Neoplasia l

A lecture on Disturbances of Growth Neoplasia by Dr. Gerald Abrams, M.D. This lecture was taught as a part of the University of Michigan Medical School's M1 - Patients and Populations Sequence.

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(From M1 Patients and Populations at University of Michigan Medical School. Lecture by Gerald Abrams, MD.)
You see the title is Disturbances of Growth in Neoplasia.

This is one of the

probably the only time

in the sequence where pathology really
meshes with what else is going on.

We will spend

much of the two hours today and
then an hour Wednesday

on the subject of neoplasms, that is
tumors

this will feed into Dr Gruber's 11 o'clock lecture on Wednesday on the genetics

aspects of neoplasia and
then a very interesting MDC in the afternoon,

dealing with some clinical aspects of
those same things.

But before we settle down

to the subject of neoplasms, tumors and such,

i want to spend a bit of time giving you
a few notions and definitions in visual images

images

dealing with other

abnormalities of growth short of
new place, in other words there are some other

some other

disturbances in the size of cells
tissues and organs

the

mode of cellular proliferation and even

lead the way that cells mature

and

look at a few of these
abnormalities first before we get onto the main

subject

let me begin

very simply with

situations

in which you might

encounter a bunch of cells, a tissue, an organ

smaller than normal

smaller than you expect

and it runs

something like this

it makes pretty good sense that the one way
that you could end up with a tissue

that's abnormally small

organized abnormally small is a
developmental situation

where it never grew up

sort of a dwarfed tissue

or organ

and on the other hand

there are situations

as i think you're already familiar with

when an organ or tissue reaches a
definitive adult size and then shrinks

that process i think you know from
Ramsburgh's lecture we call

atrophy

so those are two kinds

situations and i want to run
through first

this list of developmental problems

that we have encounter from time to time

the most complete sort of defect

you might encounter is when the
embryonic rudiment

of an organ

simply doesn't develop, it's a screw up in embryogenesis

and then there is no organ

laid down

and we referred to that

process as agenesis

there's a slight variation on the theme
and that is where the rudiment of the organ

may be

laid down in the embryo, but

the thing never grows

non-descript nubbin' of nothing

and that sometimes is referred to as aplasia

those two terms are essentially
synonymous

it's an absence

an absence of the tissue

and I'll

give you an example, a very striking example of this

here's an autopsy specimen, let me orient you to it

this is the urinary bladder down here

here is

a ureter on one side going up and connecting with a very respectable looking kidney

here's the other ureter, boom!

there was nothing outside the

it's not a camera trick, there's nothing outside there, it just ended

that way

now that is an example of the unilateral renal

agenesis

or aplasia, i don't care which word you use

this sort of thing is compatible with
long happy life and this is strictly an incidental finding

i don't remember anymore what this individual died of

but it had nothing

relating to the

urinary tract

so it's just a failure on one side for that

kidney to develop. Agenesis or aplasia.

sometimes we see this bilaterally. Both

kidneys are not there

and that

of course is not compatible with life whereas this sort of thing is

now

the next step up from

agenesis or aplasia

is a situation where the

the organ rudiment is laid down in the
embryo, and indeed

grows but not

as much as it should

so you end up with something

smaller than normal because of

well we might call it loosely a growth failure, and that we call

hypoplasia

hypo meaning under or less than

and there's an example, let me take you
through this one, it's a little bit confusing

here's

the bladder

this happens to be the aorta, forget
about that, here's the bladder

the ureter

on one side going up to a very decent looking

kidney

here is the ureter on the other side, sort
of stunted

here's

a little shrunken

well, i shouldn't say shrunken, but a tiny, miniature

kidney there

that represents a unilateral

renal hypoplasia

again sort of an embryonic defect

if you will

sometimes we see this bilaterally

and it could be all degrees, it could
be something between this and this or something

even less than this and as long as

you put it under the microscope and you see

the structure of kidney, but there's not enough of it, it's too small. that's hypoplasia.

i've shown you urinary tract here, these sorts of defects, agenesis and hypoplasia

occur in

other organs

and organ systems as well, i just happen
to have these pictures on hand

one of things you'll encounter when you
get over in the hospital because we're sort of

a funnel for odd things

is fairly often

kids born with what we call hypoplastic left heart

and that's the situation

where the chambers of the left side
of the heart and even sometimes a portion

of the aorta

simply don't develop properly, and there are little tiny nubbin's on the heart

and this hypoplastic left heart
syndrome is lethal unless some pretty fancy

surgery is done to intervene for a while

so you will see that hypoplastic left heart

one more term on that list that i gave
you, i just defined it and i want to illustrate it

and that is atresia

a-t-r-e-s-i-a, atresia

which is a situation and again it's a
developmental failure where a channel

a normal opening or channel fails

to stay open

fails to form properly so you end up with a closure where you should have

a channel

something let's say along the GI tract or along a duct

where it simply disappears because it never
opened up properly. That's atresia.

Now the second situation

i mentioned back on that list

other than developmental is a situation

where the organ has reached

a definitive size and undergoes a process of atrophy

atrophy can come about really in in
two ways

first of all

every single cell in the tissue could shrink

by some percentage

and that would produce a smaller tissue, a smaller organ

or

a certain number of cells as they start out with a million cells in the population

and

some of them disappear by apoptosis

and you end up

with eight hundred thousand cells, that's going to be a shrunken tissue

so a tissue can

undergo atrophy with shrinkage of individual cells

sometimes loss of cells or both

but it's a secondary change after the
the organ has reached its definitive size

some

examples of atrophy as some of you may know already

is perfectly physiologic in the, let's say, fetus

as various things form and come and go

there's atrophy

there's certainly atrophy of fetal structures

in the neonatal period

umbilical vessels and that sort of thing undergo

atrophy

there are examples

of physiologic atrophy

as one matures into adult life, the tonsils shrink

the thymus shrinks

and so forth

there are these things which are expected and physiologic

when

it comes to pathologic forms of atrophy, there are many reasons why

this can happen, one that Dr

Ramsburgh may have mentioned is ischemia

if you rob a tissue of its blood supply, let's say, not enough to kill it

but really to cut it down, there's

such a thing as ischemic atrophy

and you'll see that in arteriosclerotic

areas where the tissues tend to simply shrink

starvation

you don't

feed a person enough calories, starvation will produce

atrophy. there's a hierarchy of organs which i don't want to go into

for instance, the brain doesn't atrophy

in that situation

but the adipose tissue does, the liver does, and so forth

that's starvation atrophy

in the case of muscular tissues

disuse

just plain old disuse will cause atrophy

it could be very striking

i don't know if any of you have been in this situation, but you have an acute injury

like, oh let's say,

a bad knee, for some reason, just self splinting

not using that leg in the same way

will cause a shrinkage within a few weeks

you can get a loss in circumference of a thigh

i don't know how many of you are skiiers

that have gotten into

trouble and ended up with let's say a cast on an extremity

for a number of weeks and when that cast comes off, you've got a shriveled leg

compared to the other one

that is disuse atrophy

an extreme example of that is something we call neurogenic atrophy, if you cut

the motor

nerve going to a muscle

then that muscle can't work at all and is getting
no signals

it'll really shrink, it's a tremendous sort of atrophy

then

well, i'll stop this list with one more

many tissues in the body are

the way they are because they have a
certain endocrine support

they depend on a certain level of a particular
hormone, and if you withdraw that hormone, the tissue

will undergo atrophy. Morphologically

it's pretty

straight forward, i'm not going to show you much of this

is smaller

it's simply the tissue

you look at it under the microscope and the
individual cells are smaller

the number of cells, that's a tougher thing to deal

with, but basically it's a small tissue

sometimes there's partial fibrous replacement as the tissues shrink

we call that fibrous atrophy

sometimes

this seems to be an increase in adipose
tissue, marbling the tissue, we call that fatty atrophy

but basically the business cells of the tissue

are smaller

there's one variation on this theme that

Ramsburgh may have introduced you to and that's

as a cell shrinks

it basically

is undergoing a process of autophagy, it's eating itself, it's digesting

various of its

organelles and so forth

one of the things that happens
from this digestive process is that there

may be residual products

left afterwards and

they

tend to be pigmented products which we've

we refer to as lipofuscin

here's a liver where particularly in
this area, the central area, the cells

are shrunken and you'll

notice this is not a particularly good photo, but you'll notice they are brown

and that's

because of a relative concentration of lipofuscin there

they've been undergoing

autophagy

and the residual products are piling
up and sometimes we refer to this as pigment atrophy

or brown atrophy

and i've seen shrunken livers where there's perhaps half the mass of the usual liver

and they're really

definite

brown

rather than the ordinary

liver color

because of this sort of accumulation

Okay so

much for smaller than normal, let's go to the flip side

and look at situations where the tissue
or the organ may be larger

than normal

and this

can come about in two ways

you can have an increase in the size of
the cells in the tissue

and we refer to that as hypertrophy

you can have an increase in the number
of cells in the tissue, we call that hyperplasia

Now let's go back

up to hypertrophy

let me point out that size increase isn't simply cell swelling, you know

about the phenomenon of cell swelling, which involves a net accumulation of water

that we wouldn't call hypertrophy

in hypertrophy, the cells enlarge because of an increased

synthesis

of cellular components

i'll show you that in a

moment

again hyperplasia

involves an increase in cell number so you'd look

for hyperplasia only in tissues that are capable of

dividing in the adult state

another was a permanent sort of tissue

you're not going to get hyperplasia ordinarily in muscle

you're not going to get

hyperplasia, well muscle is probably the best example. but in other

organs, you may

get hyperplasia along with hypertrophy

but conceptually hypertrophy

is increase in cell size, hyperplasia is increase in cell

number

the

best example of hypertrophy is in muscular tissues

it's a response

hypertrophy in muscle is a response to an overload

or unusual workload or what not

now you need a lot of imagination for this, but imagine i went in for bodybuilding

which i never will

and you know you you pump three hundred
pounds like this

and after a while couldn't

get into the lab coat. Bulging

muscles, i told you, imagination.

the

muscles of the bodybuilder

you've all seen pictures of this and maybe some of you are into this sort of sport

this

represents

hypertrophy

of muscle, there isn't any real increase in the number of muscle cells

but any individual muscle cells instead of being this big around is this big around

and it

represents actually a synthesis of more

contractile machinery

in the muscle, it's a response

to the work

now a place where we see this that isn't so trivial

is

is, for instance, heart muscle

that is subjected to an abnormal load

for instance, a left ventricle

having to pump blood in a patient with uncontrolled hypertension

in other words, the systemic blood pressure is elevated, the arteriolar resistance is elevated

and every time that poor old left ventricle

tries to eject blood, it's doing it against an increased head of pressure

those muscles are going to undergo
hypertrophy

or

let's say the valve, the so-called
aortic valve, which is a valve between

the left ventricle and the aorta, as the blood flows out, if that valve gets narrowed

the poor old ventricle has to squeeze harder to get

the blood out to maintain life, it will
undergo hypertrophy

not hyperplasia

but hypertrophy

and the

heart gains weight

the ventricle becomes thick

and the cells become enlarged. I'll illustrate this for you.

here is

don't pay attention to the color, there have been
some post-mortem changes here but

this is a bread loaf slice

of a normal heart

you're looking at the right ventricle
over here

left ventricle over here ordinarily, this is normal, the right ventricle is very thin

because it pumps against a lesser head of pressure in the pulmonary circuit. The left ventricle

,that's about normal thickness,

now the next slide

is not a photo trick and again
don't worry about the colors, but the next

slide is taken from an individual with high blood pressure

now that first heart probably weighed

oh in the neighborhood of three hundred, three hundred and twenty five grams

this heart weighed closer

to the six or seven hundred grams, i don't remember precisely, but

it kind of speaks for itself, there is more muscle
there

and again this is not hyperplasia, this is
hypertrophy

and it looks something like this. i know you don't know much of this histology

but just

think of these as cross-sections of these cylindrical muscle cells

and this is

a normal myocardium

and

let's just cast your eyeballs around and look at the approximate

average diameter

the next slide

is taken with the same optics in the microscope

from a hypertrophic heart, now you got this?

The point

those cells are really increased in diameter, don't worry about this, I don't expect you to

pick this up on the quiz

but just to show you

the increase

and what this represents really is an increase, a very striking increase

in the myofibrillar contractile machinery

of these cells

so this is clearly an adaptive

phenomenon

and it works very well up to a point

the heart can't keep getting more and more and more hypertrophic

i've never seen a heart

weigh much more than a kilogram

and that's rare

but beyond that

it doesn't work

and one of the reasons that it doesn't work
is that the vascularity of the blood supply

of the heart

muscle doesn't keep up

with too much hypertrophy and pretty soon

the muscle to capillary ratio is unfavorable

and it plateaus, it can't go any further

and then what you get is the onset of apoptosis in cells and actually some

fibrous replacement of the myocardium so it doesn't work indefinitely

actually some

of the proteins that are formed

are not necessarily normal either

so hypertrophy

is nice and adaptive up to a point, but beyond that

i might mention that before we leave hypertrophy that this also goes on in other types of

of muscle

as you may

know for instance, the wall of the urinary bladder is muscle but

this kind of muscle is what we call smooth muscle

but if there is a chronic obstruction to
bladder outflow

you get a very thick muscular bladder

the same kind of response

hypertrophy of the muscle cells

we return to hyperplasia

lots of examples i can give you

of increased

in

the number of cells

in the tissue

and a nice example i think you've all
been there

one way or another

there's a callus that forms

in the skin

if you have a

ill-fitting pair of shoes and something is rubbing

on the spot

or God forbid if you have to do manual
labor

some concerted length of time

you develop calluses. You've all had this happen. This is an example of

hyperplasia

It's a response to this overwork stimulus

which increases

or leads to an increase in number of cells in the system

let me illustrate this

give you a little histology

this is basically normal skin

on the palmar surface of the hand

this is the dermis, the connective tissue part

this is the

epidermis, the epithelial portion

now this is a renewing

cell system

normally

a certain number of cells are mitosing down here in the basal layer

and daughter cells are moving out and maturing

as they move on out

and this upper layer where you see no nuclei is the

so-called stratum corneum

it's like a layer of shingles on the roof

these cells undergo progressive changes

in armor plate there

so the normal palmar skin is set with a certain cell population

and a certain

balance where certain cells come and go

i'll show you the callus

keep this picture in mind

and this represents the hyperplasia of the callus

now you've got

a much thicker cell population

it's still a very orderly cell population

the cells are being born down here and are maturing up here

there's actually

so much thickening going on here that I couldn't

get it all on one picture

at the same magnification

here is the beginning of the stratum

corneum

there's the rest of it

and that is a callus

So you see there is a tremendous

hyperplasia here in response to this mechanical stimulus

Now the nice thing

about hyperplasia, and also applies to hypertrophy, if you get rid of

the noxious stimulus,

things pretty much

wind back to normal. You can't always do that, but

if you can, if you quit

raking the ground or whatever you're doing,

pretty soon those hands will be the ones you know and love.

The calloused thins out

and you go back to normal. Now

I could give you

other happier examples, maybe, I'll give you one.

In a hormone sensitive

tissue that responds

that response with hyperplasia

here is a normal

lobule. This is kind of a potential

secretory unit,

a normal lobule of an adult female breast.

I don't want to go into detail, but

just to show you the little terminal

units forming this lobule. During pregnancy

and lactation,

this tremendous

hormonal stimulus to these cells

makes them undergo

hyperplasia

and that lobule

, take a look

at the size there

enlarged

couldn't even get the whole lobule on the screen there

This is a lactating mammary gland

there's a tremendous

increase in the number of cells, actually some hypertrophy

in individual cells, but basically

a whole lot of hyperplasia

there, and it responds to

the hormone.

When the hormonal stimulus is withdrawn at the end of lactation, things pretty much

go back to normal, plus or minus a little stretching of the connective tissue

but the epithelial

population goes back to normal.

That's hyperplasia, tends to be reversible

under very nice elegant control

in some situations

got to throw this in. Not all good news.

In some situations, the hyperplasia

isn't necessarily

adaptive and good. We see

examples of hyperplasia, I'll show two of them.

They're probably responses

to the subtly abnormal endocrine stimulation, somehow

we don't exactly know.

but, i think one for the guys, one for the girls

this is something that is going to afflict about

forty nine percent of us in the room, one way or the other.

and this is

a cross cut of the prostate

and the

prostate normally is about the size

of a golf

ball, a walnut, a good sized walnut

and it's right at the base

the bladder and the urethra. The outflow tract goes through the prostate.

You're looking at a cross-section there

and you see the urethra there.

The normal prostate would be

nice and smooth across the cut surface.

Here you see

a bunch of lumps and this represents

hyperplasia of

glandular and muscular tissue, glandular tissue undergoes tremendous hyperplasia.

we don't know why, and the

problem with

is not simply walk around with a tennis ball

there instead of a walnut, but it rests on the base of the bladder

and urethra and can cause outflow problems.

and also urinary tract problems.

I'll give you a little tidbit that's absolutely useless.

Eunuchs don't get prostatic hyperplasia,

but it's not a very popular preventative measure.

so there's an example, it's not a neoplasm, it's strictly hyperplasia, but it's out of

kilter and not good.

for

the rest of you

we'll talk about

a very common condition

called fibrocystic change in the breast

now this is

a non-descript looking piece of tissue

but if it were perfectly normal

mostly

it would be a yellowish background

because the breast is largely fatty tissue

and not

those big yawning things there. So what's happened in this breast

it's, first of all, increase in fibroblast

fibrous connective tissue, see these white streaks

and this represents part of the duct system.

where the cells increase in number

and fluid is accumulated in

what we call cysts,

a cyst

is a hollow space filled with fluid

lined with epithelium

and so we call this fibrocystic change.

In and of itself, it's very

common, in and of itself it's no big deal.

I'll show you

what happens conceptually, here again here's the

normal breast, this is a lobule like I showed you before and this is

part of the duct system leading to that lobule. That's normal. Now in a fibrocystic

change, what you see

is

this little garbled

Here's a lobule

that has undergone

hyperplasia, pretty evident

and the duct system, the lining is also

undergone hyperplasia, the ducts are dilating and eventually form cysts.

and again we don't know exactly why

this happens, but it represents hyperplasia

gone wrong.

All right, moving right along, what I'm doing is just ticking off these concepts. You can follow this in your reading too.

I want to move on to proliferation and maturation of cells within a population.

I'm talking about two particular situations here

we'll talk first about

metaplasia and then dysplasia.

all right, what about metaplasia? We define this as

a change in the cell population, in which one normal mature special

cell, I'll clarify this in a moment, but one

cell type is replaced by another

normal cell type,

except it doesn't belong

there, in other words, it's changed

that particular location. Now this isn't just a substitution, where this cell

changes into another cell

what this is, rather,

is change in the maturation of stem cells in the population. We've got a proliferating cell population

where ordinarily the cells mature in this direction, and metaplasia represents

a switch, under some influence, where they mature in that direction.

They become more resistant than the normal one and that represents metaplasia.

Let me illustrate this, try to make sense out of it.

Here is the lining

of the

what we call

the endocervical canal

this is the canal that goes up into the uterus. Now normally

what's going on

here is that there are certain number of, well, call them stem cells

or reserved cells that are proliferating

all the

time, but they mature

into these tall

what we call columnar

cells, they are

tall and columnar and they've got

very pale cytoplasm because they're full of mucus.

So normally this endocervical canal is lined by this mucus secreting epithelium, very

slight stimulus

is all it takes

and there may be a change

here you see the normal, here you see a plaque

of cells that looks a little bit different

and these cells

are, well, they're

odd shapes here, they're maturing into these

flat cells that we saw on top of the epidermis, and we call this

these are columnar

cells, these are squamous cells, we call this squamous

metaplasia

very very

common, some of you

in this room have this, it's a trivial change

practically

ubiquitous in the adult females in the

endocervix

it can become quite extreme. Look at this.

this whole area should be lined by these columnar cells that look this, and instead what we've got here is squamous

epithelium, looks a lot like the epidermis, doesn't it?

I would emphasize a couple things

this is perfectly orderly, you look at this

and I know you haven't become histologic experts yet

but that is a perfectly orderly

squamous epithelium, nothing unusual about it except

it doesn't belong there.

So that's an example

of metaplasia

in and of itself

trivial

or even protective.

Let's say

chemical workers were exposed to fumes might develop

this kind of

metaplasia in the lining of their trachea and bronchi, that makes them more resistant to whatever they're

inhaling, smokers develop

this sort of thing. Now, this could go on

and something

else might happen, and this might

lead to bad

things, but

in and of itself, metaplasia

is perfectly innocent.

Not so

with dysplasia.

D-y-s-p-l-a-s-i-a

Now morphologically,

dysplasia is a

variation, abnormal variation

in

the size

of the cells, the shape of the cells

the arrangement of the

cells

and the maturation of the cells

too much variation

in other words

something very well controlled like this

this epithelium is very well controlled

with all the cells down here proliferating

at a certain rate and maturing gradually

and so forth

all of this gets screwed up in dysplasia.

Here again is a normal squamous

epithelium, this isn't palmar

or skin now, this is let's say the lining of the vagina or

covering of the cervix, one of those, this happens to be cervix

perfectly normal squamous epithelium, notice how orderly

it is, it's like a

kind of like

a parade where you have cells in

a certain type down here, they all resemble one another

in this layer, cells here

resemble one another, and then there's this maturation

these flattened out cells, that's occurring in a very orderly

step fashion. In dysplasia

of the epithelium, everything gets

screwed up. All right,

this is dysplasia.

and we can see where

there's a shadow of what you looked at in the preceding slide, but now some things have

happened, there's more

variation in any

layer. In other words,

if you look down here, these cells are more variable than those cells were in the basal layer

in the normal. You look here

where in the

preceding slide, every cell in the intermediate zone is perfectly

like every other cell, there's variation

here, there's big cells and small cells, round cells and elongated cells

cells with

very dark nuclei, cells with lighter nuclei

and so forth

and gradually, though, despite

this mess, there is

slight

maturation

you can see here how this jumble of cells gradually becomes organized

up here, so what have we got

we've got abnormal

variations

in the size of the cells, the shape of the cells, the arrangement

of the cells, this is out of order. It's not in a nice, neat, locked set.

And it's not

maturing quite properly until it gets to the very top.

Actually,

this is trivial for you now, but we grade dysplasia as slight, moderate, severe depending on how much

normal

there might be there. But when you see

this degree of variation, that's a very

bad thing. There's one other thing

that's abnormal here, it's a little more subtle, ordinarily

mitosis occurs only down in this

basal layer. But these cells

are goofy enough that they forget about that and they do something very impolite.

They reproduce out

in public and you find mitotic figures at all levels of such an epithelium.

So morphologically,

this represents a lot of variation.

This is a serious change because these cells

are in a sense losing control. They're losing control of proliferation and maturation.

Any number of mutations

that occur in the cell population, this reflects genetic change in the cell, somatic cell

any number of these mutations and this happens. This I want you to remember for the rest of your lives, dysplasia

in other words, I can't tell you

that epithelium absolutely for sure will become cancer, it depends I suppose on the last garbled

mild degree of dysplasia sometimes don't necessarily progress, while very severe degrees of dysplasia can.

Here is a squamous epithelium

with what we call severe

dysplasia, and you can see close

up what's going on here

This basal layer is increased in thickness, a lot of variation

in these cells,

here is

a cell dividing, as they say, out in public and there is an absolute total

jumble

in terms of how these cells are arranged with respect to one another.

We call that a loss of polarity.

And in this instance

it occurred all the way, full thickness of this epithelium.

and we now know, from a lot of experience, severe dysplasia

really is

tantamount to cancer

that perhaps hasn't

yet invaded. Now that'll

make sense when we talk about what cancer really is. Without

any evidence of invasion or anything else that cancers usually do

when dysplasia is this severe, we can say this is like carcinoma-in-situ

which means an 'in-place' cancer

pre-invasive

cancer because we know

if this sort of

dysplasia is left alone, probably close

to 100% will

evolve into a cancer if the patient lives long enough.

While I've got this on the screen, I'll point out some cytologic changes that are very important in making

this decision. First of all

you'll notice

there's a lot of variation in size of nuclei. We call that

nuclear pleomorphism.

p-l-e-o

that's a bad sign

and none of these

is absolute, but it's a bad sign.

Some of the nuclei are very dark as you cast your eye around here.

We would call that nuclear hyperchromatism. Too much

colored material in the nucleus.

The nuclei

are very unusually shaped and sometimes

you can't see it, but

sometimes the mitotic figures are themselves

are even abnormal, may see a tripolar mitotic figure

or something like that.

These are all signs of badness in a cell population.

If something like this is left alone, it will proceed to an invasive cancer. Instead of carcinoma-in-situ, we call it invasive.

Put a line underneath all of this and now we turn to the main topic -- Neoplasia.

Spend the rest of this morning and Wednesday morning on this topic. It's ultimately

more cells than there ought to be, it's an increase in cells

it's a lump basically

and these are proliferating cells, they're not just sitting there, they're

they're dividing and making new cells. And, they're cells that have somehow

become autonomous

they don't obey the same start and stop signals

that normal cells do. Their growth

tends to be excessive and uncoordinated with the needs of the host.

In other words, this thing is taking off on its own!

It's kind of rebellious, I'm going to grow, I don't give a damn about what's going on over here, I'm not going to listen to your signals.

You want to think teleologically, serves no useful purpose, it's not adaptive.

Once the neoplasm is formed, it's off and running,

which is different from hypertrophy and hyperplasia, where once you remove the stimulus, it goes back to normal.

In some countries, it's the word tumor, which now is practically synonymous with neoplasm.

It's also one of the cardinal signs of inflammation, the old meaning of tumor simply means swelling. But

when you say a patient has a tumor, you don't mean swelling, you mean neoplasm. So tumor, neoplasm, same thing.

'oma' usually denotes a neoplasm of some sort, there are exceptions, hematoma is a lump of blood.

Different types of neoplasms are distinguished by their behavior,

which, I think you all know, is benign and malignant. Cancer is a general term which refers only to malignant neoplasms. I don't want to insult you, but

just so we're on the same page, there are many neoplasms that are not cancer. Only the malignant ones we refer to as cancer.

Looking at all of these characteristics, they are very different from hyperplasia and hypertrophy, which are generally adaptive.

A neoplasm is a living, proliferating cell and

we call this neoplastic transformation, basically, and when speaking of transformed cells, we speak of cells that have acquired

a set of these new characteristics

that define them as neoplastic and, as you will hear, usually

the wrong mutations. We talk about the clonal origin

of neoplasms, in other words, a neoplasm is a clonal proliferation of a transformed cell.

This transformed cell has a lot of characteristics

and behaviors that are quite abnormal and we can see this in vitro when we culture it.

Malignant cells, for instance,

they've often lost control of movement that they display on the surface of a plate. There's

loss of, ordinarily there's control in a cell population where proliferation reaches a certain size, not so with cancer cells. I could go on, there are many different things that occur

in vitro and in vivo, in the host, it manifests a non-equilibrium growth, at some point, and keeps on growing.

You will learn that

there's a difference between benign and malignant. I think this cartoon sums it up well.

As the neoplasm grows, the number of cells gradually increases, they tend to be cohesive

there's not any reason for this, just they tend to be cohesive, so as the neoplasm

grows, and it may grow to a very large

size, it tends to grow

by a centrifugal expansion. Now it's not a perfect circle, but

it tends to grow by expansion. As it expands,

it frequently will pick up

a

condensed capsule of connective tissue as it pushes out

causes atrophy of surrounding tissues

and will accumulate a kind of capsule almost and anyway

at any rate

it stays local, its size, and it doesn't invade

adjacent tissues, just pushes them out of the way, or it may press up, but it's like blowing up a

balloon in the thing. On the average,

this is not as cohesive as this suggests

it grows, the cells have a great tendency of invading

what we call the primary,

they tend to drift

away and don't obey the stop and start signals.

They have a very different relationship

with the cellular matrix and basically

they have

the ability, this is the primary difference, to cut their way

through

the adjacent stroma

and actually invade as clumps of cells,

lines of cells, individual cells,

Invasion is one

of the defining

characteristics of malignancy. When I said the malignant ones tend to grow faster than benign ones, that's not a defining difference.

They have to be invasive to be malignant.

One other, well this sums it up,

cohesive, expansile, circumscribed, localized

that's benign. Malignant is poorly circumscribed, invasive, metastasizing.

That means

it can spread to distant foci, we'll talk about that in just a moment. But it's invasion

and metastasis that define malignancy. Benign neoplasms do not metastasize.

Here's a uterus

cut sort of in

sagittal sections, this is the cervix

down here, this is a normal one half

this is the cavity here, here is a

neoplasm.

Benign or malignant? See, it works.

This is what you

probably grew up hearing, a fibroid.

Uterine fibroid.

That's a misnomer, because it isn't

a fibrous tumor, it's a muscular tumor

one we call a leiomyoma.

But you can see it's got, just like the cartoon, pushing at the edges.

You look at that microscopically,

same sort of thing

here's a

tumor, here's the

edge along here, no invasion.

Can see it just pushing, pressing along that adjacent line.

Here's a breast

that's been

taken off

a mastectomy specimen and it's been cut in this plane,

a section where you can see

the skin out here, and this is the neoplasm

very very hard

to define and circumscribe.

It's going out in little

sites in the adjacent

tissue, even

way beyond this microscopically

there are lines of cells that you couldn't see here.

That's invasion. A benign neoplasm

wouldn't look like that.

Here's one that's a little deceptive at first.

This is a colon cancer,

we've opened the colon and washed it off. You might

say, at first, gee that's circumscribed,

isn't it? Well, not exactly.

What I did here is

fix this in formaldehyde

and then made a cut

across it, and it looks like

this. Now this doesn't look so

awful, but it really is.

Here's the normal mucous membrane up here, this layer we call sub-mucosa,

this is the muscular wall of the colon here.

Here is that mushroom

and you can see this whitish tissue, this is neoplasm, invade

all the way through that muscular layer.

This is invasion.

This is what it looks

like microscopically, don't worry about this.

duct cells, hyperchromatic, pleomorphic nuclei,

and so forth.

These cancer cells are cutting right through the colonic wall, it's not that simple,

but they're cutting right through that colonic wall

and invading. That constitutes

the evidence

that this is a malignant neoplasm.

Let's take a break.