Difference between revisions of "Oligodendroglioma"

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Oligodendroglioma (view source)

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| Image      = Oligodendroglioma1_high_mag.jpg
| Image      = Oligodendroglioma1_high_mag.jpg
| Width      =
| Width      =
| Caption    = Oligodendroglioma. [[H&E stain]].
| Caption    = Oligodendroglioma,IDH mutant and 1p/19q codeleted. [[H&E stain]].
| Synonyms  =
| Synonyms  =
| Micro      = highly cellular lesion composed of cells resembling ''fried eggs'' (oligodendrocytes) with a round nucleus (important), distinct cell borders, +/-clear cytoplasm - useful feature (if present), acutely branched capillary sized vessels ("chicken-wire" like appearance), calcifications
| Micro      = highly cellular lesion composed of cells resembling ''fried eggs'' (oligodendrocytes) with a round nucleus (important), distinct cell borders, +/-clear cytoplasm - useful feature (if present), acutely branched capillary sized vessels ("chicken-wire" like appearance), calcifications
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* First description of the tumor in 1926.  
* First description of the tumor in 1926.  


The WHO 2016 classification recognizes four tumor subtypes:<ref>{{Cite journal  | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref>
The fifth edition of WHO classification recognizes two tumor subtypes:
*Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO Grade II (ICD-O: 9450/3).
*Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO CNS Grade 2 (ICD-O: 9450/3).
*Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO Grade III (ICD-O: 9451/3).
*Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO CNS Grade 3 (ICD-O: 9451/3).
*Oligodendroglioma, NOS, WHO Grade II (ICD-O: 9450/3).
 
*Anaplastic oligodendroglioma, NOS, WHO Grade III (ICD-O: 9451/3).
The terminology anaplastic oligodendroglioma or oligoastrocytoma is depreceated. <ref>{{Cite journal  | last1 = Louis | first1 = DN. | last2 = Perry | first2 = A. | last3 = Reifenberger | first3 = G. | last4 = von Deimling | first4 = A. | last5 = Figarella-Branger | first5 = D. | last6 = Cavenee | first6 = WK. | last7 = Ohgaki | first7 = H. | last8 = Wiestler | first8 = OD. | last9 = Kleihues | first9 = P. | title = The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 803-20 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1545-1 | PMID = 27157931 }}</ref>


==Gross/radiologic==
==Gross/radiologic==
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*Nonenhancing or enhancing.
*Nonenhancing or enhancing.
*Occasionally well-circumscribed.
*Occasionally well-circumscribed.
*Widespread dissemination in a gliomatosis cerebri fashion is very rare (DDx: Diffuse leptomeningeal glioneuronal tumour).


Clinical symptoms:
Clinical symptoms:
*Seizures.
*Seizures (2/3 of all cases).
*Intracranial pressure.
*Intracranial pressure.
*Focal neurologic decifits.
*Focal neurologic decifits.
*Cognitive changes.
*Cognitive changes.
*Incidental finding in 10%.


==Microscopic==
==Microscopic==
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*Some tumors may show a [[Polar Spongioblastoma|Spongioblastoma]]-like growth pattern.  
*Some tumors may show a [[Polar Spongioblastoma|Spongioblastoma]]-like growth pattern.  


Anaplastic (grade III) criteria:<ref>{{Cite journal  | last1 = Giannini | first1 = C. | last2 = Scheithauer | first2 = BW. | last3 = Weaver | first3 = AL. | last4 = Burger | first4 = PC. | last5 = Kros | first5 = JM. | last6 = Mork | first6 = S. | last7 = Graeber | first7 = MB. | last8 = Bauserman | first8 = S. | last9 = Buckner | first9 = JC. | title = Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading. | journal = J Neuropathol Exp Neurol | volume = 60 | issue = 3 | pages = 248-62 | month = Mar | year = 2001 | doi =  | PMID = 11245209 }}</ref>
Anaplastic (grade 3) criteria:<ref>{{Cite journal  | last1 = Giannini | first1 = C. | last2 = Scheithauer | first2 = BW. | last3 = Weaver | first3 = AL. | last4 = Burger | first4 = PC. | last5 = Kros | first5 = JM. | last6 = Mork | first6 = S. | last7 = Graeber | first7 = MB. | last8 = Bauserman | first8 = S. | last9 = Buckner | first9 = JC. | title = Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading. | journal = J Neuropathol Exp Neurol | volume = 60 | issue = 3 | pages = 248-62 | month = Mar | year = 2001 | doi =  | PMID = 11245209 }}</ref>
*"Significant" or "brisk" mitotic activity.
*"Significant" or "brisk" mitotic activity.
**That means for most neuropathologists >= 6 mitoses per 10 HPF.
**That means for most neuropathologists >= 6 mitoses per 10 HPF.
*Microvacular proliferation.
*Microvacular proliferation.
*Necrosis.
*Necrosis.
*Rarely multnucleated cells.


Note:
Note:
* The clear cytoplasm around the nucleus is a fixation artefact and not seen in smear, frozen sections or rapid fixation.
* Tumour cells may be plasmacytoid, i.e. have a [[plasma cell]]-like appearance.<ref name=pmid17284109>{{Cite journal  | last1 = Aldape | first1 = K. | last2 = Burger | first2 = PC. | last3 = Perry | first3 = A. | title = Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. | journal = Arch Pathol Lab Med | volume = 131 | issue = 2 | pages = 242-51 | month = Feb | year = 2007 | doi = 10.1043/1543-2165(2007)131[242:CAOQLA]2.0.CO;2 | PMID = 17284109 | URL = http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2007)131%5B242:CAOQLA%5D2.0.CO;2 }}</ref>
* Tumour cells may be plasmacytoid, i.e. have a [[plasma cell]]-like appearance.<ref name=pmid17284109>{{Cite journal  | last1 = Aldape | first1 = K. | last2 = Burger | first2 = PC. | last3 = Perry | first3 = A. | title = Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. | journal = Arch Pathol Lab Med | volume = 131 | issue = 2 | pages = 242-51 | month = Feb | year = 2007 | doi = 10.1043/1543-2165(2007)131[242:CAOQLA]2.0.CO;2 | PMID = 17284109 | URL = http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2007)131%5B242:CAOQLA%5D2.0.CO;2 }}</ref>
**Also called minigemistocytes.
**Also called minigemistocytes.
**The are usually strong GFAP+ve.
**The are usually strong GFAP+ve.
 
*Few neural tumours have round nuclei - DDx in intraoperative specimen:
DDx:
*[[Neurocytoma]] also have perinuclear clearing and well-defined cellular borders.
**Pineocytomatous/neurocytic rosettes = (irregular) rosette with a large meshwork of fibers (neuropil) at the centre.
*Clear cell [[ependymoma]].
*[[Dysembryoplastic neuroepithelial tumour]].
*Oligodendroglial-like cells in [[Pilocytic astrocytoma]].
*Clear cell [[meningioma]].
*Demyelinisation.
 
 
Notes:
*Few neural tumours have round nuclei - DDx:
**Oligodendroglioma.
**Oligodendroglioma.
**[[Lymphoma]].
**[[Lymphoma]].
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#***Plump/large endothelial cells.
#***Plump/large endothelial cells.
#**Necrosis.
#**Necrosis.
#**High mitotic rate (6 mitoses/10 HPF for whatever "HPF" means, see [[HPFitis]]).
#**High mitotic rate (6 or more mitoses/10 HPF of 0.55mm²).
#*Without genetic testing for [[IDH-1]]/2 and LOH 1p/19q, the tumor is called Anaplastic oligodendroglioma, NOS.
#*Without genetic testing for [[IDH-1]]/2 and LOH 1p/19q, the tumor is called Anaplastic oligodendroglioma, NOS.


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*H3K27me3 -ve (nuclear loss).<ref>{{Cite journal  | last1 = Filipski | first1 = K. | last2 = Braun | first2 = Y. | last3 = Zinke | first3 = J. | last4 = Roller | first4 = B. | last5 = Baumgarten | first5 = P. | last6 = Wagner | first6 = M. | last7 = Senft | first7 = C. | last8 = Zeiner | first8 = PS. | last9 = Ronellenfitsch | first9 = MW. | title = Lack of H3K27 trimethylation is associated with 1p/19q codeletion in diffuse gliomas. | journal = Acta Neuropathol | volume =  | issue =  | pages =  | month = May | year = 2019 | doi = 10.1007/s00401-019-02025-9 | PMID = 31065834 }}</ref>  
*H3K27me3 -ve (nuclear loss).<ref>{{Cite journal  | last1 = Filipski | first1 = K. | last2 = Braun | first2 = Y. | last3 = Zinke | first3 = J. | last4 = Roller | first4 = B. | last5 = Baumgarten | first5 = P. | last6 = Wagner | first6 = M. | last7 = Senft | first7 = C. | last8 = Zeiner | first8 = PS. | last9 = Ronellenfitsch | first9 = MW. | title = Lack of H3K27 trimethylation is associated with 1p/19q codeletion in diffuse gliomas. | journal = Acta Neuropathol | volume =  | issue =  | pages =  | month = May | year = 2019 | doi = 10.1007/s00401-019-02025-9 | PMID = 31065834 }}</ref>  
*SOX10 +ve (up to 80%).<ref>{{Cite journal  | last1 = Bannykh | first1 = SI. | last2 = Stolt | first2 = CC. | last3 = Kim | first3 = J. | last4 = Perry | first4 = A. | last5 = Wegner | first5 = M. | title = Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas. | journal = J Neurooncol | volume = 76 | issue = 2 | pages = 115-27 | month = Jan | year = 2006 | doi = 10.1007/s11060-005-5533-x | PMID = 16205963 }}</ref>
*SOX10 +ve (up to 80%).<ref>{{Cite journal  | last1 = Bannykh | first1 = SI. | last2 = Stolt | first2 = CC. | last3 = Kim | first3 = J. | last4 = Perry | first4 = A. | last5 = Wegner | first5 = M. | title = Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas. | journal = J Neurooncol | volume = 76 | issue = 2 | pages = 115-27 | month = Jan | year = 2006 | doi = 10.1007/s11060-005-5533-x | PMID = 16205963 }}</ref>
*Olig2 +ve.
*H3 K27me3 nuclear loss in most cases.
*NOGO-A often +ve.
*p53 -ve or low expressed.
*p53 -ve or low expressed.
*Ki-67 (usu. >5% in grade II).
*Ki-67 (usu. >5% in CNS grade 2).
*May have neuronal "islands" (Synapto +ve, NeuN +ve).
*May have neuronal "islands" (Synapto +ve, NeuN +ve).


==Molecular pathology==
==Molecular pathology==
Combined losses of 1p and 19q both and presence of IDH1/2 mutation is required for final diagnosis and is prognostic and therapeutic relevant:<ref name=pmid18565359>{{cite journal |author=Fontaine D, Vandenbos F, Lebrun C, Paquis V, Frenay M |title=[Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice] |language=French |journal=Rev. Neurol. (Paris) |volume=164 |issue=6-7 |pages=595–604 |year=2008 |pmid=18565359 |doi=10.1016/j.neurol.2008.04.002 |url=}}</ref><ref>{{Cite journal  | last1 = Wiestler | first1 = B. | last2 = Capper | first2 = D. | last3 = Hovestadt | first3 = V. | last4 = Sill | first4 = M. | last5 = Jones | first5 = DT. | last6 = Hartmann | first6 = C. | last7 = Felsberg | first7 = J. | last8 = Platten | first8 = M. | last9 = Feiden | first9 = W. | title = Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial. | journal = Neuro Oncol | volume = 16 | issue = 12 | pages = 1630-8 | month = Dec | year = 2014 | doi = 10.1093/neuonc/nou138 | PMID = 25028501 }}</ref><ref>{{Cite journal  | last1 = Cairncross | first1 = G. | last2 = Wang | first2 = M. | last3 = Shaw | first3 = E. | last4 = Jenkins | first4 = R. | last5 = Brachman | first5 = D. | last6 = Buckner | first6 = J. | last7 = Fink | first7 = K. | last8 = Souhami | first8 = L. | last9 = Laperriere | first9 = N. | title = Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. | journal = J Clin Oncol | volume = 31 | issue = 3 | pages = 337-43 | month = Jan | year = 2013 | doi = 10.1200/JCO.2012.43.2674 | PMID = 23071247 }}</ref>
Combined losses of 1p and 19q both and presence of IDH1 mutation in codon 132 or IDH2 mutation in codon 172 is required for final diagnosis and is prognostic and therapeutic relevant:<ref name=pmid18565359>{{cite journal |author=Fontaine D, Vandenbos F, Lebrun C, Paquis V, Frenay M |title=[Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice] |language=French |journal=Rev. Neurol. (Paris) |volume=164 |issue=6-7 |pages=595–604 |year=2008 |pmid=18565359 |doi=10.1016/j.neurol.2008.04.002 |url=}}</ref><ref>{{Cite journal  | last1 = Wiestler | first1 = B. | last2 = Capper | first2 = D. | last3 = Hovestadt | first3 = V. | last4 = Sill | first4 = M. | last5 = Jones | first5 = DT. | last6 = Hartmann | first6 = C. | last7 = Felsberg | first7 = J. | last8 = Platten | first8 = M. | last9 = Feiden | first9 = W. | title = Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial. | journal = Neuro Oncol | volume = 16 | issue = 12 | pages = 1630-8 | month = Dec | year = 2014 | doi = 10.1093/neuonc/nou138 | PMID = 25028501 }}</ref><ref>{{Cite journal  | last1 = Cairncross | first1 = G. | last2 = Wang | first2 = M. | last3 = Shaw | first3 = E. | last4 = Jenkins | first4 = R. | last5 = Brachman | first5 = D. | last6 = Buckner | first6 = J. | last7 = Fink | first7 = K. | last8 = Souhami | first8 = L. | last9 = Laperriere | first9 = N. | title = Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. | journal = J Clin Oncol | volume = 31 | issue = 3 | pages = 337-43 | month = Jan | year = 2013 | doi = 10.1200/JCO.2012.43.2674 | PMID = 23071247 }}</ref>
*Greater chemosensitivity to PCV regimen.<ref>{{Cite journal  | last1 = Cairncross | first1 = G. | last2 = Wang | first2 = M. | last3 = Shaw | first3 = E. | last4 = Jenkins | first4 = R. | last5 = Brachman | first5 = D. | last6 = Buckner | first6 = J. | last7 = Fink | first7 = K. | last8 = Souhami | first8 = L. | last9 = Laperriere | first9 = N. | title = Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. | journal = J Clin Oncol | volume = 31 | issue = 3 | pages = 337-43 | month = Jan | year = 2013 | doi = 10.1200/JCO.2012.43.2674 | PMID = 23071247 }}</ref>
*Greater chemosensitivity to PCV regimen.<ref>{{Cite journal  | last1 = Cairncross | first1 = G. | last2 = Wang | first2 = M. | last3 = Shaw | first3 = E. | last4 = Jenkins | first4 = R. | last5 = Brachman | first5 = D. | last6 = Buckner | first6 = J. | last7 = Fink | first7 = K. | last8 = Souhami | first8 = L. | last9 = Laperriere | first9 = N. | title = Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. | journal = J Clin Oncol | volume = 31 | issue = 3 | pages = 337-43 | month = Jan | year = 2013 | doi = 10.1200/JCO.2012.43.2674 | PMID = 23071247 }}</ref>
*Better prognosis compared to astrocytic tumors.<ref>{{Cite journal  | last1 = Mur | first1 = P. | last2 = Mollejo | first2 = M. | last3 = Ruano | first3 = Y. | last4 = de Lope | first4 = ÁR. | last5 = Fiaño | first5 = C. | last6 = García | first6 = JF. | last7 = Castresana | first7 = JS. | last8 = Hernández-Laín | first8 = A. | last9 = Rey | first9 = JA. | title = Codeletion of 1p and 19q determines distinct gene methylation and expression profiles in IDH-mutated oligodendroglial tumors. | journal = Acta Neuropathol | volume = 126 | issue = 2 | pages = 277-89 | month = Aug | year = 2013 | doi = 10.1007/s00401-013-1130-9 | PMID = 23689617 }}</ref>
*Better prognosis compared to astrocytic tumors.<ref>{{Cite journal  | last1 = Mur | first1 = P. | last2 = Mollejo | first2 = M. | last3 = Ruano | first3 = Y. | last4 = de Lope | first4 = ÁR. | last5 = Fiaño | first5 = C. | last6 = García | first6 = JF. | last7 = Castresana | first7 = JS. | last8 = Hernández-Laín | first8 = A. | last9 = Rey | first9 = JA. | title = Codeletion of 1p and 19q determines distinct gene methylation and expression profiles in IDH-mutated oligodendroglial tumors. | journal = Acta Neuropathol | volume = 126 | issue = 2 | pages = 277-89 | month = Aug | year = 2013 | doi = 10.1007/s00401-013-1130-9 | PMID = 23689617 }}</ref>
*TERT promotor mutation present.
*CDKN2A homozygoud deletion in <10% of grade 3 tumours.
Note: If molecular testing fails, cases should be classified as Oligodendroglioma, NOS.
DDx:
*[[Neurocytoma]] also have perinuclear clearing and well-defined cellular borders.
**Pineocytomatous/neurocytic rosettes = (irregular) rosette with a large meshwork of fibers (neuropil) at the centre.
*Clear cell [[ependymoma]].
*[[Dysembryoplastic neuroepithelial tumour]].
*Oligodendroglial-like cells in [[Pilocytic astrocytoma]].
*Clear cell [[meningioma]]. (EMA +ve)
*Clear cell renal carcinoma. (Pan-CK +ve)
*Demyelinisation.
* [[Astrocytoma]]
** [[IDH-1]] mutant, but non-codeleted tumors with oligodendrogliom histologye are no longer classified as oligodendrogliomas on molecular basis. These tumors are classified as IDH-mutant astrocytoma.
* Diffuse leptomeningeal glioneuronal tumour (1p/19q codeletion present, but IDH wildtype)


Note:
Note:
*Consider underdiagnosed Glioblastoma, IDH-wildtype when tumor is IDH1/2 wildtype and has no LOH 1p/19q and no ATRX loss.
*Consider Glioblastoma with oligo features when tumor is IDH1/2 wildtype and has no LOH 1p/19q and no ATRX loss.
*[[IDH-1]] mutant, but non-codeleted tumors are no longer classified as oligodendrogliomas on molecular basis. These tumors are classified as IDH-mutant astrocytoma.
*Dual-genotype astrocytoma/oligodendroglioma are very rare.


==See also==
==See also==
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