The 2016 World Health Organization classification of tumours of the central nervous system. Villa Chiara,Miquel Catherine,Mosses Dominic,Bernier Michèle,Di Stefano Anna Luisa Presse medicale (Paris, France : 1983) The 2016 WHO classification of tumours of the central nervous system represents the new paradigm among the specialists in the brain tumours and proposes a new approach combining histopathological and molecular features into diagnosis named 'integrated diagnosis'. The aim of this challenge is to overstep the interobserver variability of diagnosis based on previous classifications in order to ensure homogenous biological entities with a more accurate clinical significance. Over the last two decades, several molecular aberrations into gliomagenesis were highlighted and then confirmed as emerging biomarkers through prognostic stratification. In particular, IDH1/IDH2 genes mutations, 1p/19q codeletion and mutations in genes encoding histone H3 variants drastically changed the knowledge about diffuse gliomas inducing the WHO working group to consider the phenotype-genotype approach. In the present review, the historical development of the diagnosis of brain tumours from the 3D spatial configuration to the integration of multidisciplinary data up to recent molecular alterations is discussed. At the national level, the RENOCLIP network (supported by the National Cancer Institute) contributes to improve the standardization of histological diagnosis and the facilitation of access to molecular biology platforms for the detection of genetic aberrations necessary for integrated diagnosis. Importantly, the French POLA cohort allowed to test the clinical impact of the new criteria introduced by 2016 WHO classification of CNS tumours confirming the high accuracy in predicting clinical behaviour for diffuse gliomas. 10.1016/j.lpm.2018.04.015

Diffuse gliomas to date and beyond 2016 WHO Classification of Tumours of the Central Nervous System. Onizuka Hiromi,Masui Kenta,Komori Takashi International journal of clinical oncology The updated 2016 World Health Organization (WHO) Classification of Tumours of the Central Nervous System (CNS) has incorporated molecular parameters into pathological diagnosis, for the first time in the molecular era. While it has led to the more precise diagnoses of well-understood entities and the better comprehension of less-understood entities, its practical application has also created some concerns whether or not genotypes predominate over phenotypes in tumor diagnostics. In response to these concerns, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMAPCT-NOW) was established under the sponsorship of the International Society of Neuropathology to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. cIMPACT has thus far published five updates on the proposal and clarification of existing and new terms and entities. Also, recent studies have shown that WHO grading based on histology has lost its prognostic relevance, which necessitates novel, improved grading criteria. We herein highlight the current status of clinical application of WHO 2016 classification and cIMPACT proposals, and the future endeavor to incorporate DNA methylation profiling of the CNS tumors for better clinical decision-making to achieve a goal of precision medicine for each patient with brain tumors. 10.1007/s10147-020-01695-w

The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas. Rogers Te Whiti,Toor Gurvinder,Drummond Katharine,Love Craig,Field Kathryn,Asher Rebecca,Tsui Alpha,Buckland Michael,Gonzales Michael Journal of neuro-oncology 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. 10.1007/s11060-017-2710-7

WHO 2016 classification: changes and advancements in the diagnosis of miscellaneous primary CNS tumours. Sahm F,Reuss D E,Giannini C Neuropathology and applied neurobiology This short review highlights significant changes and recent findings incorporated to varying extent in the WHO 2016 definition of a variety of tumours, including peripheral nerve sheath tumours, meningiomas, mesenchymal nonmeningothelial tumours, melanocytic tumours, lymphomas and histiocytic tumours, germ cell tumours and non-neuroendocrine pituitary tumours. Most notable classification changes include: adding 'hybrid nerve sheath tumours' to the spectrum of benign nerve sheath tumours; an updated definition of atypical meningioma (WHO grade II), including cases with brain invasion; recognizing dural solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) as a single tumour entity characterized by NAB2 and STAT6 gene fusions for which the term SFT/HPC was chosen; recognizing that pituitary granular cell tumour, spindle cell oncocytoma, and pituicytoma all share nuclear expression of TTF-1, possibly representing a spectrum of a single nosological entity derived from posterior pituitary glial cells. The most significant diagnostic markers which have emerged include: inactivation of NF1, CDKN2A, and PRC2 components, SUZ12 and EED in MPNST, leading to neurofibromin and H3K27me3 expression loss; GNAQ and GNA11 mutations in CNS primary melanocytic tumours; BRAFV600E mutation in histiocytic tumours (Langerhans cell histiocytosis and Erdheim-Chester disease) and papillary craniopharyngioma, which provides both a diagnostic marker in the appropriate pathological setting and a therapeutic target. The WHO 2016 Classification has balanced cutting-edge knowledge on the molecular characteristics of the miscellaneous CNS tumours reviewed here with a practical approach for their daily diagnostic work-up. Much more progress can be expected in the classification of these neoplasms in the near future. 10.1111/nan.12397

The emerging role of exosome-derived non-coding RNAs in cancer biology. Fan Qing,Yang Liang,Zhang Xiaodong,Peng Xueqiang,Wei Shibo,Su Dongming,Zhai Zhenhua,Hua Xiangdong,Li Hangyu Cancer letters Exosomes are a new means of intercellular information exchange that have aroused great research interest. Long neglected in research, exosomes were deemed nonfunctional cellular components to be discarded. However, it has been gradually revealed that exosomes are an important tool for the exchange of intercellular information and material. Exosomes contain specific repertoires of non-coding RNAs (ncRNAs, including microRNA and lncRNA), indicating that a specific RNA sorting mechanism may exist. Correspondingly, intracellular multivesicular bodies (MVBs) are produced after fusion with the cell membrane to release exosomes rather than inducing autophagy, which reveals that there may be a specific regulatory mechanism for MVB secretion. Cells can trigger cancer-related disorders after the recognition and uptake of circulating exosomal ncRNAs, providing indications for early tumor biopsy and treatment. The use of exosomes as a biological carrier in targeted therapy has been demonstrated. However, there may be a specific, unknown switch for loading drugs. This review focuses on the mechanisms of exosome biogenesis, release, and uptake. We also review the promotion of tumor development by exosomal ncRNAs including chemotherapy resistance, metastasis and the prospective use of exosomes in cancer diagnosis and treatment. 10.1016/j.canlet.2017.10.040