Glioma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Sujit Routray, M.D. [3]

Overview

The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.[1] Genes involved in the pathogenesis of glioma include ERCC1, ERCC2, XRCC1, MGMT, IDH1, IDH2, p53, EGFR, TSC1, TSC2, RB1, APC, hMLH1, hMSH2, PMS2, PTEN, NF1, and NF2.[2][3] The gross and histopathological appearance of glioma varies with the tumor grade and type.[1][4][5][6][7]

Pathophysiology

Pathogenesis

  • The pathogenesis of cerebral glioma involves invasion of the tumor cells into the adjacent normal brain tissue. Although in certain areas the margin of the tumor may seem to be macroscopically well defined from the brain, there are always microscopic nests of tumor cells extending well out into the brain.[1]
  • Astrocytic projections interact with vessels and act as additional elements of the blood brain barrier (BBB). The tumors take advantage of the blood brain barrier to ensure survival and continuous growth.
  • Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue.
  • Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema.[8]

Genetics

Genes involved in the pathogenesis of glioma include:[2][3]

Associated Conditions

Gliomas may be associated with:[3][1]

Gross Pathology

The gross pathological appearance of glioma varies with the tumor grade and type. Common findings are listed below:[1][4][5][6][7]

Type of glioma Gross pathological features

Pilocytic astrocytoma

1. Well-circumscribed cystic tumor
2. Solid mural nodule
3. Commonly located in the cerebellum

Low-grade astrocytoma

1. Poorly demarcated tumor
2. Tumor mass causing enlargement of the involved portion of the brain and blurring of anatomical landmarks
3. Commonly located in the cerebral hemisphere

Anaplastic astrocytoma

1. Spongy or gelationous mass
2. Ill defined borders
3. Microcysts
4. Calcification
5. Commonly located in frontal lobe, temporal lobe, brain stem, or spinal cord

Glioblastoma multiforme

1. Poorly-marginated, diffusely infiltrating tumor
2. Firm or gelatinous in consistency
3. Central necrotic core
4. Commonly located in the frontal and temporal lobe

Oligodendroglioma

1. Well circumscribed tumor
2. Pinkish-white in color
3. Mucinous changes
4. Commonly located in the frontal lobe, followed by parietal and temporal lobes

Ependymoma

1. Well-differentiated tumor
2. Exophytic pattern of growth
3. Commonly located at the fourth ventricle and filum terminale


Gallery

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

Microscopic Pathology

The histopathological appearance of glioma varies with the tumor grade and type, with increasing cellular atypia, mitoses, endothelial cell proliferation, and necrosis. Common findings are listed below:[1][4][5][6][7]

Type of glioma Histopathological features

Pilocytic astrocytoma

1. Low cellularity without mitoses or anaplasia
2. Classically biphasic
  • Fibrillar
  • Microcystic
3. Hair-like fibers best observed on smear or with GFAP
4. Rosenthal fibers
5. Eosinophilic granular bodies
6. Microvascular proliferation
7. Focal pseudopalisading necrosis

Low-grade astrocytoma

1. Stellate, spindle-shaped tumor cells with fiber like processes
2. Large eosinophilic cytoplasmic mass
3. Forms microcysts

Anaplastic astrocytoma

1. Astrocytic tumor cells with:

Glioblastoma multiforme

1. Astrocytic tumor cells with:

Oligodendroglioma

1. Diffusely growing tumor
2. Highly cellular lesion resembling fried eggs with:

Ependymoma

1. Tadpole-shaped cells resembling an ice cream cone
2. Nuclear features monotonous, i.e. "boring"
  • Little variation in size, shape, and staining
3. Rosettes: circular nuclear free zones/cells arranged in a pseudoglandular fashion (2 types)
  • Perivascular pseudorosettes: tumor cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumor cells) surrounding blood vessel (nucleus-free zone). More common than ependymal rosette but less specific
  • Ependymal rosette (true ependymal rosette): rosette has an empty space at the centre


Gallery

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 Pathology of glioma. http://www.surgwiki.com/wiki/Intracranial_tumours,_infection_and_aneurysms
  2. 2.0 2.1 Pathology of glioma. Wikipedia. https://en.wikipedia.org/wiki/Glioma
  3. 3.0 3.1 3.2 Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M (2006). "Epidemiology and molecular pathology of glioma". Nat Clin Pract Neurol. 2 (9): 494–503, quiz 1 p following 516. doi:10.1038/ncpneuro0289. PMID 16932614.
  4. 4.0 4.1 4.2 Pathology of gliomas. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
  5. 5.0 5.1 5.2 Pathology of anaplastic astrocytoma. Libre Pathology. http://librepathology.org/wiki/index.php?title=Neuropathology_tumours&redirect=no#Infiltrative_astrocytomas
  6. 6.0 6.1 6.2 Pathology of glioblastoma. Libre Pathology. http://librepathology.org/wiki/index.php/Glioblastoma
  7. 7.0 7.1 7.2 Pathology of ependymoma. Libre Pathology. http://librepathology.org/wiki/index.php/Ependymoma
  8. Dubois LG, Campanati L, Righy C, D'Andrea-Meira I, Spohr TC, Porto-Carreiro I; et al. (2014). "Gliomas and the vascular fragility of the blood brain barrier". Front Cell Neurosci. 8: 418. doi:10.3389/fncel.2014.00418. PMC 4264502. PMID 25565956.


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