 Hello, in this topic, I will be dividing my topic into three different lectures. First part of it is overview of the brain tumors, what we are supposed to know. The second and third part of it is a general description of different type of brain tumors. So the first lecture is kind of more complicated, covers the genetic markers and the new developments that have happened in the new WHO classification, what the nomenclature has changed. And the second and third are more so geared towards overall general radiologists who see brain tumors very rarely, just so that they know about what a tumor looks like. As an general approach in a neuro-oncology institute, we are not so much geared towards identifying what the tumor is rather than how to treat the tumor. So my first lecture is mainly directed at those institutions and those people who practice neuro-oncology treatment, both in imaging as well as clinical services. And it is a bit more complicated and more advanced for a general radiologist. The other two lectures are basic. So one of the things that we'll be talking about what has changed in the classification. So in 2006, it was entirely almost based on histology or the cell lines of the tumor. Whereas in 2016, the WHO came up with a new classification which added the molecular markers or the genetic markers associated with the tumor. So what was the advantage of adding that? One of the things was to get a corrected diagnosis which may be different from how it looks histologically. And second or more important than that was the overall outcomes of treatment of the tumor. So how the tumor will behave, how it will respond to treatments and whether we can have directed chemotherapy. Just as an example, if we look how the histology and the molecular markers may be discordant. Now, so we have a glial tumor which is histologically appearing as an astrocytoma but has an IDH mutation and has 1P19Q co-deletion which is the chromosomal co-deletion. And another tumor which histologically resembles oligodendroglioma but by microscopy has IDH mutation, ATRX and TP53 mutations but with an intact 1P and 19Q co-deletion. In these things, the histology is trumped by the genotype. So actually the first tumor will be an oligodendroglioma as the second tumor will be actually an astrocytoma despite the fact that they are histologically appearing different. So the treatment because of this can change. Again, these are numbers that I've thrown out but I will be going through each one of these things the each one of these genetic markers. So by the end of the lecture, hopefully you will have a better idea of what I'm thinking. So as always, what did the WHO use for the classification of brain tumors? So they have four criteria. One is anaplasia. Second is the mitotic activity. Third will be the endothelial cell proliferation and fourth is necrosis. And based on which criteria and how many criteria are present they class from grade one through grade four. So grade one tumors do not have any of these criteria. So they tend to be non-enhancing, slow-growing, relatively better prognosis, non-minutant with long-term survival. So this is a case of grade one neoplasm where there's a frontal white matter subcortical area of mass with mass effect associated but with a narrow zone of transition no periturum edema and absolutely no enhancement and this is how it looks in histology. In histology throughout my residency, my medical school all I knew was blue means bad and pink means good. So as the blue gets more and more and more it means the tumor is becoming more and more aggressive and then it loses its characteristics that makes it even worse. So this is here you can see the blue is outnumbered by the pink in the slide. So this is a relatively lower grade neoplasm. In grade two WHO classification they'll have one criteria, generally psychological ATPA. These tend to be slightly more aggressive but still will overall prognosis is good. It can be both malignant and non-malignant. They tend to recur, may or may not recur after treatment. So this is a very, very similar tumor located in again in the right frontal subcortical region but if you see in the post contrast here there is a very faint enhancement seen associated with the tumor. Again, not much of peritumeral edema or abnormal signal in the associated subjects and white matter. And again if you see the blue has increased compared to this and this is grade two. In grade three there'll be two criteria, mainly anaplasia and mitotic activity. These tend to be anaplastic astrocytoma. They are more aggressive. They're relatively significantly aggressive tumors. They almost always are malignant. They almost always tend to recover but there is not much of necrosis or hemorrhage associated. Typically there is no hemorrhage associated with this. So this was a tumor in the right parietal lobe with peritumeral edema, a wide zone of transition not clearly demarcated as the other two and on contrast shows intense enhancement and see how much of blue has increased over here as opposed to the pink. And then grade four tumors will meet three or four criteria of the double which of classification would be anaplasia, mitotic activity, endothelial proliferation and or necrosis hemorrhage which will be seen in these. So this is what like classically the grade four will be gliomethosis cerebrae or glioblastoma to form a which will have central necrosis peripheral enhancing. Here there's one which is crossing the middle line through the corpus callosum which typically the GBMs do thick rind of enhancement, central necrosis these are almost aggressive, very aggressive tumors tend to recur, tend to be fatal and very rapidly growing tumors with large zones of transition, peritumeral edema. And here they've lost the characteristic and with a lot of blue almost like too many cells over here losing the characteristic and distribution and the pattern that is seen in your tissue. So this was what the WHO classification. So all that is there. This was always there. This is histological classification. Now in 2016, we added genetic classification to add on to that. So there's new nomenclature which we have. So first we'll call the tumor by the histology and then add to it the genetic marker to it. So there'll be astrocytoma which is associated with IDH mutant type or medialoblastoma which is WN2 activated. So there'll be two words now associated with the tumor. You just don't say it as astrocytoma and stop at that glioma or GBM and stop at that or oligodendroglioma and start at that. You will have to mention about the IDH type, the co-deleted or not co-deleted or the TERT or the ATRX or the P53, all these things you will have to add on. So that is the new nomenclature. They can have more than one gene markers associated with this, like an oligodendroglioma, maybe an IDH mutant as well as 1P19Q co-deleted. So that is another thing that you will have to have as many genetic markers that are associated with the tumor to be mentioned in that. Then if the tumor is lacking a genetic mutation, you call it a wild type. So if there's no association of any genetic mutation that you can find with the GBM, you will call it GBM, oligodendroglioma, IDH wild type. And occasionally you cannot do the test or the test is non-concluso or you're not equipped with the testing parameters at your institution, then you call it a not otherwise specified. So you can call it, if you don't have the genetic markers, you can call it say oligodendroglioma, not otherwise specified. And therefore some other genetic markers, alterations that are present, you can call it positive or negative, like in Ependidomoma, you can mention whether it is a deal of a fusion positive or negative. So that is all the new nomenclature that has been added. And this is what you're supposed to give out in tumor board. Again, you don't give a histological diagnosis when you're reading MRI scans, but when you're sitting together in a tumor board where there's interdisciplinary conferences and post treatment, they're showing you an MRI then and they say, this is what the tumor is. And they tell you that gene markers, then you can predict whether these are going to be recurrent tumors or these are pseudo progression or pseudo response. That is where these tumor molecules actually help you out. So I'll again go briefly through these molecules and by the end of the lecture, like I said, you will be generally be more able to differentiate. So these are the most important tumor markers that we talk about in radiology. They are IDH, which is isocetadine hardness, 1P19Q deletion of a chromosome, MGMT, TERT, ATRX, and the P53 or tumor suppressor protein 53. Again, I will go through one of each of these in brief and what their significance is. So IDH is basically an isocetadine hydrogenase. There are two types of it, IDH-1 and IDH-2. IDH-1 is basically substitutes glycine to arginine in enzyme codon 132, it is associated with tumorogenesis. So if the mutation is present, it is associated with tumorogenesis. IDH-2 is basically a mutation in codon 172 and it's associated with seizures, weak muscle tone and progressive cerebral damage. What is the significance for us in IDH? The IDH tumors, the mutations, they tend to be relatively slower going, although they tend to ricker frequently. They tend to have less peritumoral edema, so they'll have a sharp margin, a narrow zone of transition and they tend to have less enhancement. So this is an example of an IDH-positive tumor where there is this tumor, these are different cases. So there is this tumor, very little peritumoral edema, almost very little to no enhancement associated with. And this is a case of IDH negative. Again, there's a lot of peritumoral edema and enhancement associated with it. The significance of this in is that the patient with the IDH mutation will be a better outcome, overall outcome, better prognosis associated with it. So when you have a treated patient and he has had surgery and he comes back for a follow-up examination and you see an area of T2 signal intensity, is this treatment related? Is this a recurrent tumor or is this pseudo response or is this pseudo progression? So if the patient had IDH mutation, chances are he was treated and this is all treatment related as opposed to if the patient was IDH negative, this is likely recurrent tumor if the characteristic appearance of the brain is changing. So that is the significance of IDH, knowing the IDH presence or mutation presence or not presence brain tumor imaging. Next molecule marker that we talk about a lot is the 1P19Q co-deletion. This is situated on both short arm of 1P and long arm of 1919Q which is having the significance of overall prognosis. So this is a good marker of the prognosis of a tumor. And so how it affects a radiology is if it is co-deleted, then it tends to have a better prognosis. There is overall improved survival. It is overall predictive for the response of chemotherapy, radiation therapy and a treatment associated. So this was a patient who was co-deleted and you can see how the tumor is sort of localized, narrow zone of transition, very little peridumeral changes and this was a co-deleted negative again, just as you saw with the IDH mutant negative, similar changes are associated with 1P19Q co-deleted negative where there's associated significance based on genic edema, mass effect, peridumeral edema. Again, in itself, when you see this case for the first time, you don't give out the histology as co-deleted positive negative. This is something that you are supposed to know post-treatment on the follow-up studies to see whether the patient has recurred or not recurred for tumor. So any patient with co-deleted will be overall a better prognosis as opposed to negative, which will have a poor prognosis. So if you see changes or characteristics, signal abnormalities in a co-deleted negative, then you will raise concern for recurrent tumor rather than just change. The next one is MGMT. So these three markers along with P53 are probably the three most important markers in tumors. MGMT represents methyl guanine, methyl transverse gene and this is basically the ability of the gene to repair DNA. So in a tumor, when there is rapid multiplication and our approach to treatment mainly by alkylating agents is to damage that DNA and kill those cells and prevent its replication. If the MGMT is very, very effective, then it will immediately repair the DNA and the tumor will continue to grow. So, and this depends upon the promoter region of the MGMT gene and that we call, you will hear the terms unmethylated or methylated. So if it is unmethylated, these tend to be resistant to chemotherapy. So these tend to be aggressive tumors. These tend to be less response to treatment as opposed to methylated or hypermethylated promoter gene which is a favorable prognostic factor and these will be more susceptible to treatment and will be having over-prognosis. So this is a case of an promoter unmethylated which is a kind of a more aggressive tumor and less response to treatment versus methylated tumor which has a better outcome. And as you can see on the ROI, there is a thick rind of CBV, there is more tumor, more edema and all those things are higher as opposed to the methylated tumor. These are both the same GBMs, but one is methylated, one is unmethylated. And again, in the follow-up examinations, if you're supposing somebody says his IDH mutant is co-deleted and he is hypermethylated, all these will fall into better prognosis and you see a treated patient with some signal characteristics, you will talk about them being probably for treatment change as opposed to if it is not IDH mutant, it is unmethylated and it is not co-deleted, all these will be probably any signal change you will raise for tumor recurrence. The other two TERT and ATRX, these are really something that the oncologist is supposed to know when he talks to the patient, he tells them about the overall response, treatment, survival and all these things that really for us, it doesn't make a difference. The main thing is that TERT is associated with poor survival, poor response to treatment, on imaging, there is not much significant difference between what we can do one way or the other. Just clinically, we should know that if TERT is that marker is present, then the outcomes will be poorer as opposed to ATRX, which is inversely proportional to the TERT, overall ATRX, alpha thalassemia, mental retardation, syndrome, X-link, this gene has an overall inverse response as opposed to TERT, but the important thing about ATRX is it's frequently associated with other mutations like with IDH or TP53. And so again, if we talk about what, like if the patient has IDH mutant, if he is TERT negative ATRX positive and co-deleted, all these will have a better prognosis and whenever we see a signal change on the tumor post-treatment, it is more likely to be treatment change rather than recurrence as opposed to all these being negative, the reverse with ATRX low and TERT high and IDH being non-mutant and not co-deleted, these will have a poor prognosis and these will probably be recurrent tumors. The next and the last, most important of the tumor markers that we take into account is the P53, this is a tumor suppressor gene. So its presence basically decreases the tumor genesis as opposed to its loss, it causes DNA damage, hypoxia, oncogenic activation and all those damages that causes occurrence. So this is a case of increased expression of P53 where even though the patient has tumor, it is kind of localized, it has a narrow zone of transition, it doesn't have much of spread. So overall this is a better prognostic factor, post-treatment, you see this, there is signal change, the patient has P53, X-ray increase expression, you tend to call it treatment change rather than tumor as opposed to poor expression of P53, it's a more aggressive, spreads into the white matter is associated with more aggressive factors and has an overall poor prognosis and any change in signal and appearance after treatment with poor expression of P53, you would call recurrent tumor more likely. Other molecule markers that we talk about are the embryonal markers as in like the chromosome 19 which is associated with upregulation of the oncogenic tumors. So tumor, poor prognosis, then it can be W into activity and then sonic hijack active groups which are also associated with tumor genesis and these are the other markers which these are really something that we don't much talk about. The other markers that we mentioned about the IDH and the chromosomal correlation and the TRT, ATRX, P53 and MGMT, these are the main markers that we talk about in brain tumors. So if somebody wants to know about how these affect on from grade one through grade four of tumors and which is more, which is less, this is a good graph overall to give an overall idea. So again, we talked about that IDH mutant, co-deleted, ATRX negative, TRT negative, ATRX positive, P53 increased activity, these are all associated with better prognosis, treatment, post-treatment, if you see changes you would think more likely to be treatment change rather than recurrent tumor, you would more likely, before you go in, treat again, aggressively treat, you would hold back and you would do follow-up examinations before you are 100% sure that there's actually tumor and then go in as opposed to the reverse of this where you would be more inclined to have an aggressive approach and go in again and treat the patient again. So those are the main things why we should be aware of the tumor markers or the gliomas in treatment, in the oncological approach.