cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was created under the sponsorship of the International Society of Neuropathology in late 2016—following publication of the 2016 Updated 4th Edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System “blue book”—to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. While it is understood that the major impact on international brain tumor classification comes about through the WHO classification update process (cIMPACT-NOW is “Not Official WHO”), it has been hoped that this additional process will “see impact” in selected tumor types and in periods between the WHO classification updates. Thus, cIMPACT-NOW updates are not intended to supplant the existing WHO classification, but to provide possible guidelines for practicing diagnosticians and future WHO classification updates. More information on cIMPACT-NOW can be found in the following publications:
Louis DN, Aldape K, Brat DJ, Capper D, Ellison DW, Hawkins C, Paulus W, Perry A, Reifenberger G, Figarella-Branger D, Wesseling P, Batchelor TT, Cairncross JG, Pfister SM, Rutkowski, Weller M, Wick W, von Deimling A. cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy): a new initiative in advancing nervous system tumor classification. Brain Pathol 27:851-852, 2017. PMID:27997995
Louis DN, Aldape K, Brat DJ, Capper D, Ellison DW, Hawkins C, Paulus W, Perry A, Reifenberger G, Figarella-Branger D, Wesseling P, Batchelor TT, Cairncross JG, Pfister SM, Rutkowski, Weller M, Wick W, von Deimling A. Announcing cIMPACT-NOW: The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy. Acta Neuropathol 133:1-3, 2017. PMID:27909809
Since its inception, cIMPACT-NOW has at regular intervals facilitated input and consensus review of novel diagnostically relevant data and determined how such information can be practically incorporated into CNS tumor classifications. This has resulted in a series of updates, which are summarized below. Each update is the product of one of the three cIMPACT-NOW Working Committees, with vetting of the guidelines by all members of both the Steering Committee and Clinical Advisory Panel (see below). The interested reader is referred to the full publications for detailed information.
cIMPACT Update 1
cIMPACT Update 1 came from deliberations of Working Committee 3 and was published in 2018. It clarified the use of the term NOS (Not Otherwise Specified) and proposed use of the term NEC (Not Elsewhere Classified), allowing the ready distinction of diagnoses that result from lack of necessary diagnostic (e.g., molecular) information from diagnoses that have had necessary diagnostic testing that shows non-canonical results.
For an NOS designation, diagnostic information (histological or molecular) necessary to assign a more specific WHO diagnosis is not available.
For an NEC designation, necessary diagnostic testing has been successfully performed, but the results do not readily allow for a WHO 2016 diagnosis, e.g., because of mismatch between clinical, (immuno)histological and/or genetic features, or because it concerns a new/emerging entity that is not yet part of the WHO classification.
The full reference for cIMPACT Update 1 can be found at:
Louis DN, Wesseling P, Paulus W, Giannini C, Batchelor TT, Cairncross JG, Capper D, Figarella-Branger D, Lopes MB, Wick W, van den Bent M. cIMPACT-NOW update 1: Not Otherwise Specified (NOS) and Not Elsewhere Classified (NEC). Acta Neuropathol 135(3):481-484, 2018. PMID:29372318
cIMPACT Update 2
cIMPACT Update 2 also came from deliberations of Working Committee 3 and was published in 2018. It issued clarifications regarding two diagnoses: Diffuse Midline Glioma, H3 K27M-mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH-mutant.
The term Diffuse Midline Glioma, H3 K27M–mutant should be reserved for tumors that are diffuse (i.e., infiltrating), midline, gliomas and H3 K27M-mutant, and should not be applied to other tumors (e.g., ependymomas) that can be H3 K27M–mutant.
In the setting of a diffuse astrocytic-appearing WHO grade II or III glioma that has IDH mutation as well as loss of ATRX nuclear expression and/or strong, diffuse p53 immunopositivity, a diagnosis of Diffuse Astrocytoma, IDH-mutant or Anaplastic Astrocytoma, IDH-mutant can be rendered in the absence of 1p/19q testing.
The full reference for cIMPACT Update 2 can be found at:
Louis DN, Giannini C, Capper D, Paulus W, Figarella-Branger D, Lopes MB, Batchelor TT, Cairncross JG, van den Bent M, Wick W, Wesseling P. cIMPACT-NOW update 2: diagnostic clarifications for Diffuse Midline Glioma, H3 K27M–mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH-mutant. Acta Neuropathol 135:639-642, 2018. PMID: 29497819
cIMPACT Update 3
cIMPACT Update 3 came from Working Committee 1 and was published in 2018. It determined molecular criteria that could be used in the setting of an IDH-wildtype WHO grade II or grade III diffuse astrocytic glioma to infer that the tumor would follow a course more similar to a WHO grade IV glioblastoma.
For diffuse astrocytic gliomas of histologic grade II and III, the finding of any or all of the following molecular criteria corresponds to WHO grade IV behavior and tumors can be referred to as Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV:
EGFR amplification
and/or
Whole chromosome 7 gain and whole chromosome 10 loss (+7/-10)
and/or
TERT promoter mutation
The full reference for cIMPACT Update 3 can be found at:
Brat DJ, Aldape K, Colman H, Holland EC, Louis DN, Jenkins RB, Kleinschmidt-DeMasters BK, Perry A, Reifenberger G, Stupp R, von Deimling A, Weller M. cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. Acta Neuropathol. 136:805-810, 2018. PMID: 30259105
cIMPACT Update 4
cIMPACT Update 4 came from Working Committee 2 and was published in 2019. It reviewed the status of WHO grade II IDH-wt / H3-wt diffuse gliomas, focusing on those with a BRAFV600E mutation, FGFR1 alteration, or a MYB or MYBL1 rearrangement, which tend to present in childhood, and recommended the use of an integrated diagnosis to combine their histologic and genetic features, as suggested in the following:
Diffuse glioma, MYB-altered
Diffuse glioma, MYBL1-altered
Diffuse glioma, FGFR1 TKD-duplicated
Diffuse glioma, FGFR1-mutant
Diffuse glioma, BRAFV600E-mutant (but without CDKN2A/B deletion)
Diffuse glioma, other MAPK pathway alteration
The full reference for cIMPACT Update 4 can be found at:
Ellison DW, Hawkins C, Jones DTW, Onar-Thomas A, Pfister SM, Reifenberger G, Louis DN. cIMPACT-NOW update 4: diffuse gliomas characterized byMYB, MYBL1, or FGFR1 alterations or BRAFV600E mutation. Acta Neuropathol. https://doi.org/10.1007/s00401-019-01987-0. PMID: 30848347
cIMPACT-NOW Rosters
STEERING COMMITTEE
David Louis (chair)
Ken Aldape
Dan Brat
David Capper
David Ellison
Dominique Figarella-Branger
Cynthia Hawkins
Takashi Komori (round 2)
Catriona McLean (round 2)
Werner Paulus
Arie Perry
Guido Reifenberger
Andreas von Deimling
Pieter Wesseling
CLINICAL ADVISORY PANEL
Tracy Batchelor
J. Gregory Cairncross
Maryam Fouladi (round 2)
Stefan Pfister
Stefan Rutkowski (round 1)
Michael Weller
Wolfgang Wick
WORKING COMMITTEE 1:
Dan Brat (chair)
Ken Aldape
Howard Colman
Eric Holland
David Louis
Robert Jenkins
Bette Kleinschmidt-DeMasters
Takashi Komori (round 2)
Catriona McLean (round 2)
Arie Perry
Guido Reifenberger
Roger Stupp
Andreas von Deimling
Michael Weller
WORKING COMMITTEE 2 (round 1):
David Ellison (chair)
Cynthia Hawkins
David Jones
David Louis
Arzu Onar
Stefan Pfister
Guido Reifenberger
Stefan Rutkowski
WORKING COMMITTEE 2 (round 2):
David Ellison (chair)
Ken Aldape
David Capper
Maryam Fouladi
Mark Gilbert
Richard Gilbertson
Cynthia Hawkins
David Louis
Tom Merchant
Kristian Pajtler
Sriram Venneti
WORKING COMMITTEE 3 (round 1):
David Louis (chair)
Tracy Batchelor
J.Gregory Cairncross
David Capper
Dominique Figarella-Branger
Caterina Giannini
M.Bea Lopes
Werner Paulus
Martin van den Bent
Pieter Wesseling
Wolfgang Wick
WORKING COMMITTEE 3 (round 2; Utrecht meeting)
David Louis (chair, organizer)
David Ellison (organizer)
Pieter Wesseling (organizer)
Ken Aldape
Dan Brat
David Capper
Charles Eberhart
Dominique Figarella-Branger
Maryam Fouladi
Greg Fuller
Caterina Giannini
Christine Haberler
Cynthia Hawkins
Takashi Komori
Max Kros
HK Ng
Brent Orr
Sung-Hye Park
Werner Paulus
Arie Perry
Torsten Pietsch
Guido Reifenberger
Marc Rosenblum
Felix Sahm
Chitra Sarkar
David Solomon
Uri Tabori
Martin van den Bent
Andreas von Deimling
Michael Weller