foreign [Music] thank you [Music] foreign [Music] [Applause] [Music] [Applause] [Applause] [Music] [Applause] [Music] [Music] thank you [Music] foreign [Music] foreign [Music] hello and welcome to noon conference hosted by MRI online noon conference connects the global Radiology community Through free live educational webinars that are accessible for all and is an opportunity to learn alongside top Radiologists from around the world we encourage you to ask questions and share ideas to help the community learning grow you can access the recording of today's conference and previous noon conferences by creating a free MRI online account you can also sign up for a free trial of our premium membership to get access to hundreds of case-based micro learning courses across all key Radiology subspecialties today we're honored to welcome Dr sunmi cha for an update on Imaging and 2021 who CNS tumor classification Dr cha completed her neuroradiology fellowship at New York University Medical Center she is a neuroradiologist with special interests and expertise in brain tumor Imaging at University of California San Francisco Medical Center where she also serves as the program director of Diagnostic Radiology residency and the vice chair of Education at the end of the lecture please join Dr cha in a live q a session where she will address questions you may have on today's topic please remember to use the Q a feature to submit your questions so we can get to as many as we can before our time is up with that we're ready to begin today's lecture Dr cha please take it from here thank you for the nice introduction I will share my screen um he said okay to share now yes okay this will stop others screen sharing do you want to continue yes I want to do that and then and then if you could just let me know if the screen looks okay from your end looks great okay great well thank you so much for having me today um hello everyone out there I'm going to talk about some brain tumor Imaging in the context of who CNS tumor classification I don't have anything to disclose so objective today is to I'm going to highlight couple of key points from the 2021 who CNS tumor classification and really morph that into how is that relevant to neural Radiologists or general Radiologists who are looking at brain MRIs or spine MRIs for patients with brain tumor and I'm going to just illustrate some of the correlation of molecular genetic markers in terms of what are you looking for on Imaging because we're non-neuropathologists we're not basic biologists but we must keep abreast with this explosive knowledge coming from the biological side because it does have implication for Imaging so the three things that I'm going to highlight is whocns classification and neural Imaging techniques that most of you are very familiar with but put that in the context of the molecular generic era of brain tumors and then I'm just going to show you 2 case by case how things are relevant Imaging and neuropathology neuromolecular genetics are intertwined so first let's start with CNS who classification so some of you are already familiar that World Health Organization has been supporting uh classification of not just brain tumors but all tumors for CNS tumors the first version came out back in 1979 and 2000 up to 2007 and the one these four classification schemes were purely based on histological and then something magical or something really groundbreaking happened in 2016 classification where molecular genetic information became part of the official classification system so no longer just the histopathologic features of tumor was used to classify tumor now there's just very very very Advanced technique looking in molecular genetics but more interesting to us Radiologists is that for the first time ever since 1979 MRI image made it to the cover of this book and then fast forward five years later 2021 who classification the fifth edition was published and you could see that now we have two MRI images so Imaging is now really gaining attention to our neuropathology our neuropathology and neurobiology colleagues that Imaging places such an important role of how we actually look at tumors so we are well on our way to becoming a very important we were already were but now we are pushing towards being part of the classification of CNS tumors so the nutshell of who 2021 is that there are molecular markers everywhere and this is the cartoon I made and it seems like it's we're just touching the tip of the iceberg and these are some of the idea um molecular markers that are part of now ordinary conversation in tumor board but there are actually many many more to come and they're already here and next version of uh CNS classification which will be coming in maybe five to seven years we are going to see even more so what does this mean for Radiologists we just have to make sure that we know what is changing the field of classification of CNS tumors so that we could keep up with how we interpret Imaging so here's the nutshell of CNS who there are so many molecular markers and we're gonna I'm only gonna touch on the several really important ones today and at UCSF uh instead of just getting a histopathological report we get something like this this is called UCSF 500 Gene panel where we actually get not just a histological diagnosis but we get idh status but in addition to that we get a whole host of additional information and this is really becoming a part of our standard of care for brain tumor uh pathological diagnosis so I'm going to show you a couple of cases and we'll go over this at the end you may not know the answer now but I could assure you at the end of this 50-minute talk you will be an expert at it so here's a young um 19 year old came with a diagnosis of stroke because of the ADC and DWI appearance and end up having these molecular features when pathology was performed can you think of tumor type this could be second case here are three different very different histologic tumor types pilocytic astrocytoma ganglioglioma and pleomorphic xanthalas for cytoma can you think of a molecular marker that these three tumors often not always but often share so what is the molecular marker third here's a tumor with very interesting apparent calcification does not enhance has this heterogeneous T2 and diffusion abnormality can you think of a genetic marker that defines this tumor how about this one here are six different patients with a large midline tumor all pediatric patients can you think about think of a diagnosis and a molecular marker that all these six different patients share and how about this one patient two different patients with an extra axial tumor kind of look like meningioma but they do not have the typical Dural tail this one looks very destructive can you think of a molecular marker that could um unify these two at a very different type but now we know that they're very related how about this one two different patients with posterior fossa ependymomas do you know the molecular genetic difference between the patient up at the top versus patient up at the bottom and here are four different patients with four different types of medulloblastoma can you name the four main subtypes of medulloblastomas so we will go over the answer at the end of this talk so Imaging neural Imaging of 2023 still the most important technique is the structural MRI we cannot interpret physiologic or any other fancier Imaging technique without actually seeing what the tumor looks like on structural Imaging but we also do physiology-based MRI to assess for their vascularity their metabolism and another very important type of technique that we use is this hybrid Imaging called PET CT or pedemar and many institutions are beginning to use this technique to look at is this a recurrent tumor or is this a radiation necrosis so today I'm only going to highlight couple of the structural and couple of physiologic MRI and as I said before structural MRI postcon precon T1 T2 flare multi-modality multi-planar Imaging this is the bread and butter of what we do and this will never go away but we put additional tests to look for hypervascularity whether they're leaky permeability and whether there is a hypercellularity or where there's High choline metabolism so physiologic MRI gives us a lot of insight into very non-invasive way of Glenn um glancing at their tumor biology it's not as good as obviously actually looking at pathology but it's a really powerful non-invasive tool and this is what we do at UCSF and it's pretty standard at most institution pre-post T1 T2 FSC flare and DWI and ADC ADC and DW this is a must and we also do swi and ASL perfusion imaging swi is becoming more and more important in brain tumor Imaging because we use this primarily to look for areas of blood products especially after radiation therapy and we use this for assessing where the the extent of micro and macrohemorrhages and also vascular lesions that are mimicking brain tumors and primarily in the brain tumor Arena we use this to assess for the extent of radiotherapy related injuries so here are three different patients with susceptibility weighted Imaging you could see this patient as literally innumerable punctate dots of susceptibility or micro Hemorrhage this is a patient who received whole brain radiotherapy for medulloblastoma 15 years prior here's a patient with very peculiar looking branching pattern of swi this is a person with a venolitis this whole thing was removed and it's not glioblastoma this is a venolitis or veins that are partially thrombosed and this is a patient with um very clear large vascular mass and that's cavernous malformation so swi very healthy here's an example that we saw a tumorable patient had a rim enhancing very aggressive looking right brachium pontus mass in the posterior fossa but if you look at Patients swi there are new innumerable protein micro hemorrhages this is a Telltale sign that patient probably had a radiation therapy and lo and behold we got the history after the fact the patient had a nasopharyngeal carcinoma and a pituitary tumor that were radiated twice before we did not have the radiation field but with that history and with that swi appearance we feel very comfortable calling this radiation necrosis and patient was treated for steroids to control some of the edema related Mass Effect and pay this lesion slowly uh disappear DWI very important sequence we use this to assess for acute infarct abscess cellular tumor and actively demyelinating lesions so here are three different patients here's the DWI Imaging without even looking at structural Imaging when you see this homogeneous in a reduced diffusion with an irregular Mass like this this is a intracranial absence until proven otherwise here's a patient you can barely make it out the lesion on DWI kind of disappears this is what diffuse glioma looks like on a diffusion here's a patient with two lesions have a Leading Edge reduced diffusion this is pretty classic for non-neoplastic usually inflammatory actively demyelinating type of lesion and this young patient was biopsy then that's a tumor effective demyelinating lesion so diffusion is a must sequence when you're interpreting a brain brain mass here's another example this patient came to us with a pre-operative diagnosis from elsewhere right frontal glioblastoma I think that's not a bad diagnosis there's a lot of Mass Effect there's edema crossing the corpus callosum with Central necrosis rim of enhancement but once you see the DWI and ADC you know that there's homogeneous reduced diffusion within the necrotic tumor so that is a very unusual appearance of a glioblastoma so this is more classic appearance for pyogenic abscess and indeed pathology proved that this is pyogenic abscess our surgeons going in knew that this was going to be passed because we told them and they end up just doing a little burhole and sucking that puss out and patient did great here's a young woman that I showed a little bit earlier this young woman was diagnosed with stroke at an outside hospital and you could see why why because there is actual homogeneously reduced diffusion and it's very dark on ADC but I think most of you would also notice that that shape is not a good good shape for a territorial infar but nonetheless patient was fine the workup was negative was transferred to our hospital and patient underwent surgery and this is a hypercellular unfortunately what's called a molecular glioblastoma perfusion we use it to look for hypervascularity hypervascular tumors we also use perfusion for to detect recurrent tumor assess for glioma grade and sometimes postdictal changes here's a patient who came to us with a homogeneously enhancing right cerebellar mass and you could see that DWI is not reduced there's a little bit of a rim of susceptibility but not much else so the question is is this a metastasis or something else patient did undergo whole body work up and there was no mass and if you add ASL perfusion you could see that the whole lesion is very very vascular in the cerebellum and this is pretty classic appearance for a hemangioblastoma and that's indeed what it was on pathology here's a person who's been coming to us for um serial Imaging after patient had a subtotal resection but you could see here that we don't know where the recurrent tumor here is patient had a seizure they control the seizure so after they control the seizure we brought the patient back and did a perfusion imaging and you could see that there is a clear unmistakable lump of hypervascularity associated with non-mass light flare here so our Neurosurgical colleagues went in and resected this hyper perfusion area and the whole thing was a live recurrent diffuse glioma idh wild type spectroscopy we use this tool now as a problem-solving tool here is a normal single voxel spectroscopy normal NAA creatine and choline this is what you want to see and we've done the many many spectroscopic studies both 2D a single voxel 2D and 3D but I still find this single voxel very powerful and here's an example of some of our patients um that we did on spectroscopy oh by the way a single voxel only requires about less than three minute of Imaging so it's a really powerful tool that does not take up much in terms of additional Imaging and we've now kind of developed four different types of spectroscopic appearance of an abnormal lesion so what we call the proliferative where there's high high choline hypoxia profile where there is clear lactate Peak infectious profile where we see amino acids alanine and acetate and the necrotic pattern where we see predominantly very high lipid and lactate and here's an example of how we use this single voxel two minute of additional Imaging so this patient came to us with a left frontal glioblastoma as the pre-operative diagnosis does look like glioblastoma with Central necrosis but once you get DWI you know that inside of that Rim enhancing lesion there is a clear reduced diffusion that looks like pus so we brought the patient down and with a single voxel spectroscopy using te of 35 milliseconds and 288 milliseconds and we saw all the metabolites that classically seen in pyogenic abscess such as amino acid lactate acetate and the choline which is not a tumor marker it's a uh membrane turnover marker is very very low so our confidence bring the together with the diffusion that this is going to be a pyogenic absence was near 100 and our Neurosurgical colleagues just did a very small borehole and sucked out the fluid and lo and behold there is that yellowish purulent material and this is a path proven pyogenic abscess so let me now uh focus more on the brain tumors based on the molecular genetics and I'm going to start with three different types of pediatric tumors and go on to adult tumors using the Imaging techniques that I just described to you so pediatric brain tumors in the who scheme from 2016 to 2021 many different classification changes have been made the first is these two tumor types one medulloblastoma the other ependymoma and you could see that without knowing anything about the tumor so here's postcard T1 you could see that this patient has a tumor that is relatively homogeneously reduced on diffusion so this is going to be some type of a cellular tumor patient on the other hand this tumor both are midline enhancing lesion you could see that DWI is not reduced so DWI is single most helpful sequence after looking at post-contrast Imaging so we already know this patient has a hypervascular a hypercellular tumor and that's a measureloblastoma and this patient on the right this is a patient with ependymoma and DWI is really the first step towards honing down into the molecular or biologic feature of the tumor so let's start with major low blastoma medulloblastoma now genetically are divided into four main types and these some of you are already familiar with the wind Sonic Hedgehog and group 3 and group four and our colleagues from Stanford published this beautiful paper and this was already nine years ago showing the Imaging difference between the four subtypes the wind the sunny ketcha group 3 and group four and it turns out that the wind type of medulloblastoma are almost always um off midline and they're not in the fourth ventricle only they almost simulate a CP angle schwannoma that's the wind type Sonic Hedgehog are usually the hemispheric tumors with this multi-nodular solid component and there's two different types of it but we are only going to just mention that this is a Sonic Hedgehog and then these are the more common pediatric babies and infants can get this type of tumor where the tumor is in the dead midline and some enhances avidly and some don't and it turns out that the fourth ventricular midline tumor of major loblastoma with Avid enhancement are more likely to be grape group 3 and the less enhancing subtype tends to be group four I find this fascinating that Imaging although it's not 100 can give us a glance into potential genetic and molecular subtypes so here's the four main subtypes so this is an interesting tumor too so most of you are familiar that usually Supra tintorial ependymomas are intraparenchymal the fourth ventricular or posterior fossa ones are inside the ventricle and the cord one is in the intramedullary I often wondered why we don't often see ependymomas right in the in the middle of third or fourth um lateral ventricle most of the ependymomas superintendorially that I've seen they're all in the super tentorial uh parenchymal compartment but then now all these genetic information is coming out so 2016 and 2021 who now are classifying super tutorial ependymomas particularly in pediatric age group based on this very sophisticated molecular markers so the relay Fusion positive super tutorial ependymomas are one of the most aggressive appended moments more commonly occurring in pediatric age group and they look even worse than some of the more really aggressive glioblastomas and most of these ependymomas particularly the relay Fusion ones that I've seen they tend to be intra parenchymal but then when they do recur they can recur all along the Dural surface so their biology is very different than the typical ependymomas that I've seen so there are two subtypes that the who has uh clearly defined in the 2021 are the relay fusion and yet one I have yet to see a Yap one molecular altered uh ependymomas but like I said before the Super tentorial ependymomas you know young child they tend to be this very aggressive um molecular variant called relay Fusion is the most common one that I've seen and one thing that I want to stress that really happened the moments when they do recur they can recur along the dura so please if you're if you know the molecular feature please look very closely at the Dural margin because it may be the first sign of recurrence how about in traventricular posterior fossa so now we know clearly intraparenchymal super tentorial at pandemomis and posterior fossa intraventricular ependymomas are genetically molecularly completely different they may look similar on pathology but they are not related at all in terms of molecular genetics so what are the two subtypes that who defined in the 2021 and the two subtypes are posterior fossa pendulum type a posterior fossa uh epinomial type B so what are the type A versus type B so the type A looks like this they almost look like a CP angle or lower medullary cistern tumor going out into the foramen lushka often and this is called the PFA or I call it the PF ependymoma asymmetric because it's off to the one side and this is an awful prognostic ependymoma and unfortunately much more common in pediatric age group and then there's this subtype the group b are the ones that sits usually in the midline kind of simulate the appearance of a medulloblastoma group three because they are midline enhances but remember ependymomas are not reduced on diffusion and this is what I call the posterior facade pendama that looks like a ball but here you could see that they are actually very different one is in the midline one is asymmetric and it also turns out that they're very different genetically so PFA I call it a stand for asymmetric group b b stands for ball so let's look at the tumor types A little diff um more carefully so here's group a ependymoma type a asymmetric off midline and they tend to have more necrosis Hemorrhage and these are much more aggressive component and they have a unique genetic and molecular marker very different from PFA a pfb excuse me and this is much more common in pediatric age form here's the pfb group more like ball shaped in the midline and not as much as necrosis little less Hemorrhage the midline location and this is the type of ependymomas that tend to occur older children or adult patients and their main presenting symptoms they tend to present earlier because of the obstructive hydrocephalus and they're very rarely invasive or infiltrative at all compared to the PFA variant so here's PFA the awful much more prognostically worrisome type of ependymomis and this unfortunately is much more common in pediatric age group and they have a very specific molecular markers that are very different than pfb the one that looks like a ball shaped in the midline posterior fossa this is a ball shape it's a better prognosis and affects adults a little bit more than pediatric age group now moving on to Second type of tumor that pediatric patients might get is the diffuse midline glioma so these are tumors that are disorders primarily of a histone and I think some of you know that each human cell DNA is about 1.8 meters but thanks to histone which winds down the DNA into 90 micrometers but you could see that if there is a histone related abnormality it could lead to just devastating tumors like this particularly the histone H3 k27m Locus tends to cause tumors of this gigantic midline glioma so comes the name of diffuse midline glioma h3k27m altar so this is um in 2021 version change its name and it affects these midline structures and they look like this uh just terrible tumor in the midline patient is sometimes very minimal symptomatically altered but it's a tough tumor surgical resection is not a possibility because they tend to involve the Deep thalamic nuclei like this it's just an awful tumor but here's the six different patients with the same awful diagnosis and they're all even though histologically they may look very different but they have histone H3 k27m altered and they tend to occur in the midline and hence the name diffuse midline glioma and some of these spinal cord tumor and most of them now are called a diffuse midline glioma only when they could our pathologist can actually definitively identify the histone alteration particularly h 3K 27m and here's an example of a spinal cord we used to call this spinal cord astral cytoma or glioblastoma and that's that's not wrong but once they get a tissue and our Pathologists look for this particular mutation that's how we know that this is a diffuse midline glioma h3k27m altered here's a patient ISO but what does that mean for Radiologists so we're not the one who's going to diagnose h3k27m molecular features but I want you to remember that these are really terrible tumors they sneak around they actually can spread all along the CSF as if they are metastatic pineal blastomas or medulloblastomas and keep an eye on brain any lesions in the brain cannot be ignored so let me show you this is one of our patient from many years ago when we first our Pathologists start to test for the age 20 h3k27m after radiation therapy our radiation oncologist did a great job uh some of these enhancing tumor looks better the flare looks better too but remember this original flare Imaging of the brain we were not sure whether this was really a real finding or is that a tumor but five months later you could see all of those areas are now nodular and patient recurred and unfortunately the real um down uh the tumor that they couldn't control was not the spinal cord diffuse midline glioma it was the CSF ependymol leptomeningeal spread of the original tumor and this is how it diffused midline glioma h3k27 M altar tumor behave on follow-up Imaging so please make sure you get brain Imaging to make sure we don't miss this very subtle lesions that show up on flare Imaging alone these areas may not enhance at all adult tumors I'm just going to show you some of interesting molecularly conjoined tumor types one is this so meningioma and hemangio percytoma back in the day when molecular genetics was not the not a thing in terms of our daily conversation I used to think that meningiomas and hemangioparasytomas were related and just that the humanity of hercytomas were much more aggressive and angrier looking and destroying the bone and it turns out that molecular genetics have proven that these two tumors are not related at all but it turns out that solitary fibrous tumor which is a pretty rare extra axial tumor that we see but elsewhere in the body too is intimately associated with hemangioparyocytoma even though they look very different this is what's called the great one and hemangio paracytoma is grade two or three and they are related by this particular nuclear expression called stat 6. so who now lumps solitary fibrous tumor and hemangal cytoma as a one single tumor type with a varying degree of aggression so sft is usually grade one hemangio pericytoma is usually grade two and three and hemangular parasytomas can recur anywhere else in the body but both these tumor types have stats six nuclear expression and that is really needed to make the diagnosis of sft and hemango pericytomas in the brain here the circumscribed tumor and if you look at these three very different histologically tumors have a nodule and assist nodule and assist nodule and assist these are pilocytic astrocytomas gangliogliomas and pleomorphic xanthoastrocytomas and some of the super tentorial of these three types share a molecular marker called b-raph v600e mutation at our institution some of these patients with this particular mutation they have a anti-braph therapy they're in clinical trials for and we are getting pretty good response to therapy there are again three very different histologically but Imaging wise I always knew they kind of looked similar because they share this shape uh this pattern of nodule and assist and a lot of these super tentorial pilocytics ganglios and pxas have braf v600e mutation very interesting and this is a paper from more than a decade ago that already looked at over 1 000 tumors uh pxa pilocytic and ganglioma and has shown that up to 60 70 percent of these tumors will Harbor b-raph v600e mutation so this work has been going on for decades even though it now just made it to the 2016 and 2021 who the work has been going on for decades to come to the fruition and make it into the classification scheme so molecular glioblastoma before I talk about molecular let me tell you the classic glioblastomas here are eight patients that I've known in the past have the classic Central necrosis very aggressive irregular women of enhancement these are all glioblast Donuts and the classic GBM now have all these extra molecular genetic diagnosis that our pathologist is testing for and some of them will be mgmt-methylated and most some of you know the implication of MGMT hypermethylated gbn these are actually the ones that respond quite well to timizolamide chemotherapy but there's all these other things that they test for but the unifying one is that all glioblastomas are idh1 wild type so there's no more What's called the glioblastoma idh mutant does not exist anymore all glioblastomas are idh wild type now what is molecular glioblastoma these have a genetic mutation the three component here turpromotor mutation egfr Gene amplification Trisomy 7 and monosomi 10 and on Imaging they do not look like the classic glioblastoma I just showed you uh this is that 19 year old who was originally misdiagnosed as a stroke if you look at her post-con Imaging it does not enhance at all and on DWI it has really hyper intense DWI signal intensity and very low ADC this is a path proven molecular glioblastoma with these three molecular alterations third promoter egfr Trisomy 7 and monosomi 10. and this is new this is a separate tumor but nonetheless molecular glioblastoma so just as aggressive as classic glioblastoma and this young lady who received TPA and cerebral angiogram looking for a source of stroke elsewhere came to us this was resected this is a molecular glioblastoma but if you look down patient has a second focus of additional tumor and this is really bad news additional lesion and that is the lesion that turns 5 months later into a franc glioblastoma and this is a terrible prognostic situation diffuse gliomas not to be confused with diffused midline gliomas diffuse gliomas are what we used to call astrocytomas oligodendrogliomas or all uh oligo astrocytoma so we don't call oligoastro anymore diffuse gliomas are non-glioblastomas and they're infiltrating either astrocytomas or oligodendrogliomas and these are the three molecular markers that Define diffuse gliomas idh being the most important it signifies that it's going to be a lower grade one p19q chromosome number one chromosome number 19 Locus of codilation this is a disease defining chromosomal marker for oligodendroglioma atrx is a marker defining astrocytoma so at our institution almost all diffuse gliomas on Imaging and initial pathology a histologic analysis will undergo idh for sure and 1p19 Q of to make sure that it's not an oligo and if a 1p19q is intact then they will go ahead and do atrx to prove that this is an astrocytoma so this is how it's divided to physically illness is either mutant or wild type I already told you wild type diffuse gliomas are de facto molecular glioblastoma in the mutant variant they will undergo mp19q code deletion testing if that is deleted that's an oligodendroglioma period And if it's 1p19 Q intact then atrx is lost and that's an astrocytoma the wild type these are much more aggressive tumors they if they have a third promoter egfr amplification Trisomy 7 and monosomi 10. this is called the molecular glioblastoma and diffuse astrocytoma idh mutant was newly graded uh based on grade two three and four on wh for 2021 and this the most aggressive variant is now called the grade four but it has to have this particular molecular deletion called cdk and 2ab homozygous deletion but looking at the Imaging you could tell that this tumor is already trying to enhance and there's some areas of central necrosis but doesn't really look like a Frank glioblastoma you should think about grade four diffuse astrocytoma idh mutant and if your institution has the capability to do this molecular analysis cdk into a b homozygous deletion this confirms that this is a grade four diffuse astrocytoma idh mutant idh is the King right now of determining the fate of a glioma whether it's going to glioblastoma route or diffuse lower grade glioma it was discovered in 2008 and if there is a idh mutation it leads to this particular molecule two hydroxy glutarate accumulating and it's much much more common in lower grade gliomas and in primary gbms it's almost never seen but in some cases of a glioblastoma the T differentiated from a lower grade you may actually detect this but in classic glioblastoma it's never seen so what does this mean that we at least have to know what idh1 mutation 1p19q correlation atrx loss means that I just already told you so here's some of the tumors that this is from literature where T2 is super bright flare it becomes darker this has been called a T2 flare mismatch and this is not a 100 rule but this has been described as T2 flare mismatch meaning T2 is super bright flare gets darker this has been a molec Imaging correlate of a diffuse astrocytoma idh mutant atrx loss not 100 rule but you could uh assess at least guests before the surgery now here's a patient with diffuse glioma and how do I know it's more likely to be idh mutant or wild type the DWI is going to be one of the most helpful technique you could see that the tumor kind of disappears in DWI this is more likely to be idh mutant the better prognostic glioma this is that patient with molecular glioblastoma non-enhancing but look how very much aggressive the DWI looks very reduced on DWI very dark on ADC this is not a lower grade tumor at all despite the fact that it hardly enhances has apparent circumscribed border this is not a good tumor this is a idh wild type this is molecular glioblastoma how about this one this patient has a surpigenous looking calcium and that calcific marker is pretty good not a hundred percent rule for a specific type of tumor and you could see that the fluorescent inside to hybridization that's what that is shows you that 1p 19q code deletion you could see that there should be two pink and two green our Pathologists confirmed for me but there's one missing so this is so called the 1p 19q code deletion and this is a disease defining marker of an oligodendroglioma we don't do CT anymore to confirm the presence of calcification we may do swi but um TT to confirm calcification is no longer standard of care practice this is a patient this is the last case that I'll share with you he came back in 2003 and our um this was discovered after he had a car accident and CT detected a low density lesion so he came he was completely asymptomatic I looked at this and I said hmm I'm not sure if it's tumor so why don't we just see get serial Imaging so he came back every year and then it started to grow in about three years here's 2012 so nine years this lesion has almost double so I scratched my head and said doesn't lower great gliomas grow this slowly probably could but during 2020 patient called email me and said my can you take a look at my MRI and I look at it and I look at from the 2003 so these are 17 years apart and I explained to the patient this is growing we no longer can just sit around and do nothing and our Neurosurgical colleagues after hearing my brain tumor talk about 2hg he said to me why don't we get a 2 hdmrs and I thought brilliant idea so we brought the patient to our research scanner and our outstanding post-docs and phds there helped us to do a 2HD skin and lo and behold this patient within this lesion had an unmistakable not an artifactual a two-hydroxygliterate peak that you can only really see in idh mutant gliomas so this pushed us over the edge patient went for surgery growth totally resected and this is a gross totally resected idh mutant 1p19 Q code deleted oligodendroclioma and this is the first time that I was just stunned at how this non-invasive technique really helped us so this is um already three years ago now um and patient is doing very well that um 2HD is indeed a marker for idh mutant gliomas and this happens to be an idh mutant or legal dendroglioma so let's go over some of the cases that I showed you earlier patient has these three molecular markers altered so what is the tumor type I showed you this case already twice with this really profound reduced diffusion young lady who are initially thought to have a stroke unfortunately this is a molecular glioblastoma how about these three tumor types pilocytic ganglion pxa they all share sometimes this nodule and a cystic appearance what would be the defining molecular markers the braf v600 E mutation how about this tumor that I just showed you calcification this is a 1p19q code deletion of an oligodendrochlioma so if you see a tumor and you happen to have a CT and you see calcium and putting together with MRI features you could be with reasonable confidence tell that this is going to be an oligodendrochlioma and if you're ever doubt you can actually do a two HG Mrs scan and see if you can detect two HG that will be a slam dunk that this is an idh mutant tumor how about this one midline just awful looking expansile tumors in pediatric age group what would be the histologic marker and diagnosis this is diffuse midline glioma H3 k27m altered these are histone mutated really aggressive tumors but these two tumors extracts your tumors not a meningioma but they are joined together sft and hemangioparacytoma what is the molecular marker that defines these two tumor types into one that's the stat 6 nuclear expression we already discussed the two different types of posterior fossae pendamomas they're completely different genetically one is called the PFA the asymmetric type the other one is called the pfb as in ball shaped in the midline a is asymmetric pediatric age group and it's an awful prognosis the one in the midline she looks like ball shaped these are better prognostic of and very rarely these will be infiltrated so the two different types subtypes of a posterior fossa ependymomas are posterior fossae ependymoma type A the other one is posterior phosphate pandemoma type B B is better ball shaped PFA is asymmetry asymmetric and it's an awful prognosis the four main subtypes of medulloblastomas we already discussed this the one that is off with line kind of looks like CP angle or lower cranial nerve schwannoma that actually is still one of the best prognostic uh subtype of the medulla and that's the wind hemispheric multinodular solid aggressive looking reduced on diffusion that is going to be the Sonic Hedgehog two midline tumors reduced on diffusion one enhances more addedly the other one is less enhancing the one that's enhances more is the group three and the less enhancing midline medulloblastomas are the group four so here's your main four molecular genetic subtypes of metuloblastonas and imaging not not as good as a pathology or molecular genetics or UCSF 500 Gene panels but it does a pretty decent job guesstimating what the molecular genetic abnormality might be of a given tumor so with that I would like to summarize that I gave you some highlights of 2021 whocns tumor classification but I also want to highlight that this is a field that's evolving every year so the next version which I am told might come out in 2025 or 2026 may actually have even more molecular genetic markers so please stay tuned about that and I showed you some update on structural and physiologic Mr like diffusion being super important to differentiate abscess versus glioblastomas cellular versus less cellular tumors and Mr perfusion to detect recurrent high grade gliomas and spectroscopy methods that you can actually detect some of the uncle metabolite associated with idh mutant such as two hydroxycutorate and the Imaging correlates of molecular and genetic profiles of CNS tumors an example being the four subtypes of medulloblastoma and two subtypes of ependymomas that you could actually guesstimate not a hundred percent rule but with a reasonable confidence you could predict their molecular subtypes without ever touching a tissue or doing a craniotomy I think Imaging is such a powerful technique and it's non-invasive so we are in a very interesting and very important field and as I said molecular generic era of CNS tumors is here it's only gonna get more complex and advanced and imaging must keep up with its pace so with that I thank you for your attention and I will stop sharing my screen and take any questions so I think we got some in the chat q a um oh where does atrt stand in this classification so atrt stands for atypical territory rhaptoid tumor this is actually tumor that is super aggressive but they're not medullows they're not ependymomas and they have their own very specific molecular marker call ini1 so our Pathologists can specifically test that molecular marker to differentiate because atrt can look just like medulloblastoma can just like a aggressive ependymomaster PFA so we actually have the our Pathologists have the power and method to um identify atrt there's no formal classification of atrt yet but it might be next time next version might include that but like I said the molecular marker that defines atrt is this enzyme called ini1 mutation if that is altered that's an atrt and nothing else next question since gliomatosis survives obsolete now what is to be labeled according to recent recommendation this is an excellent question even though who said don't use this frankly at tumor bore I use this term because some tumors entire hemisphere is all infiltrated with non-enhancing Flare bright lesion nothing is enhancing nothing is reduced so now we use I use the term this is the gliomatosis cerebri pattern of diffuse glioma but these are usually when they do go for pathology they are idh mutant tumors and they're not oligos they're never I've never seen gliomatosis cerebral tumors that are actually oligo or 1p19q code delete it so yes it's it's obsolete and yet we still use this term is the term relay Fusion still used or is it outdated um another good question no it's the who 2021 came up with this zfta some other name but in our tumor bore we still use the term relay Fusion because everybody understands what that is but the molecular genetic term has become much more complicated but when I'm reading out with a trainee we look at them electromedical record and if we see the term relay we know that we have to really look for odd places for recurrence that's really what's important here the relay Fusion ependymomas tend to occur at least maybe half a dozen cases that I've seen in the Dural surfaces so the probably next version might end up just getting rid of relay all together but we still use it and that is still that term is still exists in the very complex pathology report so you could search for it as well uh is there any other question let me just do that there's a chat here there's a chat about your painting if you want to um say what painting that is so this is Georgia O'Keefe this is this is not a actual real painting but if anybody would like to donate this to me I will be forever grateful just kidding this is a this is one of the most beautiful painting that I've ever seen this is a Georgia O'Keefe's I don't know the name I think she just named it flower but I've been using this for the entire pandemic and thank you so much so there's no molecular marker associated with this painting uh is there anything else that I could answer for our outstanding um audience I think that's it Dr cha thank you so much for your lecture today really oh thank you thank you so much everyone have a wonderful rest of the week and thank you for this opportunity again bye bye absolutely thank you and thanks for everyone for participating in our new conference you can access the recording of today's conference in all our previous new conferences by creating a free MRI online account be sure to join us next week on Thursday September 21st at 12 pm Eastern we're featuring Dr Sheila's Chef for a noon conference entitled peripheral vascular ultrasound Venus Doppler and challenging arterial cases you can register for this free lecture at mriinline.com and follow us on social media for updates on future new conferences thanks again and have a great day [Music] thank you [Music] foreign thank you foreign [Music] foreign [Applause] [Music] [Applause] [Music] [Applause] [Music] [Applause] [Music] [Applause] [Music] foreign [Applause] [Music]