You've made it all the way through
our complete discussion of malignancy.
The final thing, is I want
to just share what with you,
what I do on a day-to-day basis,
in terms of tumor diagnosis.
One, I think it's intrinsically
really cool, but number two,
you need to understand when you are
discussing with your pathologist,
about the diagnosis, what
he or she is telling you.
So, that's we're going to go into now
and hopefully some of you will go,
“Hey that's an interesting field, that's
a good career that I could go into.”
All right, let's see.
So, the role of surgical
pathology and cytopathology,
is to basically accurately diagnose
pathology within a specimen.
This is a hunk of lung, a partial
pneumonectomy, that was taken out
and we have clearly within
it at the top a white tan,
lobulated, focally necrotic,
focally hemorrhagic lesion,
but that's not enough.
I need to actually now sample this.
One, to see if it really is a malignancy,
as opposed to some sort of funny benign tumor
or perhaps some sort of odd infection
and also, whether the
surgeon has got it all, okay.
So that's just the simple
questions that we need to ask.
I also need to be able to
talk, convey the diagnosis
and other associated relevant
information to the treating clinicians.
So, for those of you who may think that,
pathologists just sit all day at a microscope
and never interact with the outside world
or we're down in the morgue, doing autopsies,
nothing is further from the truth.
I spend the best part of my day,
talking with fellow clinicians
and saying, “Take a look at this. This is
what this is. This is what you need to do.”
I really have a very important
role in the treatment of patients,
so, hopefully again you'll say, “Hmm
that's sounding better and better.”
So, the sorts of questions that I need to answer,
so, that I can tell the treating clinicians,
the treating surgeons, the
treating oncologists etc.
What is this mass? That's number one.
Is it malignant, what type of malignancy is it?
Because it makes a difference
whether this is a sarcoma,
a metastatic tumor, a primary
lung cancer or something else.
Can we predict its behavior.
Yes. So, I need to look at this
and look at the features of this
and based on a huge volume of information,
I can in many ways say,
“This tumor tends to be fairly aggressive and
that patients who go untreated
will die within two years,” or
“This tumor surprisingly
enough has a rather indolent,
but not semi-benign course and patients
can live for years without doing anything.”
So, I looking down the microscope
and looking at the gross,
can often make some of those statements.
Are there potential treatment options and
I’ll show you examples, where
what we do in pathology,
will tell the oncologist what drug to choose.
Did they get it all? Obviously, I
mean that's a very important thing,
because if they haven't gotten it all,
we need to either go back
in and have a second surgery
or we need to radiate the field,
so that we can kill any residual tumor
cells that may be in the vicinity.
And what are the implications for the family.
Does this have a genetic basis? Is it
possible there's a germline mutation,
that's shared by sisters,
brothers, parents, children.
Those are all sorts of things
that I as a pathologist,
do in my day-to-day life.
Okay. Some painful truths, I painted the
rosiest picture I can possibly paint,
but now, I'm going to tell you some painful truths
and for those of you who may think
that the pathologist knows all,
well, sometimes we think
we do, but we really don't.
So, among the painful truths with human
tumors and in pathologic diagnosis,
one, we don't have any universal molecular
definition of what a neoplasm is,
we've talked about things that
grow on in an uncontrolled fashion,
that have genetic instability,
but there are exceptions to all of that,
so, we don't have one
universal molecular definition.
In most cases, I can say, I don't know
exactly what it is, but that's cancer,
other cases it gets a little bit fuzzy.
We have some states where it's not
clear that it's a borderline neoplasm,
so that's number one.
Number two, there's absolutely
no reliable marker of malignancy,
we can't just do a stain
or do a molecular signature
or do a particular test and say,
“That's cancer, that's not cancer.”
It does require a bit of thinking,
it requires a lot of kind
of knowledge and experience
and there are always
inconsistencies, in how we do this.
So, I wish that there was a way
that we could do, a test, and say,
“It's cancer and not cancer,”
unfortunately, we can't.
There are absolutely no
reliable predictors of outcome,
in any individual case.
So, every time I see a particular malignancy
and say, “The treatment for
this is X,” I also know that,
at very best 90% of the patients are
going to have a successful response.
But there's going to be 10% of the
patients out there that don't do well.
So we have no perfect way to say,
“You're going to live and you're not”
in any individual case, there are a lot
of other factors, that come into play.
Again, there's almost no truly
specific immunohistochemical markers,
in the same way there's no
reliable marker malignancy,
there's no antibody, that
I can dump onto a tissue,
that will come up with, a yes or no,
it's not quite like a pregnancy
test that you do at home,
wish that there were but there isn't.
Currently, we can actually
find out much more information
and stratify tumors into many more
little cubicles or little boxes,
than we have therapeutic options for.
So, I can now say this tumor
has a particular KRAS mutation
and I know that that is a likely driver mutation,
but I may not have or the oncologist may not have,
the appropriate therapeutic
option to take advantage of that.
So, pathologists are a little
bit further ahead of the game,
than are the pharmaceutical
companies that are making the drugs,
but that's changing.
And then, there are some tumors
that I don't care how hard we try,
with all of our magical tricks,
everything from electron
microscopy, flow cytometry,
cytogenetics, molecular signatures
we cannot classify them.
There are some tumors that
are so poorly differentiated,
that we have no idea what they are, we can say,
“I think that's a cancer, but we
don't know what kind of cancer.”
Okay. But many of these are
exceptions rather than the rule.
In general, I know a cancer
when I see one and I can say,
in many cases, how they're going to behave,
but I’m never ever going to be perfect at it.