We can also, based on the tricks
that we have in our pathology bag,
be able to say, what is likely to be
a way to treat a particular tumor.
So shown on the left upper corner,
is an H&E of a breast cancer.
That's fine, it's very straightforward,
there's a significant amount of desmoplasia,
it's a breast cancer, not
too much inflammatory cells.
Will this tumor respond to
Or anti-progesterone therapy?
Or do I have to give a monoclonal antibody
against a cell surface, activating
molecule receptor HER2/neu?
Well, I do my immune histochemistry
and in some of the tumors,
you get a very prominent estrogen receptor signal,
that's the brown dots, estrogen
receptor is within the nucleus,
this tumor with a positive
estrogen receptor appearance,
will respond very well to estrogen antagonists.
Similarly, I can do a progesterone receptor study
and see that, wow that tumor,
is going to respond to
progesterone receptor antagonist
or progesterone antagonist.
And then finally, this last
tumor from a different patient,
will respond to monoclonal
antibodies against HER2/neu,
a cell surface activating molecule.
And so, even though all three of
those would have looked the same,
on H&E, I can specifically tell
the surgeon now or the oncologist,
treat this patient with X or Y or Z.
Important predictive therapeutic markers as well,
increasingly because we have
immune checkpoint therapies,
that we can apply to tumors.
Being able to predict whether a tumor will
respond to those is is very important.
So, what do I mean by that?
So, in this particular case,
we are looking for a PD-L1, that stands for,
“Program Death Ligand 1” and
some tumors will express it,
some tumors will not.
If tumors express PD-L1, that acts on
lymphocytes through the PD1 receptor,
as shown there in that green
circle on the left-hand side
and will tell the lymphocyte,
“Stand down, do not respond,”
so, it's a very clever way that tumor cells have,
of turning off the immune response to them.
Well, if I know that a tumor
is making a lot of PD-L1,
such as we see here, I can
add a blocking antibody,
I can add an antibody against PD-1 or
PD-L1, that will block that interaction
and now the T-cell won't stand down,
it will continue to recognize and
aggressively pursue that cancer cell.
So, anti-PD-1, monoclonal antibodies include,
pembrolizumab, nivolumab, there's
actually a lot of, “Mabs.”
Mabs just stands for monoclonal antibodies.
But by doing this immunostaining,
I can tell the oncologist,
this patient is very likely to respond to,
immune checkpoint inhibitor
monoclonal antibody therapy
and may even save them, having
to go through chemotherapy.
So, we have a variety of ways that we
can do the classification of tumors
and these involve the cytogenetics, the
fluorescence in situ hybridization or FISH
or PCR-based technologies.
These are particularly helpful in
classifying leukaemia’s and lymphomas,
that may look very, very, very similar.
Sarcomas, which sometimes are
very poorly differentiated
and we don't know where they
came from and renal tumors.
These technologies as well, cytogenetics FISH,
PCR-based technologies are also helpful
in terms of quantitating tumor burden,
how much tumor is there left, how
much tumor was there to begin with
and then once we remove it or treat it,
is there any tumor left or is it coming back.
We can also use all of these technologies,
cytogenetics FISH, PCR-based etc.,
to help us with prognosis and
prediction in a variety of tumors,
not just the ones listed, but those leukaemia,
gastrointestinal stromal tumors,
long colon melanoma, rely very heavily
on these ancillary technologies,
to provide good prognostic prediction.
And this is just showing you one of the ways,
that we can monitor residual disease,
so, this is a patient who has
chronic myelogenous leukaemia,
this is driven, by a single driver mutation,
which is a fusion, a translocation
of the BCR-gene with the ABL gene.
The BCR provides dimerization, the
ABL gene provides kinase activity,
so it's one of the major drivers for CML.
You can see this patient comes in, with
7% positivity of the of the total DNA,
that we're looking at, containing
this BCR able fusion transcript.
So, we have a moderate amount of
disease, starting about April,
on the timeline, that patient
gets treated and we see
the amount of the BCR-able fusion transcript,
that we're measuring by polymerase
chain reaction, the PCR.
We see that curve trending down and
there is very minimal residual disease
and actually, getting the levels
where it's barely detectable.
And that patient can be maintained like that,
we can follow the BCR able in the
blood because this is a leukaemia,
we can find that fusion transcript
and provided it stays low,
we won't do anything new,
if it starts trending back
up, we may amplify therapy.
So, finally as we come around to
the very end just a cautionary note,
there are tumors that look
malignant, but they are not.
So, the title is not all that glitters is cancer.
So, here uterus cross-section,
is it benign or malignant?
Well, on this one, I can
look at and say that tumor,
which is primarily in the upper left-hand corner,
that white kind of lobular tumor,
but it's is kind of solid, but then
there's areas of hemorrhage adjacent to it,
and big areas of necrosis.
So, grossly it's got all the features
that we expect to see in a malignant tumor
and that is clearly malignant.
But take a look at this one,
as a final test of all your pathology knowledge.
Benign are malignant?
It's again it's a uterus cross-section,
the tissue that's off on the
right, is actually the uterine wall
and we've basically cut open the uterus,
bivalved it and just inlaid it open.
You can see that white tumor,
that is present on the left-hand side,
turns out that's a benign leiomyoma.
But it also turns out that when we took
out this uterus for a benign leiomyoma,
there's one other thing and I
don't know whether you notice that,
it's a benign tumor, uniform,
not necrotic not hemorrhagic.
But in the middle of that
there was also, this new growth
and the woman who had had this uterus resected
was unaware of the pregnancy, but
would not have wanted to retain that.
So, not all that looks malignant is so and
that's why we do all the special studies.
Take home points from this very last
talk, when we about cancer, is that,
you understand the role of a
surgical pathologist in patient care.
We are not just the guys behind the curtain,
we actually have a very important
role in telling pathologists
or telling oncologists, telling
surgeons, what needs to be done.
There are many, many techniques that
are used to establish a diagnosis
and inform prognosis and therapeutic
choices and we have a huge bag of tricks,
that are only getting better and better.
And with that we'll close.