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Diffuse gliomas.

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Not to be confused with diffused midline gliomas.

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Diffuse gliomas are what we used to call astrocytomas

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oligodendrogliomas or all uh, as oligo astrocytomas.

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So we don't call oligo astro anymore.

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Diffuse gliomas are non glioblastomas

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and they're infiltrating either astrocytomas

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or oligo dendro gliomas.

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And these are the three molecular markers

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that define diffuse gliomas.

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IDH being the most important.

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It's signifies that it's going to be a lower grade

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one P 19 Q chromosome number one, chromosome number 19 locus

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of code deletion.

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This is a disease defining chromosomal marker.

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For oligo dro glioma.

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A TRX is a marker defining astrocytoma.

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So at our institution,

0:59

almost all the disease gliomas on imaging

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and at initial pathology,

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a histologic analysis will undergo IDH for sure

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and one P 19 Q of to make sure that it's not an oligo.

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And if one P 19 Q is intact,

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then they will go ahead and do a T rx to prove

1:20

that this is an astrocytoma.

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So this is how it's divided.

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Diffuse gliomas is either mutant or wild type.

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I already told you. Wild type diffuse gliomas are def

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defecto molecular glioblastoma.

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In the mutant variant,

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they will undergo one P 19 Q co deletion testing.

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If that is deleted,

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that's an oligodendroglioma period N If it's one P 19 Q

1:47

intact, then a T RX is lost then that's an

1:51

astrocytoma, the wild type.

1:54

These are much more aggressive tumors.

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They, if they have a TER promoter, EGFR amplification

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trisomy seven and monosomy 10,

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this is called the molecular glioblastoma.

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And diffuse astrocytoma IDH mutant was newly

2:13

um, graded, uh, based on grade two, three and four on WH

2:18

or 2021.

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And this, the most aggressive variant is now

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called the grade four.

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But it has to have this particular molecular

2:28

deletion called CDKN two A B homozygous deletion.

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But looking at the imaging, you could tell

2:35

that this tumor is already trying to enhance.

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And there's some areas of central necrosis

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but doesn't really look like a frank glioblastoma.

2:44

You should think about grade four

2:47

diffuse astrocytoma, IDH mutant.

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And if your institution has the capability

2:52

to do this molecular analysis,

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CDK N two A B homozygous

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Deletion, this confirms that this is a grade four

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diffuse astrocytoma.

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IDH mutant IDH is the king right now

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of determining the fate of a glioma, whether it's going

3:14

to glioblastoma route or diffuse lower grade glioma.

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It was discovered in 2008.

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And if there is a IDH mutation, it leads

3:24

to this particular molecule

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to hydroxy glu rate accumulating.

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And it's much, much more common in lower grade gliomas.

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And in primary GBMs it's almost never seen.

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But in some cases of a glioblastoma

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that de differentiated from a lower grade,

3:43

you may actually detect this,

3:44

but in classic glioblastoma it's never seen.

3:48

So what does this mean?

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That we at least have to know

3:51

what IDH one mutation one P 19 Q co deletion.

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A TRX loss means that I just already told you.

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So here's some of the tumors that this is from literature

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where T two is super bright flare, it becomes darker.

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This has been called a T two flare mismatch.

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And this is not a 100% rule,

4:14

but this has been described as T two flare mismatch, meaning

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T two is super bright, flare gets darker.

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This has been a molecular imaging correlate

4:25

of a diffuse astrocytoma.

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IDH mutant A TRX loss.

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Not a hundred percent rule,

4:33

but you could, uh, assess at least guess before the surgery.

4:38

Now here's a patient with diffuse glioma

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and how do I know it's more likely

4:44

to be IDH mutant or wild type?

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The DWI is going to be one of the most helpful technique.

4:49

You could see that the tumor kind of disappears in DWI.

4:53

This is more likely to be IDH mutant the better

4:57

prognostic uh, glioma.

5:00

This is that patient with molecular

5:01

glioblastoma non enhancing.

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But look how very much aggressive.

5:06

The DWI looks very reduced on DWI,

5:10

very dark on a DC.

5:12

This is not a lower grade tumor at all, despite the fact

5:15

that it hardly enhances, has apparent circumscribed border.

5:20

This is not a good tumor. This is a IDH wild type.

5:24

This is molecular glioblastoma. How about this one?

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This patient has a serpiginous looking calcium

5:33

and that calcific marker is pretty good.

5:36

Not a hundred percent rule for a specific type of tumor.

5:41

And you could see that the fluorescent in cyto

5:43

hybridization, that's what that is, shows you that one P

5:48

19 Q code deletion.

5:50

You could see that there should be two pink and two green.

5:53

Our pathologist confirmed for me, but there's one missing.

5:56

So this is so-called the one P 19 Q code deletion.

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And this is a disease defining marker

6:05

of an oligo dendro glioma.

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We don't do CT anymore to confirm the presence

6:10

of calcification.

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We may do SWI,

6:14

but um, CT

6:16

to confirm calcification is no longer a standard

6:19

of care practice.

6:21

This is a patient, this is the last

6:23

case that I'll share with you.

6:25

He came back at 2003 and our um, this was discovered

6:30

after he had a car accident

6:32

and CT detected a low density lesion.

6:35

So he came, he was completely asymptomatic.

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I looked at this and I said, Hmm,

6:41

I'm not sure if it's tumor, so why don't we just see,

6:43

get serial imaging?

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So he came back every year

6:47

and then it start to grow in about three years.

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Here's 2012.

6:52

So nine years, this lesion has almost doubled.

6:57

So I scratched my head

6:59

and said, does lower grade gliomas grow this

7:02

slowly, probably could.

7:05

But during 2020, patient called, emailed me

7:07

and said, my, can you take a look at my MRI?

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And I look at it and I look at from the 2003.

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So these are 17 years apart.

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And I explain to the patient, this is growing.

7:20

We no longer can just sit around and do nothing.

7:24

And our neurosurgical colleagues,

7:26

after hearing my, um, brain tumor talk about two HG,

7:31

he said to me, why don't we get a two H-G-M-R-S?

7:34

And I thought, really an idea.

7:36

So we brought the patient to our research scanner

7:40

and our outstanding postdocs

7:43

and PhDs there helped us to do a two HG scan.

7:47

And lo and behold,

7:49

this patient within this lesion had an unmistakable,

7:53

not an artifactual, a two hydroxy GL rate peak

7:58

that you can only really see in IDH mutant gliomas.

8:03

So this pushed us over the edge.

8:06

Patient went for surgery, gross, totally resected.

8:10

And this is a gross totally resected IDH mutant

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one P 19 Q co-ed oligo dendro glioma.

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And this is the first time that I was just stunned at

8:24

how this non-invasive technique really helped us.

8:28

So this is, um, already three years ago now.

8:31

Um, and patient is doing very well that, um, two HG

8:36

is indeed a marker for IDH mutant gliomas.

8:40

And this happens to be an IDH mutant oligo dendro glioma.