====== Low-grade glioma old literature ====== ===== Old definition ===== Low-grade [[glioma]]s (LGGs) are a diverse group of [[WHO grade I]] - [[WHO grade II]] of glial origin with [[pilocytic astrocytoma]] (PA) being the most frequent LGG diagnosis. It is now generally accepted that PA and most other LGGs are a single pathway disease of the [[MAPK]] signal transduction pathway ((Jones DT, Gronych J, Lichter P et al. MAPK pathway activation in pilocytic astrocytoma. Cellular and molecular life sciences : CMLS 2012; 69: 1799–1811)). ===== Epidemiology ===== [[low-grade glioma Epidemiology]]. ===== Low-grade glioma classification ===== [[Low-grade glioma classification]] ===== Low-grade astrocytoma ===== see [[Low-grade astrocytoma]] ---- [[Pilomyxoid astrocytoma]] 9425/3* - [[WHO grade]] II [[Pleomorphic xanthoastrocytoma]] 9424/3 - WHO grade II [[Diffuse astrocytoma]] 9400/3 - WHO grade II [[Fibrillary astrocytoma]] 9420/3 [[Protoplasmic astrocytoma]] 9410/3 [[Gemistocytic astrocytoma]] 9411/3 e.g. [[oligoastrocytoma]] The term should not be used for a specific, non-infiltrative WHO I tumour of astrocyte-lineage such as pleomorphic xanthoastrocytoma (PXA), subependymal giant cell astrocytoma (SGCA) and pilocytic astrocytoma, as these have different prognosis, treatment and imaging features. ---- Martino et al. reviewed a consecutive series of 19 patients with GIIG within functional areas who underwent two operations separated by at least 1 year. Intraoperative Electrostimulation mapping was used in all operations for recurrence and in 14 of the initial procedures. A specific rehabilitation was provided. FINDINGS: At the first operation, we performed 14 subtotal and 5 partial resections. Eighteen patients returned to a normal socio-professional life. Nine patients received adjuvant treatment. At the second operation, we performed 1 total, 13 subtotal and 5 partial resections. Three patients with a preoperative neurological deficit improved, 13 remained unchanged, and 3 slight new deficits appeared. In 14 of the 17 patients with preoperative chronic epilepsy, the seizures were reduced or disappeared. Sixteen patients returned to a normal socio-professional life. Pathohistological examination showed that 11 tumours had progressed to high-grade glioma. The median time between the two operations was 4.1 years (range 1 to 7.8 years) and the median follow-up from initial diagnosis was 6.6 years (range 2.3 to 14.3 years). No deaths occurred during the follow-up period. CONCLUSIONS: Repeat operations guided by intra-operative Electrostimulation is an efficacious treatment for recurrent grade II glioma in an eloquent area ((Martino J, Taillandier L, Moritz-Gasser S, Gatignol P, Duffau H. Re-operation is a safe and effective therapeutic strategy in recurrent WHO grade II gliomas within eloquent areas. Acta Neurochir (Wien). 2009 May;151(5):427-36; discussion 436. doi: 10.1007/s00701-009-0232-6. PubMed PMID: 19337688. )). ====Molecular profile==== The most critical molecular alterations (IDH1/2, 1p/19q codeletion, ATRX, TERT, CIC, and FUBP1) and circumscribed (BRAF-KIAA1549, BRAF(V600E), and C11orf95-RELA fusion) gliomas. These molecular features reflect tumor heterogeneity and have specific associations with patient outcome that determine appropriate patient management. This has led to an important, fundamental shift toward developing a molecular classification of World Health Organization grade II-III diffuse glioma ((Olar A, Sulman EP. Molecular Markers in Low-Grade Glioma-Toward Tumor Reclassification. Semin Radiat Oncol. 2015 Jul;25(3):155-63. doi: 10.1016/j.semradonc.2015.02.006. Epub 2015 Feb 23. Review. PubMed PMID: 26050585; PubMed Central PMCID: PMC4500036. )). [[Low-grade glioma]]s (LGG) are classified into three distinct groups based on their IDH1 mutation and 1p/19q codeletion status, each of which is associated with a different clinical expression. The genomic sub-classification of LGG requires tumor sampling via neurosurgical procedures. ---- With the advance of [[genomics]] research, there have been a new breakthrough in the molecular classification of [[glioma]]s. [[Glioblastoma]] (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesenchymal according to the mRNA expression. [[Low-grade glioma]]s (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and [[TERT]]p (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas. Genotype and phenotype were integrated to diagnose gliomas. In the meantime, precision treatment for gliomas has also been vigorously developed ((Hua W, Mao Y. [Advance of molecular subtyping and precise treatment for gliomas]. Zhonghua Wai Ke Za Zhi. 2017 Jan 1;55(1):63-66. doi: 10.3760/cma.j.issn.0529-5815.2017.01.016. Chinese. PubMed PMID: 28056258. )). ---- With the increased understanding of glioma tumour genetics there is a need to understand the changes and their implications for patient management. There has also been an increasing trend for adopting earlier, more aggressive surgical approaches to Low-grade glioma treatment ((Larsen J, Wharton SB, Romanowski C, McKevitt FM, Bridgewater C, Zaki H, Hoggard N. Low-grade glioma: An Update for Radiologists. Br J Radiol. 2016 Dec 7:20160600. [Epub ahead of print] PubMed PMID: 27925467. )). Verma and Mehta et al., discuss the recent [[genomics]] of gliomas, and also the results of seminal LGG trials in the context of molecular and genomic stratification, with respect to both prognosis and response to therapy. They also analyze implications of these "molecular classifications". They propose separating out the worst prognostic subsets, whose outcomes resemble those of glioblastoma patients. Lastly, a brief discussion is provided regarding translating this collective knowledge into the clinic and in treatment decisions; also addressed are some of the many questions that still need to be examined in light of these strong and emerging data ((Verma V, Mehta MP. Clinical ramifications of "genomic staging" of low-grade gliomas. J Neurooncol. 2016 Sep;129(2):195-9. doi: 10.1007/s11060-016-2192-z. Review. PubMed PMID: 27401152. )). ---- [[Hemorrhagic Low-grade glioma]]. [[High risk Low-grade glioma]]. ===== By age ===== [[Pediatric low-grade glioma]].... ===== By localization ===== [[Low grade midbrain glioma]] [[Hypothalamic low-grade glioma]]. ---- {{::glioma_classification.png|}} ===== Risk Factors ===== The most frequent cancer predisposition syndromes in the LGG cohorts are [[Neurofibromatosis type 1]] (NF1), with mostly [[pilocytic astrocytoma]] constituting around 10–20 % of LGG cases, and [[Tuberous Sclerosis]] Complex (TSC) with the characteristic [[subependymal giant cell astrocytoma]] (SEGA), constituting 1–2 % of LGG cases, respectively ((HernaizDrieverP,vonHornsteinS,PietschTetal.Naturalhistoryand management of low-grade glioma in NF-1 children. Journal of neuro-oncology 2010; 100: 199–207)) ((RandleSC.TuberousSclerosisComplex:AReview.Pediatricannals 2017; 46: e166–e171)) ===== Clinical features ===== Preoperative seizures could reflect intrinsic glioma properties ((Smits A, Duffau H. Seizures and the natural history of World Health Organization grade II gliomas: a review. Neurosurgery. 2011;68:1326–1333.)). Most patients experience [[epileptic seizure]]s as a presenting symptom ((Liigant A, Haldre S, Oun A, et al. Seizure disorders in patients with brain tumors. Eur Neurol. 2001;45:46–51.)) ((Lynam LM, Lyons MK, Drazkowski JF, et al. Frequency of seizures in patients with newly diagnosed brain tumors: a retrospective review. Clin Neurol Neurosurg. 2007;109:634–638.)) ((Rosati A, Tomassini A, Pollo B, et al. Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neurooncol. 2009;93:395–400.)) ((Rudà R, Trevisan E, Soffietti R. Epilepsy and brain tumors. Curr Opin Oncol. 2010;22:611–620.)) and cause medically-intractable seizure. see [[Incidental low-grade glioma]]. The results of a genomic analysis suggest that low [[FOXO4]] expression is a significant risk factor for epileptic seizures in patients with LGGs and is associated with the seizure outcome. FOXO4 may be a potential therapeutic target for tumor-associated epilepsy ((Wang Y, Tang K, Zhao J, Liu L, Feng J. FOXO4 expression is associated with the occurrence and outcome of seizures: An RNA-sequencing analysis of low-grade gliomas. Seizure. 2017 Sep 21;52:41-45. doi: 10.1016/j.seizure.2017.09.012. [Epub ahead of print] PubMed PMID: 28963932. )). ---- In patients with low-grade glioma (LGG), language deficits are usually only found and investigated after surgery. Deficits may be present before surgery but to date, studies have yielded varying results regarding the extent of this problem and in what language domains deficits may occur. Twenty-three patients were tested using a comprehensive test battery that consisted of standard aphasia tests and tests of lexical retrieval and high-level language functions. The patients were also asked whether they had noticed any change in their use of language or ability to communicate. The test scores were compared to a matched reference group and to clinical norms. The presumed LGG group performed significantly worse than the reference group on two tests of lexical retrieval. Since five patients after surgery were discovered to have a high-grade glioma, a separate analysis excluding them were performed. These analyses revealed comparable results; however one test of word fluency was no longer significant. Individually, the majority exhibited normal or nearly normal language ability and only a few reported subjective changes in language or ability to communicate. This study shows that patients who have been diagnosed with LGG generally show mild or no language deficits on either objective or subjective assessment ((Antonsson M, Longoni F, Jakola A, Tisell M, Thordstein M, Hartelius L. Pre-operative language ability in patients with presumed low-grade glioma. J Neurooncol. 2017 Dec 1. doi: 10.1007/s11060-017-2699-y. [Epub ahead of print] PubMed PMID: 29196925. )). ===== Diagnosis ===== see [[Low-grade glioma diagnosis]]. ===== Treatment ===== see [[Low-grade glioma treatment]]. ===== Outcome ===== see [[Low-grade glioma prognosis]] see [[low-grade glioma malignant transformation]] ===== Case series ===== [[low-grade glioma case series]]. ===== Case reports ===== [[Low-grade glioma case reports]]. ===== References =====