Oligodendroglioma pathophysiology

	Oligodendroglioma Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Oligodendroglioma from other Diseases
Epidemiology & Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Diagnosis
Staging
History & Symptoms
Physical Examination
Laboratory Findings
Chest X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Oligodendroglioma pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Oligodendroglioma pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Oligodendroglioma pathophysiology
CDC on Oligodendroglioma pathophysiology
Oligodendroglioma pathophysiology in the news
Blogs on Oligodendroglioma pathophysiology
Directions to Hospitals Treating Oligodendroglioma
Risk calculators and risk factors for Oligodendroglioma pathophysiology

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

Overview

Pathophysiology

Pathogenesis

Oligodendroglioma does not arise from the bipotential oligodendrocytes, although tumor cells look very similiar.^[1]
Oligodendroglioma arises from the tripotential glial precursor cells.

Genetics

Development of oligodendroglioma is the result from multiple genetic mutations.
Genes associated with the pathogenesis of oligodendroglioma include:^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]

t[1;19][q10;p10] (co-deletion of chromosomal arms 1p and 19q; most common)
NJDS
IDH1
IDH2
CIC
FUBP1
p53
Leu-7
TCF-12
MGMT
TP73
EGFR
PTEN

There is a strong association of oligodendroglioma with expression of receptor tyrosine kinases that activate PI3K/AKT, RAS/MAP, and PLC/PKC pathways.^[10]

Gross Pathology

On gross pathology, oligodendroglioma is characterized by a well-circumscribed, gelatinous, gray mass which may expand a gyrus and remodel the skull.^[11]
Other characteristic gross pathological features associated with oligodendroglioma include:^[11]^[10]

Calcification (70-90%; one of the most frequently calcifying tumors)
Focal hemorrhage
Cystic (20%)

Common intracranial sites associated with oligodendroglioma include:^[12]

Cerebral hemispheres - distribution between frontal, parietal, temporal, and occipital lobe approximates 3:2:2:1
Posterior fossa (rare)
Intramedullary spinal cord (very rare)

Microscopic Pathology

On microscopic histopathological analysis, oligodendroglioma is characterized by:^[10] ^[13]^[14]^[15]

Diffusely growing tumor
Highly cellular lesion composed of cells resembling fried eggs with:
- Round nucleus - key feature
- Distinct cell borders
- Moderate-to-marked nuclear atypia with speckled "salt-and-pepper" chromatin pattern
- Clear cytoplasm
  - Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing
- Acutely branched capillary sized vessels - "chicken-wire" like appearance
  - Abundant, delicate appearing; may vaguely resemble a paraganglioma at low power
Calcifications - striking feature
Perifocal edema - rare
Few tumors may exhibit eosinophilic granular bodies
Some tumors may show a spongioblastoma-like growth pattern

On microscopic histopathological analysis, anaplastic oligodendroglioma is characterized by:^[13]

Focal or diffusely increased cell density
Atypical to frankly pleomorphic cells or multinucleated giant cells
Tumor cells may be plasmacytoid (i.e. have a plasma cell-like appearance)
- Also called as minigemistocytes
Significant or brisk mitotic activity (>= 6 mitoses per 10 HPF)
Necrosis
Numerous apoptotic cells
Microvacular proliferation
- Either in the form of 'glomeruloid' vessels or endothelial hyperplasia

Immunohistochemistry

Oligodendroglioma is demonstrated by positivity to tumor markers such as:^[16]^[17]^[10]

Gallery

Oligodendroglioma low magnification showing the characteristic small, branching, chicken wire-like blood vessels.H&E stain.^[18]
Oligodendroglioma high magnification showing highly cellular lesion composed of cells resembling fried eggs with distinct cell borders moderate-to-marked nuclear atypia, and a clear cytoplasm. Acutely branched capillary sized vessels - "chicken-wire" like appearance.^[18]
Low power magnification of oligodendroglioma biopsy specimen showing discrete infiltration of the surrounding brain (HE stain, x40 mag).^[19]
Histopathology of anaplastic oligodendroglioma showing minigemistocytes and mitoses among tumor cells with perinuclear halo. HE stain.^[19]
Histopathology of anaplastic oligodendroglioma (MAP2 staining) showing perinuclear immunoreactivity of tumor cells.^[19]
Histopathology of anaplastic oligodendroglioma (IDH1-R132H staining) showing immunoreactivity of tumor cells indicating presence of the isocitrate dehydrogenase 1-R132H mutation.^[19]

References

↑ General features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma#cite_note-1
↑ Molecular genetics of oligodendroglioma. https://en.wikipedia.org/wiki/Oligodendroglioma
↑ Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH; et al. (2011). "Mutations in CIC and FUBP1 contribute to human oligodendroglioma". Science. 333 (6048): 1453–5. doi:10.1126/science.1210557. PMC 3170506. PMID 21817013.
↑ Prognosis and treatment of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
↑ Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J; et al. (2012). "Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers". J Pathol. 226 (1): 7–16. doi:10.1002/path.2995. PMC 3246739. PMID 22072542.
↑ Labreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouzé E; et al. (2015). "TCF12 is mutated in anaplastic oligodendroglioma". Nat Commun. 6: 7207. doi:10.1038/ncomms8207. PMC 4490400. PMID 26068201.
↑ Suri V, Jha P, Agarwal S, Pathak P, Sharma MC, Sharma V; et al. (2011). "Molecular profile of oligodendrogliomas in young patients". Neuro Oncol. 13 (10): 1099–106. doi:10.1093/neuonc/nor146. PMC 3177666. PMID 21937591.
↑ Hagel C, Laking G, Laas R, Scheil S, Jung R, Milde-Langosch K; et al. (1996). "Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas". Eur J Cancer. 32A (13): 2242–8. PMID 9038605.
↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID doi:10.1016/S0090-3019(03)00167-8 Check |pmid= value (help).
↑ ^10.0 ^10.1 ^10.2 ^10.3 ^10.4 von Deimling, A; Hartmann, C (2005). "Oligodendrogliomas: Impact of molecular genetics on treatment". Neurology India. 53 (2): 140. doi:10.4103/0028-3886.16394. ISSN 0028-3886.
↑ ^11.0 ^11.1 Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma
↑ Gross/radiologic findings of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
↑ ^13.0 ^13.1 Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
↑ Ersen, Ayca (2008), Pathology of malignant gliomas: Challenges of everyday practice and the WHO 2007, Turkish Journal of Pathology, retrieved 9 October, 2015 Check date values in: |accessdate= (help)
↑ Eskandar EN, Loeffler JS, O'Neill AM, Hunter GJ, Louis DN (2004). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2004. A 34-year-old man with a seizure and a frontal-lobe brain lesion". N Engl J Med. 351 (18): 1875–82. doi:10.1056/NEJMcpc049025. PMID 15509821.
↑ IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma
↑ Hilbig A, Barbosa-Coutinho LM, Netto GC, Bleil CB, Toscani NV (2006). "[Immunohistochemistry in oligodendrogliomas]". Arq Neuropsiquiatr. 64 (1): 67–71. doi:/S0004-282X2006000100014 Check |doi= value (help). PMID 16622556.
↑ ^18.0 ^18.1 Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma
↑ ^19.0 ^19.1 ^19.2 ^19.3 Images of oligodendroglioma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Oligodendroglioma

Template:WikiDoc Sources

[pathogenesis-1] General features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma#cite_note-1

[transloc-2] Molecular genetics of oligodendroglioma. https://en.wikipedia.org/wiki/Oligodendroglioma

[pmid21817013-3] Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH; et al. (2011). "Mutations in CIC and FUBP1 contribute to human oligodendroglioma". Science. 333 (6048): 1453–5. doi:10.1126/science.1210557. PMC 3170506. PMID 21817013.

[prog-4] Prognosis and treatment of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma

[pmid22072542-5] Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J; et al. (2012). "Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers". J Pathol. 226 (1): 7–16. doi:10.1002/path.2995. PMC 3246739. PMID 22072542.

[pmid26068201-6] Labreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouzé E; et al. (2015). "TCF12 is mutated in anaplastic oligodendroglioma". Nat Commun. 6: 7207. doi:10.1038/ncomms8207. PMC 4490400. PMID 26068201.

[pmid21937591-7] Suri V, Jha P, Agarwal S, Pathak P, Sharma MC, Sharma V; et al. (2011). "Molecular profile of oligodendrogliomas in young patients". Neuro Oncol. 13 (10): 1099–106. doi:10.1093/neuonc/nor146. PMC 3177666. PMID 21937591.

[pmid9038605-8] Hagel C, Laking G, Laas R, Scheil S, Jung R, Milde-Langosch K; et al. (1996). "Demonstration of p53 protein and TP53 gene mutations in oligodendrogliomas". Eur J Cancer. 32A (13): 2242–8. PMID 9038605.

[pmiddoi:10.1016/S0090-3019(03)00167-8-9] Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID doi:10.1016/S0090-3019(03)00167-8 Check |pmid= value (help).

[von_DeimlingHartmann2005-10] 10.0 ^10.1 ^10.2 ^10.3 ^10.4 von Deimling, A; Hartmann, C (2005). "Oligodendrogliomas: Impact of molecular genetics on treatment". Neurology India. 53 (2): 140. doi:10.4103/0028-3886.16394. ISSN 0028-3886.

[grosspa-11] 11.0 ^11.1 Gross appearance of oligodendroglioma. Dr Henry Knipe and Dr Frank Gaillard et al. http://radiopaedia.org/articles/oligodendroglioma

[gross-12] Gross/radiologic findings of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma

[micro-13] 13.0 ^13.1 Microscopic features of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma

[turk-14] Ersen, Ayca (2008), Pathology of malignant gliomas: Challenges of everyday practice and the WHO 2007, Turkish Journal of Pathology, retrieved 9 October, 2015 Check date values in: |accessdate= (help)

[pmid15509821-15] Eskandar EN, Loeffler JS, O'Neill AM, Hunter GJ, Louis DN (2004). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-2004. A 34-year-old man with a seizure and a frontal-lobe brain lesion". N Engl J Med. 351 (18): 1875–82. doi:10.1056/NEJMcpc049025. PMID 15509821.

[IHC-16] IHC of oligodendroglioma. Libre Pathology. http://librepathology.org/wiki/index.php/Oligodendroglioma

[pmid16622556-17] Hilbig A, Barbosa-Coutinho LM, Netto GC, Bleil CB, Toscani NV (2006). "[Immunohistochemistry in oligodendrogliomas]". Arq Neuropsiquiatr. 64 (1): 67–71. doi:/S0004-282X2006000100014 Check |doi= value (help). PMID 16622556.

[microscope-18] 18.0 ^18.1 Images of microscopic appearance of oligodendroglioma. Wikipedia 2015. https://en.wikipedia.org/wiki/Oligodendroglioma

[LP-19] 19.0 ^19.1 ^19.2 ^19.3 Images of oligodendroglioma. Libre Pathology 2015. http://librepathology.org/wiki/index.php/Oligodendroglioma

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]