hello everybody this is Dr Nadeem and we are with Neelam path lectures the pursue series as you are aware all our lectures are available on YouTube we have a telegram Group which you can join where all the lecture related information is available we have a Google drive with a PDF of all lectures are available these are the disclaimers this is phase three which is recorded pathology lectures and today we have pursue 7x which is neuropathology and we are streaming from ipgmr Kolkata and the topic of the day is gliomas and glioneural tumors and to talk on that we have Dr srishti bhutta Who is an mbbs honors gold medalist MD pathology demonstrator in the oncopathology unit of the Department of pathology ipgmer and sskm Hospital Kolkata she's got 12 Publications in National International journals or special interest is neuropathology molecular genetics and hematopathology with this I would request Dr srishti bhutta to start her talk on glamorous and glioneural tumors over to you ma'am thank you so much a very good evening today we will be discussing about gliomas and glioneuronal tumors so gliomas glioneuronal tumors and neuronal tumors will be discussed with specific emphasis on who cns-5 diffuse gliomers that have been divided into the adult type and the Pediatric types will be discussed separately and in details nomenclature and Grading of adult type diffuse astrocytomas will be done pediatric type low grade and high grade diffuse gliomas will also be discussed in addition there will be a discussion on ependymomas neuroni and glioneuronal tumors so let's start there has been a paradigm shift with the emergence of Next Generation sequencing techniques Paving a way forward for the classification of gliomas from a genetic standpoint the discovery of isocyte trade dehydrogenase mutations that is the idh mutations in gliomas have led to a refinement in the diagnostic scheme of diffuse gliomas the latter batters the diffuse gliomas can be precisely classified into astrocytic and oligodendroblial tumors using idh tp53 atrx and 1p19q code deletion studies so enlisting the specific changes in gliomas and glioneurol tumors gliomas and glioneuronal tumors have been divided into six different families and 14 newly recognized types have been added to the classification in who cns-5 division of diffuse gliomas that primarily occur in adults have been named as adult type diffuse gliomas and those occurring primarily in children or the Pediatric age group have been termed as the Pediatric type diffuse gliomas so classifying gliomas glioneural tumors and neuronal tumors according to the who cns-5 first gliomas gliomas can be either adult type diffuse climas or the Pediatric type diffuse gliomas when we consider the adult time diffuse gliomas they can either be astrocytoma idh mutant right okay or it can be the oligodendroglioma idh mutant and 1p19q code deleted or for that matter it can be a glioblastoma idh wild type when we consider the Pediatric age group we have pediatric diffuse low grade pliomas and pediatric diffuse high grade cliomas now pediatric diffuse low-grade gliomers can be diffused astrocytoma myb or mybl1 altered angiocentric gliomas plenty that is polymorphous low-grade neuro-epithelial tumor of young diffuse low-grade gliomas map K pathway altered right now pediatric diffuse high grade gliomas can either be h3k27 M altered H3 g34 RV mutant or diffuse pediatric type high grade glioma H3 wild type idh wild type it can also be an infant type hemispheric glioma moving on circumscribed astrocytic gliomas have been added in the recent who and pilocytic astrocytoma has been incorporated into this group right so in this group we have pilocytic astrocytoma pleomorphic xanthoastrocytoma subependymal giant cell astrocytoma or the Sega cordoid glioma astroblastoma mn1 altered right so now ependymal tumors now these can either be the supratentorial epidymomas or it can be the posterior for cybernimumas or for that matters fine lip and dymomas now superintendoory leptinomas can either have a zfta fusion or a yak1 fusion posterior fossa ependymomas can have be have been grouped either as PFA or pfb types right spine leptinomas either shows an NYC and amplification or it might be a case of a mixopapillary ependymo which typically occurs in the coda equina note sub-ependymoma has no site predilection so it can occur either in the Supra tentorial posterior fossa or the spinal locations per se moving on to the glio neuronal and neuronal tumors which have been divided into either ganglioglioma desmoplastic infantile ganglioglioma this embryoplastic neuroepithelial tumor or the dnet okay diffuse glio neuronal tumor with oligodendroglioma like features and nuclear clusters papillary glio neuronal tumor Roseate forming glioneuronal tumor mixoid glyoneurol tumor diffuse leptomeningal glyoneuronal tumor gangliocytoma multinodular and vaculating neuronal tumor Central neurocytoma and cerebellar lipo neurocytomas so now coming to the concept of liats what are liats liats are nothing but long-term epilepsy Associated tumors compared to the adult counterparts the Pediatric diffuse gliomas generally have a prolonged clinical course and that results in characteristic drug resistant epilepsy therefore these tumors have been grouped as the apps that is long-term epilepsy Associated tumors there are several glio neuronal tumors which have also been Incorporated under this heading okay it must also be noted that pediatric diffuse gliomas often lack the characteristic genetic mutations that have been associated with their adult counterparts that is idh mutations and 1p19q correlations which are usually absent in pediatric diffuse gliomas so now coming to the characteristic genetic difference between the Pediatric type diffuse glioma and the adult type diffuse glyver if we see the Pediatric counterpart we see that the Pediatric type diffuse lyomers can either be low grade or high grade now if there is a genetic difference between the two then what is that the genetic difference is that the RAS map K pathway is altered in diffuse pediatric low-grade biomas whereas the diffuse pediatric high grade gliomas usually affect the histone or the H3 pathway specifically the h3k27m mutations or the h3g34 RV mutations are affected in pediatric high grade gliomas the rasmapki pathway on the other hand are characteristically affected in the Pediatric low-grade gliomas this is unlike the adult counterparts okay which show a characteristic mutation affecting the idh pathway or the 1p19q correlations as seen in oligodendroglioma but a unique example is a high grade cerebral astrocytoma that occurs typically in infants that Harbors receptor tyrosine kinase or the rtk fusion including the ntrk family fusions okay so that is typically very very important to note so this is the only one which is a unique case so what do we see in this figure here so we see that there is a characteristic diagrammatic representation of a pediatric type high grade and low-grade gliomas right the Pediatric type high grade gliomas can be either a diffuse hemispheric glioma affecting the cerebral hemisphere harboring the h3g34 RV mutation it can also be a diffused midline bioma where there is a mutation affecting the h3k27m on the other hand it can also be an infant type hemispheric glioma where there is a mutation characteristically uh affecting the receptor tyrosine kinase pathway on the other hand the Pediatric type uh astrocytomas that is the low grade ones or the Pediatric type oligodendrogliomas usually Harbor mutations in the fgf R1 or the braf v600e there are several other low-grade gliomas like the angiocentric glioma affecting the mybq K1 or the Plenty that affects the map K pathway so other diffuse cerebral high-grade gliomas and glioblastoma like histology without idh or H3 mutations can be grouped Under the Umbrella designation of a diffuse pediatric high grade glioma okay so that is also to be noted so if uh you have a cerebral high grade lyoma with a glioblastoma like histology but lacking any idh mutations or H3 mutations per se then that can typically be classified as a diffuse pediatric type high grade glyoma so if these mutations are lacking but there is a characteristic lyoblastoma like histology so now coming to diffuse hemispheric glyoma now that characteristically affects the cerebral hemispheres and orchest typically in children and young adults right so it is to be noted that this tumor shows a characteristic high grade morphology okay with high grade nuclear features or it may be showing a CNS and brional tumor like morphology for that matter there is a high mitotic activity microvascular proliferation and or necrosis may be present but it must be noted that even if these features are lacking for that matter but it is showing a characteristic mutation affecting the h3g34 RV pathway then that confers the diagnosis of a cnswho grade 4 glioma that is presence of this mutation irrespective of the morphology upgrades the tumor to a CNS who grade 4 glioma now coming to the diffuse midline glioma what do you see here you see a characteristic pontine mass that is identified here what about the histological feature what do you see what can you make out here it is showing an astrocytoma like morphology there is a characteristic presence of h3k27 M protein that has been highlighted by the IHC here and there is a characteristic loss of h3k27me expression right and so this qualifies as a diagnosis of a cnswh of grade 4 glioma okay so and that is referred to as a diffuse midline glioma but what is to be noted that this human characteristically affects the midline location the brain stem Thalamus and spinal cord often associated with h3k27m mutation so even if it does not Harbor the anaplastic morphology per se it can still be upgraded to a CNS who grade 4 glyoma if it shows a characteristic mutation of h3k27m in addition it must be noted that this tumor predominantly affects the children but cases have been reported in adults as well now coming to plenty what is this now this is a polymorphous low-grade neural epithelial tumor of young right so this yes you can make out that this is a cnswh of grade 1 tumor okay why because it is a diffuse pediatric low-grade glioma yes the astrocytic morphology can be easily made out here in the slide the cells uh are of variable shapes yes but they have a round to avoid morphology as you can make out okay there is variable degree of coarse calcification as you can make out in this figure B here okay but this tumor is often confused with oligodendroblioma okay now why oligo because of the glial background and somewhat these are round to opoid shape but however it must be noted that the calcification present in an oligodendroglioma is quite um my focal and micro calcifications are often noted they are much finer as compared to these coarse calcifications that you can make out here in addition it must be noted that the tumor that is the uh oligodendroglioma usually Harbors a characteristic 1p19q code deletion and often an idh mutation that is either an idh1 or an idh2 but this tumor that is plenty that is polyvor's low-grade neural epithelial tumor of young which is also a liat for that matter does not Harbor any idh mutation or 1p19q correlation as seen in oligodendroglioma rather it shows a characteristic CD 34 positivity which is so diffuse and strong right so coming to angiocentric glioma this is another pediatric diffuse low-grade glioma that occurs typically in the cerebrocortical location and it shows a characteristic round to avoid morphology somewhat a bipolar spindle cell morphology characteristic angiocentric pattern is noted in this tumor okay with the tumor cells surrounding the blood vessels that is the typical cortical blood vessels are involved sometimes you can even have pseudo rosettes in subpayal palisading that can be noted but it must be noted that this is a characteristic wh of grade 1 tumor okay the characteristic feature is the angiocentric disposition of this tube now coming to the grading of adult gliomass now moving on to adult climas the adult gliomas can be astrocytoma idh mutant which can either be who grade two three or four oligodendroglyoma idh mutant 1p19 Q code deleted which can either be who grade 2 or 3 or it can be a glioblastoma idh wild type which is obviously who grade 4. now idh wild type astrocytoma without histological features of GBM okay but having a characteristic one or more of the three parameters enlisted that is either a third promoter mutation or an egfr amplification or for that matter gain of seven loss of 10. okay should be classified as glioblastoma idh wild type or astrocytoma idh wild type with molecular features of GBM who grade four okay so that is typically very important to note right so this uh thing was also discussed in the previous class where we were discussing the recent changes in The Who crs-5 so moving on now all idh mutant diffuse astrocytomas can either be who grade 2 3 or 4 right if it is who grade 2 then what is that it is a diffuse infiltrative glioma with idh1 or idh2 mutation right but lacks any anaplasia and there is absence of cdk and 2A to be homozygous deletion so that is very important to note on the other hand a Grade Three idh mutant diffuse astrocytoma shows a characteristic mutations involving the idh1 or two pathway with focal anaplasia now presence of either cdkn2a2b homozygous deletion or necrosis or microvascular proliferation upgrades the tumor to cnswho grade 4 idh mutant astrocytoma right so if we summarize the entire thing what do we see here we see that diffuse gliomas can either be idh wild type or idh muted idh is typically idh 1 r132 H that we take into consideration because IHC is available and this is the most common mutation that typically occurs okay so if it is idh1 r132h wild type okay with one or more of the following that is either microvascular proliferation or necrosis ordered promoter mutation or for that matter egfr Gene amplification or gain of 7 loss of 10. okay then that upgrades the tumor to a glioblastoma idh wild type CNS who grade 4. so this is typically important okay so it must be noted that any diffuse uh glioma which is idh wild type okay harboring any one of this okay upgrades it to the characteristic glioblastoma idh wild type morphology okay and confers a diagnosis of glioblastoma CNS who grade 4. now moving on to the idh mutant idh1 r132h mutant diffuse glioma with atrx mutation and tp53 mutation with characteristic microvascular proliferation and or necrosis is upgraded to idh mutant astrocytoma who grade 4. okay if it lacks these then that is a astrocytoma idh mutant CNS who grade two or three okay that is CNS either it is a diffuse astrocytum or an anaplastic astrocytoma but this anaplastic astrocytoma-like morphology um who refrains from using it we now confer it as uh astrocytoma idh mutant cnswh of grade two or three okay now if it Harbors a characteristic homozygous CNN cdkn2a to be deletion then that upgrades the tumor to a astrocytoma idh mutant cnswho grade four so that also becomes typically important right in addition it must be noted that if the atrx is retained and one p19q correlation is occurring in such a tumor then that uh changes the tumor from a diffuse glioma to an oligodendroglioma idh mutant 1p19 Q codelated CNS wh grade two or grade three depending on the morphology of the tube right so now coming to the circumscribed gliomas now what are these this includes pilocytic astrocytoma pleomorphic xanthoastrocytoma high-grade astrocytoma with pyloid features okay subependental giant cell astrocytoma cordoid glioma and astroblastoma mn1 altered so let's discuss them one by one now what are the essential diagnostic criteria and the desirable diagnostic criteria that have been summed up in this slide okay for circumscribed astrocytic gliomas according to CNS who 5. as we know that it has a characteristic biphasic Compact and loose growth pattern with pyloid psychology and a low proliferative activity with or without Rosenthal fibers and or eosinophilic granular bodies but it must also be noted that any piloid astrocytic neoplasm with a solitary map K alteration such as a Kia 1549 or a B rap Fusion also makes it a pilocytic astrocytoma so let's look at the morphology now this is a pilocytic astrocytoma showing a biphasic appearance there are compact fibrillar portions that you can make out with elongated nuclei and bipolar pyloid processes that you can make out there is Rosenthal fiber and eosinophilic granular bodies that you can make out as well there is a characteristic loose microcystic appearance of this tumor that is also characteristic of pilocytic astrocytoma now this tumor typically occurs in children but cases have also been reported up to the first two decades of life it characteristically involves the cerebellum in 42 percent of the cases supratural region is affected but just in 36 percent of the cases hypothalamus and brain stem in nine percent and spinal cord in just two percent of the cases reported worldwide now coming to the other entity we have pilo mixoid astrocytoma now that is nothing but a monomorphous tumor with a characteristic mixoid background okay often there may be Rosenthal fibers and or eosinophilic granular bodies okay but shows a characteristic angiocentric pattern that is typical of pylomixoid astrocytome or it must be noted that add astrocytic neoplasm with a pylomixoid morphology and a characteristic er1549 or bra Fusion also makes it a pylomixoid astrocytoma so what do we see here we see the characteristic angiocentric growth pattern of this tumor composed of monomorphous population of cell and there is a typical mixoid background that you can make out right the cells have a characteristic elongated uh process and there is a perivascular pseudo rosette-like distribution the tumor typically occurs in infancy and early childhood most commonly it affects the hypothalamic and or chiasmatic region it is also a cnswh of grade 1 tumor so now coming to another entity that is pleomorphic xantho astrocytoma this shows a characteristic pleomorphic morphology of tumor cells there are multinucleated giant cells spindle cells and lipidized cells okay there is a desirable criteria that is presence of a characteristic mutation in the braf or other map K Gene Pathways with a combined homozygous cdkn2a2b deletion a DNA methylone profile of a pleomorphic xantho astrocytoma has also been recommended by the recent who in CNS who 5. so moving on to this tumor this is a pleomorphic xanthoastral cytoma the cells are looking very pleomorphic there are multi-nucleated giant cells that you can make out in addition to the spindle shells that are present in fascicular growth pattern okay this typically occurs in children and young adults and the site of predilection is mainly in the supratural region preferentially involving the temporal lobe now coming to another entity that is Sega what is Sega Sega is subependental giant cell astrocytoma the characteristic feature is multiple glial phenotype including the polygonal cells gemistocyte-like cells spindle cells and ganglion like cells and an immunoreactivity for glial markers that is refap and S100 and a variable expression of neuronal markers that is beta tribulent neurofilament synaptophysin and UA desirable diagnostic criteria includes a nuclear immuno expression of ttf1 okay lost or reduced expression of tuberin or harmatin okay because it is often associated with tuberous sclerosis immuno expression of phosphorylated S6 DNA methylone profile of Sega and history of tuberous sclerosis or tsc1 or tsc2 mutation may be present so if we see in the diagram we see that this is a case of a subependental joint cell astrocytoma composed of large polygonal cells okay or elongated cells resembling somewhat like a ganglion cell right with a characteristic prominent nucleoli as you can make out okay there is a bright pink cytoplasm and the nucleus is somewhat eccentric okay there is prominent uh nucleoli just like a ganglion cell as you can see presence of mitosis and Vascular proliferation or necrosis does not upgrade this tumor to an anaplastic morphology okay it must be noted that children and young adults usually in the setting of tuberous sclerosis seen in up to five percent to 15 percent of the cases has been reported it must also be noted that this usually presents as an intraventricular Mass now moving on to another entity that is cordoid glioma this is a glial neoplasm okay typically occurring in the anterior third ventricle and presents with a cordoid features the desirable criteria includes ttf1 immunopositivity okay and the mutation in PRK C A DN DNA methylation profiling aligning with cordoid glioma is also one of the diagnostic desirable criteria so if we see your what do we see here this is a CNS who grade 2 glyoma it's a cordoid glioma the cells are typically present in chords okay they have a characteristic round to avoid to epithelloid morphology okay and the background is mucomicsoid as you can make out right there may be characteristic lymphoplasmocytic infiltrate Russell bodies that may be present in the peritumeral pyloid region it typically occurs in the third ventricle and in the hypothalamic region usually it occurs in the middle aged women okay usually the median age is 45 years okay and 63 percent of the cases have occurred in women so 63 percent of the cases have been reported in the female population moving on to our last entity under the circumscribed gliomas that is the astroblastoma mn1 altered now this is a glial neoplasm with astroblastic perivascular pseudorosids and mn1 alteration there is a characteristic DNA methylation profile in astrocytoma that has been reported okay gfab immunodeactivity and Hema immunoreactivity is the desirable diagnostic criteria so now coming to the morphology of astroblastoma mn1 altered note that no who grade has been given to this tumor in the recent who cns-5 okay so no who grade has been assigned it must be noted that this is a well-circumscribed tumor with a characteristic pushing border okay it has a high grade um morphology and it shows a characteristic perivascular pseudor rosetting similar to that of an ependymoma however the cellular processes are much thicker as compared to an ependymoma okay there is vascular hyalenization and a little fibrillary background that you can make out this shows a characteristic Supra tentorial or cerebral location and the tumor typically occurs in children and young adults so now moving on to another important glial tumor that is ependymoma ependymal neoplasms occur at all ages and in compass multiple tumor types and subtypes okay they typically develop in the supratural compartment posterior fossa or in the spinal cord the newly identified biological markers and classification schemes for example have been based on the characteristic DNA Global methylation profiling that have led to the definition of 10 types of ependymomas okay and an improved prediction of patients outcome by applying the new classification system so this is a picture which has been taken from a very important publication in the brain pathology Journal okay and what do you see here you see that the ependymomas have been classified as supratural ependymomas posterior forsy ependymomas and the spinal ependymomas we also have the subependymoma which is a characteristic who grade 1 ependymoma showing a third promoter mutation or a loss of chromosome 6. can either be type A or type B type A ones usually show a easy mutation or an h3k27m mutation type B shows a characteristic chromosomal instability on the other hand you also have a spinal ependymoma which shows nf2 mutation or chromosome 22q loss spine elementymoma mycn shows a characteristic amplification in the nycn gene on chromosome 2p mixopapillary ependymoma shows a characteristic chromosomal instability okay now the criteria for the diagnosis besides the fusion it is important to note that a mix of papillary ependymoma shows a characteristic papillary architecture and a perivascular mixoid change or at least focal mixoid change there may be an immunoreactivity for g-fap and methylation class of a mix of papillary epinimoma however has not been well defined it must also be noted that a subependence is a circumscribed glioma clustering of tumor cell nuclei in expansive and focally microcystic or fibrillary Matrix is characteristically located in sub-appendioma okay so now let's discuss these entities one by one now before we go into the discussion regarding the location it is important to note that ependymomas typically occur in the supratorial posterior fossa or in this final location regarding a sub-ependymoma it is important to note that subependymomine mix of papillary ependymomas are exceptional as subependigomers can occur in all the three locations or compartments and there is a vast majority of mixopapillary ependymomage that typically occurs in the lower part of the spinal cord involving the coda equina moving on to the histology as you can make out you have monomorphous population of tumor cells usually round to avoid with speckles chromatin there is a characteristic perivascular distribution of these tumor cells okay and there is presence of ependymal roses okay the true eponymal roses that you can make out there is a characteristic uh Lumina okay and surrounding that you have tumor cells in addition there may be perivascular pseudoro setting that can also be made out here okay now coming to Supra tentorial ependymoma Supra centorial ependymoma now comprise either a zfta or a Yap one Fusion if no pathogenic Gene Fusion that is either zfta or yap1 has been detected in the supratural epidymoma then it is referred to as a suprateral ependymoma not elsewhere classified okay if a molecular diagnosis was not feasible or successful okay the tumor should be classified as a supratorial ependymoma not otherwise specified okay so the not elsewhere classified and not otherwise specified have been discussed in the previous class as well now up to now the majority of the Supra tentorial epididymomas were classified as Super syntorial rela Fusion epididymoma with the genetic fusions between zfta and rela but in the recent classification the newly defined ependymoma type that is the zfta fusion replaces the term Supra tentorial rela Fusion tumors why this pays the tribute to the fact that the fusion of the zfta gene has been shown not only to occur with rela but also with other Fusion Partners like the mam l23 NCO A1 to mn1 or ctna2 okay so besides rela there are other Fusion Partners as well and therefore it is now called as Supra tentorial zfta Fusion the second newly recognized category is the Yap one Fusion positive ependymoma such tumors typically Harbor the Yap one mam ld1 Fusion or the Yap one fam Fusion now coming to the posterior fossa ependymomas ependymomas occur typically in the posterior fossa can either be PFA or B and if the diagnostic criteria is not met then it can either be an NEC or the NOC which is similar to that of a Supra tentorial ependymoma as described earlier okay now obligatory criteria for the diagnosis of a PFA that is a posterior fossa location and evidence of a global reduction of k27me in the tumor cell nuclei is essential if a global h3k27 me reduction cannot be detected okay then a DNA methylation profile aligned with PFA can still secure the diagnosis of a PFA ependymoma according to the current who okay hyper methylation of the cpg rich islands and Global DNA hypometilation are characteristic of a posterior fossa ependymoma so besides the global reduction of k27me in tumor cell nuclei okay there is another important diagnostic criteria which if present can also be classified as a posterior fossa epididymoma type A that is nothing but the hyper methylation of the cpg rich Islands in addition it must be noted that h3k27me reduction is strongly associated with e-zip over expression right now coming to the spinal ependymoma ependymal tumors can occur in the spinal location as well and they show a characteristic nycn amplification okay now uh this amplification is very important because it is typical for spinal epidymomis besides that mixopapillary ependymoma and sub Urban diamon have also been documented to occur in the spinal location predominantly occurs in the cervical region followed by the thoracic and the lumber the median age group is around 41 years and this final ependymoma characteristically Harbors chromosomal losses of chromosome 22q where nf2 Gene is located so germline mutations of the nf2 gene usually cause a predisposition to neurofibromatosis type 2. now spinal ependymomas can be either a spine level nycn okay now this is characteristically a very novel criteria histologically this tumor typically shows uh pseudo rosettes and has a characteristic papillary or pseudo-papillary architecture okay they typically display high grade features including microvascular proliferation necrosis or a high mitotic count so that is why this uh mycn amplification in a spine level is typically important because this these tumors usually have a characteristic histology of a papillary or a pseudo papillary architecture now coming to the mix of papillary epidemoma and that is a morphologically defined entity as you can as you have already seen all right there is a partial aggressive clinical behavior and recurrence and dissemination that have been attributed to this tumor and therefore this tumor has been upgraded in the recent who from who grade one okay to a wh or grade two in the current version of The Who classification so as you can make out here this is a case of a mix of papillary ependymoma with a characteristic radial distribution of the cuboidal to epithelloid elongated glial cells okay around hyalenized fibrovascular cores right so these are the hyalenized fibrovascular cores okay with a characteristic mixoid change okay accumulation of a basophilic mixoid material can be appreciated in this area and this mixoid material is usually highlighted by pass or alcine blue so periodic acids give and alcyan blue positively stains this mixoid material in mixopapillary ependymoma moving on to the grading of ependymoma mass still classified as wh to grade 1 whereas grading of mixopapillary ependymoma has been changed from grade 1 to grade 2. according to the current update of who classification for uh Supra tentorial posterior fossil spinal ependymoma without any molecular specification histological grading that is grade two or grade three ependymomas should still be a part of the diagnosis so that remains unchanged right now coming to the glio neuronal tumors and neuronal tumors as we have seen that there is a long list of tumors encompassing the gangliogliomas desmoplastic infantile gliomas disc embryoplastic neuroepithelial tumors okay gangliocytomas Central neurocytomas and a long list right so typically it must be noted that glial glioneuronal and neuron tumors are slow growing low-grade neuroepithelial tumors with mature neuronal and less consistently glial differentiation they typically occur in young adults and in adolescent age group and show a characteristic predisposition to epilepsy and therefore they have been grouped under the low-grade epilepsy Associated tumors or the liats so this chart or rather this slide is typically very important why because the glioneuronal tumors here have been histologically defined that is those which are mainly composed of ganglion cells that is those cells which have an abundant amphiphilic cytoplasm and eccentric vesicular nucleus with a prominent nucleolus such tumors are usually a ganglioglioma or a gangliocytoma this sorry desmoplastic infantile ganglioglioma multinodular and vacculating neuronal tumors and dysplastic cerebellar gangliocytomas those tumors which are mainly composed of neurocytes include the central neurocytoma papillary glyoneuronal tumor Roseate forming neuronal tumor and diffuse leptomenidual glioneuronal tumor those tumors which are typically composed of oligodendroglioma like cells include the disc embryoplastic neuroepithelial tumor or the dnet okay mixoid glioneurol tumor and a provisional entity that is the diffuse glioneuronal tumor with oligodendroglioma like features and nuclear clusters okay so let's move into it one by one now discussing the important glioneuronal tumors we have ganglioglioma now this is a very important entity for all the postgraduate trainees it's a well-differentiated slow growing glio neuronal tumor which is composed of ganglion like cells and atypical glial cells the ganglion like cells demonstrate dysmorphic features like binucleation as you can make out there may be nuclear clustering okay and there may be cytomegaly with ballooning of the cytoplasm right now coming to the desmoplastic infantile ganglioglioma it's a Supra tentorial tumor neoplastic neuroepithelial cells are seen in a characteristic desmoplastic spindled stroma the tumor cells are arranged in a fascular and storiform pattern and there may be small number of gemostal sites like cells and ganglion cells as well or rather ganglion like cells okay the background stroma is variably desmoplastic and can be highlighted by trichrome or reticulum stain so now coming to this embryo plastic neural epithelial tumor now this tumor is composed of cystic spaces which contain alcine blue positive mucin however this is a hne stain slide right so what do you see here you see these cystic spaces which have mucin okay the bluish tinged mucin and what are these these are oligodendroglya like cells okay and these small oligodendroglyoma like cells are there with intervening neurons okay floating in this mucomicsoid Matrix okay and these are referred to as floating neurons so if we see the high power of it what do we see here we see the floating neurons and we also see the oligodendroglioma like cells moving on to diffuse glio neuronal tumor with oligodendroglioma like features and nuclear clusters so this tumor was not histologically defined but was identified in 2020 by DNA methylation profiling it is associated with recurrent monosomy 14 as its genetic signature the Ki 67 labeling index is quite high and most of the tumors occur in the characteristic cerebrum right so cerebrum is the most important site light clear cells with scattered pleomorphic nuclear features are the histological Hallmarks in addition ganglion cells or multi-nucleated cells calcification and Fermi cells may also be present the critical point is that these tumors are negative for gfab and are often positive for olig 2 and map 2. so now coming to the immuno histochemistry that is essential for identifying the neuronal differentiation of the tumor that is we have map2 we have neurofilament protein or nft we also have new n and we have synaptophizin okay map2 is a neuron specific cytoskeleton protein okay which is quite abundant in the dendrites and in the cytoplasm on the other hand neurofilament uh is characteristically present in the ganglion cells and also in the normal neurons on the other hand synaptophysin shows a characteristic cell membrane positivity in the neoplastic neurons okay while Nu n is the gene that produces the neuronal nuclei moving on to the genetically defined entities we have the diffuse glio neuronal tumor with oligodendroglioma-like features and nuclear clusters okay that is d g o n c the location is characteristically the cerebrum okay this tumor can either be who grade 2 or grade 3 okay but however this is a provisional entity now the recurrent chromosomi 14 has been associated with this tumor on the other hand you have multi-nodular and vacculating neuronal tumor which also occurs in the cerebrum associated with map K pathway alteration mixoid glyoneurol tumor which is again a grade 2 or grade 3 tumor occurring in the adults and in the Adolescent age group okay it occurs in the septum and is often associated with genetic alterations involving pdgfra we also have diffuse leptomenial glioneuronal tumors MC1 and mc2 that is methylation class 1 and Class 2 both occurring in the spinal cord often associated with Kia 1549b wrap and mutations okay and they can either be grade 2 or grade three so if we summarize what we have discussed till now then we can find that the neuronal differentiation can be attributed based on the morphology that is either it is a ganglion cell-like differentiation or a neurocytic differentiation eyelc positivity either n or NFP and based on the location that is whether it is a cerebrum location or a septum or a leptomenicious it can be divided into a multinodular vacculating glio neuronal tumor often showing a map K pathway alteration okay or a diffuse glio neural tumor with oligodendroclioma like features and nuclear clusters again occurring the cerebrum but shows a characteristic monosomy 14. it can be a mixoid glio neuronal tumor occurring in the septum showing a characteristic pdgfra mutation often the differential diagnosis is a dnet in this case okay or it can be a diffuse leptomenanger glyoneurol tumor occurring in the leptomaningers showing a characteristic b-raph mutation and a methylation Class 1 or Class 2 phenotype so now coming to the layered and structured reporting that has been advocated by who in this recent Edition it includes an integrated diagnosis that is a combined tissue-based histological and a molecular diagnosis histological diagnosis of the tumor the cnswho grade according to the recent who grading system and the molecular information that has been gathered from several molecular assays that have been performed for the tumor okay so let's see an example this example was also discussed in the previous class first of all an integrated diagnosis of a supratural ependymoma NOS has been given okay followed by that a histological diagnosis of ependymoma based on histomorphology has been given in addition a CNS who grade has been ascribed to this tumor because of its anaplastic morphology it was given a grade of grade 3. and molecular information who is written as molecular test was not done why because of the lack of facility of the molecular test at The Institute per se so summarizing the session for today we find that uh cnswho5 has taken a new approach to classify the gliomas glioneuronal tumors and neuronal tumors and has divided them into six different families as we have discussed first is the adult type diffuse gliomas now these adult type diffuse gliomas remember that chart that we had discussed can either be idh wild type or idh muted now those that are idh wild type which characteristic microvascular proliferation and or necrosis or if it has kgfr mutation or third promoter alterations all for that matter it has a gain of seven or loss of 10. then it is referred to as a glioblastoma idh wild type on the other hand if it is a characteristic idh mutant astrocytomas then those idh mutant astrocytomas based on their morphology and their genetic makeup can either be who grade 2 grade 3 or grade 4. coming to the Pediatric type diffuse gliomas they can either be the Pediatric type diffuse low-grade gliomas or the Pediatric type diffuse high grade gliomas showing a characteristic alteration in the histone pathway that is h3k27 M alter or it can be an h3g34 RV on the other hand there is also a pediatric type diffuse high grade lyoma which shows a characteristic mutation in the receptor tyrosine kinase pathway we had also discussed the circumscribed astrocytic gliomas which included the pilocytic astrocytoma the pleomorphic xanthoastrocytoma the sub-ependymal giant cell astrocytoma the astroblastoma mn1 altered and the cordoid gliomas in addition we also discussed about the glioneuronal and neuronal tumors which encompassed a number of entities showing a characteristic ganglion cell-like differentiation that is the ganglioglioma or the gangliocytoma the a disembryoplastic neural epithelial tumor which show the characteristic which showed the characteristic floating neurons and mucomic soil Matrix was also discussed ependymomas per se had been classified based on their location that is the Supra tentorial the posterior fossa or the spinal ependymomas and even the mixopapillary and the subependymomas were discussed it was to be noted further that the mixopapillary ependymoma has been upgraded from grade 1 to grade 2 because of a higher chance of recurrence further what is to be noted is that the choroid plexus tumors with marked epithelial characteristics have now been separated from this entity of gliomas glio neuronal tumors and neuronal tumors now who also has emphasized on the characteristic lead reporting or structural reporting system by adding the suffix of Nos and NEC which we had discussed in the previous class as well okay so just adding to that the fact that NOS suffix indicates that the diagnostic information that is the histological or molecular information necessary to assign a specific who diagnosis is not available this provides an alert to the oncologist that the molecular workup has not been undertaken at The Institute per se or has failed technically therefore in the example that we had enlisted just a few slides before a yes A characteristic supracentorial epidimoma was given a suffix of NOS why because the molecular workup could not be done and NEC suffix on the other hand indicates the necessary diagnostic testing that has been successfully performed but the results do not readily allow for a specific who diagnosis as per the recent who classification so in that case we use the suffix of NEC right so this is how we summarize the entire thing of gliomas glioneuronal tumors and ependymomas thank you so much for your patient hearing