CIMPACT-NOW Round 1 Updated Key Points for Brain Tumor Diagnosis

The purpose of the Committee on Molecular Information and Practice Methods for the Classification of Central Nervous System (CNS) Tumors (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, cIMPACT-NOW) is to complement existing WHO tumor classification slicing, leading to individual diagnosis and treatmentupdates that have been released to date, such as the idh wild type of low-grade astrocyte cell tumor, can be considered to have a malignant degree of GBM if eGFR amplification, or chromosome 7 amplification, or chromosome 10 loss or TERT mutation is metDavid NLouis, of the Department of Pathology at Massachusetts General Hospital, Harvard Medical School, and others, wrote a summary summarizing the diagnostic updates and clinical applications presented by cIMPACT-NOW over the past four years, published online in BrainPathology in May 2019findingsthe establishment of cIMPACT-NOW at the end of 2016 under the auspices of the International Society of Neuropathology ,ISN to evaluate and recommend changes in future CNS tumor classificationsThe brain tumor classification is mainly based on the new WHO standard, cIMPACT-NOW in the gap period of WHO classification update, providing information on selected tumor types to have an "impact", timely modification of diagnostic criteria and for future WHO classification referenceIn the first round of discussions from 2016 to 2019, cIMPACT-NOW issued four updatescIMPACT Update 1(proposed by working committee 3)"cIMPACT Update 1" to clarify the use of the term NOS (Not Otherwise Specified) or "non-specific" and to increase the use of the term NEC (Not Elsewhere Classified), or "unknown type"1NOS means that the detection information of histology or molecular science necessary for WHO diagnosis is not availableNOS hints have not been carried out or a full molecular inspection has not been carried out or has not been successful2NEC means that the necessary diagnostic tests have been successfully performed, but the test results are not diagnosed in accordance with WHO 2016 standardsIn some cases, the test results may be the result of a mismatch between clinical, histology, immune histology, or genetic characteristics; NEC tips That although adequate pathological testing is carried out, the tumor does not meet WHO diagnostic criteria NEC diagnosis is similar to the "descriptive diagnosis" that pathologists have long used, meaning that pathologists use non-WHO terms to "describe" tumors e.g.: 1 "Less protoscoccal glioblastoma, NOS", refers to histology consistent with the small protrusion glioblastoma, the presence of IDH mutation, but has not yet been analyzed 1p/19q state 2 "Diffuse glioma, IDH mutation with 1p deletion/19q retention, NEC", refers to histology tips for less protrusive glioblastoma, IDH mutation, accompanied by 1p deficiency but 19q complete This example shows that similar NEC diagnoses can be used in other hetologically consistent with "less protrusive glioblastoma" and have different genetic changes from non-diagnostic genetics 3 High-level diffuse glioblastoma with H3 G34 mutations can be diagnosed in descriptive terms, such as: "high-level astrocyma, H3 G34 mutant, NEC" or "glioblastoma, IDH wild and H3 G34 mutant, NEC") Because such conditions are not included in the current WHO classification, this term is not determined in future classifications Note: For the same amino acid residue, some nomenclatures use G35 instead of G34 In addition, if the diagnosis can be included as an entity in future WHO classifications, the name of the NEC will no longer apply cIMPACT Update 2 (proposed by working committee 3) "cIMPACT Update 2" is about the diagnosis of two tumor types: diffuse midline glioblastoma, H3 K27M mutant type" and "diffuse astrocytes/intersastatic amorphous glioma, IDH mutant type." 1 "Diffuse midline glioblastoma, H3 K27M mutant type" refers to diffuse (i.e leaching), midline, and H3 K27M mutant glioblastoma, this diagnosis is not used for other tumors with H3 K27M mutation, such as ventoral membrane tumors Tumors with H3 K27M mutations but non-diffuse midline glioblastomas should be reported as "mutations and NEC" should be considered The reason for the 2016 WHO classification states that the H3 K27M mutation "only occurs" in diffuse midline glioblastoma, but is now reported in other brain tumors Note: For the same amino acid residue, some nomenclatures use K28 instead of K27 However, there are currently clinical mutations that occur only in diffuse midline glioblastoma 2 In WHO-grade II or III diffuse astrocyte cell tumors with idh mutations and ATRX nuclear expression deficiency or diffuse p53 immune-positive, diagnosis of diffuse astrocyma, IDH mutant or interdesmotosagliote, IDH mutation can be made without 1p/19q test The reason is that in the context of idh1 R132H positive, ATRX nuclear expression deficiency or diffuse p53 immuno-positive diffuse astrocyma histology, a purely immunohistotic examination can be obtained without the need for 1p/19q test cIMPACT update 3 (proposed by the Working Committee 1) 2016 WHO classification clearly distinguishes between IDH mutant and IDH wild diffuse astrocyte cell tumors Overall, the prognosis of IDH wild tumors was worse However, some of these IDH wild diffuse astrocymas do not have a much lower prognosis than IDH mutant tumors, indicating that IDH wild tumors actually contain a variety of subtypes "cIMPACT Update 3" determined that in the background of IDH wild diffuse or interdesmostatic amorphous glioblastoma, the molecular criteria used can be used to speculate on the current non-glioblastoma histological characteristics (i.e., microvascular hyperplasia or tumor necrosis), but its biological behavior and clinical course is similar to THE WHO IV-grade glioblastoma of idh wild diffuse or interstitial amorphous glioblastoma in pervasive and interdesatoinant glioblastomas without IDH mutations, any or all of the following molecular indicators were found: (1) EGFR amplification; ;(3) TERT promoter mutation, indicating that when the tumor conforms to WHO IV-level behavior, the term is recommended as "diffuse astrocyma, IDH wild type, with the molecular characteristics of glioblastoma, WHO IV." "cIMPACT Update 3" indicates that the prognosis of the special subtypes of the IDH wild-type diffuse glioblastoma, which has one or more of the three molecular changes, and lack microvascular hyperplasia or tumor necrosis, is similar to the prognosis of glioblastoma Therefore, the clinical neuro-oncology team must pay attention to the prognosis and potential treatment information of this type of patient cIMPACT update 4 (presented by working committee 2) the 2016 WHO classification distinguishes idh mutant and IDH wild-type diffuse astrocyma, and considers the prognostics of IDH wild tumors to be worse However, in children and some young adult patients, the idh wild and H3 wild type diffuse glioma prognosis is better "cIMPACT Update 4" reviews the status of IDH wild/H3 wild diffuse gliomas consistent with histology WHO II, focusing on patients with BRAF V600E mutation, FGFR1 change, or MYB or MYBL1 rearrangement or other MAPK pathway changes; For these tumors, the working committee recommends the use of a combination of histological and genetic characteristics of a comprehensive diagnosis, as follows: "diffuse glioblastoma, MYB change"; "diffuse glioblastoma, MYBL1 change"; "diffuse glioblastoma, FGFR1 TKD replication"; Diffuse glioblastoma, FGFR1 mutant type"; "diffuse glioblastoma, BRAF V600E mutant (but no CDKN2A/B deficiency)" and "diffuse glioblastoma, other MAPK pathway changes" "cIMPACT Update 4" indicates that in children and young adults, the type of IDH wild/H3 wild diffuse glioblastoma may have different clinical characteristics in the case of BRAF V600E mutation, FGFR1 change, other MAPK pathway changes, or MYB or MYBL1 rearrangement conclusions concluded, the author concludes that the cIMPACT-NOW Committee has successfully completed the first round of discussions and published updates and has now begun the second round of deliberations In the second round of deliberations, Working Committee 1 is discussing the possibility of developing a new classification method for IDH mutant diffuse glioblastoma; These recommendations are expected to be updated in the next edition of the Blue Book of who CNS Oncology Classification, which is scheduled to be completed by the end of 2020.