Oligoastrocytoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Overview

Oligoastrocytomas are mixed tumors that arise from the proliferation of both oligodendrocytes and astrocytes. Genes associated with the pathogenesis of oligoastrocytoma and anaplastic oligoastrocytoma include IDH1, p53, EGFR, ATRX, EGFR, PTEN, MGMT, CIC, and FUBP1. 30-70% of oligoastrocytomas show loss of heterozygosity (LOH) of 1p and 19q. On gross pathology, oligoastrocytoma is characterized by a soft, well-defined, grey-tan, mucoid or hemorrhagic, calcified mass with or without necrosis, which may expand the gyrus and cause blurring of the grey-white junction. On microscopic histopathological analysis, oligoastrocytoma is characterized by highly cellular lesions composed of both oligodendroglial and astrocytic components. In addition to the histological features of oligoastrocytoma, anaplastic oligoastrocytoma also has significant or brisk mitotic activity, marked cytologic and nuclear atypia, necrosis, apoptosis, and microvacular proliferation. Oligoastrocytoma is demonstrated by positivity to tumor markers such as MAP2, GFAP, IDH1, OLIG-1 protein, OLIG-2 protein, and Iba-2 protein.

Pathophysiology

Pathogenesis

Oligoastrocytomas are mixed tumors that arises from the proliferation of both oligodendrocytes and astrocytes.^[1]
Oligoastrocytomas are low-grade (grade II) tumors and anaplastic oligoastrocytomas are high-grade (grade III) tumors that occur in the brain.^[2]

Genetics

Development of oligoastrocytoma is the result of multiple genetic mutations.
Oligoastrocytomas are mixed tumors that have overlapping molecular genetics with both oligodendrogliomas and astrocytomas.^[3]
30-70% of oligoastrocytomas show loss of heterozygosity (LOH) of 1p and 19q.^[3]^[4]^[5]
Genes associated with the pathogenesis of oligoastrocytoma and anaplastic oligoastrocytoma include:^[3]^[6]^[7]^[8]^[9]^[10]^[11]^[4]

IDH1
p53
EGFR
ATRX
EGFR
PTEN
MGMT
CIC
FUBP1

Gross Pathology

On gross pathology, oligoastrocytoma is characterized by a soft, well-defined, grey-tan, mucoid or hemorrhagic, calcified mass with or without necrosis, which may expand the gyrus and cause blurring of the grey-white matter junction.^[4]
Oligoastrocytomas are commonly found in the supratentorial region.
Common intracranial sites associated with oligoastrocytoma include:^[12]^[13]^[14]^[3]
- Frontal lobe (most common)
- Temporal lobe
- Parietal lobe
- Occipital lobe
- Insula
- Diencephalon
- Spinal cord

Microscopic Pathology

Low-Grade Oligoastrocytoma

On microscopic histopathological analysis, oligoastrocytoma is characterized by:^[15]^[16]^[17]^[18]^[19]

Highly cellular lesions composed of both oligodendroglial and astrocytic components
Two types of pattern: biphasic and diffuse
- Biphasic pattern demonstrates oligodendroglial and astrocytic differentiation, whereas diffuse pattern demonstrates intermingling of both the components
Oligodendrocytes
- Fried-egg shaped cells
- Composed of minigemistocytes
- Round nucleus
- Distinct cell borders
- Moderate-to-marked nuclear atypia with speckled "salt-and-pepper" chromatin pattern and perinuclear halo
- Focal microcalcification
Astrocytes
- Star-shaped cells
- Composed of gemistocytes
- Multinucleated giant cells
- Ovoid nucleus
- Nuclear atypia

Anaplastic Oligoastrocytoma

On microscopic histopathological analysis, anaplastic oligoastrocytoma is characterized by:^[15]^[16]^[17]

Significant or brisk mitotic activity (≥ 6 mitoses per 10 high power field)
Marked cytologic and nuclear atypia
Necrosis
Apoptotic cells
Microvacular proliferation
- 'Glomeruloid' vessels or endothelial hyperplasia

Gallery

_{Biopsy specimen of an oligoastrocytoma (HE stain).^[20]}

Immunohistochemistry

Oligoastrocytoma is demonstrated by positivity to tumor markers such as:^[21]^[22]^[11]^[23]^[4]

Gallery

_{Histology of oligoastrocytoma cells demonstrating positivity to tumor marker GFAP.^[24]}
_{Histology of oligoastrocytoma cells demonstrating positivity to tumor marker Ki-67.^[25]}

References

↑ Introduction of oligodendroglioma and oligoastrocytoma. American Brain Tumor Association. http://www.abta.org/secure/oligodendrioma-oligo.pdf. Accessed on October 16, 2015
↑ Mixed Gliomas. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/brain-spinal/brain-and-spinal-tumours/mixed-glioma/?region=on#ixzz3okGrTzyi. Accessed on October 16, 2015
↑ ^3.0 ^3.1 ^3.2 ^3.3 Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J; et al. (2002). "Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets". Am J Pathol. 161 (1): 313–9. doi:10.1016/S0002-9440(10)64183-1. PMC 1850690. PMID 12107116.
↑ ^4.0 ^4.1 ^4.2 ^4.3 Adesina, Adekunle (2010). Atlas of pediatric brain tumors. New York: Springer. ISBN 9781441910622.
↑ Cause of oligoastrocytoma. American Brain Tumor Association 2015. http://www.abta.org/secure/oligodendrioma-oligo.pdf. Accessed on October 21, 2015
↑ Sahm F, Reuss D, Koelsche C, Capper D, Schittenhelm J, Heim S; et al. (2014). "Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma". Acta Neuropathol. 128 (4): 551–9. doi:10.1007/s00401-014-1326-7. PMID 25143301.
↑ Viana-Pereira M, Lopes JM, Little S, Milanezi F, Basto D, Pardal F; et al. (2008). "Analysis of EGFR overexpression, EGFR gene amplification and the EGFRvIII mutation in Portuguese high-grade gliomas". Anticancer Res. 28 (2A): 913–20. PMID 18507036.
↑ Ermoian RP, Furniss CS, Lamborn KR, Basila D, Berger MS, Gottschalk AR; et al. (2002). "Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival". Clin Cancer Res. 8 (5): 1100–6. PMID 12006525.
↑ van den Bent MJ, Erdem-Eraslan L, Idbaih A, de Rooi J, Eilers PH, Spliet WG; et al. (2013). "MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951". Clin Cancer Res. 19 (19): 5513–22. doi:10.1158/1078-0432.CCR-13-1157. PMID 23948976.
↑ Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM, de Wilde RF; et al. (2012). "Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas". Oncotarget. 3 (7): 709–22. PMC 3443254. PMID 22869205.
↑ ^11.0 ^11.1 Liang Y, Bollen AW, Nicholas MK, Gupta N (2005). "Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas". BMC Clin Pathol. 5: 6. doi:10.1186/1472-6890-5-6. PMC 1182359. PMID 16018821.
↑ Location of oligoastrocytoma. Dr. Bruno Di Muzio and Dr. Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/oligoastrocytoma. Accessed on October 19, 2015
↑ Shimizu T, Saito N, Aihara M, Kurihara H, Nakazato Y, Ueki K; et al. (2004). "Primary spinal oligoastrocytoma: a case report". Surg Neurol. 61 (1): 77–81, discussion 81. PMID 14706386.
↑ Oligoastrocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligoastrocytoma. Accessed on October 20, 2015
↑ ^15.0 ^15.1 Pathology of oligoastrocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/oligoastrocytoma. Accessed on October 16, 2015
↑ ^16.0 ^16.1 Naugle DK, Duncan TD, Grice GP (2004). "Oligoastrocytoma". Radiographics. 24 (2): 598–600. doi:10.1148/rg.242035069. PMID 15026604.
↑ ^17.0 ^17.1 Pathology of oligoastrocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligoastrocytoma. Accessed on October 16, 2015
↑ Love, S.; Loius, D. & Ellison, D.W. (2008), Greenfield's neuropathology, 1 (8th ed.), Boca Raton, Florida: Hodder Arnold
↑ Histology of anaplastic oligoastrocytes. Dr. Frank Gaillard. Radiopaedia 2015. http://radiopaedia.org/cases/anaplastic-oligoastrocytoma. Accessed on October 19, 2015
↑ Classification and external sources of oligoastrocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligoastrocytoma. Accessed on October 20, 2015
↑ IHC of oligoastrocytoma. Librepathology 2015. http://librepathology.org/wiki/index.php/Oligoastrocytoma. Accessed on October 16, 2015
↑ Kolenda-Roberts HM, Harris N, Singletary E, Hardisty JF (2013). "Immunohistochemical characterization of spontaneous and acrylonitrile-induced brain tumors in the rat". Toxicol Pathol. 41 (1): 98–108. doi:10.1177/0192623312452492. PMID 22821367.
↑ Grier, J. T. (2006). "Low-Grade Gliomas in Adults". The Oncologist. 11 (6): 681–693. doi:10.1634/theoncologist.11-6-681. ISSN 1083-7159.
↑ Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file here). Creative Commons BY-SA-NC
↑ Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file here). Creative Commons BY-SA-NC

Template:WikiDoc Sources

[pathogenesis-1] Introduction of oligodendroglioma and oligoastrocytoma. American Brain Tumor Association. http://www.abta.org/secure/oligodendrioma-oligo.pdf. Accessed on October 16, 2015

[pathogenesis2-2] Mixed Gliomas. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/brain-spinal/brain-and-spinal-tumours/mixed-glioma/?region=on#ixzz3okGrTzyi. Accessed on October 16, 2015

[pmid12107116-3] 3.0 ^3.1 ^3.2 ^3.3 Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J; et al. (2002). "Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets". Am J Pathol. 161 (1): 313–9. doi:10.1016/S0002-9440(10)64183-1. PMC 1850690. PMID 12107116.

[pathoOA1-4] 4.0 ^4.1 ^4.2 ^4.3 Adesina, Adekunle (2010). Atlas of pediatric brain tumors. New York: Springer. ISBN 9781441910622.

[OAsymp3-5] Cause of oligoastrocytoma. American Brain Tumor Association 2015. http://www.abta.org/secure/oligodendrioma-oligo.pdf. Accessed on October 21, 2015

[pmid25143301-6] Sahm F, Reuss D, Koelsche C, Capper D, Schittenhelm J, Heim S; et al. (2014). "Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma". Acta Neuropathol. 128 (4): 551–9. doi:10.1007/s00401-014-1326-7. PMID 25143301.

[pmid18507036-7] Viana-Pereira M, Lopes JM, Little S, Milanezi F, Basto D, Pardal F; et al. (2008). "Analysis of EGFR overexpression, EGFR gene amplification and the EGFRvIII mutation in Portuguese high-grade gliomas". Anticancer Res. 28 (2A): 913–20. PMID 18507036.

[pmid12006525-8] Ermoian RP, Furniss CS, Lamborn KR, Basila D, Berger MS, Gottschalk AR; et al. (2002). "Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival". Clin Cancer Res. 8 (5): 1100–6. PMID 12006525.

[pmid23948976-9] van den Bent MJ, Erdem-Eraslan L, Idbaih A, de Rooi J, Eilers PH, Spliet WG; et al. (2013). "MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951". Clin Cancer Res. 19 (19): 5513–22. doi:10.1158/1078-0432.CCR-13-1157. PMID 23948976.

[pmid22869205-10] Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM, de Wilde RF; et al. (2012). "Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas". Oncotarget. 3 (7): 709–22. PMC 3443254. PMID 22869205.

[pmid16018821-11] 11.0 ^11.1 Liang Y, Bollen AW, Nicholas MK, Gupta N (2005). "Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas". BMC Clin Pathol. 5: 6. doi:10.1186/1472-6890-5-6. PMC 1182359. PMID 16018821.

[locOA-12] Location of oligoastrocytoma. Dr. Bruno Di Muzio and Dr. Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/oligoastrocytoma. Accessed on October 19, 2015

[pmid14706386-13] Shimizu T, Saito N, Aihara M, Kurihara H, Nakazato Y, Ueki K; et al. (2004). "Primary spinal oligoastrocytoma: a case report". Surg Neurol. 61 (1): 77–81, discussion 81. PMID 14706386.

[wikigross-14] Oligoastrocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligoastrocytoma. Accessed on October 20, 2015

[patho1-15] 15.0 ^15.1 Pathology of oligoastrocytoma. Dr Bruno Di Muzio and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/oligoastrocytoma. Accessed on October 16, 2015

[pmid15026604-16] 16.0 ^16.1 Naugle DK, Duncan TD, Grice GP (2004). "Oligoastrocytoma". Radiographics. 24 (2): 598–600. doi:10.1148/rg.242035069. PMID 15026604.

[pathowiki-17] 17.0 ^17.1 Pathology of oligoastrocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligoastrocytoma. Accessed on October 16, 2015

[bookneuropathologyoligoastro-18] Love, S.; Loius, D. & Ellison, D.W. (2008), Greenfield's neuropathology, 1 (8th ed.), Boca Raton, Florida: Hodder Arnold

[histoOA-19] Histology of anaplastic oligoastrocytes. Dr. Frank Gaillard. Radiopaedia 2015. http://radiopaedia.org/cases/anaplastic-oligoastrocytoma. Accessed on October 19, 2015

[microwikiOA1-20] Classification and external sources of oligoastrocytoma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligoastrocytoma. Accessed on October 20, 2015

[IHC-21] IHC of oligoastrocytoma. Librepathology 2015. http://librepathology.org/wiki/index.php/Oligoastrocytoma. Accessed on October 16, 2015

[pmid22821367-22] Kolenda-Roberts HM, Harris N, Singletary E, Hardisty JF (2013). "Immunohistochemical characterization of spontaneous and acrylonitrile-induced brain tumors in the rat". Toxicol Pathol. 41 (1): 98–108. doi:10.1177/0192623312452492. PMID 22821367.

[Grier2006-23] Grier, J. T. (2006). "Low-Grade Gliomas in Adults". The Oncologist. 11 (6): 681–693. doi:10.1634/theoncologist.11-6-681. ISSN 1083-7159.

[ihc1OA-24] Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file here). Creative Commons BY-SA-NC

[ihc02OA-25] Image courtesy of Dr. Frank Gaillard. Radiopaedia (original file here). Creative Commons BY-SA-NC

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Oligoastrocytoma pathophysiology

Overview

Pathophysiology

Pathogenesis

Genetics

Gross Pathology

Microscopic Pathology

Low-Grade Oligoastrocytoma

Anaplastic Oligoastrocytoma

Gallery

Immunohistochemistry

Gallery

References

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