Astrocytoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D., Shivali Marketkar, M.B.B.S. [2], Ammu Susheela, M.D. [3]

Overview

The exact pathogenesis of astrocytoma is not completely understood but it is believed that this tumor has a close association with genetic mutations. Microscopic pathologic findings in pilocytic astrocytoma include normal cells with slow growth rate, biphasic pattern (dense fibrillar tissue within loose myxoid tissue), calcification, vascular hyalinization, and nested fibrotic pattern. In diffuse astrocytoma, we may see atypical cells, relatively slow mitosis rate, diffusely infiltrate neuropil and poorly defined cytoplasm. In anaplastic astrocytoma, we may see pleomorphic and malignant cells, high mitosis rate, hyperchromatosis, and prominent small vessels. In glioblastoma multiform, we may see pleomorphic cells, naked nuclei, multi-focal necrosis, pseudopalisading pattern, scattered pyknotic nuclear debris in the center, micro-vascular proliferation, and vascular thrombi.

Pathophysiology

Associated conditions

  • There are no conditions associated with astrocytoma.

Genetics

Low-Grade Astrocytomas

High-Grade Astrocytomas


 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Stem cell
• Precursor cell
• Glial cell
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• IDH1 mutation
 
 
 
 
 
• 10q loss
• PTEN mutation
• EGFR overexpression
• MDM2 overexpression
 
 
 
 
 
• KIAA1549-BRAF fusion
• MAPK/ERK abnormalities
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• p53 mutation
• PDGF/PDGFRA overexpression
 
 
 
 
 
Primary glioblastoma grade IV
 
 
 
 
 
Pilocytic astrocytoma grade I
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diffuse astrocytoma grade II
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chr 19q loss
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anaplastic astocytoma grade III
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10q loss
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Glioblastoma (secondary) grade IV
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Gross Pathology

http://commons.wikimedia.org/wiki/File:Gemistocytic_Astrocytoma_003.jpg

Microscopic Pathology

Pathological findings diagnostic of astrocytoma include:[26][27][28][29]

https://librepathology.org/wiki/File:Pilocytic_astrocytoma_-_smear_-_very_high_mag.jpg
https://librepathology.org/wiki/File:Diffuse_astrocytoma_HE_stain.jpg
https://librepathology.org/wiki/File:Mitoses_astro_III.jpg
https://librepathology.org/wiki/File:Glioblastoma_-_high_mag.jpg

Histopathological Video

Video

{{#ev:youtube|O0b4zyDQcyI}}


References

  1. Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.
  2. Jones DT, Kocialkowski S, Liu L, Pearson DM, Ichimura K, Collins VP (2009). "Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma". Oncogene. 28 (20): 2119–23. doi:10.1038/onc.2009.73. PMC 2685777. PMID 19363522.
  3. Jones DT, Kocialkowski S, Liu L, Pearson DM, Bäcklund LM, Ichimura K; et al. (2008). "Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas". Cancer Res. 68 (21): 8673–7. doi:10.1158/0008-5472.CAN-08-2097. PMC 2577184. PMID 18974108.
  4. Forshew T, Tatevossian RG, Lawson AR, Ma J, Neale G, Ogunkolade BW; et al. (2009). "Activation of the ERK/MAPK pathway: a signature genetic defect in posterior fossa pilocytic astrocytomas". J Pathol. 218 (2): 172–81. doi:10.1002/path.2558. PMID 19373855.
  5. Bar EE, Lin A, Tihan T, Burger PC, Eberhart CG (2008). "Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma". J Neuropathol Exp Neurol. 67 (9): 878–87. doi:10.1097/NEN.0b013e3181845622. PMID 18716556.
  6. Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H; et al. (2009). "Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma". Acta Neuropathol. 118 (3): 401–5. doi:10.1007/s00401-009-0550-z. PMID 19543740.
  7. Horbinski C, Hamilton RL, Nikiforov Y, Pollack IF (2010). "Association of molecular alterations, including BRAF, with biology and outcome in pilocytic astrocytomas". Acta Neuropathol. 119 (5): 641–9. doi:10.1007/s00401-009-0634-9. PMID 20044755.
  8. Yu J, Deshmukh H, Gutmann RJ, Emnett RJ, Rodriguez FJ, Watson MA; et al. (2009). "Alterations of BRAF and HIPK2 loci predominate in sporadic pilocytic astrocytoma". Neurology. 73 (19): 1526–31. doi:10.1212/WNL.0b013e3181c0664a. PMC 2777068. PMID 19794125.
  9. Lin A, Rodriguez FJ, Karajannis MA, Williams SC, Legault G, Zagzag D; et al. (2012). "BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants". J Neuropathol Exp Neurol. 71 (1): 66–72. doi:10.1097/NEN.0b013e31823f2cb0. PMID 22157620.
  10. Hawkins C, Walker E, Mohamed N, Zhang C, Jacob K, Shirinian M; et al. (2011). "BRAF-KIAA1549 fusion predicts better clinical outcome in pediatric low-grade astrocytoma". Clin Cancer Res. 17 (14): 4790–8. doi:10.1158/1078-0432.CCR-11-0034. PMID 21610142.
  11. Horbinski C, Nikiforova MN, Hagenkord JM, Hamilton RL, Pollack IF (2012). "Interplay among BRAF, p16, p53, and MIB1 in pediatric low-grade gliomas". Neuro Oncol. 14 (6): 777–89. doi:10.1093/neuonc/nos077. PMC 3367847. PMID 22492957.
  12. Mistry M, Zhukova N, Merico D, Rakopoulos P, Krishnatry R, Shago M; et al. (2015). "BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma". J Clin Oncol. 33 (9): 1015–22. doi:10.1200/JCO.2014.58.3922. PMC 4356711. PMID 25667294.
  13. Janzarik WG, Kratz CP, Loges NT, Olbrich H, Klein C, Schäfer T; et al. (2007). "Further evidence for a somatic KRAS mutation in a pilocytic astrocytoma". Neuropediatrics. 38 (2): 61–3. doi:10.1055/s-2007-984451. PMID 17712732.
  14. Dahiya S, Haydon DH, Alvarado D, Gurnett CA, Gutmann DH, Leonard JR (2013). "BRAF(V600E) mutation is a negative prognosticator in pediatric ganglioglioma". Acta Neuropathol. 125 (6): 901–10. doi:10.1007/s00401-013-1120-y. PMID 23609006.
  15. Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD, Tang B; et al. (2013). "Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas". Nat Genet. 45 (6): 602–12. doi:10.1038/ng.2611. PMC 3727232. PMID 23583981.
  16. Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J; et al. (2010). "Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease". J Clin Oncol. 28 (18): 3061–8. doi:10.1200/JCO.2009.26.7252. PMC 2903336. PMID 20479398.
  17. Bax DA, Mackay A, Little SE, Carvalho D, Viana-Pereira M, Tamber N; et al. (2010). "A distinct spectrum of copy number aberrations in pediatric high-grade gliomas". Clin Cancer Res. 16 (13): 3368–77. doi:10.1158/1078-0432.CCR-10-0438. PMC 2896553. PMID 20570930.
  18. Ward SJ, Karakoula K, Phipps KP, Harkness W, Hayward R, Thompson D; et al. (2010). "Cytogenetic analysis of paediatric astrocytoma using comparative genomic hybridisation and fluorescence in-situ hybridisation". J Neurooncol. 98 (3): 305–18. doi:10.1007/s11060-009-0081-4. PMID 20052518.
  19. Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Lyons-Weiler MA, LaFramboise WA; et al. (2011). "IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children's Oncology Group". Childs Nerv Syst. 27 (1): 87–94. doi:10.1007/s00381-010-1264-1. PMC 3014378. PMID 20725730.
  20. Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K; et al. (2012). "Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma". Nature. 482 (7384): 226–31. doi:10.1038/nature10833. PMID 22286061.
  21. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J; et al. (2012). "Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas". Nat Genet. 44 (3): 251–3. doi:10.1038/ng.1102. PMC 3288377. PMID 22286216.
  22. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C; et al. (2012). "Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma". Cancer Cell. 22 (4): 425–37. doi:10.1016/j.ccr.2012.08.024. PMID 23079654.
  23. Gielen GH, Gessi M, Hammes J, Kramm CM, Waha A, Pietsch T (2013). "H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas". Am J Clin Pathol. 139 (3): 345–9. doi:10.1309/AJCPABOHBC33FVMO. PMID 23429371.
  24. Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E; et al. (2012). "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas". Acta Neuropathol. 124 (3): 439–47. doi:10.1007/s00401-012-0998-0. PMC 3422615. PMID 22661320.
  25. "National Caner Institute Astrocytoma".
  26. Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.
  27. Nafussi, Awatif (2005). Tumor diagnosis : practical approach and pattern analysis. London New York: Arnold Distributed in the U.S.A. by Oxford University Press. ISBN 0340809442.
  28. Schniederjan, Matthew (2011). Biopsy interpretation of the central nervous system. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health. ISBN 9780781799935.
  29. Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.

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