Hi, I'm Dr. Andrei Shustov
from the University of Washington.
I'm a Medical Oncologist with
expertise in lymphomas.
The focus of my clinical work and
research are a rare and
diverse group of lymphomas called
T-cell lymphomas, or
peripheral T-cell lymphomas, or
simply, PTCLs.
Taking care of thousands of patients
over the years and
counseling their families I learned that the
best way for me to manage their
care and care for my patients
is to empower them to be part of the
team. To educate them about
their disease. Where it comes
from, types of treatments,
and bring them onboard
in making an important decision about their life
their treatment, and how we approach
their overall care.
To make decisions, you
need knowledge, and
today, we will learn about
how we establish
the diagnosis of lymphoma.
And, how we
stage the lymphoma, or find out
how far it's spread, and what
it means for treatments, and what
happens between the first presentation
of lymphoma and
and just before you start your therapy.
T-cell lymphomas are a rare
and diverse group of lymphomas
that represent only
6-10% of non-Hodgkin's
lymphomas.
There are over 20 different
types of T-cell lympomas and we
are starting to appreciate how
different they are by
origin, their biology,
clinical behavior, response
to therapy, and that
we most likely will
end up treating every
T-cell lymphoma differently
in the coming years.
That is why it's so important
to make the right diagnosis
and to determine what specific
type of PTCL
do you or your family member have?
Because this can really impact
the proper therapy
and the right decision,
how to approach it.
How do we make a diagnosis?
First of all,
to make a diagnosis of lymphoma, you
have to go to the source. We
need to perform a lymph node biopsy.
Lymphomas are tumors of the immune
system, they start in the lymph
node, they develop in the lymph
node, and the best way
to look at the whole
process, what's going on, is to take
the lymph node out, slice it
up, and look under a microscope.
I will take a second here and
emphasize
that for medical
oncologists specializing in lymphomas,
The most important part that I can teach
my colleagues and patients in the community
and academia is for
lymphoma diagnosis, you should
never do
needle aspiration of the lymph node
or needle biopsy of the lymph node.
It is sufficient for any other
cancer that we deal with in humans, but
for lymphomas, you have to do
what's called an excisional biopsy.
You have to take the entire lymph node out.
Because taking a little piece
with a needle sets you up for potential
mistakes that will have
consequences on
treatment and how
we discuss management and
discuss prognosis, because
guess what? Different parts of the
lymph nodes, can have different lymphomas.
Or you can biopsy a part of
the lymph node that doesn't have a lymphoma.
And then you miss the diagnosis.
For other cancers like
melanomas and breast cancer and
pretty much any other cancer
that humans can develop, needle
biopsy is appropriate because
all you need to do is find
the cell that doesn't belong in a lymph node.
Lymphomas, lymph
nodes are their homes. Just
having cells in the lymph node is
not going to give you the diagnosis. You have
to look at the entirety of the lymph node,
how those cells talk to each other,
because, making
diagnosis of lymphoma in general
does not help us.
There are 50+ different types
you HAVE to nail the right diagnosis
to advise the right therapy.
Once the lymph node is out of
the human body, it's
processed by the pathologist, we
look at it under a microscope,
and most of the time, it
gives us an idea about
fifty percent
we're there, making the right diagnosis.
But in order to pinpoint the subtype
of lymphoma, the species of lymphoma,
you have to go further, you have to
do chemical tests, and
nowadays there is a very
specialized and very sensitive
technique called flow cytometry
that allows us to look at every single
cell in the lymph node
what molecules are present
on its surface, how it looks
and define
the diagnosis with nearly
one hundred percent accuracy.
So what is flow cytometry? How do
we make a diagnosis?
Most of you will receive your pathology
report as part of your medical records
and it will describe that there are
certain cells in your lymph node
and there is this very long
sentence that says that
tumor cells are positive for
this, this, this, this, negative
for this, this, this, and then the
pathologist says, that's your diagnosis.
Frequent questions that I hear from
the patient is, "Was it the right diagnosis?"
"Did the pathologist make a mistake? Can
somebody confirm it?"
And it's a very legitimate
and it's the right question to pose
because making mistakes at the beginning
can have dire consequences
down the road if you choose the wrong treatment.
The truth is nowadays,
American pathologists
are equipped with such a scientific
method, such technology that
making mistakes in the diagnosis
is not very common.
You say how come?
Let's go back to the basics of
how we define cells and how
we call this is a T-cell, this is
a B-cell, T-cell lymphoma, B-cell lymphoma.
Shown in this slide is
the presentation of the
concept that every cell
in the human body has
special molecules
sticking out of the membrane.
Why do they have that?
cells have to communicate, they have to know
who is around, who is
their neighbor, who are they bumping into,
and you can imagine that cells
specific lymphocytes, they
don't have eyeballs, ears, antennas
they have to sense it somehow.
So they have these cells sticking out
called receptors. And these
receptors tell the cell
what's around them, what
is the neighboring cell, is it an enemy, is it
an infection? But we can use that
to define what
cell we are looking at because every
particular cell out of all the thousands
of types we have in the human body,
has a specific set
of these receptors sticking out
Pertaining to our discussion
today, T-cells have a very specific
array of molecules sticking out
and some of them are
unique to T-cells, that's why
we can say right away "This is a
T-cell lymphoma, not a B-cell lymphoma."
This particular set
consists of something called
CD3, CD4,
CD2, CD 8,
CD5, and by the way
CD is just a uniform marker
that we had to come up with because
there re thousands of them and putting
different names on it would be impractical.
So CD is the type of molecule
and then the number designates
its place in classification, but now
if you learn about
which of these markers are present in every
particular cell, you can know
exactly what type of cell it is.
Now think about it, if we can
define every cell in the human body like
this, we can also define
any type of cancer like this.
Because, when cancers develop
from normal cells,
they mutate, they change
the set of molecules that sticks out
of the cancer cells, so every
type of lymphoma has a very
unique set of molecules
sitting on top of the surface
and that is how having all
those tools, we're able to define
all these CD markers
on tumor cells, we can
come up with a signature for every
lymphoma. As an example
your pathology report can read
"The tumor cells are
CD20 negative, CD5 negative,
CD-something negative, but -
they are CD3 positive,
CD4 positive, CD2 positive,
etc. etc." and
when the pathologist looks at this readout,
coming out of this machine called
a flow cytometer, there is no doubt
that this cell belongs to the
type of lymphoma that's stated
on your diagnosis.
Now, things are not always
that easy, because tumor cells
can be slick. Sometimes
they mimic normal cells,
and what comes out in the readout
says well, it's not that different from a
normal cell. That's where it takes
a real skill of
a specialized pathologist, we call them
hematopathologists, to
really use their experience
their expertise, just like clinicians
when we treat patients, to
say that most
likely we're dealing with this lymphoma
that looks like a normal cell
but definitely, this is
anaplastic large cell lymphoma,
or angioimmunoblastic T-cell lymphoma, etc. etc.
Making the correct diagnosis
again, is extremely important
because, there are very unique
treatments for subtypes of lymphomas
that give you the best chance of curing it.
Another way of looking at the cells
besides the flow cytometry is to
apply a special stain so these
special dyes that are carried
by specific antibodies that
recognize those
CD markers, and
this is just for your visual understanding
how pathologists make the diagnosis
they look in the microscope, and every
time they apply the marker,
and cells turn brown, that means
that there are a lot of
CD30 molecules in these cells.
And, there are very
few cells that carry this particular
molecule, so then they write
it down and there we have your diagnosis.
So now you understand that
diagnosis is very important
to make for particular type of lymphoma
and there is scientific
technology that allows us to do that.
Once a diagnosis is established,
it goes for any
type of cancer, but specifically
to lymphomas, we have to find
out how far they've spread.
And this is something that we call staging.
Staging of lymphomas is extremely
important step between the
diagnosis and treatment, because
it also informs us how
best to treat this patient.
By and large, we
recognize early stage lymphomas
and advanced stage lymphomas.
As the name implies, early stage
they have not spread far,
advanced stage, there is a widespread
cancerous process in
the human body. Where do we make
the cut?
We recognize 4 stages of lymphoma,
from one to four.
How do we make this determination?
There are two types of technologies that have
evolved in the past couple of decades.
One is very familiar to you called
a CT scan.
CT scans are very
sophisticated x-rays, they take
several thousand cuts of human
body, and then combine
it into this singe image and
you can see every organ inside
the body, you can see every
single lymph node, and then you
determine whether the lymph nodes are normal
or abnormal, mostly by size.
Lymph nodes are always visible
on a CT scan, but they're supposed to be
tiny. Once they become bigger
then you know that something is going on.
If the patient already has the diagnosis of lymphoma,
it's easy to assume that enlarged lymph nodes
are involved by lymphoma.
However, think about if lymphomas
spread to the lymph nodes early,
but it's not enough to make it big,
how do you determine that? That's where PET
scans come along. PET scans
are technology that
uses the radioactive material
that is put in the human body
and it's attached to this sugar, to glucose.
Tumor cells have to divide rapidly
they have a high metabolism,
so they would eat more sugar than
surrounding cells. If they
consume more of this radioactive material,
they're gonna light up on the PET scan.
This way you can see
where a lymphoma has spread even before
it becomes enlarged.
As an example, the PET
scan of the patient is shown
on this slide, and you see that
those bright areas
in the neck, around the liver,
and somewhere in the pelvis,
indicate that there is something
metabolic, something really
"hot" is going on.
If this patient already has established
diagnosis of lymphoma, it is
easy to make that leap of faith and say
"this is lymphoma spread" especially
because things that are lighting up are lymph nodes.
So the chances that
the person has something besides lymphoma
is extremely low.
And now we see that lymphoma involves
the lymph nodes around the neck,
on both sides, around the wind-pipe
trachea, in the left
armpit, in the groin,
what do we call this?
Is it early stage, advanced stage?
Intuitively, you would say yeah this is all
over the place and it's advanced stage lymphoma.
But let's put some science to it because
your doctors will be talking to you and saying
you have stage 3, stage 1
stage 4, etc. etc.
For the purpose of staging we divide
the human body into 2 halves
and we use the diaphragm
as the natural border, the breathing
muscle in the middle as a
division line. As shown in the slide
the diaphragm in the middle,
and then you have
human body above the diaphragm, and below
the diaphragm. So if you find the
lymph nodes by using PET scan
or CT scan, just one
area, let's make an example of
the left armpit.
Nowhere else, left armpit
PET scan lights up,
nowhere else, this is stage 1.
So stage 1 is
lymph node involvement in one
area only. If the lymphoma
spreads to several areas
of lymph nodes but all of them are
above or below the
diaphragm, just one side of the human
body - we call it a stage 2.
Further spread on both sides of
the diaphragm makes it a stage
3, and if the lyphoma has
spread in other areas
outside the lymph nodes we call it
extranodal spread, it could be the bone marrow
could be any other organ
liver, lung, skin,
etc. It's a stage four.
Intuitively, you would probably think
that stage 1 and 2
is early stage, 3 and 4 is
advanced stage, and you would be correct.
That's how we roughly separate
advanced and early stage lymphomas.
We also assign them
definitions A and B
and it's very important because
it also has implications sometimes on
how we manage patients. Lymphomas
are notorious for causing symptoms
that you would typically
experience if you have an infection. Fever,
night sweats, weight loss,
and if any of those
is present, we call it a B.
And by the way we call them
constitutional symptoms, sometimes
you hear that word from doctors. If you have no
symptoms like that, we put a
designation A.
So now you understand that
person can have stage 2A,
3B, 4A, 1B,
based on how extensive the
lymphoma's spread, and based on whether or
not you have those specialized symptoms.
Why is it important to
determine? It's important to
determine because early stage
lymphomas and advanced stage lymphomas
I approach differently.
In early stages we have learned
through a lot of studies in the past
especially in B-cell lymphomas,
in T-cell lymphomas it's not as clear,
that you can do actually
limited number of chemotherapy treatments.
And you can bring radiation
along, combine those,
and you can cure the majority of patients
with early stage, cutting
chemotherapy in half. If you
have to treat advanced stage lymphoma,
you cannot do that. First of all
radiation is no help, and
patients would receive twice as
much chemotherapy or
twice as many chemotherapy cycles
to achieve the same cure rate.
That's why it's so important if you
understage it, then you can
undertreat patients.
If you overshoot, you can bring a lot of
toxicity that patients don't need, so
staging is a very important part
of preparation for your treatment.
What else is important?
In a future discussion, we will
talk about treatment of lymphomas but I will
just mention that
the mainstay of cancer treatment
at this day and age with all the
developments still remains chemotherapy.
Chemotherapy is very toxic,
and not everybody can
tolerate it, so we have to determine
whether this particular person
or you as a patient can tolerate
multiple chemotherapy cycles.
So in preparation for treatment,
your doctor will be checking your heart,
checking your lungs, checking your
kidney and liver, and bone marrow
function to make sure
that if we try to cure this lymphoma.
and it requires a lot of
toxic treatments, that your body can tolerate it.
So if you combine all the information we just talked about,
Proper diagnosis,
review by expert pathologist,
staging to determine how far
the lymphoma has spread, and
preparation by determining your
organ function status,
is the complex evaluation
that allows doctors
to prepare you for treatment.
In future discussions, we
will focus on specifically
what treatment we use for lymphomas.
With that I will close this
part of our educational
forum, and
I'll see you back for future discussions.
Thank you.
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