Oligodendroglioma 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

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
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

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