0:00

More than 50% of adult gliomas

0:03

are IDH wild type.

0:06

And this is a classic example where you have

0:10

a large necrotic enhancing mass in the right

0:14

frontal lobe, has a very high blood

0:16

volume on the perfusion maps.

0:18

Very typical histopathology showing

0:20

you glomerular proliferation,

0:23

vascular endothelial hyperplasia and mitosis.

0:28

And there is no doubt that

0:30

this is a primary GBM.

0:32

But the most important thing to me

0:34

is the clinical presentation.

0:36

It's an older individual presenting with one

0:39

month history of left-side weakness

0:41

and difficulty speaking,

0:42

some kind of subacute neurological deficit.

0:46

And again, as I said, you know,

0:49

this is a classic glioblastoma.

0:51

This is how our tumor board discussion used to

0:54

look like a few years back, you know,

0:57

mostly will be centered around imaging perfusion

0:59

maps, history, maybe some immuno stains.

1:02

Not anymore, you know,

1:04

the majority of the discussion nowadays is

1:07

centered around this thing called methylation

1:11

profile or next-gen sequencing where a tumor

1:14

tissue after the methylation profile and

1:18

genomic sequencing is pitched against the

1:21

library of a few thousand gliomas and a

1:25

classification score is given, for example,

1:28

this one is a glioblastoma. MGMT is unmethylated as you can see, and an

1:32

EGFR is amplified over here,

1:34

you can see the EGFR amplification.

1:37

And that is the reason I don't call my GBMs as

1:40

GBMs anymore to me, these are either good,

1:44

bad or mad.

1:47

And this one is clearly an example

1:48

of a mad GBM to have, you know,

1:51

and I get wild glioma. MGMT UNL as we know,

1:53

these have the worst prognosis,

2:01

median survival around one year.

2:03

On the other hand,

2:04

a bad GBM to me is an IDH wild

2:07

type with MGMT unmethylated.

2:09

These are the ones which respond to temozolomide

2:12

a little bit better and also have higher

2:15

incidence of sore and hence a little bit better

2:19

prognosis, median survival around 2 to 3 years.

2:23

So IDH wild type gliomas,

2:25

these are different examples

2:27

occur in older individuals,

2:30

symptomatic subacute neurological deficit,

2:32

very important,

2:33

majority of them will present with some kind of

2:36

neurological deficit going on for

2:37

a few days to a few weeks.

2:39

These are usually necrotic large enhancing

2:42

masses, may even have hemorrhage in them,

2:46

a lot of edema swelling and can almost occur

2:49

in any lobe. But predominantly,

2:52

we see them in the temporal

2:53

or the frontal lobes also.

2:55

And and these are your IDH type Gliomas with very

2:59

poor prognosis. On the other hand,

3:02

this is an example, you know,

3:04

a 43-year-old female presenting with a tumor in

3:08

the left frontal lobe, which is infiltrative,

3:10

predominantly nonenhancing,

3:12

maybe a little bit of restricted diffusion and

3:14

slightly increased blood volume in

3:16

the medial part of the tumor.

3:17

This patient undergoes resection and

3:22

histopathology comes back as a nonaplastic

3:24

astrocytoma or grade three.

3:26

But more importantly,

3:28

this is an IDH Y type anaplastic astrocytoma.

3:32

Why it is important because we know IDH Y type

3:35

glioma even though it may be a lower grade,

3:38

grade two or grade three. For example,

3:40

this one is grade three.

3:41

They do much worse than IDH

3:45

mediated glioblastoma,

3:47

and you can see this patient comes back within

3:49

two months after therapy with a recurrence,

3:52

undergoes a complete resection

3:54

of this recurrence.

3:55

And this time the histopathology comes back as

3:58

a glioblastoma, not a grade three anymore.

4:00

Within two months,

4:02

this patient undergoes multiple therapy

4:05

judgments using different combinations of

4:08

chemotherapies and radiation and still

4:12

continues to progress and does poorly

4:14

as expected for an IDH Y type glioma.

4:17

And this is what we know from this paper in

4:21

Negm that these diffuse

4:23

grade two or grade three,

4:24

lower grade gliomas if they don't have IDH

4:28

mutation and around 20 to 25% of

4:30

these won't have IDH mutation.

4:32

These are your IDH Y type gliomas which behave

4:36

almost like a GBM and people will call

4:39

them molecular GBM or pre GBM.

4:43

And this is one of the updates.

4:45

The C Impact Consortium came up with the in

4:49

2018 where the C Impact Consortium

4:53

said that, you know,

4:55

if the glioma has any of these

4:57

EDFR amplification combined,

5:01

whole chromosome seven gain or whole chromosome

5:04

10 loss or third perter mutation.

5:07

These gliomas,

5:08

even if they have a histological diagnosis

5:11

of grade two or grade three,

5:13

these should be called as

5:16

diffuse astrocyte gliomas.

5:18

IDH wild type with molecular features

5:21

of glioblastoma WHO grade four.

5:23

The reason for this update was that because

5:26

these are aggressive tumors and now they could

5:29

be eligible to be enrolled in trials which

5:33

include majority glioblastomas.

5:35

This is an example,

5:38

another example over here,

5:39

a large necrotic enhancing mass

5:40

in the right hemisphere.

5:42

And you can see clearly there is again

5:47

of chromosome seven, a loss of chromosome 10,

5:50

which kind of gives you that this is gonna be

5:53

IDH wild type or mutated glioblastoma.

5:57

And more importantly, you know, as I mentioned,

5:59

these methylation profile of this tumor

6:03

tissue is put against, you know,

6:07

a AAA library of glioma tissue,

6:10

the neuropathologist have and,

6:12

and I can show you over here, you know,

6:14

the query sample is kind of fitting into this

6:17

green cluster of tumors which we know

6:21

are glioblastomas. Right? So again,

6:23

over here showing you that this

6:24

is a GBM RT K type two.

6:27

Another thing we know that

6:29

these IDH Y type gliomas,

6:31

they are very aggressive and they progress

6:35

very quickly. This is an example, you know,

6:39

and 57-year-old female presenting with

6:42

headaches had an MRI done in November 2015,

6:45

which was kind of read as almost normal.

6:49

And, and you know, quite rightly so,

6:52

but if I show you a follow-up scan

6:55

done just five months later,

6:58

and you can see a huge tumor developing.

7:01

This is a classic butterfly glioblastoma

7:04

going across the corpus callosum.

7:07

And maybe if you go back on the baseline study,

7:11

you can see there was a little bit of

7:13

signal abnormality right here,

7:15

adjacent to the corpus callosum in

7:17

the right cerebral hemisphere.

7:19

And that's probably the site where the

7:21

tumor cells were already there.

7:23

Just not visible enough on MRI.

7:26

And you can see the progression

7:28

so quickly within five months.

7:30

It's a full-blown tumor as expected for an IDH

7:33

M type glioma. Another example over here again,

7:38

an older individual who had a stroke

7:40

in the right basal ganglia.

7:42

It... two years ago and this is the scan

7:46

we were reading. Now, this time, you know,

7:48

the patient came with another episode

7:52

which sounded like almost like an acute stroke.

7:54

And I'm just showing you how this stroke has

7:57

already resolved in the right basal ganglia.

8:00

But more importantly there,

8:02

there was another range of signal abnormality

8:04

seen in the medial left frontal lobe over here,

8:07

which was presumed to be stroke because one,

8:10

the patient had a stroke in the past the second,

8:13

you know,

8:14

the clinical presentations from the ed sounded

8:16

like a stroke and, you know,

8:20

not totally wrong. You know,

8:21

the neuroradiologist who read it called it

8:24

potentially an acute or sub acute infarct.

8:26

But this is what happens to this patient.

8:29

You know, this is three weeks later,

8:31

the patient gets a follow-up scan.

8:33

And now you can clearly see that this lesion

8:36

is increasing in size is showing necrotic

8:39

enhancement. And you can see, you know,

8:41

seven weeks later and,

8:43

and almost 100 days later.

8:46

So you can see that this tumor is progressing

8:49

rather fast, right? This is, again,

8:51

a necrotic enhancing mass with a lot of hyper

8:54

increased blood volume over here.

8:56

And this is again,

8:57

clearly an IDH Y Wild type Glioblastoma.

9:04

Another example over here, you know,

9:07

you have

9:08

a patient who came up for an

9:11

annual follow-up imaging exam.

9:12

This patient actually had a right temporo

9:15

in which was resected in the past.

9:16

And he was getting annual follow

9:20

up exams on this follow-up exam.

9:22

We saw this non-enhancing infiltrative

9:25

signal abnormality,

9:26

which was developing in the left middle frontal

9:29

gyrus maybe showing some restricted diffusion. So,

9:32

and this is just the scan done

9:34

a year before that or,

9:35

or at least a year and a half before that.

9:38

You can see there was no signal abnormality

9:41

in the left middle frontal gyrus, right.

9:43

So this is a lesion which

9:45

is developing very recently.

9:49

And this is how we will read it.

9:50

The reason we will call this an ID wild type

9:54

infiltrated glioma and not call this a glioma

9:57

because this is an older individual. And,

10:00

and you know,

10:00

whenever we see a new tumor developing

10:02

in an older individual,

10:03

even if it looks very small

10:06

or non-enhancing or, or,

10:08

or kind of not very aggressive

10:09

on the initial exam,

10:10

we know that these tumors can grow very

10:13

quickly and this is what happens, you know,

10:15

a month later. In fact, even not a month,

10:18

three weeks follow-up,

10:19

you can see the tumor is actually increasing

10:22

in thickness over here.

10:23

And that's when the neurosurgeon

10:25

decided to take it to the OR,

10:28

and this actually came back as a grade three

10:31

astrocytoma. More importantly, IDH Y type.

10:33

And that's the reason, you know,

10:35

these are called molecular glioblastoma because

10:37

these are the ones which are gonna do

10:40

poorly and progress very quickly.

10:42

Another very quick example over here,

10:45

a patient slightly younger 39 and had

10:48

a scan done in November of 2011.

10:51

You don't see any signal abnormality

10:53

and this is a year later.

10:55

You can see there is an infiltrated tumor

10:58

in the medial temporal lobe starting to show

11:01

some enhancement over here. And as we know,

11:03

these tumors grow very quickly,

11:05

this is a month later,

11:06

you can start to see more enhancement and

11:10

more swelling in this region. Uh Again,

11:12

this is an IDH wild-type grade four glioblastoma

11:16

which progresses rather quickly.