====== Diffuse intrinsic pontine glioma ====== {{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1-WjP5N_oaMKcreoqah-wAZjXi7CloLNbzmSUPCs1Ewttrk977/?limit=15&utm_campaign=pubmed-2&fc=20231108021713}} see also [[Diffuse midline glioma H3 K27M-mutant]]. [[Diffuse midline glioma H3 K27M-mutant]] includes tumors previously referred to as diffuse intrinsic pontine glioma (DIPG). ===== Epidemiology ===== Approximately 300 children are diagnosed with diffuse [[intrinsic pontine glioma]]s (DIPG) each year, usually between the ages of 5 and 9. They account for 10% to 25% of [[pediatric brain tumor]]s. The majority of DIPGs are astrocytic, infiltrative, and localized to the [[pons]]. ===== Etiology ===== The majority of the tumors were positive for GFAP (24/24), MIB1 (23/24), OLIG2 (22/24), p16 (20/24), p53 (20/24), SOX2 (19/24), EGFR (16/24), and BMI1 (9/24). The results suggest that dysregulation of EGFR and p53 may play an important role in the development of DIPGs. The majority of DIPGs express stem cell markers such as SOX2 and OLIG2, consistent with a role for tumor stem cells in the origin and maintenance of these tumors ((Ballester LY, Wang Z, Shandilya S, Miettinen M, Burger PC, Eberhart CG, Rodriguez FJ, Raabe E, Nazarian J, Warren K, Quezado MM. Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas. Am J Surg Pathol. 2013 Sep;37(9):1357-64. doi: 10.1097/PAS.0b013e318294e817. PubMed PMID: 24076776; PubMed Central PMCID: PMC3787318. )). Results suggest that dual targeting of NOTCH and MYCN in DIPG may be an effective therapeutic strategy in DIPG and that adding a γ-secretase inhibitor during radiation therapy may be efficacious initially or during reirradiation ((Taylor IC, Hütt-Cabezas M, Brandt WD, Kambhampati M, Nazarian J, Chang HT, Warren KE, Eberhart CG, Raabe EH. Disrupting NOTCH Slows Diffuse Intrinsic Pontine Glioma Growth, Enhances Radiation Sensitivity, and Shows Combinatorial Efficacy With Bromodomain Inhibition. J Neuropathol Exp Neurol. 2015 Jun 25. [Epub ahead of print] PubMed PMID: 26115193. )). ===== Clinical Features ===== The symptoms of DIPG usually develop very rapidly prior to diagnosis, reflecting the fast growth of these tumors. Most patients start experiencing symptoms less than three months—and often less than three weeks—before diagnosis. The most common symptoms include: Rapidly developing problems controlling [[eye movement]]s, facial expressions, speech, chewing, and swallowing (due to problems in the cranial nerves) Weakness in the arms and legs Problems with walking and coordination. ===== Diagnosis ===== Frameless robotic assisted biopsy of DIPG in pediatric population is an easier, effective, safe and highly accurate method to achieve diagnosis ((Coca HA, Cebula H, Benmekhbi M, Chenard MP, Entz-Werle N, Proust F. Diffuse intrinsic pontine gliomas in children: Interest of robotic frameless assisted biopsy. A technical note. Neurochirurgie. 2016 Dec;62(6):327-331. doi: 10.1016/j.neuchi.2016.07.005. PubMed PMID: 28120771. )). ---- After the start of the era of [[biopsy]], DIPGs bearing [[Histone H3K27 mutation]]s have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group ((Porkholm M, Raunio A, Vainionpää R, Salonen T, Hernesniemi J, Valanne L, Satopää J, Karppinen A, Oinas M, Tynninen O, Pentikäinen V, Kivivuori SM. Molecular alterations in pediatric brainstem gliomas. Pediatr Blood Cancer. 2017 Aug 9. doi: 10.1002/pbc.26751. [Epub ahead of print] PubMed PMID: 28792659. )). ---- Platelet-derived growth factor receptor A is altered by amplification and/or mutation in diffuse intrinsic pontine glioma (DIPG). A retrospective review of magnetic resonance imaging (MRI) scanning in a pure population of DIPG was undertaken. Baseline diagnostic MRI findings included; local tumour extension in upper medulla (74%) or midbrain (62%), metastatic disease (3%), basilar artery encasement (82%), necrosis (33%), intratumoural haemorrhage (26%), hydrocephalus (23%) and dorsal exophytic component (18%). Post-treatment MRI scans demonstrated increases in; leptomeningeal metastatic disease (16%), cystic change/necrosis (48%), enhancement (72%) and intratumoural haemorrhage (32%). Response rates were calculated according to both RECIST (4%) and WHO (24%) criteria. No MRI parameter in either the diagnostic or response scans had prognostic significance ((Hargrave D, Chuang N, Bouffet E. Conventional MRI cannot predict survival in childhood diffuse intrinsic pontine glioma. J Neurooncol. 2008 Feb;86(3):313-9. Epub 2007 Oct 2. PubMed PMID: 17909941. )). ---- Accurately determining diffuse intrinsic pontine glioma (DIPG) tumor volume is clinically important. Eight patients from a Phase I clinical trial testing convection-enhanced delivery (CED) of a therapeutic antibody were included in the study. Pre-CED, post-radiation therapy axial T2-weighted images were analyzed using 2 methods requiring high degrees of subjective judgment (picture archiving and communication system [[[PACS]]] polygon and Volume Viewer auto-contour methods) and 1 method requiring a low degree of subjective judgment (k-means clustering segmentation) to determine tumor volumes. Lin's concordance correlation coefficients (CCCs) were calculated to assess interobserver agreement. RESULTS The CCCs of measurements made by 2 observers with the PACS polygon and the Volume Viewer auto-contour methods were 0.9465 (lower 1-sided 95% confidence limit 0.8472) and 0.7514 (lower 1-sided 95% confidence limit 0.3143), respectively. Both were considered poor agreement. The CCC of measurements made using k-means clustering segmentation was 0.9938 (lower 1-sided 95% confidence limit 0.9772), which was considered substantial strength of agreement. The poor interobserver agreement of PACS polygon and Volume Viewer auto-contour methods highlighted the difficulty in consistently measuring DIPG tumor volumes using methods requiring high degrees of subjective judgment. k-means clustering segmentation, which requires a low degree of subjective judgment, showed better interobserver agreement and produced tumor volumes with delineated borders ((Singh R, Zhou Z, Tisnado J, Haque S, Peck KK, Young RJ, Tsiouris AJ, Thakur SB, Souweidane MM. A novel magnetic resonance imaging segmentation technique for determining diffuse intrinsic pontine glioma tumor volume. J Neurosurg Pediatr. 2016 Jul 8:1-8. [Epub ahead of print] PubMed PMID: 27391980. )). ===== Biopsy ===== [[Diffuse intrinsic pontine glioma biopsy]] ===== Treatment ===== see [[Diffuse intrinsic pontine glioma treatment]]. ===== Outcome ===== see [[Diffuse intrinsic pontine glioma outcome]]. ===== Complications ===== see [[Diffuse intrinsic pontine glioma complications]]. ===== Case series ===== [[Diffuse intrinsic pontine glioma case series]]. ===== References =====