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This is Sal here and I'm at Stanford Medical School with Dr. Andy Connelly.

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Hi there Sal, I'm here to discuss with you histology today.

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Histology! And, and forgive me, for what is probably a simple question, but what is histology?

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So it will be the -ology, the study of, in this case the histo-, means tissues.

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We're going to be looking up the cellular components of organs.

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Cool... yeah.

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So what we're going to be looking at today is the histology of the colon.

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And so for the colon we often have colon specimens coming in from pathology.

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And so the colon, like you were saying before, is the large intestine.

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So if you have this piece of large intestine, and its removed from the patient because there is an area

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of cancer.

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It might be cancer, they're actually pretty good now about doing colonoscopy.

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Looking from the inside--

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They'll often have looked inside think it looks like cancer

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take a little piece and send it to us before hand, and then they remove it.

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And the reason why they want to send it to you is

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even if they know its cancer how severe is this cancer?

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How severe is the cancer? They also want to get a really good tissue diagnosis

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to make sure if they're going to go remove a piece of your colon, that they really know that its cancer

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rather than it just looks like cancer.

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So its the definitive proof before they remove it.

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So then if this is the cancer that's removed they clearly want to be able to check the margins

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to make sure its removed in its entirety.

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But often inside of there, they'll find other pieces of tissues, like here's a polyp

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And when we say check the margins, this is literally, just making sure

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you've covered enough material so that you've gotten all the cancer in it

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that you're not kind of cutting through the cancer and that you've missed something.

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That's right, because this is actually one of the traditional

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surgical cures of cut it out to cure.

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Colon cancer, that tends to still be the case.

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Because you cut it out to make sure you cure it.

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There are many other kinds of cancers that which spread so widely early on

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that you don't usually cut out.

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So then the polyp can be found in a piece of colon removed

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a polyp is something that just sticks up.

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Any tissue that sticks up. It's not necessarily cancer.

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No, so for instance another common place you hear about is

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some people in the sinuses might have sinus trouble

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and they'll have a sinus polyp

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those are almost always just inflamed.

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And then we'll find areas in which it's just the lining

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that's been roughened, and we'll take sections of those.

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And that can happen from just someone being allergic to food

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Yeah, irritations of such.

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Yes, irritations of certain sites.

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So we're going to have the areas where its kind of irritated

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some in which there's a polyp sticking out

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and we'll look at it under a microscope

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and then that's the thing that we're mainly worried about

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So that's what we're going to cover in the slides

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that we look at today.

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So this first one we're looking at is an example of

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a normal margin

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And so it's from a little piece

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from the edge

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So they actually call the tissue margin?

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Yeah, tissue margin

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Normal tissue.

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So this is the edge of the specimen, and [the surgeons will] say, "Is the margin clear?"

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Dr: In this case this is an example where the margin IS clear.

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This is normal-looking colon.

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S: This is a cross-section, crossing the boundary of the colon,

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this area at the top right here, would be the inside of the colon, where the poop is...

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Dr: Doctors say stool. That's the stool in the middle, and the supportive tissue is underneath.

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S: Part of the structural tissue of the tube?

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Dr: Right. Now let's drive around the slide.

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This is a virtual slide where we took the typical glass microscope slide, and put it in a special

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machine which took lots and lots of photographs at high power, then stitched them all together

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as one massive image. So that allows you to zoom in and look around.

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S: To let me get my own bearings, this polyp...

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Dr: No, this is just regular tissue--a little bit of a fold, not a polyp.

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S: So how large is this, about a centimeter?

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Dr: About like that. If I had to guess, about 5-6mm.

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So, now to drive around, these are the controls for zooming in and out.

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So I can look at something more closely, and this is the mucosa.

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S: Mucosa. Sounds very similar to mucus.

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Dr: Right. The mucosa is the lining that makes the mucus, it's the slimy part.

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S: This white stuff up here?

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Dr: This suff is the slimy mucus. So, it keeps the insides from drying out--

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because it's a very hydrated gel. It also means that things can glide along without

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abrading the surface. When you look at it, it has architecture in which

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these glands, they're like test-tubes sticking down, and the purpose is to increase the surface area.

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S: And the term gland, is any structure containing fluid and releases the fluid?

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Dr: A gland is an epithelial structure, so it's made of cells that are packed tightly,

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and the cells have a top and a bottom, and they're formed into some sort of enfolding

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or structure, so that there is a middle and an outside.

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S: When we say something is epithelial, it's the stuff facing the outside world?

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Dr: Yes. The epithelium is a special class of cells in which they are facing the outside world,

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again, tightly packed, and there's a top and a bottom.

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S: And even though to a layperson this area right here does not seem like the outside world,

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it seems like it's inside of you, we're kind of like big donuts.

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Dr: That's right. And the colonoscopist proves that it's connected to the outside world.

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S: MUAHAHA!! I guess they do prove that! XD

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Dr: So that's still the outside world. This is the architecture where you have enfoldings to increase

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the surface area. And it's creating this mucus.

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Let me look at the highest power. Look at these cells! When we look at these cells,

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there are two main types of cells. There's this one here, which is the goblet cell.

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S: Goblet cell. It's not just this white part, it goes all the way down there?

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Dr: Yeah...let me have that pen! It has a top like that, and you see this wine glass?

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S: It's literally shaped like a goblet! I was circling the wrong handle.

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Dr: That nucleus belonged to some other cell.

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What's next to it is these thin cells here, which do not have all the mucus inside of them.

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These guys are the tall ones.

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S: Where you see only the nucleus? The white part is just the mucus inside the cell.

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Dr: Yes. Mucus is the term for either the overall structure or the material that is elaborated up here,

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chemically it is called mucin, and mucin is almost like that goo runners eat,

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it is just a lot of sugar holding a lot of water.

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S: I see. I guess it would be bad branding to call it Mucus-In-A-Bag. MUAHAHA!! >:-}

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Dr: Exactly! So they stick with "goo". But this one has a lot of sugar, takes in lots of water,

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that is released and it forms this surface here.

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S: To let stuff flow by.

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Dr: What the other cell does is the other main thing in addition to letting things flow through,

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is to absorb water. So the idea is you do not want to release the 2L of fluid you have

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around every one of your meals. You want to get a lot of that back.

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S: That's one of the main functions of the large intestine?

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Dr: It is. It is a consolidation process to the stool. So you're going to absorb a lot of water

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and doing it through these cells.

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S: The mucin comes out here, and the water absorbed by parts without mucin, so right there.

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Dr: Yupperz. That's right. The two main functions of the colon are right there with those two cells.

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S: To get a perspective of where we are, the whole thing is about .5cm, what's our scale here?

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Dr: Our favorite scale-bar here is to look for blood vessels, for red blood cells,

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One right there, is 7micro- m in diameter.

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S: 7micro-m. A micrometer is a millionth of a meter, or 1/1000th of 1mm.

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Dr: That's right. Let's round off to 1/100th of 1mm.

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S: You put 100 of these next to each other you get 1mm. So 1mm would be bigger than our entire screen.

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Dr: Right. You see with these glands, 1mm would be this span, which we're saying is about like that,

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That's why from here to here it might be about 7mm.

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Dr: RBCs are found in just about every microscopic field, and they're always 7micro-m.

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When looking here, this is very well formed. You can see these tubular glands,

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just a hint over here, because they are like test-tubes, sometimes they're not going straight up and

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down, sometimes they look a little on an angle...

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S: They actually are reaching the surface, we just don't see it based on the way it's cut?

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So this one right here, it was cut at an angle, so it looks embedded there in 2D,

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but in 3D we would see a full tube.

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Dr: Just to go back to the microscopy, we're seeing this because it's only 4microns thick,

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and we're sending light through this tissue.

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So that's why you can get a cross-section that doesn't show you 3D. Very much 2D.

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S: Cool! So this is what a healthy margin tissue would look like?

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Dr: Yes, this is a healthy colon, so you would thankfully say on the proximal margin,

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which is up more towards the mouth, that's clear. You take another section like this from the distal

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margin, more towards the end, and you say that's clear, so that means they removed the cancer.

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S: When you say proximal margin is close to the mouth,

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you're saying the mouth of that cut of the tube, not mouth of the person.

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Dr: That's right. So the proximal and distal margins are clear, if they look like this.