Difference between revisions of "Oligodendroglioma"

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(WHO diagnostic guidelines)
(→‎IHC: SOX10 and H3k27me3 added)
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*IDH-1 (R132H) +ve (approx 85%).
*IDH-1 (R132H) +ve (approx 85%).
**18% +ve in one series of children,<ref name=pmid24805856>{{Cite journal  | last1 = Rodriguez | first1 = FJ. | last2 = Tihan | first2 = T. | last3 = Lin | first3 = D. | last4 = McDonald | first4 = W. | last5 = Nigro | first5 = J. | last6 = Feuerstein | first6 = B. | last7 = Jackson | first7 = S. | last8 = Cohen | first8 = K. | last9 = Burger | first9 = PC. | title = Clinicopathologic features of pediatric oligodendrogliomas: a series of 50 patients. | journal = Am J Surg Pathol | volume = 38 | issue = 8 | pages = 1058-70 | month = Aug | year = 2014 | doi = 10.1097/PAS.0000000000000221 | PMID = 24805856 }}</ref> 23% +ve in another series.<ref name=pmid23361281>{{Cite journal  | last1 = Sipayya | first1 = V. | last2 = Sharma | first2 = I. | last3 = Sharma | first3 = KC. | last4 = Singh | first4 = A. | title = Immunohistochemical expression of IDH1 in gliomas: a tissue microarray-based approach. | journal = J Cancer Res Ther | volume = 8 | issue = 4 | pages = 598-601 | month =  | year =  | doi = 10.4103/0973-1482.106567 | PMID = 23361281 }}</ref>
**18% +ve in one series of children,<ref name=pmid24805856>{{Cite journal  | last1 = Rodriguez | first1 = FJ. | last2 = Tihan | first2 = T. | last3 = Lin | first3 = D. | last4 = McDonald | first4 = W. | last5 = Nigro | first5 = J. | last6 = Feuerstein | first6 = B. | last7 = Jackson | first7 = S. | last8 = Cohen | first8 = K. | last9 = Burger | first9 = PC. | title = Clinicopathologic features of pediatric oligodendrogliomas: a series of 50 patients. | journal = Am J Surg Pathol | volume = 38 | issue = 8 | pages = 1058-70 | month = Aug | year = 2014 | doi = 10.1097/PAS.0000000000000221 | PMID = 24805856 }}</ref> 23% +ve in another series.<ref name=pmid23361281>{{Cite journal  | last1 = Sipayya | first1 = V. | last2 = Sharma | first2 = I. | last3 = Sharma | first3 = KC. | last4 = Singh | first4 = A. | title = Immunohistochemical expression of IDH1 in gliomas: a tissue microarray-based approach. | journal = J Cancer Res Ther | volume = 8 | issue = 4 | pages = 598-601 | month =  | year =  | doi = 10.4103/0973-1482.106567 | PMID = 23361281 }}</ref>
*ATRX +ve.
*ATRX +ve (nuclear retention).
**Useful for differentiating ''astrocytoma'' vs. ''oligodendroglioma''.<ref>{{Cite journal  | last1 = Reuss | first1 = DE. | last2 = Sahm | first2 = F. | last3 = Schrimpf | first3 = D. | last4 = Wiestler | first4 = B. | last5 = Capper | first5 = D. | last6 = Koelsche | first6 = C. | last7 = Schweizer | first7 = L. | last8 = Korshunov | first8 = A. | last9 = Jones | first9 = DT. | title = ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. | journal = Acta Neuropathol | volume = 129 | issue = 1 | pages = 133-46 | month = Jan | year = 2015 | doi = 10.1007/s00401-014-1370-3 | PMID = 25427834 }}</ref>
**Useful for differentiating ''astrocytoma'' vs. ''oligodendroglioma''.<ref>{{Cite journal  | last1 = Reuss | first1 = DE. | last2 = Sahm | first2 = F. | last3 = Schrimpf | first3 = D. | last4 = Wiestler | first4 = B. | last5 = Capper | first5 = D. | last6 = Koelsche | first6 = C. | last7 = Schweizer | first7 = L. | last8 = Korshunov | first8 = A. | last9 = Jones | first9 = DT. | title = ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. | journal = Acta Neuropathol | volume = 129 | issue = 1 | pages = 133-46 | month = Jan | year = 2015 | doi = 10.1007/s00401-014-1370-3 | PMID = 25427834 }}</ref>
*p53 -ve.
*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>
*p53 -ve or low expressed.
*Ki-67 (usu. >5% in grade II).
*Ki-67 (usu. >5% in grade II).
*May have neuronal "islands" (Synapto +ve, NeuN +ve).
*May have neuronal "islands" (Synapto +ve, NeuN +ve).

Revision as of 07:35, 15 May 2019

Oligodendroglioma
Diagnosis in short

Oligodendroglioma. H&E stain.
LM 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
LM DDx neurocytoma, clear cell variant of ependymoma, seminoma / dysgerminoma / germinoma
Molecular +/-loss of 1p and 19q (common)
Site neuropathology tumours - cerebral hemispheres, posterior fossa (rare), spinal cord (very rare)
Radiology intra-axial mass, +/-calcifications (best seen on CT), nonenhancing or enhancing
Prognosis moderate - dependent on grade

Oligodendroglioma is CNS tumour that is typically in the cerebral hemispheres.

General

  • Do not arise from oligodendrocytes, although tumor cells look very similiar.[1]
    • Arise from glial precursor cells.

Prognosis by flavours (average survival):[2]

  • WHO grade II: 10-15 years.
  • WHO grade III: 3-5 years.

Oligodendrogliomas account for approx 5% of all gliomas.

  • Numbers may be higher when stringent classifiation criteria are not applied.
  • Peak incidence: 40-45 years.
  • First description of the tumor in 1926.

The WHO 2016 classification recognizes four tumor subtypes:[3]

  • Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO Grade II (ICD-O: 9450/3).
  • Anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO Grade III (ICD-O: 9451/3).
  • Oligodendroglioma, NOS, WHO Grade II (ICD-O: 9450/3).
  • Anaplastic oligodendroglioma, NOS, WHO Grade III (ICD-O: 9451/3).

Gross/radiologic

Location:

  • Cerebral hemispheres - most often (50-60%) frontal lobe, followed by parietal and temporal lobes.[4]
  • Posterior fossa (rare).
  • Intramedullary spinal cord (very rare).

Radiologic features:[4]

  • Intra-axial mass.
  • +/-Calcifications (best seen on CT).
  • Nonenhancing or enhancing.
  • Occasionally well-circumscribed.

Clinical symptoms:

  • Seizures.
  • Intracranial pressure.
  • Focal neurologic decifits.
  • Cognitive changes.

Microscopic

Features:

  • Diffusely growing tumor.
  • Highly cellular lesion composed of:
    • Cells resembling fried eggs (oligodendrocytes) with:
      • Round nucleus - key feature.
      • Distinct cell borders.
      • Moderate-to-marked nuclear atypia.
      • Clear cytoplasm - useful feature (if present).
        • 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 - important feature.[5]
  • Perifocal edema uncommon.
  • Few tumors may exhibit eosinophilic granular bodies.
  • Some tumors may show a Spongioblastoma-like growth pattern.

Anaplastic (grade III) criteria:[6]

  • "Significant" or "brisk" mitotic activity.
    • That means for most neuropathologists >= 6 mitoses per 10 HPF.
  • Microvacular proliferation.
  • Necrosis.

Note:

  • Tumour cells may be plasmacytoid, i.e. have a plasma cell-like appearance.[7]
    • Also called minigemistocytes.
    • The are usually strong GFAP+ve.

DDx:


Notes:

Images

  • Oligodendroglioma high mag. (WC)

  • Oligodendroglioma low mag. (WC)

  • Discrete invasion in a oligodendroglioma. (WC/jensflorian)

  • Minigemistocytes and mitoses. (WC/jensflorian)

  • Perinuclear MAP2 immunoreactivity in oligodendroglioma. (WC/jensflorian)

  • Demonstration of IDH1 R132H mutation in oligodendroglioma. (WC/jensflorian)

www:

Histologic grading

Come in two flavours:

  1. WHO grade II.
    • This is most oligodendrogliomas.
    • Without genetic testing for IDH-1 and LOH 1p/19q, the tumor is called Oligodendroglioma, NOS.
  2. WHO grade III.
    • Features for calling high grade:[2]
      • Endothelial hypertrophy.
        • Plump/large endothelial cells.
      • Necrosis.
      • High mitotic rate (6 mitoses/10 HPF for whatever "HPF" means, see HPFitis).
    • Without genetic testing for IDH-1 and LOH 1p/19q, the tumor is called Anaplastic oligodendroglioma, NOS.

IHC

Features:

  • MAP2 +ve.[8]
  • GFAP +ve (variable).
    • Some subtypes +ve - should not be used to distinguish.[9]
  • EMA +ve.
  • IDH-1 (R132H) +ve (approx 85%).
    • 18% +ve in one series of children,[10] 23% +ve in another series.[11]
  • ATRX +ve (nuclear retention).
    • Useful for differentiating astrocytoma vs. oligodendroglioma.[12]
  • H3K27me3 +ve (nuclear loss).[13]
  • SOX10 +ve (up to 80%).[14]
  • p53 -ve or low expressed.
  • Ki-67 (usu. >5% in grade II).
  • May have neuronal "islands" (Synapto +ve, NeuN +ve).

Molecular pathology

Combined losses of 1p and 19q both is required for final diagnosis and is prognostic and therapeutic relevant:[15][16][17]

  • Greater chemosensitivity
  • Better prognosis.

Note:

  • Consider underdiagnosed Glioblastoma, IDH-wildtype 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 either as IDH-mutant astrocytoma or glioblastoma, depending on histologic features present.

See also

References

  1. ↑ Hartmann, C.; von Deimling, A. (2009). "Molecular pathology of oligodendroglial tumors.". Recent Results Cancer Res 171: 25-49. doi:10.1007/978-3-540-31206-2_2. PMID 19322536.
  2. ↑ 2.0 2.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 98. ISBN 978-0443069826.
  3. ↑ Louis, DN.; Perry, A.; Reifenberger, G.; von Deimling, A.; Figarella-Branger, D.; Cavenee, WK.; Ohgaki, H.; Wiestler, OD. et al. (Jun 2016). "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.". Acta Neuropathol 131 (6): 803-20. doi:10.1007/s00401-016-1545-1. PMID 27157931.
  4. ↑ 4.0 4.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 94. ISBN 978-0443069826.
  5. ↑ URL: http://www.emedicine.com/radio/topic481.htm.
  6. ↑ Giannini, C.; Scheithauer, BW.; Weaver, AL.; Burger, PC.; Kros, JM.; Mork, S.; Graeber, MB.; Bauserman, S. et al. (Mar 2001). "Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading.". J Neuropathol Exp Neurol 60 (3): 248-62. PMID 11245209.
  7. ↑ Aldape, K.; Burger, PC.; Perry, A. (Feb 2007). "Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma.". Arch Pathol Lab Med 131 (2): 242-51. doi:10.1043/1543-2165(2007)131[242:CAOQLA]2.0.CO;2. PMID 17284109.
  8. ↑ Suzuki SO, Kitai R, Llena J, Lee SC, Goldman JE, Shafit-Zagardo B (May 2002). "MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration". J. Neuropathol. Exp. Neurol. 61 (5): 403–12. PMID 12025943.
  9. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 98. ISBN 978-0443069826.
  10. ↑ Rodriguez, FJ.; Tihan, T.; Lin, D.; McDonald, W.; Nigro, J.; Feuerstein, B.; Jackson, S.; Cohen, K. et al. (Aug 2014). "Clinicopathologic features of pediatric oligodendrogliomas: a series of 50 patients.". Am J Surg Pathol 38 (8): 1058-70. doi:10.1097/PAS.0000000000000221. PMID 24805856.
  11. ↑ Sipayya, V.; Sharma, I.; Sharma, KC.; Singh, A.. "Immunohistochemical expression of IDH1 in gliomas: a tissue microarray-based approach.". J Cancer Res Ther 8 (4): 598-601. doi:10.4103/0973-1482.106567. PMID 23361281.
  12. ↑ Reuss, DE.; Sahm, F.; Schrimpf, D.; Wiestler, B.; Capper, D.; Koelsche, C.; Schweizer, L.; Korshunov, A. et al. (Jan 2015). "ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma.". Acta Neuropathol 129 (1): 133-46. doi:10.1007/s00401-014-1370-3. PMID 25427834.
  13. ↑ Filipski, K.; Braun, Y.; Zinke, J.; Roller, B.; Baumgarten, P.; Wagner, M.; Senft, C.; Zeiner, PS. et al. (May 2019). "Lack of H3K27 trimethylation is associated with 1p/19q codeletion in diffuse gliomas.". Acta Neuropathol. doi:10.1007/s00401-019-02025-9. PMID 31065834.
  14. ↑ Bannykh, SI.; Stolt, CC.; Kim, J.; Perry, A.; Wegner, M. (Jan 2006). "Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas.". J Neurooncol 76 (2): 115-27. doi:10.1007/s11060-005-5533-x. PMID 16205963.
  15. ↑ Fontaine D, Vandenbos F, Lebrun C, Paquis V, Frenay M (2008). "[Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice]" (in French). Rev. Neurol. (Paris) 164 (6-7): 595–604. doi:10.1016/j.neurol.2008.04.002. PMID 18565359.
  16. ↑ Wiestler, B.; Capper, D.; Hovestadt, V.; Sill, M.; Jones, DT.; Hartmann, C.; Felsberg, J.; Platten, M. et al. (Dec 2014). "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.". Neuro Oncol 16 (12): 1630-8. doi:10.1093/neuonc/nou138. PMID 25028501.
  17. ↑ Cairncross, G.; Wang, M.; Shaw, E.; Jenkins, R.; Brachman, D.; Buckner, J.; Fink, K.; Souhami, L. et al. (Jan 2013). "Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402.". J Clin Oncol 31 (3): 337-43. doi:10.1200/JCO.2012.43.2674. PMID 23071247.
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