 So sorry, this is the Schonbrunn Zoo in Vienna, and this is kind of just a really ornate place you get sandwiches, which is beautiful. It's got a skylight, it's got gargoyles on there, it's very beautiful. And then, of course, everybody's favorite, the pandas. And so they just kind of sit on their haunches and munch bamboo, basically. So they don't want to be bothered by tourists yelling at them. So they kind of sit with their backseat and just, you know, munch away on the bamboo. But they are cute, you know, when you look at them, so you can see why people love seeing the pandas. There you go. See, just munch away on the bamboo. There's a little better picture of them. They are cute, though, let's say everybody loves the pandas. The other thing everybody loves is koalas. So everybody loves koalas, and they just kind of sit there, and they're interesting. They just kind of sit there in the tree and snooze, too. So they're just kind of snoozing again. They're not really concerned about tourists trying to zoom in and take pictures of them. But again, they're almost as cute as pandas. OK, so today we want to talk about tumors. And the first thing I want to do is I want to talk about the differential diagnosis of leukocoria. And leukocoria, literally white pupil, what language? Greek, leukowite, quaria pupil. Very easy, white pupil. So let's say we're looking at a child and we're seeing a white pupil. What's the differential diagnosis? One thing. Rectovastoma. So, another. Cataracts. Cataracts, another. We're just some fetal vascular. OK. Cuts disease. Cuts disease. They said all of them. See, now it gets a little bit difficult. Now we're really going down the tube. Rental detachment. Rental detachment, exactly. Could have a. R-O-P. Yeah, ran up to the prematurity. Any others? Well, come on. Toxoplasma. Which toxo? Oxopara. Oh, great toxoplasma. Oxoplasma. You know what, boy, you're living good, because that's pretty much it. So really obscure things. And so we're looking here. Let's say this is an 18-month-old. And we're looking in. What are we seeing right here? So, superiorly, you see kind of that white opacity in a dilated fundus exam that's posterior. So what you're actually seeing here, believe it or not, that's the retina sitting right behind the crystalline lens. And so there is a mass behind the retina pushing everything forward. And so when we look at this, what we see, we see something like this. What would you be concerned about here? Retinoblastoma. Why? It looks. Exactly. So you see these kind of flecks here. And you see the lesion rising from the retina here. And these flecks are calcium. So again, retinoblastoma, one of the characteristics of retinoblastoma that helps you discern this from other causes of white people. Leucochorea is the calcification. Calcification, very important finding. And we look again. Here's an eye that is cut in half-sadually. Here's the cornea up here, iris crystalline lens. And sure enough, here's this mass completely filling the glow. And all these areas of white are calcium. So one of the things we can do to help diagnose these is we can actually take a B-scan ultrasound. You put it on the eye. You'll see the tumor there. You see the eye. And you slowly turn the gain down. And the eye will literally start to disappear. But the tumor will still have flecks all over. Because when those sound waves hit the calcium, it bounces them back. And so you get the spikes of sound waves. And so sometimes it's hard. And in 18 months, they're not going to let you put a probe on there. But if you're doing an exam under anesthesia, one of the things you want to do is do an ultrasound. That'll tell you the presence of calcium. CT scan will also. So that'll tell you the presence of calcium. All right, Tina. There's two different growth patterns for retinoblastoma. What are the two different growth patterns? So there's exophitic and endophytic, depending on which way it grows out of the retina. OK. So what would this one be? So that looks like it's endophitic. Sorry, exophitic. Is that underneath the retina? It's underneath the retina. So it's easy to remember. Endophytic means inside. Endo inside of the retina, exophitic outside of it. So you can get two different growth patterns. One pattern you can get. The tumor will grow underneath the retina. And that was like that first picture we showed you guys. So you can see, here's the retina dreddovreti here. You've got this huge extrudative detachment. And you've got these tumor cells underneath the retina. So exophitic underneath the retina. And then you can get them to grow inside of the retina. Here's the retina here. And it'll grow inside. So this is what we call endophitic. All right, this is the classic growth pattern of endophthalmide, endophthalmide, retinoblastoma. So what do we see here? What's the classic growth pattern that we see here? So we see a lot of necrosis in this picture. Then we see these kind of, I guess, so blood vessels around it by a lot of tumor cells, kind of a circular pattern around the blood vessels. All right, so here's the blood vessel in the center. So these tumor cells grow so fast, they literally outgrow their blood supply. And what you end up getting is you get what we call dystrophic calcification. So the tumor cells literally outgrow their blood supply. They die off and you get this necrotic area here and that's where the calcification occurs. And so you get these areas of viable tumor cells surrounding the vessels, cells dying off here and then calcification secondarily. Here's a close-up showing you all this magenta color here is the calcification. And that's just because you have such a rapid growth of these tumor cells that the blood vessels just can't keep up. So you get that intense calcification. Weish, what are we looking at right here? So these are Flexner wintersteiner rosettes. Exactly, so these are the classic findings you see in these. So as you see, it forms these little round structures, rosettes, Flexner wintersteiner rosette. What is that right there? Pneumatic figure. Yeah, so these still are active. So you get a mitotic figure, they're pretty active. They're even attempting to make part of the outer retina right here. There's even some crude rods trying to be made right here as you go around. And so these are the classic findings. And now just because you have a rosette doesn't mean it's a retinoblastoma. There are rosettes in other neural tumors. Neuroblastomas have rosettes, but those don't occur inside the eye. Those are usually outside the eye. And so those are the called the Homerite rosettes, but they look very similar. So this is a sign of differentiation. When you see the Flexner wintersteiner rosettes, it's a sign that it's a differentiated tumor, which is, you know, prognostically a better thing to have it more differentiated than less differentiated. Now, what kind of stain is this, Caleb? And what is ocean blue stain? It's mucopolysaccharide. Mucopolysaccharide, exactly. So this is showing you that you really have, remember where the outer retinal segments are? You've got some mucopolysaccharide there. So this is attempting to actually, you know, make these outer segments in between these Flexner wintersteiner rosettes. So you actually have mucopolysaccharide out there. Okay, what is this thing? Reset. No, those are the neuroblastomas. Only different word here. These are called florets. And florets are like a rosette that somebody has unwound. And so it's laying out. This is even more of a sign of differentiation. So floret, you get a rosette that starts to unwind and it starts laying out. Look, it's almost making outer retina here. And so this is even more a sign of differentiation. So florets even a better sign. It's a much more differentiated tumor. Now, remember these tumor cells come from the pluripotential retinoblasts, if you will, primitive retina. They don't come from mature retina. They come from primitive retina when you see these retinoblastomas. Becca, what am I trying to show here? Give you a higher power. There's low power. There's higher power. Calcium there in the... So not only calcium, but you get a lot of dark stuff around the blood vessels here. These are the veins actually here. And what happens is when these tumor cells break down, all the material from the nucleus kind of dumps out. And so if you do analysis on this, this is all kinds of DNA and nuclear material. And so this breakdown of the cellular material as it cells up with the blood supply, you'll often get a cuff of this material around the blood vessels. So you'll see this dark stain, especially around the veins around the blood vessels here. And it has a lot of DNA. It's DNA-rich material that's there. And there you see a real high power closeup. I don't think they've ever asked this on boards, but it's kind of cool to see the picture of it. So all right, where are we right here? Catherine, what part of the eye is this? So it looks like we're capsule, so I would probably guess the, or sorry, the zone. Got it. In fact, these are little ciliary processes seen almost in a flat prep. So we're kind of out in the periphery. These are ciliary processes. And this is to remind us that these tumors can extend anteriorly, even more so from the retina. So this is actually little seedlings of tumor cells here up into the ciliary process. So here's the iris. These are ciliary processes. These are tumor cells anteriorly between the ciliary processes. Like, where are we right here? The iris up top, maybe in the angle. Exactly, what's wrong with this picture? I'm upside down. Yeah, so I do this just periodically. I'll throw it upside down and let's see if everybody's awake yet. So this is upside down. We usually put the corny on top, you know. So this is upside down. But sure enough, here's iris. Here's anterior chamber angle. And these are tumor cells in the angle. It's uncommon, but there have been presentations of retinoblastoma that have been like a sterile hypopion. And so people will look in these kids' eyes and they'll see this white, flocculant stuff in the inferior angle and they'll think it's an infection or an inflammation and it's actually tumor cells. And so you can actually get tumor cells breaking loose, coming forward and you get these tumor cells here in the anterior chamber angle. And so again, that's not a good sign. Oh, we've got good timing here, doctors. So you're just right on time. In fact, before you can even open your bag there, what are we looking at right here? They're just an overstained tumor sitting in there. All right, so what tumor leads out of the eye, gets out of the eye by going to the optic nerve? Retinoblastoma. So it's really important to remember when a retinoblastoma spreads, it spreads via the optic nerve. And so it'll actually go beyond the laminar crebrosa into the optic nerve itself. And here we see it here. Here's the laminar crebrosa. Here it is going in. This is an old slide I copied from the AFIP. This is probably from the early 70s. And this was kind of the mortality. And so this was in the 1970s. If you had tumor at the posterior edge of the optic nerve when you did any nucleation, there was about a 65% mortality rate. And then don't memorize these because these aren't valid anymore, but this just shows you how important it was if it goes beyond the laminar crebrosa. So if it was beyond the laminar crebrosa but not at the cut edge, it was about 44%. And then if it was inside the eye, even then you still had an 8% mortality rate. And so you want to look real carefully and when we get retinoblastoma globes in the lab, we actually cut the distal nerve and process it just to make sure that the distal nerve is okay. And then we carefully look to see if the tumor is spreading into the optic nerve itself. And so again, these numbers are all moot now because we've got new treatments. In fact, the last two years we've seen a more decrease in the nucleations for retinoblastoma because of the fact that people are treating them now with intraoperative and even intravitral chemotherapy to try to save the eye. So a lot different treatment now the last few years. This is what can happen if it gets out of the eye. This is a young child in Nigeria. And once the tumor gets out of the eye, it's a very aggressive, nasty tumor. All right, Tina, what are we looking at right here? It looks more major to the photo, but it looks a little more yellow. It looks like in this case, this is retina. You can see kind of retinal vasculature being pushed right up against the blurry margin with sort of big vessels. Yeah, another word we call these are telangieces. So really dilated vessels, kind of a yellowish tint to that. What would you be concerned about here? Coats disease. So this is a classic picture of coats disease. And so you get this exudative retinal detachment, but you have this kind of yellow, lipid-rich material under the retina. You've got all these little telangieces on the surface. So bilateral or unilateral usually coats. Unilateral. What's the age range? Nails eight to 10. Yeah, so older than retinoblastoma. So for some reason, males don't know why, not sure why that is. Unilateral and again, older retinoblastoma is roughly 18 months, you know, average diagnosis. Here it's more like eight years old. So it's a little bit older. And here we see, here's some telangieces. Here's the retina with all this yellow, lipid-rich exudate underneath it. There you see here again, when you look at this in a glow, this stuff almost looks like gelatin. So this exudate that's in there is almost like jello. You can bounce your little foreset off it. And of course, here's your telangiectatic vessels. And they leak like crazy into the retina and then under the retina. What are these little sickle-shaped areas? Cholesterol claps. And so for some reason, cholesterol looks like a banana or a sickle. So the lipid dissolves when we do our processing and it leaves these little sickle or banana shapes underneath the retina. So this is again, a very lipid-rich exudate. Bonus points, what kind of cells are these? Those are macrophages. So again, when you take oral boards, you say things with conviction. You say macrophages. If you say macrophages, then they know you're guessing and you won't get credit. They go, well, yeah, but you guessed. So even if you're wrong, you say it with conviction, macrophages. And so these are almost like little, remember the game Pac-Man? They're little, they're in there munching up what's left of that lipid and protein-rich exudate. So little Pac-Man under here, trying to clean that up. They can't do it, because it leaks too much. All right, what do we see in right here, Chris? So we're seeing an external photo, leukocorrhea here. It looks kind of a raised white mass here again, kind of coming up. Maybe behind the lens? Yeah, maybe even right behind the lens or maybe even in the lens. Man, I'm really upset about the resolution on this picture here, because my screen is gorgeous. What I really wanna show, you guys have to really almost hallucinate these. There's little vessels stretched out right here, going into this mass right behind the lens, maybe even in the lens. What could that be? Something like persistent fetal vasculature. Exactly, and so you may see the term in the literature, PHPV, because that's what we used to call it. Persistent or primary, you know, let's see, pH, primary hyperplastic. Primary vitreous. Persistent, hyperplastic, primary vitreous. That's what you call it, PHPV. And so now they just call it persistent fetal vasculature. So it's an embryonic remnant. And what you can do is you can sometimes get this little retro-lental mass or even a mass going into the lens itself. This is it from behind. And what happens is the ciliary processes, they just get drawn forward as this mass, it's got fibroblasts and vessels in it and it tends to contract and really pull those ciliary vessels to the center, the ciliary processes to the center. And what is this right here? So that's the remnant of the hyaloid system, I think. Exactly, so that's the remnant hyaloid artery. And you can see here's this mass anteriorly going into the crystalline lens itself with these blood vessels pulling those ciliary processes forward and then here's that persistent hyaloid artery coming forward. And so persistent fetal vasculature is just a better way, but you may see the term PHPV if you look in some older literature, some older books and there's just a different view. All right, so here we see a nice stock coming all the way from the optic nerve to this mass behind the lens, even involving the lens itself. So again, unilateral or bilateral? Yeah, unilateral. Now these are tough to treat because even if you take out the crystalline lens and all the vasculature and do a complete protractomy, the retina's just not normal in these kids. So sometimes you end up doing all that surgery and it doesn't do anything. So here's the crystalline lens. Here's that stock of hyaloid artery and there's all these little vessels and just lipid and exudate leaking out and so all in the crystalline lens. This is the anterior variation of the persistent fetal vasculature. And here, here's the iris, here's the ciliary body and look at it being pulled forward. It's being yanked forward here with this mass. I'm going into the crystalline lens right here and there was even kind of a pseudo-hypopian in the anterior chamber, this eye was a mass. So this was the eye just to show you you can't win. This was a kid, they did exams under anesthesia and they found this mass and there was even some calcium in there and they said, God, we don't know. This could be a retinoblastoma. And we even tried to do a fine needle biopsy and we couldn't get any good cells out of there one way or another and so this was a few years ago and so the decision was made with real consultation with the family saying, you know what, we should probably remove this. This could be a tumor. They talked to them at length so they did the nucleation and we did the pathology and we went back and we said, wow, great news. This wasn't a tumor. It was a condition that we call persistent fetal vasculature. That's great news. Your kid doesn't have a tumor and they turned around and they sued everybody. So, you know, that's our legal system in America. They sued everybody because they removed his eye and it wasn't a tumor. So needless to say it got chucked out of court but you can't win for trying. I mean, you know, the good news is that, now this eye wouldn't have seen anyway. And so, but the good news is, wow, good news. You don't have it. There's no tumor in your kid's eye. Oh, that's great. Well, we're gonna sue you. So, welcome to America. Lots of lawyers in America. All right, there's a close up. Look at that silly process. Way up here, this is actually the peripheral retina being yanked up into this, into this lesion. So, very interesting. Okay, what are we seeing right here, Vaish? So, off the optic nerves, there's like this corkscrew-shaped vessel there. So, this might be kind of like a workmaster perpillae or to make a smaller remnant of the hyalurid artery. Exactly. So this is kind of the posterior remnant of that hyalurid artery system that's regressed. And so, you'll get this little corkscrew vessel coming out. These are pretty cool when you see them. But usually, vision here is normal. So, a little corkscrew vessel here, and then, of course, here's your remnant hyalurid artery coming back into that. Now, when you get connective tissue around that, in addition to the artery, then we call it a birdmeister's perpillae. So, you'll have this little veil of gliotic tissue with the little corkscrew vessel in it. And that's kind of the posterior remnant of the hyalurid artery system. Again, here's the artery coming up. Here's some gliotic tissue around it. So, corkscrew vessel, birdmeister's perpillae. The posterior, your variant of the persistent fetal vasculature. All right, Caleb, what do we see in here? So, young patient external photo, the cochorean both eyes. Yeah, so this is both eyes now. So, that changes your differential a little bit. What are entities that can cause the cochory that can occur in both eyes simultaneously? General cataracts, good. Yep, those can be. So, the most common ones are gonna be, of course, cataract, I wanna miss those, but also end stage retinopathy of prematurity or ROP. And what are we looking at here? Does this tell us what the diagnosis is? Let's say you could look inside. Yeah, so this is, so the optic tissue is stretched and this is characteristic of ROP. So, we call this the dragged disc. So, you know, ROP, what happens is, is these kids are born prematurely. Their retina, especially temporally, hasn't gone all the way out to the aura. It hasn't completely vascularized and completely formed. And so, when you put these kids on high doses of oxygen, what would happen then is that you would get a frond of neovascularization right at that leading edge. And then you end up getting scarring and you get that disc pulled over. In the nowadays, we monitor the disc much more carefully and they watch their oxygen closely. But now we're saving fetuses at even 24 weeks, which is just stunning, but they're still at a high risk of ROP. And so, we really wanna check them regularly because if you have that avascular peripheral retina, then you can get fronds in neovascularization, then you get dragged discs. You can even get the end stage of this, which we used to call this retro-lental fibroplasia. What it is is it's a total funnel-shaped retinal detachment behind the lens. So that was kind of the end stage of ROP and that's why you got that leukocorea. So hopefully we don't see that as much lately because we're really monitoring the oxygen very carefully in these kids, but again, they're being born younger and younger. And there we see total funnel-shaped retinal detachment attached at the optic nerve and here at the auricirata. What the heck is this? It's a sclerobuckle. Sclerobuckles. So they've tried to save this eye by doing a sclerobuckle. So we wanna try to keep it from becoming a total retinal detachment. And so you do that by, we used to do cryotherapy and then avascular retina. Now we do laser, we'll do endo-laser or laser through an indirect to try to kill off that ischemic peripheral retina and prevent it from going on to the full retro-lental fibroplasia and the full total RD. All right, another weird entity here. What do we see in here? So we've got, looks like, a lot of white, fibrous tissue in the vitreous. And it looks like sort of the ret attached. Yeah, so this mass of this white stuff may even be pulling the retina into it. And so this is a unilateral condition. It's again a kid, maybe three years old. And we look, what the heck is that thing? It's like toxocara. Exactly, so toxocara cani. And so what do little puppies do? Puppies eat their poop, basically. And then what do little kids do? They get down and play with the puppies, the puppies lick them on the face and the kids end up getting these toxocara ingested. It actually goes into the GI tract and then it'll proliferate and then it'll go through the wall of the GI tract and then it'll disseminate to various end organs. And one of the end organs that the toxocara can disseminate to is actually the eye. So you actually get this little beast, this little parasite inside the eye and it'll induce a tremendous inflammation. So it's interesting if you kill it, it gets even more inflammation. And so then people try to go in and do a vitrectomy and get it out. But these are rare, but difficult to treat. So toxocara can cause leukocorrhea. What do we see in right here? Here's the angle. What tissue are we in right here? Ciliary body. Ciliary body? What is that stuff? As there's like a round collection of cells with like a lot of clear, like foamy looking cytoplasm in them. And nodular peering. I know that's something you'd never expect, but believe it or not, that is cartilage. So what's an entity that can give you leukocorrhea that has cartilage in the ciliary body? There might usually aren't in the ciliary body. This is a specific entity. It's usually not conductive toward long life, certainly, or much life. This is just something you need to memorize for boards. This is trisomy 13. So trisomy 13 is an entity where you can get cartilage in the ciliary body. And then in addition to that, you get a dysplastic retina and you get all of these rosettes forming, you know, dysplastic, not meaning tumor involving, but just meaning disorder retina. So trisomy 13, you get all these rosettes in the retina posteriorly and then you can get cartilage in the ciliary body. So you really want to memorize that because that can pop up on boards. You know, they'll say, okay, what is an entity that can cause cartilage in the ciliary body? And the two entities are trisomy 13. Beckham, what's another entity that can cause cartilage in the ciliary body? Mediolopathylioma, exactly. So those are good PIMP questions to remember because those are the two. Those are the two. All right, enough with leukocorrhea. Let's kind of shift gears a little bit. Look at some other tumors. All right, Catherine, what are we seeing right here? It's like there's a literally shaped mass in the iris in front of us. Concerned about here. The melanoma. Okay, melanoma or nevus. You know, you can still get iris nevi too. And the key thing here, you always want to put a goniomere on people who have, you know, pigmented lesions of the iris because you want to make sure that that is not going at the angle but a pretty good view here. You've got pretty clear there. That thing's not going into the angle. And so your differential would be nevus versus melanoma. What's a test that can be done that'll help you a little bit with that? Well, you can do a biopsy, but short of a biopsy, less invasive. You can do an ultrasound. So Dr. Harry has got a way, he's got a high frequency ultrasound handpiece. You can put it in a water bath so that, you know, because if you put that thing right on the cornea, it really kind of washes out all the anterior segment structure. So put a water bath in there and you put this high frequency ultrasound. You can see if that lesion is growing into the ciliary body, if it's growing behind, you can measure the thickness and make sure this looks more like a nevus. So this is more nevus looking. All right, what do we see in right here? So this is another, you know, pigmented mass in the anterior chamber. Almost opposing the cornea, looks like towards the inferior cornea. Look at that. Look at that slit lamp beam. So that thing is really thick. What else is worrisome with this? They're early shaped and it seems like it's almost pulling iris for it a little bit as well. And it looks like it's going all the way into the angle when you look here with a slit lamp. You'd be very concerned here about the possibility of being a melanoma. Now, when I was a resident, we used to, you know, they teach us, okay, iris melanomas have a very good prognosis. And they say, well, because you find them early and you can get them out of there and they don't spread. And so good prognosis. And I think the reason for that good prognosis is it turns out the vast majority of what used to be called iris melanomas are actually variations of Nevi. So Fred Jakobiak went through all these files at the AFIP, they found like 180 iris lesions. Sorry, they'll drop numbers. 186 lesions, you know. And they looked at all of the slides and then they said, wait a minute, of all of these quote melanomas, it turns out that, you know, about a third of them are melanomas. The other two are just variations of Nevi. So they went through and they actually categorize iris pigmented lesions. And it's really important that you guys memorize these because, you know, what we used to call melanomas aren't really melanomas. And so the first most benign iris lesion we see right here. Rachel, what are we looking at here? Yeah, and what's their shape? Their spindle shape. And so you look at these little spindly shaped nucleus, kind of an indistinct cytoplasm around them. No nucleoline, no mycotic figures, totally benign spindle shaped melanocytes in the iris. What do we call this? This is a spindle nevus. This would be the equivalent of a spindle A in the chloride. And so this is called a spindle nevus of the iris. All right, Tina, these have kind of similar cells, but I'm showing that low power. What are we seeing here? A lot of part of the iris. So we literally call this spindle nevus with plaque. So you've got pure spindle nevus. It's just a nevus. Spindle nevus with plaque. That's kind of the second category. Chris, what do we see in here that's a little different? Here we're seeing, it's similar. The cells have a little bit, I think we see some, maybe some nucleoline there. Yeah, some are looking a little bit rounder here rather than spindle shaped. Maybe a little clump chromatin here. So instead of being pure spindly, they're kind of showing a few little features that are a little bit suspicious. So we call this a borderline spindle nevus. And so something that's moving along toward a little bit more of a suspicious lesion. And then, Weish, what are we seeing here? Here, practically, all the cells have nucleoli and they look just plastic, so this is more of a spindle cell melanoma. Exactly, so this is a spindle cell melanoma. So if the spindly cells that are there, you can have just a pure spindle nevus, spindle nevus with plaque, borderline spindle nevus, and finally, spindle melanomas. If you look at these, the cells are now rounder oval. There's that distinct nucleolus in them. And so this is kind of akin to the spindle B melanoma, the coroid. And so this is up here, spindle melanoma. What are we seeing right here, Caleb? So these are more epithelioid-type cells. They have this more distinct cytoplasm and more clear border. So this is more of, or excuse me, nevus. Yeah, so this is, if you look at it, this is kind of a bleach specimen because these can be pretty heavily pigmented. But if you look, the really the nuclei are benign here, but they're bigger cells or more. And so you can get an epithelioid cell nevus, very uncommon, but you can get an epithelioid cell nevus. And of course, if I showed you that first, what's the next one gonna be? That would be epithelioid melanoma. Exactly, epithelioid melanoma. So if you look, these are big cells, big nucleolus, clump chromatin, distinct cellular borders around them, pleomorphic, different sizes, different shapes. And so epithelioid melanomas can also occur in the iris, but they're really uncommon. And then you can even get mixed melanomas in there. Now, the other thing you can get, you can get a melanocytoma of the iris, which is really rare. I don't have path on one of those. I've just not seen one before, but they're very uncommon. So I think the reason why, quote, iris melanomas, that's such a good prognosis, two-thirds of them are really variations of neovire rather than melanomas. All right, so what are we looking at right here? All right, so you see this mass here, right here. But if you look real carefully, look, maybe it's right there. So this is a picture I took myself as a resident. This guy was a University of Illinois alumni and went to the football games. And the first game of the season, he could read the scoreboard with his sign, then started getting fuzzy by the third game. And then by the fifth game, he couldn't see the scoreboard. And so he came to the VA in Chicago and we looked at him, sure enough, there's this tumor growing here, but behind there pushing against the lens and he developed a cataract from the tumor pushing on it. That's what he was seeing. And so he came in. So indeed, there is this pigmented lesion growing from the... Cylary body. So when you think of pigmented lesions of the eye, iris is separate. We covered that separately. Cylary body and coroid are all under the classification of UVO melanoma. So they all have a similar classification. So we look right here again. Here's a tumor. You can see it starting to peek out here anteriorly and then it's growing posterior to the iris and pushing on that lens, giving you a focal cataract. And here's a gony ovu. Big tumor behind the iris and even forming a synechia, overlying it as it's pushing forward. What is this thing? Beca. So there's an enlarged vessel inferiorly. We call that a sentinel vessel. The reason we call it a sentinel is because it points out to where that tumor is. And so if you see somebody with just an isolated dilated vessel there, that should really raise red flags because it's kind of pointing to something saying, hey, wait a minute, there might be a tumor here. So, you know, look in that area. And of course we dilated the patient, sure enough, there was a vision there in the Cylary body. So here we see, here's this lesion arising from the Cylary body, heavily pigmented, pushing up against the crystalline lens and eventually leading to a cataract, which was the patient's symptom. The reason why these Cylary body tumors are bad actors is two. First off, they're hiding behind the iris so they can grow over time. But secondly, they're really close to the anterior chamber angle. They're close to those vessels that drain the anterior chamber angle, you know, the aqueous vessels. And so you have more chance of these getting out of the eye. So that's why they're bad actors. Here we see, here's this tumor in the Cylary body coming up actually into the trabecular meshwork. So here we have again, here's iris, tumor in the Cylary body into the trabecular meshwork. And of course what we worry about is, look, here's tumor cells here along the outside of one of those aqueous veins that's sure enough right there. So when we look at these globes in the lab, we look very carefully at the outside surface of the sclera to make sure there's not little black areas there because these tumors in the Cylary body, they can go out through the aqueous veins and then they can actually come up here to the epi sclera. And you'll see tumor cells up there. So we look for these little black areas there. All right, so what do we see in, right? Did I ask, did you do the last one? No, I didn't get it, I didn't get it. Okay, get it. What are we seeing here? I think a nevus, it's flat pigment. All right, so this is your standard kind of choroidal nevus. It's flat, you don't see fluid, you don't see lipofucin on the surface, little orange deposits on the surface. So you could do an ultrasound here, but if it's that flat, they've really gotta be more than a millimeter thick, maybe even closer to two millimeters thick before Dr. Harry's ultrasound could really pick it up. But so this one's just a nevus, nothing suspicious. You just photograph, measure, and follow. All right, what do we see in here? So I would say, you know, find this photo of the retina, it's out of focus, looks like it's raised up a little bit. Exactly, so it's in focus here, it's out of focus down there, so this thing's coming toward you. So big subretinal lesion here. And then as we look at the surface, you start to see kind of this orange-ish lipofucin, elevated lesion, so your concern here would be? Corretal melanoma. Corretal melanoma, so you'd be worried about a corretal melanoma here. So what's the classic growth pattern of a corretal melanoma? Like a mushroom, why is that? As we hear about it grows and grows and grows, and then breaks through elastic brooks membrane and then kind of expands after that. Exactly, so brooks membrane, remember, brooks membrane has kind of an elastic layer in it, and so that tumor starts growing in the coroid, it grows and grows and grows, and brooks membrane eventually breaks, and the tumor breaks through there, but then brooks membrane still has kind of a little elastic property, a little tethering effect there, and then the tumor will mushroom out underneath the retina. So that's your classic mushroom melanoma, rises from the coroid, breaks through brooks, mushrooms underneath the retina, so that's kind of the classic growth pattern. There you just see, well, Rachel, what is this right next to it here? Yeah, so what could that be? What could be really acellular and kind of diffuse pinkly staining? This is actually exudate, and so oftentimes when you look at these, the tumor can look bigger when you're looking at it because it can have an exudative retinal detachment next to it or around it, and so you want to be careful not to overdo, yes. Yeah, you can get a halo around that, you can even get on top of it an exudative detachment, so now Roger can tell the difference on an ultrasound, he's really good at that, so he'll be able to tell that. All right, now, how do we classify this back to Tina? Who first came up with the classification for melanomas? It was calendar, it was calendar's classification, so what is the classification? What's the, first one, what is this one? Spindle A, again, say it with conviction, say it, spindle A. Spindle A. Spindle A, so if you look at this, this looks like the spindle nevis of the iris, little spindly-shaped nuclei, indistinct cytoplasm, no nucleolides, so if you have a pure spindle a lesion, it's really a nevis, it's not a melanoma. So what are these now? Spindle B. Spindle B, so let's see if I have a pie. That was easy. So spindle B, they are more oval rather than total spindle shape, almost like cigar-shaped, and you've got this distinct nucleolus looking back at you, so it's almost like there's little eyes staring back at you from each one of these. Again, though, indistinct kind of cellular borders and cytoplasm, they all kind of run together. So spindle B, these are actually melanomas. Weish, what are these? These are epithelioid. Epithelioid, you can tell the difference. These are really nasty-looking cells, I mean, they're big, there's clumped chromatin, there's multiple necliolide, they have a distinct cellular border around them, and the pleomorphic, look, some of them are small, some of them are huge. And so this is epithelioid, and of course you can get what we call a mixed, so that's spindle B and epithelioid, so kind of the progression. Spindle A, probably more like a nevus, if you will. Spindle B, melanoma mixed, a mixture of spindle B and epithelioid, and then pure epithelioid are very uncommon. But the reason that that's important is prognostically the cell type is the most important thing. So the more aggressive the cell type, the more aggressive the tumor is. Now people are doing genetic testing, we're looking at other things, but before we had that, cell type was first, and then size, and then location. So those are the important facts, but now you can look at the genetics of these, and so we'll often take tissue from these fresh and do genetic analysis. Why are we showing this picture? Is that behind the eye? That's exactly, here's the optic nerve, that's the posterior sclera. Might be erupting through the sclera posteriorly. Yes, and believe it or not, we are holding a small vein right here. O.C.F. theater? So that's a vortex vein, it's a vortex vein. So when melanomas spread from the eye, they spread through any of the emissariat. You know, what's an emissariat? Someone who kind of goes through the enemy lines, you know, to talk to the other side, so you wave your white flag, you go through the line, and so any time a vessel either goes out of the sclera or penetrates into the sclera, that's a spot where melanomas can get out. And so melanomas don't just eat through sclera. I mean, sclera is really tough stuff, you can't just eat through it. And so the melanomas will spread via the vortex veins, which drain the chloride, or even if they're more posteriorly around the optic nerve, where the posterior, ciliary arteries and nerves come in, they can actually go out through those channels also. So they usually, most commonly, will go out through one of the vortex veins, which drains the chloride. And here you can see, here's the sclera here, here's a vein, and it doesn't go through the vein itself, it goes along where the vein is. So that's a weak spot, and the tumor works its way out. Sure enough, now here's the outside surface of the sclera, here's the vessel, and the tumor cells will go out. So we again, look for those little black spots, you know, on the surface of the sclera, outside where the tumor is, to see if there's signs of extension. Where do they metastasize when melanomas leave the eye? To the liver. So the saying you remember, beware the yellow man with the glass eye. Think about it. You can say, art after that. Beware the yellow man with the glass eye. So when these do metastasize, they metastasize to the liver. And these can metastasize years later. It's very strange. I don't know if you get micro-metastases, and then the immune system keeps them intact until finally they grow, but there's been reports of metastases years later in the liver of melanoma from an eye that had been enucleated long before. Now there was controversy when I was a resident also, because as people were enucleating eyes to treat melanoma, they did a little study and they said, wow, if you enucleate them, more people die of metastatic disease than if you don't enucleate them. And Lawrence Zimmerman, who used to run the AFIP presented this data and people just went nuts. They said, that can't be. And so what it turned out is that you weren't comparing apples to apples. And so what was happening is these tumors would start to really grow. They'd hit a really rapid growth phase, which means they're becoming more epithelioid and becoming more aggressive. And then you would enucleate them. And so sure they would have more metastases in that case than they would have if you had just left them alone, because the ones that were left alone were not growing rapidly. So that was discredited, but there were all these bizarre treatments we had at the time. People would try to freeze the eye before you enucleated. We had what was called the no-touch technique. You'd try to enucleate it, but not squeeze the eye at all. You wouldn't press those tumor cells out, but the bottom line is once these tumor cells hit their rapid growth phase, those cells are going out of the eye anyway. So whether you enucleate them or not, it's not gonna make a difference. But now when we're treating them with plaque or external beam radiation, we're much better at looking at these early on than this is what people try to prevent is these metastases at this point. Was interesting because that really was the impetus behind the COMT study. So they did a study comparing plaque radiation to enucleation, and they found it didn't really make a whole lot of difference. But they took large tumors and they actually irradiated the whole eye in the orbit before enucleation to see if that went up, did make any difference. So bottom line now is when we see these, you can treat these with plaque radiation. You can treat them with external beam radiation. Now the problem with external beam radiation is you need something that makes really accelerated protons. I.e. an accelerator. You don't have those in the basement of your hospital usually. You kind of need like a nuclear accelerator and make those proton beams. And so there's very few places. From here we could send them to San Francisco, Devin Char does them, you can send them to Chicago or to Boston. And so yeah, you just don't have this nuclear accelerator in your basement to make protons to treat these. Okay, I guess we were at, Theresa did you do that last one? Okay, Becca. What are we seeing here? Kind of fuzzy, non-distinct. What's your concern be here? I would still be thinking about tumor, but maybe more like a metastasis, something amelanotic. Exactly, so you can still have an amelanotic melanoma. Now remember, they don't necessarily have to be pigmented, but remember, you can get metastatic tumors to the coroid also. And so metastatic tumors and again, they kind of mimic the tumors that you see in people. So if it's a 75-year-old woman, you'd worry that this would be a breast carcinoma. If it's a 65-year-old guy who smokes, you'd worry about lung cancer. And it used to be that by far the most common tumor in women was breast and then lung was much, much less, but now lung cancer is almost caught up. So there was a commercial in the 70s when cigarette commercials were still on TV and there'd be this really sleek dynamic woman and she would have this cigarette in their Virginia Slims and the tagline was you've come a long way, baby. And so it meant you could compete with men and you've come away and you could even smoke and be sophisticated and cool. And so yeah, they did come a long way. Now women can die of lung cancer just like men can, so women have come a long way. So when you think of metastatic tumors, you think of what the most common are. Now you can still get metastatic GI tumors, prostatumers there, but they're less common. So by far and away, women is breast, men is lung, but lung is catching up in women. So this turned out to be an adenocarcinoma of the breast. And so this is actually a musin stain. So this was actually a musinus, adenocarcinoma, metastatic to the correlate. And this turned out to be, this was a gentleman and this was a metastatic lung tumor. And so again, metastatic tumors can occur to the core, it's a metastatic lung tumor. And we say goodbye to the gardens there at the Shonbrun Zoo. So next week we're gonna just go over as many pictures as we can squeeze in in an hour to do a review of path for OCAPS. So any questions? All right, very good.