The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas

Abstract

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

Non-methylated MGMT as Predictive Factor in Newly Diagnosed Glioblastoma Multiforme Treated with Bevacizumab Concurrent with Radiotherapy Followed by Adjuvant Bevacizumab plus Irinotecan versus Temozolomide Concurrent with Radiotherapy Followed by Adjuvant Temozolomide

“…It is responsible for 15% of all intracranial tumors and 60-75% of astrocytoma's [1]. The duration of survival has not changed much over the past few decades (4%) [2,3].…”

Microvascular characteristics of lower-grade diffuse gliomas: investigating vessel size imaging for differentiating grades and subtypes

“…In addition, the sub-classifications of oligodendroglioma and oligoastrocytoma are still indistinct. When the genotype is IDH wildtype with 1p/19q co-deletion, the tumour is classified as “not otherwise specified” [3]. The relationship between this type and IDH-wildtype glioblastoma is still unclear.…”

“…It is superior to the histological classification [2]. The 2016 classification criteria classify LGGs into three categories [3]. The vast majority of astrocytomas are classified as the IDH mutant with 1p/19q-intact (IDH MUT /1p/19q + ) type, while oligodendrogliomas are classified as the IDH mutant with 1p/19q co-deletion (IDH MUT /1p/19q − ) type.…”

Cell to cell communication is an early event in glioblastoma

“…Glioblastoma multiforme (GB) is the most frequent and aggressive primary malignant brain tumour with a 3 per 100.000 incidence per year (Gallego, 2015). GB patients´ median survival is 12-15 months, with less than 5% of survival after 5 years (Gallego, 2015;Louis et al, 2016;McGuire, 2016;Rogers et al, 2018). The causes of GB are under debate (McGuire, 2016), 5% of the patients develop GB after a low grade astrocytoma (Alifieris and Trafalis, 2015) and the most frequent mutations include gain of function of the epidermal growth factor receptor (EGFR) (97%) and the phosphatidylinositol-3 kinase (PI3K)/phosphatase and tensin homologue (PTEN) pathways (88%) (Hayden, 2010).…”