds to say the diagnosis and we're just gonna flash as many pictures as we possibly can in an hour so they'll be kind of fresh on your minds when you take OCAPs. All right, very good. Thank you. You're welcome.