0:01

I'd like to introduce the concept

0:02

of the pediatric gliomas,

0:05

and in this case, we're going to emphasize the

0:10

high grade pediatric gliomas rather than the low grade.

0:13

We will deal with low grade pediatric

0:15

tumors at another time.

0:17

So the two markers that, uh, we have to be aware

0:21

of are the H three markers,

0:23

and there are two varieties, H three K 27 M

0:27

and H 3G three four,

0:30

and then the bra, uh, gene marker.

0:33

And that's usually the BRA V 600 gene.

0:37

So as I mentioned in the new concepts in the 2021 WHO

0:42

classification, the H three K 27 M mutation

0:47

defined the entity of diffuse midline glioma.

0:52

Remember, it used to be sort of the, you know, the pontine,

0:54

high grade midline glioma

0:56

or PIMG for a pontine, intrinsic midline glioma

1:00

that's been replaced now with the H three K 27 M mutation

1:05

as the molecular marker for diffuse midline glioma.

1:10

For those diffuse gliomas that are out in the hemisphere.

1:13

They were defined with the H 3G 34 mutation.

1:18

And both of these, as I mentioned, are high grade tumors.

1:21

They're grade four tumors.

1:23

So this has replaced the diffuse intrinsic pontine gliomas

1:27

and the other midline classifications of tumors.

1:32

Now, as I mentioned, there are low grade tumors.

1:34

We will not be dealing with them specifically here,

1:37

but remember that we still have our, you know,

1:41

low grade astrocytomas, including our diffuse astrocytomas,

1:45

our angio gliomas, our new term, plenty polymorphous,

1:50

low grade neuro epithelial tumor of the young P-L-N-T-Y

1:55

and sort of the diffuse low grade glioma.

1:57

So, and you might still hear the terms of

2:00

pilocytic astrocytoma, for example.

2:03

And these have specific genetic markers as well.

2:07

So within the diffuse high grade gliomas, as I mentioned,

2:12

we have our midline glioma, which is the H three K 27 M.

2:16

We have our diffuse hemispheric glioma, which is

2:19

that H 3G 34 M.

2:21

And then we also have some of the

2:25

classification from the adults

2:26

with the IDH wild type tumors.

2:29

And uh, there is an infantile hemispheric glioma.

2:35

I mentioned that there was another, uh, gene that we have

2:39

to consider with pediatric tumors, and that is the bra gene.

2:43

This is within the RAs mitogen activated protein kinase

2:48

or MAPK pathway, which also leads

2:52

to tumorgenesis.

2:54

Within that pathway, that mapk pathway, you have

2:58

A breath mutation that is referred to as the V 600 E

3:03

mutation most commonly.

3:04

And this is a mutation which leads to activation

3:09

of the kinase domain and increased proliferation

3:12

and tumorgenesis.

3:14

The breath V 600 E gene is associated

3:18

with three low grade tumors, which include polymorphic,

3:24

zho, astrocytoma, ganglio gliomas,

3:27

and your pilocytic astrocytomas.

3:30

What you note about all of these is these are all tumors

3:32

that have imaging characteristics of CYS and nodules.

3:38

And once again, this is very well described in Sumi Cha's

3:42

lecture on the WHO classification,

3:45

and I refer you to that for more specifics.

3:49

The one that we're going to deal with today,

3:51

as I mentioned also is the H three mutation,

3:55

which has the different varieties of H three K 27 M.

4:00

This is if the, for those of you

4:01

who are interested in the uh, actual DNA, you have a lysine

4:04

to meth in substitution at that amino acid residue,

4:08

which leads to that tumorogenic mutation.

4:13

And you have the H 3G three four mutation, which

4:18

also is another amino acid substitution in

4:22

that genetic code, which leads to tumorgenesis,

4:26

this one being the midline, this one being the hemispheric,

4:29

both of which are WHO grade four tumors.

4:33

So let's look at pediatric high grade gliomas

4:37

and how they are defined.

4:39

So we have that H three characterization

4:43

and the ones that have the H three K 27 mutation

4:46

are the diffuse midline gliomas.

4:49

We have the H 3G 34 mutation,

4:52

and these are diffuse hemispheric gliomas.

4:57

And then we have the alteration here,

5:00

which is an IDH wild type tumor

5:03

where you have grade four tumor on the basis of histology.

5:07

And that specific genetic alteration.

5:12

Where do these tend to occur?

5:14

So the diffuse astrocytomas

5:17

and diffuse low grade, these tumors all occur in the

5:21

cortical areas and in the periphery, whereas those

5:24

that are in the midline are the, the

5:29

genetic marker with the specific for the midline tumors

5:33

and those that are hemispheric

5:34

for those genetic markers as well.

5:37

So let's see some of these, uh, tumors.

5:39

So this is, uh, from a Journal

5:41

of Neurosurgery article in 2019,

5:45

A-B-C-D-E, gh.

5:49

All of these are H three K 27,

5:53

M grade four, high grade

5:56

Gliomas. So

5:57

you can see that vast majority

5:59

of these are in the midline.

6:00

This one actually looks like it's in the hypothalamic region

6:03

above the pituitary cell.

6:05

Here's one that's in the cerebellum.

6:07

This is a little bit of an unusual one.

6:08

This is more into the hemisphere,

6:10

and that would be more of the H 3G 34 M mutation.

6:14

But in this specific case, it was indeed H three K 27 M

6:20

mutation, typically in the midline.

6:22

Here is a graph of the location

6:26

of these H three K 27 M tumors.

6:28

You can see thalamic region, hypothalamic region.

6:32

They got something in the corpus coum.

6:34

The brainstem notice

6:36

that you also can get these in the spine.

6:39

So these midline gliomas

6:42

do populate the spinal cord as well.

6:46

And are some of the astrocytomas

6:48

that we see in the spinal cord.

6:50

Very few are gonna be out in the periphery.

6:52

And you see this, these couple dots here

6:55

that are a little bit unusual,

6:57

and those are the peripheral H three K 27 msms.

7:00

But you can see the vast majority are in the midline.

7:03

Here's another example of one.

7:05

Um, this would've been called diffuse intrinsic pontine

7:08

glioma or DIPG in the previous classification.

7:12

It's now considered a diffuse midline glioma,

7:15

H three K 27 M mutated,

7:18

and you see the diffuse enlargement of the pons

7:20

with some areas of contrast enhancement.

7:22

Sort of got that big pregnant belly

7:24

of the pons on the non-contrast scan.

7:27

And then on the post contrast scan, not

7:31

dramatic enhancement, but certainly some enhancement.

7:34

These are grade four. These have a very poor prognosis.

7:39

Now we turn to the H 3G 34 M.

7:42

These are the ones that are supposed to be in the

7:45

hemisphere in the periphery.

7:47

And here you see an example of such

7:50

where there is abnormal signal intensity in the right

7:53

hemisphere on the post gadolinium enhanced scan.

7:57

Despite this being a grade four tumor,

7:59

not a lot of enhancement.

8:01

There is reduction in a DC on the profusion map.

8:06

I would put this as equivocal for hyperperfusion.

8:10

Many of these are not hyper perfused, they're just sort

8:13

of a diffuse glioma pattern as you see here.

8:16

And this was indeed a diffuse hemispheric glioma,

8:19

H 3G 34 M genetic markers.

8:23

Well, I hope that helps introduce the concept

8:26

of these various genetic markers that are used

8:30

for classification of pediatric gliomas.

8:33

Thanks for your attention.