cIMPACT‐NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT‐Utrecht meeting on future CNS tumor classification and grading

Abstract

cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT-NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles-relating to classification categories, approaches to classification, nomenclature, and grading-that the group hopes will also inform the future classification of CNS neoplasms.

Homozygous deletion of CDKN2A by fluorescence in situ hybridization is prognostic in grade 4, but not grade 2 or 3, IDH-mutant astrocytomas

“…To address these shortcomings, a number of groups have investigated molecular correlates of aggressive behavior in IDHm astrocytomas [5][6][7][8][9][10][11]. Based on these studies, homozygous deletion of the CDKN2A gene, which encodes the cell-cycle regulators p16INK4A and p14ARF, has emerged as a leading candidate molecular marker of high-grade behavior in these tumors [3,7,[10][11][12].…”

BRAF V600E mutation mediates FDG-methionine uptake mismatch in polymorphous low-grade neuroepithelial tumor of the young

“…P-LGNTs have different characteristics than their adult counterparts, and are commonly driven by genomic alterations in the Ras/ mitogen-activated protein kinase (MAPK) pathway, such as mutations in BRAF and NF-1 [23,29]. Recent large-scale genomic studies and genome-wide methylation analyses allowed a thorough characterization of P-LGNTs [24], and cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) currently classifies P-LGNTs as distinct disease entities [4,17]. In 2017, Huse et al described ten cases of polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which were histologically characterized by oligodendroglioma-like cellular components with intense CD34 immunopositivity.…”

Diffuse leptomeningeal glioneuronal tumor: a double misnomer? A report of two cases

“…However, recent studies have reported DLGNT cases without diffuse growth nor leptomeningeal dissemination, at diagnosis and during long follow-up, suggesting that DLGNTs do not necessarily present with leptomeningeal dissemination on MRI [6][7][8]. Accordingly, DLGNTs were defined in the sixth cIMPACT-NOW update as "A glioneuronal neoplasm composed of oligodendrocyte-like cells; chromosome arm 1p deletion and a mitogen-activated protein kinase (MAP-Kinase) pathway gene alteration, KIAA1549:BRAF fusion being most frequent; without IDH mutation; and commonly with diffuse leptomeningeal tumor spread" [9]. Because the pathological features of DLGNT are not specific, and with a large panel of differential diagnoses including pilocytic astrocytoma, ganglioglioma or extraventricular neurocytoma, the diagnosis might be particularly challenging in the cases lacking leptomeningeal dissemination.…”

“…Furthermore, the authors showed that the molecular DLGNT class can be subdivided into two subgroups with distinct molecular alterations and clinical course. According to these findings, the c-IMPACT-NOW consortium suggested that DLGNT should be considered as a distinct tumor type with two distinct subtypes recognized on DNA-methylation profiling [9].…”