Difference between revisions of "Neuropathology tumours"

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[[Image:Gemistocytic Astrocytoma 003.jpg|thumb|right|A brain stem [[astrocytoma]]. (WC)]]
The article covers '''tumours in neuropathology'''.  Tumours are a large part of [[neuropathology]].  [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.
The article covers '''tumours in neuropathology'''.  Tumours are a large part of [[neuropathology]].  [[Cytopathology]] of CNS tumours is dealt with in the article ''[[CNS cytopathology]]''.


There is a separate article for '''[[peripheral nerve sheath tumours]]'''.
There are separate articles for ''[[peripheral nerve sheath tumours]]'' and ''[[pituitary gland|pituitary/peri-pituitary lesions]]''.


==Brain tumours - overview==
==Brain tumours - overview==
===Adult===
===Alphabetical===
For overview see [[:Category:Neuropathology_tumours|here]]
 
===By age group===
====Adult====
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
Four most common types of brain tumours:<ref>[http://neurosurgery.mgh.harvard.edu/abta/primer.htm http://neurosurgery.mgh.harvard.edu/abta/primer.htm]</ref>
# Metastatic brain tumours (barely edges out primary tumours)
# Metastatic brain tumours (barely edges out primary tumours)
#*Lung (most common),
#*[[Lung cancer|Lung]] (most common).
#*Breast,
#*[[Invasive breast cancer|Breast]].
#*Melanoma,
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
#*[[Renal cell carcinoma]] (RCC).
# Glioblastoma aka ''glioblastoma multiforme''.
# [[Glioblastoma]], IDH-wildtype.
# Anaplastic (malignant) astrocytoma.
# [[Astrocytoma, IDH-mutant]].
# Meningioma.
# [[Meningioma]].


===Children===
====Children====
# Astrocytoma.
# [[Pilocytic astrocytoma]].
# Medulloblastoma.
# [[Medulloblastoma]].
# Ependymoma.
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].


===Location (most common)===
===By location===
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
Certain tumours like to hang-out at certain places:<ref>URL: [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif] and [http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html]. Accessed on: 2 November 2010.</ref>
*Cerebrum:
====Cerebrum====
**Cortical based - oligodendroglioma.
*Cortical based - [[oligodendroglioma]].
**Grey-white junction - metastases.
*Grey-white junction - metastases.
**White matter - astrocytoma, glioblastoma.
*White matter - astrocytoma, [[glioblastoma]].
**Periventricular - CNS lymphoma.
*Periventricular - CNS lymphoma.
**Cystic - ganglioglioma, pilocytic astrocytoma, pleomorphic xanthoastrocytoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
*Cerebellum:
====Cerebellum====
**Midline/central - medulloblastoma.
*Midline/central - [[medulloblastoma]].
**Cystic lesion - pilocytic astrocytoma (younger individual), hemangioblastoma (older individual).
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
**Solid lesion (older individual) - metastasis.
*Solid lesion (older individual) - [[metastasis]].
*Spinal cord:
====Sella turcica====
**Ependymoma, glioblastoma.
* [[Pituitary adenoma]].
**Filum terminale - myxopapillary ependymoma, paraganglioma.
* [[Craniopharyngioma]].
 
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
====Filum terminale====
*Filum terminale = bottom end of the spinal cord - has a limited differential.
*[[Meningioma]].
 
*[[Myxopapillary ependymoma]].
DDx:<ref>JLK. 31 May 2010.</ref>
*[[Neurofibroma]].
*Meningioma.
*[[Schwannoma]].
*Myxopapillary ependymoma.
*[[Paraganglioma]].
*Neurofibroma.
====Meninges====
*Schwannoma.
* [[Meningioma]].
*Paraganglioma.
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
 
* [[Hemangioblastoma]].
====Cerebellopontine angle====
less common:
DDx:<ref>R. Kiehl. 8 November 2010.</ref>
* [[Melanoma]] / Melanocytoma.
*Schwannoma.
* Lymphoproliferative diseases.
*Meningioma.
* [[Sarcoidosis]]
*Dermoid cyst/epidermoid cyst.
* [[Arachnoid cyst]].
*Ependymoma.
* Disseminated oligodendroglial-like leptomeningeal tumour.
*Choroid plexus papilloma.
* Desmoplastic infantile astrocytoma / ganglioglioma.
* Meningioangiomatosis.
* Calcifying pseudoneoplasm.  
====Skull====
* [[Fibrous dysplasia]].
* [[Paget disease]].
* [[Histiocytosis]].
* [[Hemangioma]].
* [[Aneurysmal bone cyst]].
* [[Plasma_cell_neoplasms#Multiple_myeloma|Multiple myeloma]].
====Skull base / Cerebellopontine angle====
* [[Schwannoma]].
* [[Meningioma]].
* [[Dermoid cyst]] / epidermoid cyst.
less common:
* [[Ependymoma]].
* [[Choroid plexus papilloma]].
* [[Glomus tumour]].
* [[Chordoma]].
* [[Chondrosarcoma]].
* [[Olfactory neuroblastoma]].
* [[Endolymphatic sac tumour]].


===Primary vs. secondary===
===Primary versus secondary===
Glial tumours:
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|Glial tumours]]:
*Cytoplasmic processes - '''key feature'''.
*Cytoplasmic processes - '''key feature'''.
**Best seen at highest magnification - usu. ~1 micrometer.
**Best seen at highest magnification - usu. ~1 micrometer.
**Processes may branch.
**Processes may branch.
*Ill-defined border/blend with the surrounding brain/.
*Ill-defined border/blend with the surrounding brain.
 
[[Meningioma]]:
*Lesion often dura-based.
*Mesenchymal tumor (often contains collagen).
 
[[Lymphoma]]:
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**~2x size of resting lymphocyte, nucleoli.
*Lesion predominantly perivascular.
 
====Secondary====
*Carcinomas:
**Well-demarcated border between brain and lesion - '''key feature'''.
**No cytoplasmic processes.
**Usu. have nuclear atypia of malignancy.
**Nuclei often ~3-4x the size of a [[RBC]].
**+/-Glandular arrangement.
**+/-Nucleoli.
*Melanoma.
*Secondary Lymphoma.
*Sarcomas (rare).
 
===By growth pattern===
====Infiltrative astrocytomas====
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH-wildtype.
 
Notes:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
 
====Non-infiltrative astrocytomas====
**[[Pilocytic astrocytoma]]
**[[Pleomorphic xanthoastrocytoma]]
**[[Subependymal giant cell astrocytoma]].
 
====Cystic tumours====
DDx:<ref>URL: [http://path.upmc.edu/cases/case320/dx.html http://path.upmc.edu/cases/case320/dx.html]. Accessed on: 14 January 2012.</ref>
*[[Pilocytic astrocytoma]].
*[[Pleomorphic xanthoastrocytoma]].
*[[Ganglioglioma]].
*[[Hemangioblastoma]].
*[[Craniopharyngioma]].<ref>URL: [http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral]. Accessed on: 14 January 2012.</ref>
 
 
Notes:
**Non-glial: no radiating glial processes.
*Rosenthal fibres within the tumour... often seen in [[pilocytic astrocytoma]].
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. [[cerebral infarct]], [[multiple sclerosis]]) - esp. if this is a primary lesion.<ref>URL: [http://path.upmc.edu/cases/case79/dx.html http://path.upmc.edu/cases/case79/dx.html]. Accessed on: 2 January 2012.</ref>
 
====Grading====
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).
 
Mitotic figures present:
*At least grade III (anaplastic astrocytoma).
 
Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).
 
Notes:
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
**Grading does not reflect molecular divergent groups within a tumor class  or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).<ref>{{Cite journal  | last1 = Louis | first1 = DN. | last2 = von Deimling | first2 = A. | title = Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare. | journal = Acta Neuropathol | volume =  | issue =  | pages =  | month = Aug | year = 2017 | doi = 10.1007/s00401-017-1765-z | PMID = 28801693 }}</ref>
 
===By IHC===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane) of most [[Astrocytoma]]s.
*[[IDH-1]](R132H) (isocitrate dehydrogenase 1) in [[Astrocytoma, IDH-mutant]].<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref><ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>
*[[H3F3A|H3F3A K27M]] in [[Diffuse midline glioma, H3 K27-altered]].
*[[ATRX]] -ve in [[Astrocytoma, IDH-mutant]] or [[Diffuse hemispheric glioma, H3 G34-mutant]].
*[[CD20]] in PCNSL.
*Cytokeratins in Carcinoma brain metastases, Plexus choroid tumours, [[AT/RT]], [[Papillary tumour of the pineal region]], [[Craniopharyngioma]].
*[[EMA]] in [[Meningioma]] and carcinoma brain metastases.
*PrgR in [[Meningioma]] and carcinoma metastases.
*[[Synaptophysin]] in glioneuronal tumours and Pituitary adenoma and embryonal tumours.


===Common brain tumours in a table===
===Common neuropathology tumours in a table===
{| class="wikitable"
{| class="wikitable"
|'''Type'''
|'''Type'''
Line 77: Line 195:
|missed lesion?
|missed lesion?
|nil
|nil
|[http://commons.wikimedia.org/wiki/File:Grey_matter_and_white_matter_-_very_high_mag.jpg very high mag.], [http://commons.wikimedia.org/wiki/File:Grey_matter_and_white_matter_-_high_mag.jpg high mag.]
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|Normal. (WC)]]
|-
|-
|Reactive astrocytes
|[[Reactive astrocytes]]
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia
|small lesion? / deep lesion?
|small lesion? / deep lesion?
|variable
|variable
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|missed lesion / close to a lesion; non-specific pathologic process - need more tissue
|nil
|GFAP
|[http://commons.wikimedia.org/wiki/File:Reactive_astrocytes_-_lfb_-_high_mag.jpg high mag.]
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Schwannoma]]
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx, DDx: [[meningioma]]
|S100, SOX10
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|-
|[[Meningioma]]
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: [[schwannoma]], choroid plexus
|EMA, PR, Ki-67
|[[Image:Meningioma_intermed_mag.jpg |thumb|center|150px|Meningioma. (WC)]]
|-
|[[Astrocytoma, IDH-mutant]] (CNS [[WHO]] grade 2 or grade 3)
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|common
|IDH-1(R132H)+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|High-grade astrocytoma. (WC)]]
|-
|-
|Astrocytoma (grade II or worse)
|[[Glioblastoma]], IDH-wildtype (CNS [[WHO]] grade 4)
|glial processes (esp. on smear), nuclear atypia (size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres
|glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|usu. old, occ. young
|very common, esp. glioblastoma
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
|IDH-1+/-, GFAP+
|[http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_high_mag.jpg high mag.], [http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg very high mag.]
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|-
|Metastasis
|[[Metastatic brain tumours|Metastasis]]
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|sharp interface with brain, often glandular, +/-nucleoli, no glial processes
|often cerebellular, well-circumscribed
|often cerebellular, well-circumscribed
|usu. old
|usu. old
|often suspected to have metastatic disease
|often suspected to have metastatic disease
|TTF-1, CK7, CK20, BRST-2
|[[TTF-1]], CK7, [[CK20]], BRST-2
|[http://commons.wikimedia.org/w/index.php?title=File:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg very low mag.], [http://commons.wikimedia.org/w/index.php?title=File:Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg high mag.]
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|-
|Meningioma
|whorls, psammomatous calcs, nuclear inclusions
|extra-axial + intradural
|old or young
|may be diagnosed on smear, DDx: choroid plexus, schwannoma
|EMA, PR, Ki-67
|[http://commons.wikimedia.org/wiki/File:Meningioma_intermed_mag.jpg intermed. mag.]
|-
|Schwannoma
|cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies)
|extra-axial + intradural
|old or young
|need frozen section to Dx
|S100
|[http://commons.wikimedia.org/wiki/File:Peripheral_schwannoma_Antoni_type_A_(1).JPG intermed. mag.]
|}
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.


==Metastatic tumours==
==Brain metastasis==
===General===
{{Main|Brain metastasis}}
*Most common brain tumour in adults.
 
 
===Molecular===
See also:  [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]
 
==Gliomas==
{{Main|Glioma}}


===Microscopic===
Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.
Features:
*Vary by subtype.


Images:
===Astrocytic tumours===
*[http://commons.wikimedia.org/wiki/File:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg CRC metastasis to cerebellum - very low mag. (WC)].
{{Main|Astrocytoma}}
*[http://commons.wikimedia.org/wiki/File:Metastatic_adenocarcinoma_-_cerebellum_-_high_mag.jpg CRC metastasis to cerebellum - high mag. (WC)].


==Astrocytomas==
* [[Astrocytoma]], IDH-mutant.
===Overview===
* [[Glioblastoma]], IDH-wildtype.
*Pilocytic astrocytomas (WHO Grade I).  
** [[Gliosarcoma]] (a glioblastoma subtype)
*Dysembryoplastic neuroepithelial tumour (DNT), (WHO Grade I).
*Low-grade (diffuse) astrocytomas (Grade II).
*Anaplastic astrocytomas (Grade III).
*Glioblastoma (Grade IV).


===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*Glial processes - '''key feature'''.
*Glial processes - '''key feature'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*No Rosenthal fibres within the tumour itself.


Images:
Images:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].


Notes:
Depreceated:
*Glial vs. non-glial tumours:
* Diffuse [[Astrocytoma]]
**Glial: "blends into brain"/gradual transition to non-tumour brain.
* [[Anaplastic astrocytoma]]
**Non-glial: no glial processes.
* [[Gliomatosis cerebri]]
* Spongioblastoma


====Grading====
===Oligodendroglial tumours===
At least grade II:
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.
*Nuclear pleomorphism.


At least grade III:
Depreceated:
*Mitotic figures.
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma


At least grade IV:
===Pediatric-type diffuse high-grade glioma===
*Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells.
{{Main|Pediatric-type diffuse high-grade glioma}}
**Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of pales forming a defense barrier or fortification.
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]


===Glioblastoma IHC===
===Pediatric-type diffuse low-grade glioma===
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
{{Main|Pediatric-type diffuse low-grade glioma}}
*Ki-67 - usu. high >20% of cells.
*p53 - often +ve.
*IDH1 (isocitrate dehydrogenase 1).
**+ve in tumours that arose from low-grade gliomas.<ref name=pmid19228619>{{cite journal |author=Yan H, Parsons DW, Jin G, ''et al.'' |title=IDH1 and IDH2 mutations in gliomas |journal=N. Engl. J. Med. |volume=360 |issue=8 |pages=765–73 |year=2009 |month=February |pmid=19228619 |pmc=2820383 |doi=10.1056/NEJMoa0808710 |url=}}</ref>
***Image: [http://en.wikipedia.org/wiki/File:IDH1_GBM_20x.jpg IDH1 +ve in glioblastoma (WP)].


Notes:
*IDH1 and IDH2 mutations - better survival.<ref name=pmid20975057>{{cite journal |author=Houillier C, Wang X, Kaloshi G, ''et al.'' |title=IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas |journal=Neurology |volume=75 |issue=17 |pages=1560–6 |year=2010 |month=October |pmid=20975057 |doi=10.1212/WNL.0b013e3181f96282 |url=}}</ref>


==Gliosarcoma==
===Circumscribed astrocytic gliomas===
===General===
* [[Pilocytic astrocytoma]] (PA)
*Considered to be a variant of glioblastoma by WHO.<ref name=pmid19618114>{{cite journal |author=Han SJ, Yang I, Tihan T, Prados MD, Parsa AT |title=Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity |journal=J. Neurooncol. |volume=96 |issue=3 |pages=313–20 |year=2010 |month=February |pmid=19618114 |pmc=2808523 |doi=10.1007/s11060-009-9973-6 |url=}}</ref>
** [[Pilomyxoid astrocytoma]] (PMA)
*Rare ~ 200 cases reported in the literature.<ref name=pmid19618114/>
* [[Pleomorphic xanthoastrocytoma]] (PXA)
*Definition: gliosarcoma = glioblastoma + sarcomatous component.<ref name=pmid20415184>{{cite journal |author=Ayadi L, Charfi S, Khabir A, ''et al.'' |title=[Cerebral gliosarcoma: clinico-pathologic study of 8 cases] |language=French |journal=Tunis Med |volume=88 |issue=3 |pages=142–6 |year=2010 |month=March |pmid=20415184 |doi= |url=}}</ref>
* [[Subependymal giant cell astrocytoma]] (SEGA)
*Usual location (like glioblastoma): temporal lobe.
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].


===Microscopic===
====Astroblastoma====
Features:
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*[[Glioblastoma]].
*Very rare superficial tumor of young age.<ref>{{Cite journal  | last1 = Narayan | first1 = S. | last2 = Kapoor | first2 = A. | last3 = Singhal | first3 = MK. | last4 = Jakhar | first4 = SL. | last5 = Bagri | first5 = PK. | last6 = Rajput | first6 = PS. | last7 = Kumar | first7 = HS. | title = Astroblastoma of cerebrum: A rare case report and review of literature. | journal = J Cancer Res Ther | volume = 11 | issue = 3 | pages = 667 | month =  | year =  | doi = 10.4103/0973-1482.140800 | PMID = 26458709 }}</ref>
*Sarcomatous component (one of the following):<ref name=pmid19618114/><ref name=pmid20415184/>
*Large, cystic. Pushing margin towards CNS.
**Fibroblastic.
*Vasocentric growth, plump cells with absence of fibrillary pattern.
**Cartilaginous.
*GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
**Osseous.
*Molecular profile overlaps with classical [[CNS-PNET]].
**Smooth muscle.
**Gene fusions invoving meningioma gene (MN1)<ref>{{Cite journal  | last1 = Sturm | first1 = D. | last2 = Orr | first2 = BA. | last3 = Toprak | first3 = UH. | last4 = Hovestadt | first4 = V. | last5 = Jones | first5 = DT. | last6 = Capper | first6 = D. | last7 = Sill | first7 = M. | last8 = Buchhalter | first8 = I. | last9 = Northcott | first9 = PA. | title = New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. | journal = Cell | volume = 164 | issue = 5 | pages = 1060-72 | month = Feb | year = 2016 | doi = 10.1016/j.cell.2016.01.015 | PMID = 26919435 }}</ref>
**Striated muscle.
**Adipocyte.  


Image: [http://commons.wikimedia.org/wiki/File:Gliosarcoma_Histopathology_200x_EVG.jpg Gliosarcoma - elastic von Gieson (WC)].


==Pilocytic astrocytoma==
<gallery>
===General===
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
*Low-grade astrocytoma.  
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
*Classically in the cerebellum in children; most common glioma in children.<ref name=Ref_PSNP82>{{Ref PSNP|82}}</ref>
File:Astroblastoma.jpg | Astroblastoma (AFIP)
*The ''optic glioma'' associated with neurofibromatosis 1.
</gallery>


===Gross===
====Chordoid glioma of the third ventricle====
Features:<ref name=Ref_PSNP82>{{Ref PSNP|82}}</ref>
* WHO grade II.
*Usually well-circumscribed.
* Slowly growing, non-invasive, in adults.
*Cystic ''or'' solid.
* Clusters of epithelioid cells in mucinous stroma.
*Do '''not''' smear. (Ref. ?)
* Lymphocytic infiltrates, adjacent Rosenthal fibers.
* Fibrosis may be present.
* Few mitoses.
* [[GFAP]]+ve,  MIB-1 1-3%.
* [[TTF-1]]+ve.
* CD34+ve.
* [[IDH-1]]-ve, [[p53]]-ve.
* PRKCA D463H mutations.<ref>{{Cite journal  | last1 = Goode | first1 = B. | last2 = Mondal | first2 = G. | last3 = Hyun | first3 = M. | last4 = Ruiz | first4 = DG. | last5 = Lin | first5 = YH. | last6 = Van Ziffle | first6 = J. | last7 = Joseph | first7 = NM. | last8 = Onodera | first8 = C. | last9 = Talevich | first9 = E. | title = A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. | journal = Nat Commun | volume = 9 | issue = 1 | pages = 810 | month = 02 | year = 2018 | doi = 10.1038/s41467-018-02826-8 | PMID = 29476136 }}</ref>


===Microscopic===
<gallery>
Features:<ref name=Ref_PSNP82-4>{{Ref PSNP|82-4}}</ref>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
*Classically biphasic (though either may be absent):
</gallery>
*#Fibrillar.
*#Microcystic/loose.
*Hair-like fibres ~ 1 micrometer; ''pilo-'' = hair.<ref>URL: [http://dictionary.reference.com/browse/pilo- http://dictionary.reference.com/browse/pilo-]. Accessed on: 24 November 2010.</ref>
**Best seen on smear or with GFAP [[IHC]].
*Rosenthal fibres - '''key feature'''.
**May be rare.  Not pathognomonic (see below).
*Eosinophilic granular bodies.
*Low cellularity - when compared to medulloblastoma and ependymoma.


Notes:
*+/-Microvascular proliferation.
*+/-Focal necrosis.
**Necrosis with pseudopalisading more likely glioblastoma.
*+/-Mitoses - not significant in the context of the Dx.


Images:
===Ependymal tumours===
*Smears:
* [[Subependymoma]]
**[http://commons.wikimedia.org/wiki/File:Pilocytic_astrocytoma_-_smear_-_very_high_mag.jpg Bipolar cells with hair-like processes - smear - very high mag. (WC)].
* [[Myxopapillary Ependymoma]]
**[http://www.wikidoc.org/index.php/Image:Pilocytic_astrocytoma_10.jpg EGBs - smear (wikidoc.org)].
* [[Ependymoma]]
**[http://www.wikidoc.org/index.php/Image:Pilocytic_astrocytoma_11.jpg Rosenthal fibres - smear (wikidoc.org)].
* Anaplastic ependymoma
*Sections:
**[http://commons.wikimedia.org/wiki/File:Rosenthal_HE_40x.jpg Rosenthal fibres (WC)].
**[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q19-Ans.htm Rosenthal fibre (ouhsc.edu)].


DDx (of Rosenthal fibers):<ref>MUN. 9 Mar 2009.</ref>
==Choroid plexus tumours==
*Chronic reactive gliosis.
* [[Choroid plexus papilloma]]
*Subependymoma.
* Atypical choroid plexus papilloma
*Ganglioma.
* [[Choroid plexus carcinoma]]
*Alexander's disease (rare leukodystrophy).


DDx of pilocystic astrocytoma (brief):
==Other neuroepithelial tumours==
*Piloid gliosis.
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].
*Oligodendroglioma.
*Glioblastoma (uncommon - but important).


===IHC/special stains===
Features:<ref name=Ref_PSNP84>{{Ref PSNP|84}}</ref>
*GFAP +ve (fibres).
*PAS-D: eosinophilic granular bodies +ve.
*CD68: may have a significant macrophage component.
*KI-67: may be "high" (~20% ???).


===Grading===
===Cribiform neuroepithelial tumour===
*''WHO Grade I'' by definition.
AKA: '''CRINET'''.
*Not listed in the current WHO classification.
*First description in 2009.<ref>{{Cite journal  | last1 = Hasselblatt | first1 = M. | last2 = Oyen | first2 = F. | last3 = Gesk | first3 = S. | last4 = Kordes | first4 = U. | last5 = Wrede | first5 = B. | last6 = Bergmann | first6 = M. | last7 = Schmid | first7 = H. | last8 = Frühwald | first8 = MC. | last9 = Schneppenheim | first9 = R. | title = Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 12 | pages = 1249-55 | month = Dec | year = 2009 | doi = 10.1097/NEN.0b013e3181c06a51 | PMID = 19915490 }}</ref>
*Around ventricles.<ref>{{Cite journal  | last1 = Arnold | first1 = MA. | last2 = Stallings-Archer | first2 = K. | last3 = Marlin | first3 = E. | last4 = Grondin | first4 = R. | last5 = Olshefski | first5 = R. | last6 = Biegel | first6 = JA. | last7 = Pierson | first7 = CR. | title = Cribriform neuroepithelial tumor arising in the lateral ventricle. | journal = Pediatr Dev Pathol | volume = 16 | issue = 4 | pages = 301-7 | month =  | year =  | doi = 10.2350/12-12-1287-CR.1 | PMID = 23495723 }}</ref>
*Young children.<ref>{{Cite journal  | last1 = Park | first1 = JY. | last2 = Kim | first2 = E. | last3 = Kim | first3 = DW. | last4 = Chang | first4 = HW. | last5 = Kim | first5 = SP. | title = Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review. | journal = Neuropathology | volume = 32 | issue = 5 | pages = 570-6 | month = Oct | year = 2012 | doi = 10.1111/j.1440-1789.2011.01293.x | PMID = 22239490 }}</ref>
*Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
*MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
*INI-1 loss, but no rhabdoid features and good prognosis.
*Stable genomic profile.<ref>{{Cite journal  | last1 = Gessi | first1 = M. | last2 = Japp | first2 = AS. | last3 = Dreschmann | first3 = V. | last4 = Zur Mühlen | first4 = A. | last5 = Goschzik | first5 = T. | last6 = Dörner | first6 = E. | last7 = Pietsch | first7 = T. | title = High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. | journal = J Neuropathol Exp Neurol | volume = 74 | issue = 10 | pages = 970-4 | month = Oct | year = 2015 | doi = 10.1097/NEN.0000000000000239 | PMID = 26352987 }}</ref>


==Pilomyxoid astrocytoma==
==Neuronal and mixed neuronal/glial tumours==
===General===
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
* [[Dysembryoplastic neuroepithelial tumour]]
*A variant of ''pilocytic astrocytoma''.
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
**Some have suggested it is a unique entity.<ref name=pmid16048293>{{cite journal |author=Komotar RJ, Mocco J, Jones JE, ''et al.'' |title=Pilomyxoid astrocytoma: diagnosis, prognosis, and management |journal=Neurosurg Focus |volume=18 |issue=6A |pages=E7 |year=2005 |month=June |pmid=16048293 |doi= |url=}}</ref>
* Cerebellar liponeurocytoma
*Childhood or adolescence.
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]


===Gross===
===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
* Abbreviated ''DIA'' or ''DIG''.
*Classically - hypothalamic location.
* ICD-O code: 9412/1
*Solid.
* Large, superficial, cystic tumor of the infancy.
*Well-circumscribed.
* Biologic course corresponds to WHO grade I.
* Very rare, included in the WHO since 1993.
* Prominent desmoplastic stroma.
* Astrocytic cells within stroma.
**GFAP+.
**MIB-1 usu. 1%.
* Frequent BRAF V600E or V600D mutations.<ref>{{Cite journal  | last1 = Wang | first1 = AC. | last2 = Jones | first2 = DTW. | last3 = Abecassis | first3 = IJ. | last4 = Cole | first4 = BL. | last5 = Leary | first5 = SES. | last6 = Lockwood | first6 = CM. | last7 = Chavez | first7 = L. | last8 = Capper | first8 = D. | last9 = Korshunov | first9 = A. | title = Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations. | journal = Mol Cancer Res | volume =  | issue =  | pages =  | month = Jul | year = 2018 | doi = 10.1158/1541-7786.MCR-17-0507 | PMID = 30006355 }}</ref>
*Single case with BRAF indel or BRAF fusion.
<gallery>
File:DIG-histology.jpg | Histopathology of DIG (HE stain)
File:DIG-histology2.jpg | Prominent ganglioid cells in DIG (HE stain)
</gallery>


===Microscopic===
===Cerebellar liponeurocytoma===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
*Consists of small round/ovoid bland cells in a myxoid stroma.
* Mean age: 50 years.
*Hair-like fibres ~ 1 micrometer.
* As the name states: A tumour of the cerebellum.
**Often difficult to appreciate on standard (H&E) histologic sections.
** But cases outside cerebellum reported that would qualify.<ref>{{Cite journal  | last1 = Gupta | first1 = K. | last2 = Salunke | first2 = P. | last3 = Kalra | first3 = I. | last4 = Vasishta | first4 = RK. | title = Central liponeurocytoma: case report and review of literature. | journal = Clin Neuropathol | volume = 30 | issue = 2 | pages = 80-5 | month =  | year =  | doi =  | PMID = 21329617 }}</ref>
*Usually angiocentric (surround blood vessel) - '''key feature'''.
* WHO grade II <ref>{{Cite journal  | last1 = Nishimoto | first1 = T. | last2 = Kaya | first2 = B. | title = Cerebellar liponeurocytoma. | journal = Arch Pathol Lab Med | volume = 136 | issue = 8 | pages = 965-9 | month = Aug | year = 2012 | doi = 10.5858/arpa.2011-0337-RS | PMID = 22849747 }}</ref> (upgraded from WHO grade I in 2007)<ref>{{Cite journal  | last1 = Brat | first1 = DJ. | last2 = Parisi | first2 = JE. | last3 = Kleinschmidt-DeMasters | first3 = BK. | last4 = Yachnis | first4 = AT. | last5 = Montine | first5 = TJ. | last6 = Boyer | first6 = PJ. | last7 = Powell | first7 = SZ. | last8 = Prayson | first8 = RA. | last9 = McLendon | first9 = RE. | title = Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition. | journal = Arch Pathol Lab Med | volume = 132 | issue = 6 | pages = 993-1007 | month = Jun | year = 2008 | doi = 10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2 | PMID = 18517285 }}</ref>
*ICD-O code: 9506/1


Notes:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
====Histo====
*Rosenthal fibres are absent - '''key negative'''.
* Advanced neuronal and lipomatous differentiation.
*Monophasic (unlike classical pilocytic astrocytomas) - '''key negative'''.
* Neurocytes: round to oval nuclei with clear cytoplasm.
*May rarely have eosinophilic granular bodies.
* Quite cellular.
* Mitoses almost absent.  


===Grading===
====IHC====
*''WHO Grade II'' by definition.<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.


==Atypical teratoid/rhabdoid tumour==
====Molecular====
*Commonly abbreviated ''AT/RT''.
* Distinct methylation profile.
*May be written ''atypical teratoid rhabdoid tumour'', i.e. without the forward slash.
* Recurent losses on 2p and Chr. 14.<ref>{{Cite journal  | last1 = Capper | first1 = D. | last2 = Stichel | first2 = D. | last3 = Sahm | first3 = F. | last4 = Jones | first4 = DTW. | last5 = Schrimpf | first5 = D. | last6 = Sill | first6 = M. | last7 = Schmid | first7 = S. | last8 = Hovestadt | first8 = V. | last9 = Reuss | first9 = DE. | title = Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. | journal = Acta Neuropathol | volume =  | issue =  | pages =  | month = Jul | year = 2018 | doi = 10.1007/s00401-018-1879-y | PMID = 29967940 }}</ref>


===General===
<gallery>
*Usually supratentorial, occasionally in posterior fossa, case reports of spinal cord.
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>


===Microscopic===
====DDx====
Features:
* [[Medulloblastoma]]
*Cellular.
* [[Neurocytoma]]
*Small round cells usu. with a prominent nucleolus.
*Rhaboid cells.
**Cells with eosinophilic granular cytoplasm + eccentric nucleus. (???)
*Mitoses.


Images:
===Gangliocytoma===
*[http://commons.wikimedia.org/wiki/File:Rhabdoidtumourcell.jpg Rhabdoid tumour cell (WC)].
* Grade I WHO neuronal tumour.
*[http://commons.wikimedia.org/wiki/File:ATRT-HE-Overview.jpg AT/RT (WC)].
** ICD-O code: 9492/0
*[http://commons.wikimedia.org/wiki/File:ATRT-INI1.jpg AT/RT -ve for INI1 (WC)].
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.


DDx:
===Ganglioglioma===
*Primitive neuroectodermal tumour (PNET).
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
*Diffuse astrocytoma.
====General====
*Choroid plexus carcinoma.
*Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
*Embryonal carcinoma.
*Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
 
*Rare (approx. 0.5% of all CNS tumors).
===IHC===
*Usu. temporal lobe.
*BAF-47 -ve ([[AKA]] ''INI1'') - virtually diagnostic.
*Predominantly children (mean age: 9 years).  
**Endothelial cells +ve control.
*Recognized as a cause of [[epilepsy]].<ref name=pmid12125968>{{Cite journal  | last1 = Im | first1 = SH. | last2 = Chung | first2 = CK. | last3 = Cho | first3 = BK. | last4 = Lee | first4 = SK. | title = Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome. | journal = J Neurooncol | volume = 57 | issue = 1 | pages = 59-66 | month = Mar | year = 2002 | doi =  | PMID = 12125968 }}</ref>
*S-100 +ve.
*Favourable prognosis (survival rates up to 97%)
**Few other brain tumours express it.
**Insufficient data für anaplastic ganglioglioma.
*Vimentin +ve (perinuclear condensation).
 
Others:
*GFAP +ve (focal - in tumour cells).
*EMA +ve (patchy cytoplasmic).
*Smooth muscle actin +ve.


==Oligodendroglioma==
====Macroscopic====
===General===
*Circumscribed lesion.
*Do ''not'' arise from oligodendrocytes.
*Usu. contrast enhancing.
**Arise from ''glial precursor cells''.
*Solid, but intracortical cysts may be present.
*Little mass effect.


Usual location:
*Fourth ventricle.
*Intramedullary spinal cord.


Prognosis by flavours (average survival):<ref name=Ref_PSNP98>{{Ref PSNP|98}}</ref>
====Microscopic====
*WHO grade II: 10-15 years.
*WHO grade III: 3-5 years.
 
===Microscopic===
Features:
Features:
*Highly cellular lesion composed of:
*Dysplastic neurons.
**Cells resembling ''fried eggs'' (oligodendrocytes) with:
**Out of regular architecture / abnormal location.
***Round nucleus - '''key feature'''.
**Cytomegaly
***Distinct cell borders.
**Clustering
***Moderate-to-marked nuclear atypia.
**Binucleated (very occassionally).
***Clear cytoplasm - useful feature (if present).
*Atypical glia.
****Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing.
*Eosinophilic granular bodies.
**Acutely branched capillary sized vessels - "chicken-wire" like appearance.
*Calcification.
***Abundant, delicate appearing; may vaguely resemble a paraganglioma at low power.
*Prominent capillary network.
*Calcifications - important feature.<ref>URL: [http://www.emedicine.com/radio/topic481.htm http://www.emedicine.com/radio/topic481.htm].</ref>
*Lymphocytic cuffing.
*May contain some reticulin.
*Glial component may resemble:
**Fibrillary astrocytoma.
**Oligodendroglioma.
**Pilocytic astrocytoma.


Images:
Anaplastic ganglioglioma:
*[http://commons.wikimedia.org/wiki/File:Oligodendroglioma1_high_mag.jpg Oligodendroglioma high mag. (WC)].
*Brisk mitotic activity
*[http://commons.wikimedia.org/wiki/File:Oligodendroglioma1_low_mag.jpg Oligodendroglioma low mag. (WC)].
*Necrosis


Notes:
====IHC====
*Few neural tumours have round nuclei - DDx:
*Neurons:
**Oligodendroglioma.
**[[MAP2]] +ve
**Lymphoma.
**Synaptophysin +ve
**Clear cell variant of ependymoma.
** Neurofilament +ve
**Germ cell tumour (dysgerminoma/seminoma).
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).


====Histologic grading====
====Molecular====
Come in two flavours:
*BRAF V600E-mutated(approx. 25%).
# WHO grade II.
*IDH1/2 wt.
#*This is most oligodendrogliomas.
*No 1p/19q codeletion.
# WHO grade III.
*Usu. Chr. 7 gain.  
#*Features for calling high grade:<ref name=Ref_PSNP98>{{Ref PSNP|98}}</ref>
*CDKN2A deletions in anaplastic ganglioglioma.  
#**Endothelial hypertrophy.
#***Plump/large endothelial cells.
#**Necrosis.
#**High mitotic rate (6 mitoses/10 HPF for whatever "HPF" means, see [[HPFitis]]).


===IHC===
====DDx:====
Features:
*[[DNT]].
*MAP-2 +ve.<reF name=pmid12025943>{{cite journal |author=Suzuki SO, Kitai R, Llena J, Lee SC, Goldman JE, Shafit-Zagardo B |title=MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration |journal=J. Neuropathol. Exp. Neurol. |volume=61 |issue=5 |pages=403–12 |year=2002 |month=May |pmid=12025943 |doi= |url=}}</ref>
*[[Oligodendroglioma]].
*GFAP -ve.
*Trapped cortical neurons in diffuse astrocytoma.
**Some subtypes +ve - should not be used to distinguish.<ref name=Ref_PSNP>{{Ref PSNP|98}}</ref>
*Papillary glioneuronal tumor.
*EMA +ve.
*Dysembryoplastic neuroepithelial tumor.
*IDH-1 -ve. (???).
*p53 -ve.
**Useful for differentiating ''astrocytoma'' vs. ''oligodendroglioma''.
*Ki-67.


===Molecular pathology===
====Images====
Losses of 1p and 19q both helps with diagnosis and is prognostic:<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>
<gallery>
*Greater chemosensitivity
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
*Better prognosis.
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
</gallery>
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].


==Oligoastrocytoma==
===Lhermitte-Duclos disease===
===General===
*Abbreviated ''LDD''.
*Mixed tumour.
*[[AKA]] ''dysplastic cerebellar gangliocytoma''.<ref name=pmid20060133>{{Cite journal  | last1 = Yağci-Küpeli | first1 = B. | last2 = Oguz | first2 = KK. | last3 = Bilen | first3 = MA. | last4 = Yalçin | first4 = B. | last5 = Akalan | first5 = N. | last6 = Büyükpamukçu | first6 = M. | title = An unusual cause of posterior fossa mass: Lhermitte-Duclos disease. | journal = J Neurol Sci | volume = 290 | issue = 1-2 | pages = 138-41 | month = Mar | year = 2010 | doi = 10.1016/j.jns.2009.12.010 | PMID = 20060133 }}</ref>
*[[AKA]] ''dysplastic gangliocytoma of the cerebellum''.
{{Main|Lhermitte-Duclos disease}}
<gallery>
File:Dysplastic_gangliocytoma_lhermitte_duclos.jpg | Dysplastic gangliocytoma (low mag).
</gallery>


===Microscopic===
===Papillary glioneuronal tumour===
Features:
* Abbreviated ''PGNT''.
*Astrocytoma-like and oligodendroglioma-like:
* A benign, supratentorial tumor of childhood.
*#Oligodendroglioma-like cells = round nucleus, peri-nuclear clearing.
** Biologic course corresponds to WHO grade I.
*#Astrocytoma-like cells = non-ovoid/elongated nucleus.
** Before WHO 2000, considered a [[Ganglioglioma]] variant.
*Prominent pseudopapillary architecture.
*Neurocytes to medium-sized ganglion cells.
*GFAP+ core, GFAP- layer
*Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>


DDx:
===Rosette-forming glioneuronal tumour of the fourth ventricle===
*Anaplastic astrocytoma.
* Abbreviated ''RGNT''.
*Oligodendroglioma. (???)
* Provisional ICD-O code: 9509/1
* A rare benign infratentorial tumour of the midline of children and adults.
* Biologic course corresponds to WHO grade I.
* Glial component corresponds to [[pilocytic astrocytoma]].
* Neurocytic rosettes.
* Eosinopil fibrillary cores / pseudorosettes.
* GFAP+ in fibrillary areas, Syn+ in rosettes.
* Neurocytic cells: MAP2+
* MIB-1 usu. below 3%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>


===IHC===
===Polymorphous low-grade tumor of the young (PLNTY)===
*Oligodendroglioma-like cells: MAP-2 +ve (cytoplasm).
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]
*Astrocytoma-like cells: GFAP +ve (cytoplasm, nuclear membrane).


Others:
==Pineal tumours==
*Ki-67 ~10%. (???)
{{Main|Pineal gland}}
*p53 - focally +ve. (???)
*IDH-1 -ve. (???)


==Meningioma==
* [[Pineocytoma]]
{{Main|Meningioma}}
* [[Pineal parenchymal tumour of intermediate differentiation]]
===General===
* [[Pineoblastoma]]
*Very common.
* [[Papillary tumour of the pineal region]]
*May be part of a syndrome.


===Microscopic===
==Embryonal tumours==
Features (memory device ''WTC''):
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
*Whorled appearance - '''key feature'''.
* [[Medulloblastoma]]
*Calcification, psammomatous.
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)


Grading: see ''[[meningioma]]''.
DDx:
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]


==Peripheral nerve sheath tumours==
==Peripheral nerve sheath tumours==
{{Main|Peripheral nerve sheath tumours}}
{{Main|Peripheral nerve sheath tumours}}
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Benign:
'''Benign:'''
**Schwannoma.
*[[Schwannoma]].
**Neurofibroma.
*[[Neurofibroma]].
**Perineurioma.
*[[Perineurioma]].
**Traumatic neuroma.
*Ganglioneuroma.
*Malignant:
**[[Traumatic neuroma]].
**Malignant peripheral nerve sheath tumour (MPNST).
'''Malignant:'''
 
*[[Malignant peripheral nerve sheath tumour]] (MPNST).
==Schwannoma==
 
{{Main|Peripheral nerve sheath tumours#Schwannoma}}
===General===
*Tumour of tissue surrounding a nerve.
**Axons adjacent to the tumour are normal... but may be compressed.
 
===Microscopic===
Features:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Antoni A:
**Cellular.
**'Fibrillary, polar, elongated'.
*Antoni B:
**Pauci-cellular.
**Loose microcystic tissue.
*Verocay bodies - paucinuclear area surrounded by palisaded nuclei.
*In the GI tract: classically have a ''peripheral lymphoid cuff''.<ref name=pmid15728600>{{cite journal |author=Levy AD, Quiles AM, Miettinen M, Sobin LH |title=Gastrointestinal schwannomas: CT features with clinicopathologic correlation |journal=AJR Am J Roentgenol |volume=184 |issue=3 |pages=797–802 |year=2005 |month=March |pmid=15728600 |doi= |url=http://www.ajronline.org/cgi/content/full/184/3/797}}</ref>
 
Images:
*[http://www.pathguy.com/~lulo/lulo0003.htm Antoni A (pathguy.com)].
*[http://www.ajnr.org/cgi/content/full/28/9/1633/F8 Antoni A & Antoni B side-by-side (ajnr.org)].
 
Notes:
*Several subtypes exist.


==Neurofibroma==
===Ganglioneuroma===
{{Main|Peripheral nerve sheath tumours#Neurofibroma}}
:'''Not''' to be confused with ''[[ganglioglioma]]''.
===General===
*May be a part of [[neurofibromatosis]] 1.
*Composed of Schwann cells, axons, fibrous material.<ref name=pmid17893219/>
 
===Microscopic===
Features:<ref name=pmid17893219/>
*Plexiform growth pattern - "bag of worms".
 
Image:
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(1).jpg Neurofibroma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(2).jpg Neurofibroma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(3).jpg Neurofibroma - high mag. (WC)].
 
==Ganglioneuroma==
===General===
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
*May be retroperitoneal.
{{Main|Ganglioneuroma}}


===Microscopic===
Features:
*Ganglion cells - '''key feature'''.
**Large cells with large nucleus.
***Prominent nucleolus.
*Disordered fibrinous-like material.
*Eosinophilic granular bodies.<ref>R. Kiehl. 8 November 2010.</ref>


Images:
*[http://it.wikipedia.org/wiki/File:Ganglioneuroma_(1).jpg Ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?n=4&Case=84 Ganglioneuroma (webpathology.com)].


See: ''[[Adrenal gland]]''.
==Meningioma==
 
{{Main|Meningioma}}
==Ependymoma==
===General===
*Called the forgotten glial tumour.
 
Comes in two flavours:
#Ependymoma (not otherwise specified).
#Myxopapillary ependymoma.
#*Classically at filum terminale.
 
===Microscopy===
====Classic ependymoma====
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*[[Rosette]]s - cells arranged in a pseudoglandular fashion.
*"Nucleus free zones" - cells arranged around a blood vessel (perivascular pseudorosettes); nuclei of cells distant from the blood vessel, i.e. a rim of cytoplasm (from tumour cells) surrounds the blood vessel.
''Perivascular pseudorosettes'' = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone)
 
**The nucleus free zone is composed of tumour cell cytoplasm that is adjacent to an unseen blood vessel.
*Nuclear feature monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Ependymoma_intermed_mag.jpg Ependymoma - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Ependymoma_low_intermed_mag.jpg Ependymoma - low mag. (WC)].
 
DDx (classic ependymoma):
*Subependymoma.
*Glioblastoma (GBM).
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
 
====Myxopapillary ependymoma====
Features:
*Perivascular pseudorosettes:
**Myxoid material surround blood vessels.
***Myxoid material surrounded by tumour cells.
 
Images:
*[http://careers.bmj.com/article-images/cf0708.f2_default.gif Myxopapillary ependymoma (bmj.com)] - part of [http://careers.bmj.com/careers/advice/view-article.html?id=351 careers.bmj.com article on paediatric pathology].
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma.jpg Myxopapillary ependymoma - cytology (WC)].
 
====Grading====
Easy:
*Subependymoma = WHO grade I.
*Myxopapillary ependymoma = WHO grade I.
Not-so-easy:
*Classic ependymoma = WHO grade II.
*Anaplastic ependymoma = WHO grade III.
 
Grade II vs. Grade III:
*Cellular density.
*Mitoses.
*Necrosis.
*Microvascular proliferation.
 
Notes:
*Many tumours fall between grade II and grade III.  These are called "indeterminate" by many.
 
===IHC===
*Reticulin.
*GFAP.
*MIB-1.
 
==Choroid plexus papilloma==
===Microscopy===
Features:
*Simple epithelium.
*Papillae.
*Psammoma bodies.
 
Image:
*[http://commons.wikimedia.org/wiki/File:Choroid_plexus_papilloma_micrograph.jpg Choroid plexus papilloma (WC)].


==Chordoma==
==Chordoma==
===General===
{{Main|Chordoma}}
*Location: usually sacrum or clivus.
 
===Microscopic===
Features:<ref name=Ref_DCHH184>{{Ref DCHH|184}}</ref>
*Architecture: islands of cells surrounded by fibrous tissue.
**Also described as "lobulated" architecture; may not be apparent.
*Myxoid background - grey extracellular material, variable amount present.
*Mixed cell population:
*#Abundant eosinophilic cytoplasm.
*#''Physaliphorous cells'' or ''bubble cells'' - '''key feature'''.
*#*Have a very large clear bubble with a sharp border; bubble does not compress nucleus - nucleus may be in bubble.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Chordoma_-_low_mag.jpg Chordoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Chordoma_-_high_mag.jpg Chordoma - high mag. (WC)].
*[http://library.med.utah.edu/WebPath/COW/COW062.html Chordoma (med.utah.edu)].
*[http://www.ucl.ac.uk/cancer/research-groups/genetics-of-sarcoma/index.htm Chordoma - several images (acl.ac.uk)].
 
 
===IHC===
Features:
*S100 +ve.
*CK +ve.
*Brachyury +ve -- '''key stain'''.
**Protein important for axial development, affects notochord development.<ref>URL:[http://www.ncbi.nlm.nih.gov/omim/601397 http://www.ncbi.nlm.nih.gov/omim/601397]. Accessed on: 18 May 2010.</ref>
**''Brachyury'' literally means ''short tail''.<ref>URL: [http://www.jstor.org/pss/86845 http://www.jstor.org/pss/86845]. Accessed on: 18 May 2010.</ref>


==Hemangioblastoma==
==Hemangioblastoma==
===General===
{{Main|Hemangioblastoma}}
*Usually ''cerebellar''.
*Associated with [[von Hippel-Lindau syndrome]].
*WHO grade I.<ref>URL: [http://www.expertconsultbook.com/expertconsult/ob/book.do?method=display&type=bookPage&decorator=none&eid=4-u1.0-B978-1-4160-4580-9..00019-8--sc0155&isbn=978-1-4160-4580-9 http://www.expertconsultbook.com/expertconsult/ob/book.do?method=display&type=bookPage&decorator=none&eid=4-u1.0-B978-1-4160-4580-9..00019-8--sc0155&isbn=978-1-4160-4580-9]. Accessed on: 9 December 2010.</ref>
 
===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/340994-media http://emedicine.medscape.com/article/340994-media]. Accessed on: 23 June 2010.</ref>
*Vascular.
*Polygonal stromal cells with:
**Hyperchromatic nuclei.
**Vacuolar cytoplasm.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Cerebellar_hemangioblastoma_intermed_mag.jpg Hemangioblastoma - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Cerebellar_hemangioblastoma_high_mag.jpg Hemangioblastoma - high mag. (WC)].
 
DDx:
*Metastatic clear cell renal cell carcinoma.
 
===IHC===
Features:<ref>URL: [http://www.nature.com/modpathol/journal/v18/n6/full/3800351a.html http://www.nature.com/modpathol/journal/v18/n6/full/3800351a.html]. Accessed on: 9 December 2010.</ref>
*Alpha-inhibin +ve (cytoplasm).
*EMA -ve.
**RCC typically +ve.
*NSE +ve (nucleus + cytoplasm).
**RCC typically -ve.
 
==Medulloblastoma==
===General===
*Mostly paediatric population.
*May be seen as a component of [[nevoid basal cell carcinoma syndrome]] (NBCCS).
 
===Gross===
*Location: cerebellum - '''key feature'''.
**Morphologically identical supratentorial tumours are called ''primitive neuroepithelial tumour'' (PNET).
 
===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm]. Accessed on: 26 October 2010.</ref>
*Homer-Wright [[rosette]]s= rosette with a meshwork of fibers (neuropil) at the centre.<ref>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488–92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref>
 
Image:
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm Medulloblastoma (ouhsc.edu)].
 
====Subtypes====
*Classic medulloblastoma (~85% of all medulloblastomas).
*Variants of medulloblastoma (~15% of all medulloblastomas together):
*#Anaplastic variant.
*#Large cell variant.
*#Desmoplastic/nodular medulloblastoma (DNMB).
*#Medulloblastoma with extensive nodularity (MBEN).
 
Notes:
*Prognosis:<ref name=pmid18841049>{{cite journal |author=Gulino A, Arcella A, Giangaspero F |title=Pathological and molecular heterogeneity of medulloblastoma |journal=Curr Opin Oncol |volume=20 |issue=6 |pages=668–75 |year=2008 |month=November |pmid=18841049 |doi=10.1097/CCO.0b013e32831369f4 |url=}}</ref><ref name=pmid20940197>{{cite journal |author=Rutkowski S, von Hoff K, Emser A, ''et al.'' |title=Survival and Prognostic Factors of Early Childhood Medulloblastoma: An International Meta-Analysis |journal=J Clin Oncol |volume=28 |issue=33 |pages=4961–4968 |year=2010 |month=November |pmid=20940197 |doi=10.1200/JCO.2010.30.2299 |url=}}</ref> DNMB & MBEN > classic > anaplastic variant, large cell variant.
 
=====Anaplastic variant=====
Features:
*Larger cells.
*Severe anaplasia.
*Polygonal cells.
 
==Primitive neuroepithelial tumour==
===General===
*Abbreviated ''PNET''.
 
===Microscopic===
Features:
*See ''medulloblastoma''.
 
DDx: Embryonal tumor with abundant neuropil and true rosettes (ETANTR).<ref>{{cite journal |author=Buccoliero AM, Castiglione F, Degl'Innocenti DR, ''et al.'' |title=Embryonal tumor with abundant neuropil and true rosettes: morphological, immunohistochemical, ultrastructural and molecular study of a case showing features of medulloepithelioma and areas of mesenchymal and epithelial differentiation |journal=Neuropathology |volume=30 |issue=1 |pages=84–91 |year=2010 |month=February |pmid=19563506 |doi=10.1111/j.1440-1789.2009.01040.x |url=}}</ref>


==CNS lymphoma==
==CNS lymphoma==
Line 681: Line 613:
**Nucleolus - common.
**Nucleolus - common.
*Perivascular clustering.
*Perivascular clustering.
====Images====
www:
*[http://frontalcortex.com/?page=image&topic=1&qid=1237 CNS lymphoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case403.html Primary CNS lymphoma - several images (upmc.edu)].
<gallery>
Image:Primary CNS lymphoma - low mag.jpg | CNS lymphoma - low mag. (WC)
Image:Primary CNS lymphoma - intermed mag.jpg | CNS lymphoma - intermed. mag. (WC)
Image:Primary CNS lymphoma - high mag.jpg | CNS lymphoma - high mag. (WC)
Image:Primary CNS lymphoma - very high mag.jpg | CNS lymphoma - very high mag. (WC)
</gallery>
<gallery>
Image: CNS lymphoma (1) B-cell type.jpg | CNS lymphoma. (WC/KGH)
Image: CNS lymphoma (2) B-cell type.jpg | CNS lymphoma. (WC/KGH)
</gallery>


===IHC===
===IHC===
Line 686: Line 633:


Common pattern:
Common pattern:
*CD20 +ve - key stain.
*[[CD20]] +ve - key stain.
*CD3 -ve.
*CD3 -ve.
*Ki-67 ~40%.
*Ki-67 ~40%.
*Bcl-6 +ve.
*Bcl-6 +ve.
*Bcl-1 -ve.
*Bcl-1 -ve.
==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).
===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.
<gallery>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma  - Low power (SKB)
Image:Adrenal Ganglioneuroblastoma MP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma  - Medium power (SKB)
Image:Adrenal Ganglioneuroblastoma HP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP3 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma - High power (SKB)
Image:Adrenal Ganglioneuroblastoma HP2 CTR.jpg|thumb|Adrenal Ganglioneuroblastoma  - High power (SKB)
</gallery>
Images:
*[http://path.upmc.edu/cases/case530.html Ganglioneuroblastoma - several images (upmc.edu)].
===IHC===
*NSE +ve -- small cells.
==Lesions of the sella turcica==
{{Main|Pituitary gland}}
Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:
*[[Pituitary adenoma]].
*[[Craniopharyngioma]].
*[[Rathke cleft cyst]].
*[[Germ cell tumour]].
*[[Meningioma]].
*[[Pilomyxoid astrocytoma]] - in children.


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

Latest revision as of 09:04, 14 April 2022

A brain stem astrocytoma. (WC)

The article covers tumours in neuropathology. Tumours are a large part of neuropathology. Cytopathology of CNS tumours is dealt with in the article CNS cytopathology.

There are separate articles for peripheral nerve sheath tumours and pituitary/peri-pituitary lesions.

Brain tumours - overview

Alphabetical

For overview see here

By age group

Adult

Four most common types of brain tumours:[1]

  1. Metastatic brain tumours (barely edges out primary tumours)
  2. Glioblastoma, IDH-wildtype.
  3. Astrocytoma, IDH-mutant.
  4. Meningioma.

Children

  1. Pilocytic astrocytoma.
  2. Medulloblastoma.
  3. Ependymoma.
  4. Pontine glioma, often Diffuse midline glioma, H3 K27-altered.

By location

Certain tumours like to hang-out at certain places:[2]

Cerebrum

Cerebellum

Sella turcica

less common:

Spinal cord

Filum terminale

Meninges

less common:

  • Melanoma / Melanocytoma.
  • Lymphoproliferative diseases.
  • Sarcoidosis
  • Arachnoid cyst.
  • Disseminated oligodendroglial-like leptomeningeal tumour.
  • Desmoplastic infantile astrocytoma / ganglioglioma.
  • Meningioangiomatosis.
  • Calcifying pseudoneoplasm.

Skull

Skull base / Cerebellopontine angle

less common:

Primary versus secondary

  • AKA (primary) brain tumour versus metastatic cancer.

Primary

Glial tumours:

  • Cytoplasmic processes - key feature.
    • Best seen at highest magnification - usu. ~1 micrometer.
    • Processes may branch.
  • Ill-defined border/blend with the surrounding brain.

Meningioma:

  • Lesion often dura-based.
  • Mesenchymal tumor (often contains collagen).

Lymphoma:

  • Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
  • Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
    • ~2x size of resting lymphocyte, nucleoli.
  • Lesion predominantly perivascular.

Secondary

  • Carcinomas:
    • Well-demarcated border between brain and lesion - key feature.
    • No cytoplasmic processes.
    • Usu. have nuclear atypia of malignancy.
    • Nuclei often ~3-4x the size of a RBC.
    • +/-Glandular arrangement.
    • +/-Nucleoli.
  • Melanoma.
  • Secondary Lymphoma.
  • Sarcomas (rare).

By growth pattern

Infiltrative astrocytomas

Notes:

    • Glial: "blends into brain"/gradual transition to non-tumour brain.

Non-infiltrative astrocytomas

Cystic tumours

DDx:[3]


Notes:

    • Non-glial: no radiating glial processes.
  • Rosenthal fibres within the tumour... often seen in pilocytic astrocytoma.
    • Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
  • Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. cerebral infarct, multiple sclerosis) - esp. if this is a primary lesion.[5]

Grading

Nuclear pleomorphism present:

  • At least grade II (diffuse astrocytoma).

Mitotic figures present:

  • At least grade III (anaplastic astrocytoma).

Microvascular proliferation or necrosis with pseudopalisading tumour cells:

  • Grade IV (glioblastoma AKA glioblastoma multiforme).

Notes:

  • Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
  • WHO Grading is currently based on expected biologiocal behaviour without treatment.
    • Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).[6]

By IHC

Common neuropathology tumours in a table

Type Key feature(s) Imaging History Notes IHC Images
Normal tissue cells regularly spaced, no nuc. atypia small lesion? / deep lesion? variable missed lesion? nil
Normal. (WC)
Reactive astrocytes astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia small lesion? / deep lesion? variable missed lesion / close to a lesion; non-specific pathologic process - need more tissue GFAP
Reactive astrocytes. (WC)
Schwannoma cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies) extra-axial + intradural old or young need frozen section to Dx, DDx: meningioma S100, SOX10
Schwannoma. (WC)
Meningioma whorls, psammomatous calcs, nuclear inclusions extra-axial + intradural old or young may be diagnosed on smear, DDx: schwannoma, choroid plexus EMA, PR, Ki-67
Meningioma. (WC)
Astrocytoma, IDH-mutant (CNS WHO grade 2 or grade 3) glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis often enhancing (suggests high grade), usu. supratentorial, usu. white matter usu. old, occ. young common IDH-1(R132H)+/-, GFAP+
High-grade astrocytoma. (WC)
Glioblastoma, IDH-wildtype (CNS WHO grade 4) glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis often enhancing (suggests high grade), usu. supratentorial, usu. white matter usu. old, occ. young very common, esp. glioblastoma IDH-1+/-, GFAP+
Glioblastoma. (WC)
Metastasis sharp interface with brain, often glandular, +/-nucleoli, no glial processes often cerebellular, well-circumscribed usu. old often suspected to have metastatic disease TTF-1, CK7, CK20, BRST-2
Metastasis. (WC)

† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

Brain metastasis

Main article: Brain metastasis


Molecular

See also: Molecular Neuropathology

Gliomas

Main article: Glioma

Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

Astrocytic tumours

Main article: Astrocytoma

Features:[9][10]

  • Glial processes - key feature.
    • Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
  • No Rosenthal fibres within the tumour itself.

Images:

Depreceated:

Oligodendroglial tumours

Depreceated:

Pediatric-type diffuse high-grade glioma

Main article: Pediatric-type diffuse high-grade glioma

Pediatric-type diffuse low-grade glioma

Main article: Pediatric-type diffuse low-grade glioma


Circumscribed astrocytic gliomas

Astroblastoma

  • No WHO grade yet.[11]
  • Very rare superficial tumor of young age.[12]
  • Large, cystic. Pushing margin towards CNS.
  • Vasocentric growth, plump cells with absence of fibrillary pattern.
  • GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
  • Molecular profile overlaps with classical CNS-PNET.
    • Gene fusions invoving meningioma gene (MN1)[13]


  • HE. (WC/jensflorian)

  • HE. (WC/jensflorian)

  • Astroblastoma (AFIP)

Chordoid glioma of the third ventricle

  • WHO grade II.
  • Slowly growing, non-invasive, in adults.
  • Clusters of epithelioid cells in mucinous stroma.
  • Lymphocytic infiltrates, adjacent Rosenthal fibers.
  • Fibrosis may be present.
  • Few mitoses.
  • GFAP+ve, MIB-1 1-3%.
  • TTF-1+ve.
  • CD34+ve.
  • IDH-1-ve, p53-ve.
  • PRKCA D463H mutations.[14]

  • Chordoid Glioma. (WC/jensflorian)


Ependymal tumours

Choroid plexus tumours

Other neuroepithelial tumours


Cribiform neuroepithelial tumour

AKA: CRINET.

  • Not listed in the current WHO classification.
  • First description in 2009.[15]
  • Around ventricles.[16]
  • Young children.[17]
  • Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
  • MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
  • INI-1 loss, but no rhabdoid features and good prognosis.
  • Stable genomic profile.[18]

Neuronal and mixed neuronal/glial tumours

Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma

  • Abbreviated DIA or DIG.
  • ICD-O code: 9412/1
  • Large, superficial, cystic tumor of the infancy.
  • Biologic course corresponds to WHO grade I.
  • Very rare, included in the WHO since 1993.
  • Prominent desmoplastic stroma.
  • Astrocytic cells within stroma.
    • GFAP+.
    • MIB-1 usu. 1%.
  • Frequent BRAF V600E or V600D mutations.[19]
  • Single case with BRAF indel or BRAF fusion.

  • Histopathology of DIG (HE stain)

  • Prominent ganglioid cells in DIG (HE stain)

Cerebellar liponeurocytoma

  • Previously called lipomatous medulloblastoma (name changed in WHO 2000).
  • Mean age: 50 years.
  • As the name states: A tumour of the cerebellum.
    • But cases outside cerebellum reported that would qualify.[20]
  • WHO grade II [21] (upgraded from WHO grade I in 2007)[22]
  • ICD-O code: 9506/1

Histo

  • Advanced neuronal and lipomatous differentiation.
  • Neurocytes: round to oval nuclei with clear cytoplasm.
  • Quite cellular.
  • Mitoses almost absent.

IHC

  • GFAP +/-ve (focal).
  • MAP2 +ve.
  • Synaptophysin +ve.
  • NeuN +ve.
  • MIB-1: usu 1-3%.

Molecular

  • Distinct methylation profile.
  • Recurent losses on 2p and Chr. 14.[23]

  • Liponeurocytoma, HE (WC/Marvin101).

  • Liponeurocytoma, Synapto (WC/Marvin101).

  • Liponeurocytoma, HE (WC/jensflorian).

  • Liponeurocytoma, Synapto (WC/jensflorian).

DDx

Gangliocytoma

  • Grade I WHO neuronal tumour.
    • ICD-O code: 9492/0
  • Groups of irregular large neurons.
  • Non-neoplastic, reticulin-rich glial stroma.

Ganglioglioma

Not to be confused with ganglioneuroma.

General

  • Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
  • Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
  • Rare (approx. 0.5% of all CNS tumors).
  • Usu. temporal lobe.
  • Predominantly children (mean age: 9 years).
  • Recognized as a cause of epilepsy.[24]
  • Favourable prognosis (survival rates up to 97%)
    • Insufficient data für anaplastic ganglioglioma.

Macroscopic

  • Circumscribed lesion.
  • Usu. contrast enhancing.
  • Solid, but intracortical cysts may be present.
  • Little mass effect.


Microscopic

Features:

  • Dysplastic neurons.
    • Out of regular architecture / abnormal location.
    • Cytomegaly
    • Clustering
    • Binucleated (very occassionally).
  • Atypical glia.
  • Eosinophilic granular bodies.
  • Calcification.
  • Prominent capillary network.
  • Lymphocytic cuffing.
  • May contain some reticulin.
  • Glial component may resemble:
    • Fibrillary astrocytoma.
    • Oligodendroglioma.
    • Pilocytic astrocytoma.

Anaplastic ganglioglioma:

  • Brisk mitotic activity
  • Necrosis

IHC

  • Neurons:
    • MAP2 +ve
    • Synaptophysin +ve
    • Neurofilament +ve
  • Glia:
    • CD34+/-ve
  • BRAF V600E +ve (approx. 25%, mainly ganglion cells).

Molecular

  • BRAF V600E-mutated(approx. 25%).
  • IDH1/2 wt.
  • No 1p/19q codeletion.
  • Usu. Chr. 7 gain.
  • CDKN2A deletions in anaplastic ganglioglioma.

DDx:

  • DNT.
  • Oligodendroglioma.
  • Trapped cortical neurons in diffuse astrocytoma.
  • Papillary glioneuronal tumor.
  • Dysembryoplastic neuroepithelial tumor.

Images

  • Lymphocytic cuffing in ganglioglioma (WC/jensflorian)

  • Calcification in ganglioglioma (WC/jensflorian)

  • CD34 immunostain in ganglioglioma (WC/jensflorian)

  • Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)

Lhermitte-Duclos disease

  • Abbreviated LDD.
  • AKA dysplastic cerebellar gangliocytoma.[25]
  • AKA dysplastic gangliocytoma of the cerebellum.
Main article: Lhermitte-Duclos disease

  • Dysplastic gangliocytoma (low mag).

Papillary glioneuronal tumour

  • Abbreviated PGNT.
  • A benign, supratentorial tumor of childhood.
    • Biologic course corresponds to WHO grade I.
    • Before WHO 2000, considered a Ganglioglioma variant.
  • Prominent pseudopapillary architecture.
  • Neurocytes to medium-sized ganglion cells.
  • GFAP+ core, GFAP- layer
  • Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.

  • PGNT (HE) (WC/jensflorian)

Rosette-forming glioneuronal tumour of the fourth ventricle

  • Abbreviated RGNT.
  • Provisional ICD-O code: 9509/1
  • A rare benign infratentorial tumour of the midline of children and adults.
  • Biologic course corresponds to WHO grade I.
  • Glial component corresponds to pilocytic astrocytoma.
  • Neurocytic rosettes.
  • Eosinopil fibrillary cores / pseudorosettes.
  • GFAP+ in fibrillary areas, Syn+ in rosettes.
  • Neurocytic cells: MAP2+
  • MIB-1 usu. below 3%.

  • RGNT, HE stain (WC/jensflorian).

  • RGNT, higher magnification (WC/jensflorian).

Polymorphous low-grade tumor of the young (PLNTY)

Pineal tumours

Main article: Pineal gland

Embryonal tumours

DDx:

Peripheral nerve sheath tumours

Main article: Peripheral nerve sheath tumours

A classification:[26] Benign:

Malignant:

Ganglioneuroma

Not to be confused with ganglioglioma.
Main article: Ganglioneuroma


Meningioma

Main article: Meningioma

Chordoma

Main article: Chordoma

Hemangioblastoma

Main article: Hemangioblastoma

CNS lymphoma

Classification:

  • Primary CNS lymphoma.
  • Non-primary CNS lymphoma - see lymphoma article.

General - primary CNS

  • Classically periventicular distribution.
  • Usually large B cell; can be considered a type of diffuse large B cell lymphoma (DLBCL).
    • Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.[28]

Microscopic

Features:

  • Large cell lymphoma.
    • Size = 2x diameter normal lymphocyte.
    • Nucleolus - common.
  • Perivascular clustering.

Images

www:

  • CNS lymphoma - low mag. (WC)

  • CNS lymphoma - intermed. mag. (WC)

  • CNS lymphoma - high mag. (WC)

  • CNS lymphoma - very high mag. (WC)

  • CNS lymphoma. (WC/KGH)

  • CNS lymphoma. (WC/KGH)

IHC

Can be subclassified in GCB (germinal centre B-cell-like) and non-GCB by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.[28]

Common pattern:

  • CD20 +ve - key stain.
  • CD3 -ve.
  • Ki-67 ~40%.
  • Bcl-6 +ve.
  • Bcl-1 -ve.


Ganglioneuroblastoma

Main article: Neuroblastoma

General

  • Uncommon.
  • Part of the neuroblastic tumours group which includes:[29]

Microscopic

Features:

  • Ganglion-like cells with a prominent nucleolus.
  • Small undifferentiated cells with scant cytoplasm.

  • Adrenal Ganglioneuroblastoma - Low power (SKB)

  • Adrenal Ganglioneuroblastoma - Medium power (SKB)

  • Adrenal Ganglioneuroblastoma - High power (SKB)

  • Adrenal Ganglioneuroblastoma - High power (SKB)

  • Adrenal Ganglioneuroblastoma - High power (SKB)

Images:

IHC

  • NSE +ve -- small cells.

Lesions of the sella turcica

Main article: Pituitary gland

Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:

See also

References

  1. ↑ http://neurosurgery.mgh.harvard.edu/abta/primer.htm
  2. ↑ URL: http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif and http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html. Accessed on: 2 November 2010.
  3. ↑ URL: http://path.upmc.edu/cases/case320/dx.html. Accessed on: 14 January 2012.
  4. ↑ URL: http://www.pathologyoutlines.com/Cnstumor.html#cystsgeneral. Accessed on: 14 January 2012.
  5. ↑ URL: http://path.upmc.edu/cases/case79/dx.html. Accessed on: 2 January 2012.
  6. ↑ Louis, DN.; von Deimling, A. (Aug 2017). "Grading of diffuse astrocytic gliomas: Broders, Kernohan, Zülch, the WHO… and Shakespeare.". Acta Neuropathol. doi:10.1007/s00401-017-1765-z. PMID 28801693.
  7. ↑ Yan H, Parsons DW, Jin G, et al. (February 2009). "IDH1 and IDH2 mutations in gliomas". N. Engl. J. Med. 360 (8): 765–73. doi:10.1056/NEJMoa0808710. PMC 2820383. PMID 19228619. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820383/.
  8. ↑ Houillier C, Wang X, Kaloshi G, et al. (October 2010). "IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas". Neurology 75 (17): 1560–6. doi:10.1212/WNL.0b013e3181f96282. PMID 20975057.
  9. ↑ Rong Y, Durden DL, Van Meir EG, Brat DJ (June 2006). "'Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis". J. Neuropathol. Exp. Neurol. 65 (6): 529–39. PMID 16783163.
  10. ↑ http://dictionary.reference.com/browse/palisading
  11. ↑ The International Agency for Research on Cancer (Editors: Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.) (2007). Pathology and Genetics of Tumours of Tumors of the Central Nervous System (IARC WHO Classification of Tumours) (4th ed.). Lyon: World Health Organization. pp. 88. doi:10.1007/s00401-007-0243-4. ISBN 978-9283224303.
  12. ↑ Narayan, S.; Kapoor, A.; Singhal, MK.; Jakhar, SL.; Bagri, PK.; Rajput, PS.; Kumar, HS.. "Astroblastoma of cerebrum: A rare case report and review of literature.". J Cancer Res Ther 11 (3): 667. doi:10.4103/0973-1482.140800. PMID 26458709.
  13. ↑ Sturm, D.; Orr, BA.; Toprak, UH.; Hovestadt, V.; Jones, DT.; Capper, D.; Sill, M.; Buchhalter, I. et al. (Feb 2016). "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.". Cell 164 (5): 1060-72. doi:10.1016/j.cell.2016.01.015. PMID 26919435.
  14. ↑ Goode, B.; Mondal, G.; Hyun, M.; Ruiz, DG.; Lin, YH.; Van Ziffle, J.; Joseph, NM.; Onodera, C. et al. (02 2018). "A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle.". Nat Commun 9 (1): 810. doi:10.1038/s41467-018-02826-8. PMID 29476136.
  15. ↑ Hasselblatt, M.; Oyen, F.; Gesk, S.; Kordes, U.; Wrede, B.; Bergmann, M.; Schmid, H.; Frühwald, MC. et al. (Dec 2009). "Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis.". J Neuropathol Exp Neurol 68 (12): 1249-55. doi:10.1097/NEN.0b013e3181c06a51. PMID 19915490.
  16. ↑ Arnold, MA.; Stallings-Archer, K.; Marlin, E.; Grondin, R.; Olshefski, R.; Biegel, JA.; Pierson, CR.. "Cribriform neuroepithelial tumor arising in the lateral ventricle.". Pediatr Dev Pathol 16 (4): 301-7. doi:10.2350/12-12-1287-CR.1. PMID 23495723.
  17. ↑ Park, JY.; Kim, E.; Kim, DW.; Chang, HW.; Kim, SP. (Oct 2012). "Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review.". Neuropathology 32 (5): 570-6. doi:10.1111/j.1440-1789.2011.01293.x. PMID 22239490.
  18. ↑ Gessi, M.; Japp, AS.; Dreschmann, V.; Zur Mühlen, A.; Goschzik, T.; Dörner, E.; Pietsch, T. (Oct 2015). "High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System.". J Neuropathol Exp Neurol 74 (10): 970-4. doi:10.1097/NEN.0000000000000239. PMID 26352987.
  19. ↑ Wang, AC.; Jones, DTW.; Abecassis, IJ.; Cole, BL.; Leary, SES.; Lockwood, CM.; Chavez, L.; Capper, D. et al. (Jul 2018). "Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations.". Mol Cancer Res. doi:10.1158/1541-7786.MCR-17-0507. PMID 30006355.
  20. ↑ Gupta, K.; Salunke, P.; Kalra, I.; Vasishta, RK.. "Central liponeurocytoma: case report and review of literature.". Clin Neuropathol 30 (2): 80-5. PMID 21329617.
  21. ↑ Nishimoto, T.; Kaya, B. (Aug 2012). "Cerebellar liponeurocytoma.". Arch Pathol Lab Med 136 (8): 965-9. doi:10.5858/arpa.2011-0337-RS. PMID 22849747.
  22. ↑ Brat, DJ.; Parisi, JE.; Kleinschmidt-DeMasters, BK.; Yachnis, AT.; Montine, TJ.; Boyer, PJ.; Powell, SZ.; Prayson, RA. et al. (Jun 2008). "Surgical neuropathology update: a review of changes introduced by the WHO classification of tumours of the central nervous system, 4th edition.". Arch Pathol Lab Med 132 (6): 993-1007. doi:10.1043/1543-2165(2008)132[993:SNUARO]2.0.CO;2. PMID 18517285.
  23. ↑ Capper, D.; Stichel, D.; Sahm, F.; Jones, DTW.; Schrimpf, D.; Sill, M.; Schmid, S.; Hovestadt, V. et al. (Jul 2018). "Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience.". Acta Neuropathol. doi:10.1007/s00401-018-1879-y. PMID 29967940.
  24. ↑ Im, SH.; Chung, CK.; Cho, BK.; Lee, SK. (Mar 2002). "Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome.". J Neurooncol 57 (1): 59-66. PMID 12125968.
  25. ↑ Yağci-Küpeli, B.; Oguz, KK.; Bilen, MA.; Yalçin, B.; Akalan, N.; Büyükpamukçu, M. (Mar 2010). "An unusual cause of posterior fossa mass: Lhermitte-Duclos disease.". J Neurol Sci 290 (1-2): 138-41. doi:10.1016/j.jns.2009.12.010. PMID 20060133.
  26. ↑ Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A (October 2007). "Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns". AJNR Am J Neuroradiol 28 (9): 1633–8. doi:10.3174/ajnr.A0682. PMID 17893219. http://www.ajnr.org/cgi/reprint/28/9/1633.
  27. ↑ URL: http://medical-dictionary.thefreedictionary.com/ganglioma. Accessed on: 8 November 2010.
  28. ↑ 28.0 28.1 Raoux D, Duband S, Forest F, et al. (June 2010). "Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance". Neuropathology 30 (3): 232–40. doi:10.1111/j.1440-1789.2009.01074.x. PMID 19925562.
  29. ↑ Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B (July 1999). "Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee". Cancer 86 (2): 349–63. PMID 10421272.

External links

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