0:01

So the very first dichotomy that has

0:04

to be made when looking at the molecular genetics

0:07

of glial tumors is, is it IDH mutant

0:11

or IDH wild type?

0:14

And I wanna describe the features

0:16

of IDH wild type gliomas in this short PowerPoint.

0:22

So as you know, the year was significant changes

0:26

between the WHO classification 2016

0:30

and 2021.

0:32

And one of the fundamental changes that was made was that

0:39

glioblastoma was defined as a glioma that is

0:43

of IDH wild type.

0:46

So there is increasing reliance on the molecular

0:50

biomarkers in the genotypes in 2 20 21

0:53

and they now define GBM, not histologically,

0:57

but by the basis of IDH wild type.

1:02

There are a couple other changes that I'll highlight here.

1:05

They use the term type rather than entity or variant.

1:09

They separate the adult gliomas from the pediatric gliomas

1:13

and we are, we will do the same in this course.

1:16

They no longer have the entity

1:19

of anaplastic astrocytoma.

1:22

It's now just one of the IDH mutant astrocytomas.

1:27

Remember that they also eliminated gliosis cerebri, um,

1:31

back in the 2016 uh, classification.

1:36

And we are no longer using Arabic numbers, just uh,

1:39

I mean we're only using Arabic numbers,

1:41

not Roman numerals anymore.

1:44

So let's talk about the difference

1:46

between IDH mutant versus IDH wild type.

1:50

As I mentioned, the IDH wild type is now

1:54

by definition the requirement

1:56

for calling something a glioblastoma.

2:01

The one P 19 Q co deletion is now used

2:06

to specifically classify oligo dentro gliomas.

2:10

And the A T RX mutation is the marker

2:14

for identifying something as an astrocytoma.

2:17

Now we have sort of two different dichotomies.

2:19

We have the astrocytomas, which are marked by the A T Rx

2:24

uh gene and the one P 19 Q code deletion

2:27

for the oligo gliomas

2:29

and the IDH wild type for glioblastoma.

2:35

In addition to the IDH wild type variant.

2:39

In the glioblastomas one also sees

2:43

see TURT promoter mutations, EGFR amplification

2:47

and chromosome seven, trisomy

2:51

chromosome 10 monosomy, which is

2:54

by definition now the molecular glioblastoma,

2:58

Which is a WHO grade four tumor.

3:02

So those combinations of molecular markers

3:07

are by definition the molecular glioblastoma.

3:10

So again, TER premierer mutation, EGFR amplification

3:15

and trisomy seven, MONOSOMY 10

3:19

are the additional genetic markers that confer glioblastoma

3:24

as a diagnosis of molecular glioblastoma.

3:28

We'll talk about these other entities as well.

3:33

So once again, if we go down the pathway from a glioma,

3:37

we separate them into the wild type versus the mutant.

3:41

In the mutant category, we're gonna separate those patients

3:44

who have one P 19 Q code deletion as oligo dendro gliomas.

3:48

We're gonna separate those that have the A T RX mutation

3:51

and often we also include TP 53 mutation as the definition

3:56

of astrocytoma.

3:57

And then these are all the different classifications

3:59

of astrocytoma.

4:01

However, the initial dichotomy which separates things into

4:05

the wild type, which has also these other genetic findings

4:09

and or microvascular proliferation

4:11

and necrosis, will define either molecular glioblastoma

4:15

or glioblastoma IDH wild type based on the histologic

4:19

findings of microvascular perforation and necrosis.

4:23

And those are WHO grade four tumors.

4:26

How often do we see these various types of tumors?

4:29

Well, here you can see

4:30

that the IDH wild type actually constitutes greater than 50%

4:35

of all adult gliomas.

4:38

The astrocytoma IDH mutant

4:40

and the oligo DDR glioma, again,

4:43

a T RX versus one P 19 Q co deletion are almost

4:48

equal in frequency.

4:51

And then we have all these other entities which we'll talk

4:53

about at a later time.

4:56

So here is an example of glioblastoma.

4:59

Remember we're not using the term glioblastoma

5:02

multiforme anymore.

5:04

People like me, we still say GBM when we mean just

5:07

glioblastoma based on the classification

5:10

that was made in 2016 and now 2021.

5:14

So this is IDH wild type and

5:16

therefore we know it's a glioblastoma

5:17

and we will have that A T rx, et cetera.

5:19

And EGFR and trisomy seven, MONOSOMY 10.

5:23

And this is pretty typical where we have a necrotic tumor,

5:26

which is convincing quite a bit of vasogenic edema.

5:31

On the A DC maps, we see that there are areas

5:34

of dark signal which confers low A DC

5:38

that would be brighter on the DWI image.

5:41

And on this perfusion map, we see that the rim

5:45

of the tumor, which is the enhancing part,

5:48

shows hyperperfusion.

5:51

It's almost the same as the gray matter frankly.

5:54

At Johns Hopkins, we do a qualitative

5:56

Assessment of perfusion, not, uh, quantitative assessment.

6:01

I think that's what's being done in most people's practices.

6:04

So this is pretty typical of a glioblastoma necrosis,

6:08

peripheral enhancement, vasogenic edema, mass effect,

6:12

et cetera, with hyper perfused area and reduction in a DC.

6:18

This, however, is another example

6:20

of a glioblastoma based on the molecular genetics.

6:24

And you notice this tumor is pretty well defined.

6:29

It's showing still peripheral enhancement.

6:31

It's still has relative low

6:34

A DC in the perimeter

6:36

and it still has on our RCBV cerebral blood volume perfusion

6:41

map hyperperfusion.

6:43

So even though this is a very well-defined lesion,

6:46

it has all the characteristics on imaging of a

6:51

glioblastoma and was eight, uh, IDH wild type tumor.

6:56

So this is showing the varying appearance of glioblastoma

7:01

that is defined by the IDH type rather than

7:05

necessarily histopathologically.

7:07

So even though this is a well-defined lesion,

7:09

this is indeed a glioblastoma defined by

7:14

IDH wild type characteristics.