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So, let's discuss the T2 FLAIR mismatch sign and

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the importance of this sign in identifying

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IDH mutated astrocytomas.

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So in 2016 or so,

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when we got a little more comprehensive knowledge

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about the genomic subtypes of adult gliomas,

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we realized that we are looking also at a certain

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subgroup of gliomas, adult diffuse gliomas,

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which looked very symmetrically,

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homogeneously bright on T2-weighted images,

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non-enhancing,

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and also showed dark signal in

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majority of the central part of the tumor on the

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FLAIR images, except the peripheral thin bright rim.

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As I said, majority of these tumors,

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they also had facilitated diffusion

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and very low blood volume.

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And when we started to look at the genomic profile

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and the methylation profile of these tumors,

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we realized that almost all of

1:05

these tumors, for example,

1:08

in this paper we published in Clinical Cancer

1:10

Research in 2017, we showed this sign.

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We called it T2 FLAIR mismatch sign,

1:17

had 100% positive

1:18

predictive value to detect

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IDH mutated, non-codeleted astrocytomas.

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Now, just one caveat,

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not all IDH mutated non-codeleted astrocytomas

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showed this sign.

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Only 15% to 20% of this big group showed this

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particular T2 FLAIR mismatch sign.

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But once we see this sign,

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it's almost 100% specific for this subgroup of gliomas.

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And this is the same example over here.

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You know,

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these tumors, they occur in younger patients,

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35-year-old female,

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and majority of the time,

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you know,

1:57

they are either incidentally detected

1:58

or patient presenting with headaches.

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And the methylation profile shows these to be

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T2 FLAIR mismatch sign

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and IDH mutated non-codeleted astrocytoma.

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Another example over here,

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another 34-year-old male patient presenting with seizures,

2:15

has this sign where there is diffusely

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homogeneously bright T2 lesion in

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the posterior left frontal lobe,

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which shows dark signal in the center part

2:25

of the tumor on the FLAIR images,

2:26

except the thin bright peripheral rim.

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Majority of these lesions are non-enhancing

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and also show facilitated diffusion.

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And once we see this sign, as I said,

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you know,

2:36

these are IDH mutated non-codeleted astrocytomas.

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Now, since that publication,

2:42

this sign has been validated by multiple different

2:47

groups in different publications.

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Here is another example,

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two different patients who are showing

2:56

these T2 FLAIR mismatch signs.

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Again, homogeneously bright on T2,

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dark on FLAIR in the center,

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except this peripheral thin rim.

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Another example over here in the lower panel from

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the review article we published in 2020.

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Now, some of these T2 FLAIR mismatch signs,

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you know,

3:17

the tumors are large

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and because of how they are kind of growing

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around a gyrus and a sulcus,

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you might see some heterogeneity

3:29

on the T2-weighted images.

3:30

For example,

3:31

you do see some dark signal in the central part of

3:35

the tumor over here on this axial T2 image.

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But this is, in fact,

3:39

if you look at the coronal or the sagittal,

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this is the gyrus,

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which is kind of draped around which the

3:46

tumor is draped around this gyrus.

3:49

And this actual tumor is in fact dark on FLAIR

3:53

images in the central part and consistent with,

3:56

again,

3:56

T2 FLAIR mismatch sign and histopathologically

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and genomically proven to be an IDH mutated

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non-codeleted astrocytoma.

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Now, I will show you a few examples of other

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gliomas, IDH mutated gliomas,

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but, you know, why we don't want to call it

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a T2 FLAIR mismatch sign,

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for example, in this patient.

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This is an astrocytoma.

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As I mentioned,

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you know,

4:22

not all astrocytomas show T2 FLAIR mismatch sign.

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The reason we don't want to call this

4:27

as a T2 FLAIR mismatch sign,

4:29

because it's very bright on FLAIR.

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You know,

4:31

the central part of the tumor

4:32

is not dark on FLAIR,

4:34

as we expect for a T2 FLAIR mismatch sign.

4:37

Another example over here,

4:38

where, you know, the tumor

4:39

we don't want to call it a T2 FLAIR mismatch sign.

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And the reason for that,

4:43

again,

4:44

it's bright on FLAIR

4:46

and not homogeneously bright

4:49

on T2-weighted images.

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And this one turned out to be an IDH mutated

4:53

1p19q codeleted oligodendroglioma.

4:56

Another example over here,

4:58

even though it's an IDH mutated

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non-codeleted astrocytoma,

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the reason we don't want to call it

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a T2 FLAIR mismatch sign

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because the tumor is not very

5:07

homogeneously bright on T2-weighted images

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over here,

5:10

it's actually iso- or hypointense

5:12

on T2-weighted images.

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And

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another fallacy,

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we see

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some of these tumors, they have macrocysts,

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and that could be confused with

5:25

a T2 FLAIR mismatch sign.

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And why we don't want to call this a T2 FLAIR

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mismatch sign is because of these macrocysts,

5:34

which could look dark on FLAIR and

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bright on T2-weighted images.

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And this one turned out to be an oligodendroglioma.

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And this is another example,

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you know,

5:42

if you stick to the stringent criteria

5:45

of T2 FLAIR mismatch sign,

5:47

you will get 100% positive predictive value to

5:49

diagnose these IDH mutated astrocytomas.

5:53

Another example

5:55

of not calling it the T2 FLAIR mismatch sign.

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These are again a tumor with large cysts,

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even though it's an astrocytoma.

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But I would not call it a T2 FLAIR mismatch

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sign because these are cystic portions of the tumor

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and not really the solid component of the tumor

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which should show the T2 FLAIR mismatch sign,

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if you really want to be stringent with your

6:16

criteria for the T2 FLAIR mismatch.

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Now, T2 FLAIR mismatch sign,

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you can see in different parts of the tumor,

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this is a rare example,

6:24

you know,

6:25

where you have a multifocal tumor.

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You can see two different parts of the tumor,

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another one separated over here and both these

6:32

components of the tumor are showing

6:34

you T2 FLAIR mismatch sign.

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And once I see that,

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you know,

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this is clearly an IDH mutated,

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non-codeleted astrocytoma.

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Some of the tumors,

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you know,

6:45

which show T2 FLAIR mismatch sign,

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in fact, even on recurrence,

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also show the exact sign.

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You can see over here,

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this is a patient showing a T2 FLAIR mismatch sign,

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IDH mutated astrocytoma,

6:59

got operated or partial resection,

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there is some residual tumor left and the residual

7:04

tumor started to grow a few years later.

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And you can see even the recurrent tumor is

7:11

showing you the T2 FLAIR mismatch sign.

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Now, there is an exception to this rule,

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and we published this a couple of years back where

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we shown that some of the pediatric tumors,

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we should not be using the T2 FLAIR mismatch sign

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as we use it in adult diffused gliomas.

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As some of the pediatric tumors,

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for example, some of the BRAF-driven tumors,

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pilocytic astrocytoma,

7:37

or even H3K27 mutated glioma over here,

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showing you a T2 FLAIR mismatch sign.

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And we should not be using this sign in pediatric

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age group as the specificity of the sign

7:49

goes down rather dramatically.