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This is Sal, and I am still at Stanford Medical School with Dr. Connely.

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C: "Sal, we're going to continue. Sal, you're going to have to get one unit of credit for today."

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S: "Oh, my mother would be proud!"

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C: "So, what we're looking at today is a colon polyp."

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S: "So, what we saw in the last video was not a polyp, but an irritated part of the bowel?"

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C: Yeah, it was very low lying, it was really just a patch of irritant.

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C: We have a bigger piece now, so you can see the glands look tiny here.

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S: So on the last slide, about how big would it be on here?

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C: It would be about a piece like that. To be fair, it was probably what was underlying this area here.

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C: And then, it grew on to be something more.

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S: It wasn't this exact one, but it could've grown on to be something like this.

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C: Yes. When we have a colon resection, if there's a cancer, there's often a polyp...

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...an area, a patch like we saw with hyperplasia.

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S: [The patch is] not necessarily where the cancer is, just [the cancer would be close]?

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C: Yeah, we find that if people have a colon cancer, they have a lot of pre-cancer regions.

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S: So, you can see that their bowel has been going through a lot of trauma.

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C: Some of its familial susceptibility, but a lot of it is that they are showing a propensity to do this...

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...don't know if it's from environmental exposures or what.

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S: I see. So just to remind myself on what we're doing here, you cut out a piece of colon...

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...because there was cancer there, and there might be a polyp in the same section

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that you cut out, and that 2nd slide where we saw the irritation might be right there.

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C: As a matter of fact, it's important you normally wouldn't see this slide in a patient,

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because almost all polyps, the colonoscopist is coming in, and they remove it through the colonoscope.

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S: Because they don't know if it's cancer or not.

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C: They'll remove it, but you wouldn't see the full wall. So right here, that's all the way through t

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wall and what you got here is muscle. So this really a full piece of the wall.

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C: So this is a larger piece, to show the polyp in its natural environment.

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C: So we're going to look at the polyp. First, way out here, the normal architecture

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C: So we said there are supposed to be tubes. Luckily, this one is cut right down the middle of the tubes

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C: so you can see how big the holes are.

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C: So, this is normal architecture there. If I go out a little bittle, you'll see an area here

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in which there is a bit of irritation. So, it's a thrown up [?] a bit like we saw before,

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but the real trouble is this thing sticking out. And we wonder, what is this thing sticking out.

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C: And so, for the medical students, we tell them to think like the pathologists,

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First need to look at the overall architecture: This is an abnormal architecture.

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We don't usually see a polyp sticking out.

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S: In 3D, would it look like a mushroom?

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C: Yeah. Actually, they tend to have a folding in the tops so they are more like cauliflower.

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S: Color?

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C: They don't have much color to them. The colonoscopist, when they look at them,

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can kinda tell if there's a chance of cancer because they begin having weird blood vessels.

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S: Just to be clear, they're not this purplish color.

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C: No, we have to stain these thin-sections or it would be colorless.

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C: So now, I am going to draw an area where I'm going to do a comparison. See this box here?

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C: So these are cells which are relatively normal. And these [on the top] are cells which are abnormal.

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C: A pathologist immediately say, "These look angry."

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S: They do! They do look angry! I would say that, too!

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C: What's angry about them: First of all, they are not committed to behaving.

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C: Proper behavior over here: nuclei belong at the bottom; things you're supposed to do for your job

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are at the top. So, when you look at these guys, you're like, "Where's your job?"

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C: And so, a few of them are making mucin, but these ones have nuclei of different sizes and shapes.

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C: They're just doing their own thing, not producing mucin, all they're doing is growing.

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C: Usually there's a playoff between, if you're committed to your specific job, we call it differentiation.

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C: So if you're committed to your differentiation, you tend not to have as much propensity to grow,

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and if you grow a lot, you tend not to do the differentiation.

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C: And so, this is largely that you have this chaos of nuclei, less commitment to the normal structures,

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and you're not producing as much.

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C: And so, what this is, is this is now called 'dysplasia.' ['Dys' is from Greek for 'mal'; malformation.]

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C: We're saying: We don't like their looks. These individual cells look dysplastic in their growth.

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C: So then, to tell whether it's cancer: Cancer means, in this organ, that you've grown across this line

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in the sand.

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S: So, literally, if you've crossed this boundary--cancer.

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C: Right.

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S: So, even if I'm in the polyp up here and I'm growing uncontrollably,

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and mutated and not killing itself [when it should; not responding to apoptotic signals]

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you still would not officially call it cancer?

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C: No, what happens is that there is a middle-term for a cancer that remains in its usual place:

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That's "carcinoma in situ."

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C: So, carcinoma in situ means that it's not an invasive cancer,

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so most people would not even call it a cancer.

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But it's just so wild looking up here, you know that it would [become "real cancer"]

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if given chance and time.

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S: What we're saying is that if there were carcinoma in situ out here, that it eventually would make

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its way.

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C: Right, it would continue to grow, because there is so little differentiation that you know it would

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continue to grow until [it became cancer.]

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C: With here, though, it's still dysplasia, where it's upsetting that it's growing so fast,

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but what's important about this, is that in hyperplasia, if you took away the stimulus or irritant,

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it would go back to normal--this would not [go back to normal.]

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S: If the irritant were removed in hyperplasia, it would go away in time.

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S: This dysplasia is here to stay.

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C: So the key word is "autonomous." So it will grow no matter what.

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It doesn't care about clues from neighboring cells, it doesn't need something driving it,

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so what you have then is if this is growing, and if it's growing all by itself, it's called a "neoplasia."

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S: So neoplasia means showing dysplasia?

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C: Dysplasia is when you look at these features, these cells aren't growing right.

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C: And then, overall, this lump is a "new growth," a neoplasia.

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We reserve the term in the medical field for meaning: It's growing on its own.

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S: How do we know it's new? How do we know it wasn't around for a year?

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C: I think it was. It probably came from this area here,

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and the thinking is that you probably had irritant here, hence hyperplasia,

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it would continue to grow--cells divide, cells divide too much,

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and then, [mutations occur (cancerous cells are rarely a result of only 1 mistake)],

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the cell says, "You know what? From now on, I'm not listening to any clues."

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S: And then, its descendants would be crazy, too?

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C: Right, they would have a real mean streak. And then they would grow from here.

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S: (I see that pattern in my own family!)

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C: So here, these are more normal glands, but even these--that's dysplasia.

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C: So these are growing without a good pattern of growth.

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And overall, this lump, is a neoplasia.

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S: So when we say "new," we mean, "newer than the other tissue"?

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C: We don't mean newer than the other so much as it's its own thing.

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C: New kid on the block.

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C: So this one right here is a polyp, it has features of dysplasia, but we see no cancer.

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S: How would you know? Oh, because it didn't cross the boundary line.

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C: There is a reason why the boundary is important, because if you look here,

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these are all the surface cells, down here, these are the vessels that go to the rest of the body.

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C: So these are blood vessels, these are called lymphatics,

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and what lymphatics are, they take the clear fluid [v. blood fluid]

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S: These right here, these are the lymphatics, the clear fluid.

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S: Fluid can go back and forth between the blood vessels and the lymph system?

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C: Yeah, usually what happens is: Blood comes in an artery like this,

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goes on down to these little vessels, and then a little bit of the clear parts of it,

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will kind of leak out.

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S: The blood cells are too big [to leak]?

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C: Yeah. So, some clear stuff comes out, and this is how it returns to the rest of your body,

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through these lymphatics.

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C: So you can see, you do not want neoplastic cells in here.

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S: Right, because once they are in there they can go to any part of the body.

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C: Go to a new place, and guess what? Set up shop, new kids on the block, they just do what they wanna.

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S: So that's called...I can't pronounce it...

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C: Metastasis. So, metastasis would be, if it gets into these things,

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it can get out of the colon and go anywhere.

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C: So this is one where it is not cancer, it has not invaded these areas where it can [metastasize.]

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S: Fascinating.