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Astrocytoma: Diffuse (G2) and Anaplastic (G3)

Astrocytoma: Diffuse (G2) and Anaplastic (G3)

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Radiographic Highlights
  • Diffuse (G2) astrocytomas typically arise from deep, midline regions (ie, the thalamus) and are ill-defined with blurred anatomical boundaries from tissue infiltration (hence their categorization as "infiltrative astrocytomas").
  • Anaplastic astrocytomas (G3) are better circumscribed than diffuse astrocytomas and have a higher proclivity for contrast enhancement.
Histopathology
  • Moderate cellularity, overall: anaplastic astrocytomas will have more cellularity than diffuse astrocytomas.
    • The term "diffuse" helps us remember the lack of cellular concentration in a grade 2 astrocytoma.
  • Diffuse astrocytomas comprise oval, hyperchromatic nuclei with rare mitoses.
  • Anaplastic astrocytomas comprise greater degrees of pleomorphic (variable-shaped) atypical nuclei and mitoses than diffuse astrocytomas, a greater tendency for hemorrhage, and a greater likelihood of having multinucleated cells.
  • Astrocytomas bear a threadlike, filamentous background from fibrillary processes.
    • GFAP (Glial fibrillary acidic protein) staining highlights these processes.
    • This can be remembered because astrocytomas are glial tumors.
    • Consider that reactive astrocytes, instead, have star-like, elongated processes.
Variants
  • Fibrillary:
    • Minimal cytoplasm. The sparse cytoplasm gives the cells a "naked nuclei" appearance.
  • Gemistocytic:
    • Gemistocytes - tumor cells with bulging (plump), eosiniphilic cytoplasmic bellies and eccentric nuclei.
  • Protoplasmic:
    • Astrocytes have sparse processes, oval-shaped nuclei, minimal cytoplasm, and a microcystic background.
Genetic Mutations
  • Anaplastic Astrocytoma
Common Mutations
    • TP53
    • IDH1
    • ATRX
    • Note that 1p19q deletion is common in oligodendrogliomas but not in anaplastic astrocytoma.
Prognosis
  • In diffuse astroctyomas, the prognosis is far better in children than in adults: the majority of diffuse astrocytomas in adults will undergo malignant transformation; whereas, in children, the minority of diffuse astrocytomas will do so.
  • In anaplastic astrocytomas, survival is typically poor (often < 1 year), regardless of the patient's age.
  • Mixed oligoastrocytomas have a better prognosis than pure astrocytomas (but worse prognosis than pure oligodendrogliomas).
Radiation
  • Note that radiation is an established risk factor for the development of glioma.
    • Typically, there is radiation for a CNS tumor that later leads to development of an aggressive glioma, later in life.
  • Also note that although radiation is one of the few actual well-established risk factors for development of glioma (chromosomal abnormalities being another notable risk factor).
    • Thus, although it's common for tobacco use and immunosuppression to be associated with development of malignancy, they are NOT associated with development of a glioma.
    • And although infection (such as EBV with lymphoma) can be a trigger for malignancy, they are NOT for glioma.
    • Also, although there has been great media attention given to cell phone use and cancer risk, it has NOT been shown to be associated with glioma.
References
  • Adesina, Adekunle M., Tarik Tihan, Christine E. Fuller, and Tina Young Poussaint. Atlas of Pediatric Brain Tumors. Springer, 2016.
  • Chaichana, Kaisorn L., Thomas Kosztowski, Ashwini Niranjan, Alessandro Olivi, Jon D. Weingart, John Laterra, Henry Brem, and Alfredo Quiñones-Hinojosa. “Prognostic Significance of Contrast-Enhancing Anaplastic Astrocytomas in Adults.” Journal of Neurosurgery 113, no. 2 (August 2010): 286–92. https://doi.org/10.3171/2010.2.JNS091010.
  • “File: 405663-PLEOMORPHIC XANTHOASTROCYTOMA.Jpg - Wikipedia.” Accessed June 18, 2018. https://it.m.wikipedia.org/wiki/File:405663-PLEOMORPHIC_XANTHOASTROCYTOMA.jpg.
  • Jensflorian. 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.
  • Killela, Patrick J., Christopher J. Pirozzi, Zachary J. Reitman, Sian Jones, B. Ahmed Rasheed, Eric Lipp, Henry Friedman, et al. “The Genetic Landscape of Anaplastic Astrocytoma.” Oncotarget 5, no. 6 (October 16, 2013): 1452–57.
  • Louis, David N., Arie Perry, Guido Reifenberger, Andreas von Deimling, Dominique Figarella-Branger, Webster K. Cavenee, Hiroko Ohgaki, Otmar D. Wiestler, Paul Kleihues, and David W. Ellison. “The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary.” Acta Neuropathologica 131, no. 6 (June 1, 2016): 803–20. https://doi.org/10.1007/s00401-016-1545-1.
  • Molavi, Diana Weedman. The Practice of Surgical Pathology: A Beginner’s Guide to the Diagnostic Process. Springer Science & Business Media, 2008.
  • Nephron. English: High Magnification Micrograph of an Anaplastic Astrocytoma. H&E Stain. [object HTMLTableCellElement]. Own work. https://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_high_mag.jpg.
  • ———. English: High Magnification Micrograph Showing Reactive Astrocytes in Massive Cerebral Ischemia Leading to Pseudolaminar Necrosis. H&E-LFB Stain. [object HTMLTableCellElement]. Own work. https://commons.wikimedia.org/wiki/File:Reactive_astrocytes_-_lfb_-_high_mag.jpg.
  • ———. English: Very High Magnification Micrograph of an Anaplastic Astrocytoma. H&E Stain. [object HTMLTableCellElement]. Own work. https://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_very_high_mag.jpg.
  • 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, R. A., and M. L. Estes. “Protoplasmic Astrocytoma. A Clinicopathologic Study of 16 Tumors.” American Journal of Clinical Pathology 103, no. 6 (June 1995): 705–9.
  • 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.
  • Wippold, F. J., A. Perry, and J. Lennerz. “Neuropathology for the Neuroradiologist: Rosenthal Fibers.” American Journal of Neuroradiology 27, no. 5 (May 1, 2006): 958–61.
Image References:
  • Diffuse Astrocytoma: Fibrillary Pattern
    • Jensflorian. 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.
  • Diffuse Astrocytoma: Gemistocytic Pattern
    • Jensflorian. 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.
  • Anaplastic Astrocytoma
    • Nephron. English: High Magnification Micrograph of an Anaplastic Astrocytoma. H&E Stain. [object HTMLTableCellElement]. Own work. https://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_high_mag.jpg.
    • Nephron. English: Very High Magnification Micrograph of an Anaplastic Astrocytoma. H&E Stain. [object HTMLTableCellElement]. Own work. https://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_very_high_mag.jpg.

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