Glioblastoma Multiforme
Overview
- Most malignant astrocytic tumor (G4); comprises poorly differentiated astrocytic tumor cells with profound microvascular proliferation and necrosis.
- Typically present in patients > 50 yo and have a poor overall prognosis (12-18 months).
- Presenting symptoms are often focal neurological deficits and seizures, and features of increased intracranial pressure, eg headaches (especially upon awakening).
- Note that butterfly lesions are nearly pathognomonic of GBM (but also found in CNS lymphoma).
- Butterfly lesions cross the corpus callosum in a butterfly-shaped pattern.
IDH-mutant vs IDH wildtype
IDH-wildtype: primary (de novo) glioblastoma* - NO malignant precursor.
- Represents the vast majority (~ 90%) of cases.
- Generally occurs in patients > 55 yrs old
- IDH-mutant: secondary glioblastoma - prior, low-grade diffuse astrocytoma precursor.
- Represents a minority (~ 10%) of cases.
- Generally occurs in younger patients.
Pathological Findings
- Serpiginous (wavy) zones of pseudopalisading necrosis are characteristic.
- Pseudopalisading necrosis comprises swaths of large, hyperchromatic cells that palisade (enclose) a region of necrosis (dead tissue).
- Highly malignant cellular histopathology:
- Frequent mitoses (mitotic figures) and nuclear atypia.
- High degree of microvascular proliferation (large glomeruloid tufts may form) and necrosis.
- GFAP (Glial Fibrillary Acidic Protein) positive because it's an astrocytic (the most abundant macroglial cell) tumor.
Molecular Alterations
- Three key molecular groups:
- TERT promoter mutation
- IDH mutation
- 1p/19q codeletion
- As a simplification: the more mutations, the better the prognosis, thus:
- Triple-positive gliomas (mutations in TERT promoter & IDH with 1p/19q codeletion) perform the best, whereas those with only TERT promoter mutation perform the worst.
Treatment
- Surgical resection
- Temozolomide
- Alkylating chemotherapeutic agent.
- Note that O-6-methylguanine-DNA methyltransferase (MGMT) reduces the effect of the alkylating agents (eg, temozolomide); thus tumors that are MGMT-methylated (those with reduced MGMT expression) respond better to temozolomide than those without this methylation.
- Radiation
- Several week therapy, target dose ~ 60Gy.
- Bevacizumab is used in recurrent GBM.
- Monoclonal antibody that antagonizes (binds) vascular endothelial growth factor (VEGF), thus it typically reduces tumor edema.
References
- Adesina, Adekunle M., Tarik Tihan, Christine E. Fuller, and Tina Young Poussaint. Atlas of Pediatric Brain Tumors. Springer, 2016.
- Molavi, Diana Weedman. The Practice of Surgical Pathology: A Beginner’s Guide to the Diagnostic Process. Springer Science & Business Media, 2008.
- Newton, Herbert B. Handbook of Brain Tumor Chemotherapy, Molecular Therapeutics, and Immunotherapy. Academic Press, 2018.
- Orkin, Stuart H., David E. Fisher, A. Thomas Look, Samuel Lux, David Ginsburg, and David G. Nathan. Oncology of Infancy and Childhood E-Book. Elsevier Health Sciences, 2009.
- Perry, Arie. “WHO’s Arrived in 2016! An Updated Weather Forecast for Integrated Brain Tumor Diagnosis.” Brain Tumor Pathology 33, no. 3 (July 1, 2016): 157–60. https://doi.org/10.1007/s10014-016-0266-4.
- Prayson, Richard A., and Mark L. Cohen. Practical Differential Diagnosis in Surgical Neuropathology. Springer Science & Business Media, 2000.
- Reni, Michele, Elena Mazza, Silvia Zanon, Gemma Gatta, and Charles J. Vecht. “Central Nervous System Gliomas.” Critical Reviews in Oncology/Hematology 113 (May 2017): 213–34. https://doi.org/10.1016/j.critrevonc.2017.03.021.
- Ryall, Scott, Uri Tabori, and Cynthia Hawkins. “A Comprehensive Review of Paediatric Low-Grade Diffuse Glioma: Pathology, Molecular Genetics and Treatment.” Brain Tumor Pathology 34, no. 2 (April 1, 2017): 51–61. https://doi.org/10.1007/s10014-017-0282-z.
- Samuels, Martin A., Allan H. Ropper, and Joshua Klein. Adams and Victor’s Principles of Neurology 10th Edition. McGraw-Hill Education, 2014.
- Sharma, Suash, and Prabal Deb. “Intraoperative Neurocytology of Primary Central Nervous System Neoplasia: A Simplified and Practical Diagnostic Approach.” Journal of Cytology / Indian Academy of Cytologists 28, no. 4 (2011): 147–58. https://doi.org/10.4103/0970-9371.86339.
- Wang, Y.Y., K. Wang, S.W. Li, J.F. Wang, J. Ma, T. Jiang, and J.P. Dai. “Patterns of Tumor Contrast Enhancement Predict the Prognosis of Anaplastic Gliomas with IDH1 Mutation.” American Journal of Neuroradiology 36, no. 11 (November 2015): 2023–29. https://doi.org/10.3174/ajnr.A4407.
Image References
- Jensflorian. English: Biopsy Specimen of a Glioblastoma Showing Oligodendroglial Differantiation (HE Stain). October 18, 2010. Own work. https://commons.wikimedia.org/wiki/File:Glioblastoma_oligodendroglial_features.jpg.
- ———. English: Glioblastoma Showing Areas of Pseudopalisading Necrosis. May 1, 2010. Own work. https://commons.wikimedia.org/wiki/File:GBM_pseudopalisading_necrosis.jpg.
- ———. English: Histopathology Specimen (FFPE) of a Diffuse Astrocytoma, WHO Grade II, Fibrillary Type. October 22, 2015. Own work. https://commons.wikimedia.org/wiki/File:Diffuse_astrocytoma_HE_stain.jpg.
- ———. English: Histopathology Specimen of Diffuse Astrocytoma, Gemistocytic Appearance (H&E Stain, High Magnification). November 2, 2015. Own work. https://commons.wikimedia.org/wiki/File:Gemistocytic_astrocytoma.jpg.