(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
it's simply the tissue
is smaller
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.