Cancerous colon tissue

SAL: This is Sal again, and this part four on the series that we're doing at Stanford Medical School, with Doctor Connolly. DR. CONNOLLY: All right Sal, we're back here again. This is now the fourth of the slides. And this would be now the business for why that segment of colon was removed. This is the colon cancer. SAL: Wow, wow. DR. CONNOLLY: And so just to orient, we'll go now to the drawing. Which is, like you were saying before, up here this is the lumen. SAL: Right. DR. CONNOLLY: Up here. Out here, that's the-- SAL: Lumen is the inside of the colon. DR. CONNOLLY: The inside. That's the inside. Out here, this is the rest of your belly. SAL: Right. DR. CONNOLLY: Where the bowel is all kind of rotating around in the abdomen. And so-- SAL: Is there a word for like intra-abdominal-- DR. CONNOLLY: Yeah, peritoneal. SAL: Peritoneal, OK. DR. CONNOLLY: The peritoneal cavity is where all the bowel loops are kind of just moseying around. And then what we have here is, this is an important part, which is this is the muscle that allows peristalsis. SAL: Yes, that's the peri-- I learned that in high school. That's the kind of moving, the undulating motion to the push stuff. DR. CONNOLLY: Yep. It'll go and it'll sort of milk it along in order for the contents to move along. So you can see, the muscle looks all fine there. That's how thick it's supposed to be. And it all looks fine over here. SAL: Just on a scale, what scale is this? Like how thick is that muscle? DR. CONNOLLY: So we're now, once again, our tiny little red blood cells are those little dots there. SAL: Right. DR. CONNOLLY: So we're talking about the thickness here as a few millimeters. SAL: That muscle is about a few millimeters. DR. CONNOLLY: Remember back to this guy, that was about six millimeters. So that's about six-- SAL: OK, OK. DR. CONNOLLY: Millimeters thick. That's actually strong. That's a very, very strong muscle. And you can kind of see it goes up here, it kind of comes around here, but it's looking like it's troubled all along this area. SAL: Yes. And this stuff, all this stuff, this once was probably a polyp, and now it's turned into a kind of this massive polyp? DR. CONNOLLY: Yeah, so we have the normal over here, for the lining. This is where it's going dysplastic. It's looking a little bit bad there. There's where it's going dysplastic. And so now what happens is, you've got these edges of dysplasia-- SAL: When people in the medical field say plastic, they're saying, that word means tissue? DR. CONNOLLY: Well plastic in general, like plastic surgery, or the plastics as far as a material science, means moldable. SAL: I see. DR. CONNOLLY: But it also means you can grow with it, and it can change shape. SAL: Right. So when you call something plastic it's moldable tissue. DR. CONNOLLY: It's the shape change. SAL: It's a shape change. I see. DR. CONNOLLY: And so the shape changes were wrong. SAL: I see. DR. CONNOLLY: And actually dysplasia can refer to a cell, a tissue, an organ, or an entire limb. SAL: Oh, OK. DR. CONNOLLY: So it just means it grew wrong. Or molded wrong. So now this is where we have the cell dysplasia. This is all the bad stuff. And it basically started probably somewhere up there, and is invading in all of these directions. SAL: This one cell up there just started dividing uncontrollably-- DR. CONNOLLY: That's right. SAL: And it's descendants. DR. CONNOLLY: It could have started from one cell being very bad. It often though starts-- and I'm going to change now, so we'll lose our art, and so what I'm going to do is change this-- that it often starts, though, from one of these. Meaning maybe a cell went bad right around there. And now really is starting to grow. SAL: And when you say grow, it's not just one cell, it's all of its descendants. DR. CONNOLLY: It's descendants. And billions of cells are growing. Billions and billions are growing downward in order to now, in this case, grow all the way through. SAL: Wow. DR. CONNOLLY: And so you can see the scale is, it not only grew a little bit, it went right through the muscle. So going back to this guy here, this is now-- SAL: And there are some, the body does have things to fight this off, but it was unsuccessful. DR. CONNOLLY: Oh that's right. And so there are certain conditions where if you decrease the immune functions, you'll get cancer. And so it's still argued though whether it's that your immune system is decreased, you got a virus, and then the virus caused the cancer. Or whether there's a lot of surveillance there to eliminate cancer. SAL: And the whole notion that viruses-- it's fascinating. It's because viruses are messing with our-- isn't a significant chunk of our own DNA from ancient viruses? DR. CONNOLLY: Yep. And I think there's a couple big categories is that viruses can get into your DNA and really screw up the DNA. Like getting integrated into it. But they also, like we said before, can lead to irritation. And then more cell growth and have trouble there. SAL: Makes sense, makes sense. DR. CONNOLLY: So now we're back here, in which we're looking at the cancer. Which probably, like you said, started here. And is growing, including spreading out all the normal tissue around it. SAL: Wow. DR. CONNOLLY: And so we're going to look now at the cells. So zoom in. Zoom time. Hang on to your hat. OK, so what we're going to do is first-- probably go into a lower power here-- is look at the edges of this. So once again, we find normal. And so this is even not perfectly normal, you can see it's a little bit dividing and a little bit irritated. So this is irritated along the edge. SAL: Hyperplasia. DR. CONNOLLY: Exactly. SAL: I'm like, I'm learning something. DR. CONNOLLY: All right. So then what we have now is, as you go in deeper, these are the areas which are normal, but this is all kind of coming out. Like we were saying up here, kind of growing out in all directions. This is now where you can see the cancer, next to the normal. You know we had talked before about dysplasia. This is really bad. SAL: With a capital B. DR. CONNOLLY: Yep. Small children off the street could be able to tell you that this is bad. SAL: Right. After they watch this video. DR. CONNOLLY: Exactly. And so these are the normal ones. They're doing their J-O-B job. Making the mucin, nuclei at the bottom. What is this guy doing? It's just chaos. So before we talk about carcinoma in situ, a cancer in spot. If you saw cells this bad, you'd say do not let them go far. Because they will have a tendency to invade. They're crazy. So this right here's a bunch of the cells, that's a bunch of the cells, they're these guys here. You can see they're really haphazard, they're growing, they're not doing their-- SAL: So if we found a polyp that had this stuff that didn't cross that boundary line yet, we still would say no, we've got to take this-- Well I guess we already took it out. DR. CONNOLLY: We took it out. So cancer of the colon is one of the ones where surgical cure is still a classic. Cut it out, and you're probably in pretty good shape. And so there you'd say, well if it's the tip of the polyp that looked like this, I think we got it out. But you'd say to yourself, we better watch this person. SAL: I see. So if the whole polyp kind of looked like that, you're like, oh let's cut out a bigger section. DR. CONNOLLY: Yeah then you might. So if it's going down into the neck, or getting a little further, or if you've cut across it at the margin, then watch out. But here's the problem. Is remember how I said up here it's not a big deal, but once you get down near the veins and arteries? These guys are running amok down by the veins, the arteries. SAL: And so you can actually see these cells have split off. And they're infiltrating. Wow. DR. CONNOLLY: So you can see these guys here. So that's one little nest of cells. There's one. That's probably, right there, a cancer cell just dying to get into that little vein. SAL: So this is actually, I can never say the word, meta-- DR. CONNOLLY: Metastasis. SAL: This is it. We're seeing it. DR. CONNOLLY: This is where it would come from. SAL: This is where it's starting to happen. DR. CONNOLLY: So these guys are the bad actors. They're growing in next to these very fragile little blood vessels, and so that guy is knocking on the door. Once he gets in here, that's a venule, meaning a little vein. That's the road out. SAL: Right. And it just looks like a circle here because it's a two-dimensional cross-section of it, but you can imagine it popping in and out of our screen. DR. CONNOLLY: Yes. It would be popping in and out of our screen. So this guy would kind of go in and out of the screen, connect to this one, and then it would go out. SAL: And it's officially-- I can never say the word-- metastasized once it's found a beachhead someplace else? DR. CONNOLLY: That's right. So it's considered a metastasis where, let's say, the cell got into the vessel, if it left the region. So it went to the lung, the liver. This is looking like you really are worried that this could metastasize. SAL: Right. DR. CONNOLLY: And so what's interesting about this is that when you look at something like this, there's such a thing called, for cancer, grade. And what grade is, is basically what we we've been just talking about, how bad does that look? SAL: Right. DR. CONNOLLY: And so the grade is, wow, that looks nasty. I think that-- SAL: Is nasty a technical term? DR. CONNOLLY: Actually we use it quite a bit. Some people say, oh what did that tumor show? We say it was nasty. When we talk about nastiness, it's a lack of behavior. If you can get a cell where the nucleus gets that big, or sometimes it's that big, there's chaos. And there's chaos not just in nuclear size, but how it behaves. SAL: And I guess the nuclear size is a telltale, because that means that the cell is devoting a lot of its resources for replication and-- DR. CONNOLLY: It's for replication, but it also means, to me, that normally things in the cellar are very orderly. You do not divide your DNA until these things are already [INAUDIBLE]. And now it's just left and right. So yeah, this would be a high grade tumor. And then stage is the other main thing. SAL: Yes, I've heard of stage. DR. CONNOLLY: Stage means, where is it in the body? So in this case, if it's these nasty cells at the very top, it's actually a lower stage then if they're nasty cells and they've come all the way down here. SAL: So in situ carcinoma would still get a stage. DR. CONNOLLY: It's a stage 0. SAL: Stage 0. DR. CONNOLLY: So it's basically you're nowhere. And then if you begin to just cross over, like here, and invade, then you're in stage 1. And then there are depths as you go for stages. And then there's always the other thing, where did it go off to other parts of your body. And that's the very highest stage. SAL: And so this isn't a-- and this is true of all cancers, when people about breast cancer, I've heard it in that context a lot. Stage 1, or stage 0 through 4. So it isn't just the size. If the cancerous tissue is big, but if it's in a safe place, it could still be stage 1 or stage 0. DR. CONNOLLY: It is. What's interesting about staging is almost the whole world has agreed to do the same kind of staging. And that staging is what we're calling TNM. And T has to do with how big it is, and the one site, and how much it's crossed any barriers. SAL: Right. But the barrier crossing sounds like the most important thing. DR. CONNOLLY: It does. Although this one here is, are they in lymph nodes? SAL: Oh, right. DR. CONNOLLY: And the lymph nodes are nearby structures where the lymph goes. And so that's one road out. And the other one is metastases. And so yeah, the staging has to do with all three. SAL: I see. And metastases always happens through the circulatory system-- Through the blood, the vessels? Or does it also happen through the lymph network? DR. CONNOLLY: And so it's something where going through the lymph nodes, for something like this, is one of the first steps. But getting to the liver and the lung, it's got to get into the blood vessels somehow. The lymphatic in your colon connects to a local lymph node, but does not connect through lymph only to the lung. SAL: I see. DR. CONNOLLY: So it must have gone into the blood somewhere. So that's the way it looks here. And then the final thing here, when looking at this cancer, is if we go over here, this is the greatest depth of invasion. You had asked me about the body's immune function. Well if you look here, now you see how it's kind of loose and there are all these little immune cells? That's what these guys are. Those are-- SAL: What's the immune cell? DR. CONNOLLY: These guys here. See the little round guys? Those are lymphocytes. SAL: I see. I should circle it, actually. How can you tell the difference between the lymphocytes and the cancer cells? DR. CONNOLLY: That's because I'm a pathologist. SAL: That's because you've had many years of training. DR. CONNOLLY: No, but they're the little round ones. So this one right here is a classic cell, which is called a plasma cell, in which there's a nucleus here, and all the rest of this is making antibodies. SAL: You're not circling that area? DR. CONNOLLY: No, I'm just drawing. SAL: Oh, OK. You're just drawing. DR. CONNOLLY: So this guy is this one. I drew him right-- SAL: OK, you're zooming in on this. DR. CONNOLLY: Yeah, zooming in on that. So yeah, that's a plasma cell, meaning it's a nucleus-- SAL: I just want to clarify, what you've circled there, just because it could be a little bit confusing, but we have this big circle is maybe we [INAUDIBLE]. DR. CONNOLLY: This is why I should leave it to the pros. SAL: No, just because I'm getting confused. You're not circling that area. DR. CONNOLLY: No, no, I'm not doing that. SAL: You were just showing what it looks like zoomed in. DR. CONNOLLY: Right, so that's a plasma cell. SAL: That's a plasma cell. DR. CONNOLLY: That's making antibodies, probably against the tumor. And so that's the immune response in that spot. SAL: And how do you know that's-- That looked very similar to the cancerous cells to me. DR. CONNOLLY: This one's a little hard to tell. And if you had a real microscope you'd turn up the light. And we'd have a very specific look to the nucleus. And then these guys over here have little pink granules in them, which is a type of immune cell. And so when looking through here-- SAL: On this depth, which ones are cancerous here? DR. CONNOLLY: OK, so now let me just get over here, to this one here, and then come out just a little bit. Let me go over here. Is that when looking at these guys, these are all inflammation. The nearest cancer cell where I could bet the farm are these guys up here. SAL: Oh, OK. See, when you see on this view it becomes more obvious. They definitely look different. DR. CONNOLLY: They look different. And so then when you come out here, you can see, there's the cancer. This is the body's reaction to the cancer right there. SAL: I see. DR. CONNOLLY: At the deepest zone. And there are therapies based on trying to get more of this immune response. SAL: That's amazing. Very cool.