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==
==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.


==Astrocytomas==
[[Meningioma]]:
===Overview===
*Lesion often dura-based.
*Pilocytic astrocytomas (WHO Grade I).
*Mesenchymal tumor (often contains collagen).
*Dysembryoplastic neuroepithelial tumour (DNT), (WHO Grade I).
*Low-grade (diffuse) astrocytomas (Grade II).
*Anaplastic astrocytomas (Grade III).
*Glioblastoma (Grade IV).


===Microscopic===
[[Lymphoma]]:
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>
*Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
*Glial processes - '''key feature'''.
*Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
**~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).


Images:
===By growth pattern===
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0A002-PQ01-M.htm Endothelial proliferation in a GBM (ouhsc.edu)].
====Infiltrative astrocytomas====
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[[Astrocytoma, IDH-mutant]].
*[[Glioblastoma]], IDH-wildtype.


Notes:
Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.


====Grading====
====Non-infiltrative astrocytomas====
At least grade II:
**[[Pilocytic astrocytoma]]
*Nuclear pleomorphism.
**[[Pleomorphic xanthoastrocytoma]]
**[[Subependymal giant cell astrocytoma]].


At least grade III:
====Cystic tumours====
*Mitotic figures.  
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>


At least grade IV:
*Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells.
**Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of pales forming a defense barrier or fortification.


===Glioblastoma IHC===
Notes:
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
**Non-glial: no radiating glial processes.
*Ki-67 - usu. high >20% of cells.
*Rosenthal fibres within the tumour... often seen in [[pilocytic astrocytoma]].
*p53 - often +ve.
**Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
*IDH1 (isocitrate dehydrogenase 1).
*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>
**+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:
====Grading====
*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>
Nuclear pleomorphism present:
*At least grade II (diffuse astrocytoma).


==Pilocytic astrocytoma==
Mitotic figures present:
===General===
*At least grade III (anaplastic astrocytoma).
*Low-grade astrocytoma.
*Classically in the cerebellum in children; most common glioma in children.<ref name=Ref_PSNP82>{{Ref PSNP|82}}</ref>
*The ''optic glioma'' associated with neurofibromatosis 1.


===Gross===
Microvascular proliferation ''or'' necrosis with pseudopalisading tumour cells:
Features:<ref name=Ref_PSNP82>{{Ref PSNP|82}}</ref>
*Grade IV (glioblastoma [[AKA]] glioblastoma multiforme).
*Usually well-circumscribed.
*Cystic ''or'' solid.
*Do '''not''' smear. (Ref. ?)


===Microscopic===
Notes:
Features:<ref name=Ref_PSNP82-4>{{Ref PSNP|82-4}}</ref>
*Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
*Classically biphasic (though either may be absent):
*WHO Grading is currently based on expected biologiocal behaviour without treatment.
*#Fibrillar.
**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>
*#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:
===By IHC===
*+/-Microvascular proliferation.
*GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane) of most [[Astrocytoma]]s.
*+/-Focal necrosis.
*[[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>
**Necrosis with pseudopalisading more likely glioblastoma.
*[[H3F3A|H3F3A K27M]] in [[Diffuse midline glioma, H3 K27-altered]].  
*+/-Mitoses - not significant in the context of the Dx.
*[[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.


Images:  
===Common neuropathology tumours in a table===
*[http://commons.wikimedia.org/wiki/File:Rosenthal_HE_40x.jpg Rosenthal fibres (WC)].
{| class="wikitable"
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q19-Ans.htm Rosenthal fibre (ouhsc.edu)].
|'''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
|[[Image:Grey_matter_and_white_matter_-_very_high_mag.jpg |thumb|center|150px|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
|[[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)]]
|-
|[[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+
| [[Image:Glioblastoma (1).jpg | thumb| center| 150px|Glioblastoma. (WC)]]
|-
|[[Metastatic brain tumours|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
|[[Image:Metastatic_adenocarcinoma_-_cerebellum_-_very_low_mag.jpg | thumb| center|150px |Metastasis. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.


DDx (of Rosenthal fibers):<ref>MUN. 9 Mar 2009.</ref>
==Brain metastasis==
*Chronic reactive gliosis.
{{Main|Brain metastasis}}
*Subependymoma.
*Ganglioma.
*Alexander's disease (rare leukodystrophy).


DDx of pilocystic astrocytoma (brief):
*Piloid gliosis.
*Oligodendroglioma.
*Glioblastoma (uncommon - but important).


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


===Grading===
==Gliomas==
*''WHO Grade I'' by definition.
{{Main|Glioma}}


==Pilomyxoid astrocytoma==
Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.
===General===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*A variant of ''pilocytic astrocytoma''.
**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>
*Childhood or adolescence.


===Gross===
===Astrocytic tumours===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
{{Main|Astrocytoma}}
*Classically - hypothalamic location.
*Solid.
*Well-circumscribed.


===Microscopic===
* [[Astrocytoma]], IDH-mutant.
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
* [[Glioblastoma]], IDH-wildtype.
*Consists of small round/ovoid bland cells in a myxoid stroma.
** [[Gliosarcoma]] (a glioblastoma subtype)
*Hair-like fibres ~ 1 micrometer.
**Often difficult to appreciate on standard (H&E) histologic sections.
*Usually angiocentric (surround blood vessel) - '''key feature'''.


Notes:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</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>
*Rosenthal fibres are absent - '''key negative'''.
*Glial processes - '''key feature'''.
*Monophasic (unlike classical pilocytic astrocytomas) - '''key negative'''.
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*May rarely have eosinophilic granular bodies.
*No Rosenthal fibres within the tumour itself.


===Grading===
Images:
*''WHO Grade II'' by definition.<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*[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://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].


==Atypical teratoid/rhabdoid tumour==
Depreceated:
*Commonly abbreviated ''AT/RT''.
* Diffuse [[Astrocytoma]]
*May be written ''atypical teratoid rhabdoid tumour'', i.e. without the forward slash.
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma


===General===
===Oligodendroglial tumours===
*Usually supratentorial, occasionally in posterior fossa, case reports of spinal cord.
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.


===Microscopic===
Depreceated:
Features:
* Anaplastic oligodendroglioma
*Cellular.
* [[Oligoastrocytoma]]
*Small round cells usu. with a prominent nucleolus.
* Anaplastic oligoastrocytoma
*Rhaboid cells.
**Cells with eosinophilic granular cytoplasm + eccentric nucleus. (???)
*Mitoses.


DDx:
===Pediatric-type diffuse high-grade glioma===
*Primitive neuroectodermal tumour (PNET).
{{Main|Pediatric-type diffuse high-grade glioma}}
*Diffuse astrocytoma.
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]
*Choroid plexus carcinoma.
*Embryonal carcinoma.


===IHC===
===Pediatric-type diffuse low-grade glioma===
*BAF-47 -ve ([[AKA]] ''ANI1'') - virtually diagnostic.
{{Main|Pediatric-type diffuse low-grade glioma}}
**Endothelial cells +ve control.
*S-100 +ve.
**Few other brain tumours express it.
*Vimentin +ve (perinuclear condensation).


Others:
*GFAP +ve (focal - in tumour cells).
*EMA +ve (patchy cytoplasmic).
*Smooth muscle actin +ve.


==Oligodendroglioma==
===Circumscribed astrocytic gliomas===
===General===
* [[Pilocytic astrocytoma]] (PA)
*Arise from oligodendrocytes.
** [[Pilomyxoid astrocytoma]] (PMA)
* [[Pleomorphic xanthoastrocytoma]] (PXA)
* [[Subependymal giant cell astrocytoma]] (SEGA)
* [[Neuropathology_tumours#Astroblastoma|Astroblastoma MN1-altered]].
* [[Neuropathology_tumours#Chordoid glioma of the third ventricl|Chordoid glioma]].


Usual location:
====Astroblastoma====
*Fourth ventricle.
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*Intramedullary spinal cord.
*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>
*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)<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>


Prognosis by flavours (average survival):<ref name=Ref_PSNP98>{{Ref PSNP|98}}</ref>
*WHO grade II: 10-15 years.
*WHO grade III: 3-5 years.


===Microscopic===
<gallery>
Features:
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
*Highly cellular lesion composed of:
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
**Cells resembling ''fried eggs'' (oligodendrocytes) with:
File:Astroblastoma.jpg | Astroblastoma (AFIP)
***Round nucleus - '''key feature'''.
</gallery>
***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.<ref>URL: [http://www.emedicine.com/radio/topic481.htm http://www.emedicine.com/radio/topic481.htm].</ref>


Images:
====Chordoid glioma of the third ventricle====
*[http://commons.wikimedia.org/wiki/File:Oligodendroglioma1_high_mag.jpg Oligodendroglioma high mag. (WC)].
* WHO grade II.
*[http://commons.wikimedia.org/wiki/File:Oligodendroglioma1_low_mag.jpg Oligodendroglioma low mag. (WC)].
* 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.<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>


Notes:
<gallery>
*Few neural tumours have round nuclei - DDx:
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
**Oligodendroglioma.
</gallery>
**Lymphoma.
**Clear cell variant of ependymoma.
**Germ cell tumour (dysgerminoma/seminoma).


====Histologic grading====
Come in two flavours:
# WHO grade II.
#*This is most oligodendrogliomas.
# WHO grade III.
#*Features for calling high grade:<ref name=Ref_PSNP98>{{Ref PSNP|98}}</ref>
#**Endothelial hypertrophy.
#***Plump/large endothelial cells.
#**Necrosis.
#**High mitotic rate (6 mitoses/10 HPF for whatever "HPF" means, see [[HPFitis]]).


===IHC===
===Ependymal tumours===
Features:
* [[Subependymoma]]
*GFAP +ve.
* [[Myxopapillary Ependymoma]]
*EMA +ve.
* [[Ependymoma]]
* Anaplastic ependymoma


===Molecular pathology===
==Choroid plexus tumours==
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>
* [[Choroid plexus papilloma]]
*Greater chemosensitivity
* Atypical choroid plexus papilloma
*Better prognosis.
* [[Choroid plexus carcinoma]]


==Meningioma==
==Other neuroepithelial tumours==
{{Main|Meningioma}}
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].
===General===
*Very common.
*May be part of a syndrome.


===Microscopic===
Features (memory device ''WTC''):
*Whorled appearance - '''key feature'''.
*Thick-walled blood vessels, usually prominent.
*Calcification.


Grading: see ''[[meningioma]]''.
===Cribiform neuroepithelial tumour===
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>


==Peripheral nerve sheath tumours==
==Neuronal and mixed neuronal/glial tumours==
{{Main|Peripheral nerve sheath tumours}}
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
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>
* [[Dysembryoplastic neuroepithelial tumour]]
*Benign:
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
**Schwannoma.
* Cerebellar liponeurocytoma
**Neurofibroma.
* [[Papillary glioneuronal tumour]] (PGNT)
**Perineurioma.
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
**Traumatic neuroma.
* Gangliocytoma / Ganglioglioma
*Malignant:
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
**Malignant peripheral nerve sheath tumour (MPNST).
* [[Paraganglioma]]


==Schwannoma==
===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.<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>


{{Main|Peripheral nerve sheath tumours#Schwannoma}}
===Cerebellar liponeurocytoma===
===General===
* Previously called ''lipomatous medulloblastoma'' (name changed in WHO 2000).
*Tumour of tissue surrounding a nerve.
* Mean age: 50 years.
**Axons adjacent to the tumour are normal... but may be compressed.
* As the name states: A tumour of the cerebellum.
** 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>
* 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


===Microscopic===
====Histo====
Features:<ref name=pmid17893219/>
* Advanced neuronal and lipomatous differentiation.
*Antoni tissue (type A and type B).
* Neurocytes: round to oval nuclei with clear cytoplasm.
*Verocay bodies - paucinuclear area surrounded by nuclei.
* Quite cellular.
* Mitoses almost absent.  


Notes:
====IHC====
*Tumour does ''not'' smear well.<ref>MUN. 24 November 2010.</ref>
* [[GFAP]] +/-ve (focal).
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.


====Antoni A====
====Molecular====
*Cellular.
* Distinct methylation profile.
*'Fibrillary, polar, elongated'.
* 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>


Comment: May look somewhat like scattered matchsticks.
<gallery>
====Antoni B====
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
*Loose microcystic tissue.
File:Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/Marvin101).
*Adjacent to Antoni A.
File:Cerebellar Liponeurocytoma HE.jpg | Liponeurocytoma, HE (WC/jensflorian).
File:Cerebellar Liponeurocytoma Synaptophysin.jpg | Liponeurocytoma, Synapto (WC/jensflorian).
</gallery>


Micrographs:
====DDx====
*[http://www.pathguy.com/~lulo/lulo0003.htm Antoni A (pathguy.com)].
* [[Medulloblastoma]]
*[http://www.ajnr.org/cgi/content/full/28/9/1633/F8 Antoni A & Antoni B side-by-side (ajnr.org)].
* [[Neurocytoma]]


==Neurofibroma==
===Gangliocytoma===
{{Main|Peripheral nerve sheath tumours#Neurofibroma}}
* Grade I WHO neuronal tumour.
===General===
** ICD-O code: 9492/0
*May be a part of [[neurofibromatosis]] 1.
* Groups of irregular large neurons.
*Composed of Schwann cells, axons, fibrous material.<ref name=pmid17893219/>
* Non-neoplastic, reticulin-rich glial stroma.


===Microscopic===
===Ganglioglioma===
Features:<ref name=pmid17893219/>
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
*Plexiform growth pattern - "bag of worms".
====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]].<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>
*Favourable prognosis (survival rates up to 97%)
**Insufficient data für anaplastic ganglioglioma.


Image:
====Macroscopic====
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(1).jpg Neurofibroma - low mag. (WC)].
*Circumscribed lesion.
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(2).jpg Neurofibroma - high mag. (WC)].
*Usu. contrast enhancing.
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(3).jpg Neurofibroma - high mag. (WC)].
*Solid, but intracortical cysts may be present.
*Little mass effect.


==Ganglioneuroma==
===General===
*[[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.


===Microscopic===
====Microscopic====
Features:
Features:
*Ganglion cells - '''key feature'''.
*Dysplastic neurons.
**Large cells with large nucleus.
**Out of regular architecture / abnormal location.
***Prominent nucleolus.
**Cytomegaly
*Disordered fibrinous-like material.
**Clustering
*Eosinophilic granular bodies.<ref>R. Kiehl. 8 November 2010.</ref>
**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.


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


See: ''[[Adrenal gland]]''.
====IHC====
*Neurons:
**[[MAP2]] +ve
**Synaptophysin +ve
** Neurofilament +ve
*Glia:
**CD34+/-ve
*BRAF V600E +ve (approx. 25%, mainly ganglion cells).


==Ependymoma==
====Molecular====
===General===
*BRAF V600E-mutated(approx. 25%).
*Called the forgotten glial tumour.
*IDH1/2 wt.
*No 1p/19q codeletion.
*Usu. Chr. 7 gain.
*CDKN2A deletions in anaplastic ganglioglioma.  


Comes in two flavours:
====DDx:====
#Ependymoma (not otherwise specified).
*[[DNT]].
#Myxopapillary ependymoma.
*[[Oligodendroglioma]].
#*Classically at filum terminale.
*Trapped cortical neurons in diffuse astrocytoma.
*Papillary glioneuronal tumor.
*Dysembryoplastic neuroepithelial tumor.


===Microscopy===
====Images====
====Classic ependymoma====
<gallery>
Features:
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
*Cells have a "tadpole-like" morphology.
File:Ganglioglioma calcification.jpg | Calcification in ganglioglioma (WC/jensflorian)
**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>
File:Ganglioglioma Cd34 x200.jpg | CD34 immunostain in ganglioglioma (WC/jensflorian)
*[[Rosette]]s - cells arranged in a pseudoglandular fashion.
File:Anaplastic ganglioglioma HE.jpg | Pleomorphic ganglion cells in ganglioglioma (WC/jensflorian)
*"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.
</gallery>
''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)
*[http://path.upmc.edu/cases/case142.html Ganglioglioma - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case282.html Ganglioglioma - case 2 (upmc.edu)].


**The nucleus free zone is composed of tumour cell cytoplasm that is adjacent to an unseen blood vessel.
===Lhermitte-Duclos disease===
*Nuclear feature monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
*Abbreviated ''LDD''.
**There is little variation in size, shape and staining.
*[[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>


Images:
===Papillary glioneuronal tumour===
*[http://commons.wikimedia.org/wiki/File:Ependymoma_intermed_mag.jpg Ependymoma - intermed. mag. (WC)].
* Abbreviated ''PGNT''.
*[http://commons.wikimedia.org/wiki/File:Ependymoma_low_intermed_mag.jpg Ependymoma - low mag. (WC)].
* 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.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>


DDx (classic ependymoma):
===Rosette-forming glioneuronal tumour of the fourth ventricle===
*Subependymoma.
* Abbreviated ''RGNT''.
*Glioblastoma (GBM).
* Provisional ICD-O code: 9509/1
**Invasive border = GBM; circumscribed border of lesion = ependymoma.
* 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>


====Myxopapillary ependymoma====
===Polymorphous low-grade tumor of the young (PLNTY)===
Features:
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]
*Perivascular pseudorosettes:
**Myxoid material surround blood vessels.
***Myxoid material surrounded by tumour cells.


Images:
==Pineal tumours==
*[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].
{{Main|Pineal gland}}
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma.jpg Myxopapillary ependymoma - cytology (WC)].


====Grading====
* [[Pineocytoma]]
Easy:
* [[Pineal parenchymal tumour of intermediate differentiation]]
*Subependymoma = WHO grade I.
* [[Pineoblastoma]]
*Myxopapillary ependymoma = WHO grade I.
* [[Papillary tumour of the pineal region]]
Not-so-easy:
*Classic ependymoma = WHO grade II.
*Anaplastic ependymoma = WHO grade III.


Grade II vs. Grade III:
==Embryonal tumours==
*Cellular density.
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
*Mitoses.
* [[Medulloblastoma]]
*Necrosis.
* [[Primitive neuroectodermal tumour]] (PNET)
*Microvascular proliferation.
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)


Notes:
DDx:
*Many tumours fall between grade II and grade III.  These are called "indeterminate" by many.
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]


===IHC===
==Peripheral nerve sheath tumours==
*Reticulin.
{{Main|Peripheral nerve sheath tumours}}
*GFAP.
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>
*MIB-1.
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).


==Choroid plexus papilloma==
===Ganglioneuroma===
===Microscopy===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
Features:
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
*Papillae.
{{Main|Ganglioneuroma}}
*Psammoma bodies.


Image:
*[http://commons.wikimedia.org/wiki/File:Choroid_plexus_papilloma_micrograph.jpg Choroid plexus papilloma (WC)].


==Chordoma==
===General===
*Location: usually sacrum or clivus.


===Microscopic===
==Meningioma==
Features:<ref name=Ref_DCHH184>{{Ref DCHH|184}}</ref>
{{Main|Meningioma}}
*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.


Image(s):
==Chordoma==
*[http://www.surgical-pathology.com/Chordoma4_image.htm Chordoma - crappy quality image (surgical-pathology.com)].
{{Main|Chordoma}}
 
===IHC===
Features:
*S100 +ve.
*CK +ve.
*Brachyury +ve.
**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]].
 
===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:
==CNS lymphoma==
*[http://commons.wikimedia.org/wiki/File:Cerebellar_hemangioblastoma_intermed_mag.jpg Hemangioblastoma - intermed. mag. (WC)].
Classification:
*[http://commons.wikimedia.org/wiki/File:Cerebellar_hemangioblastoma_high_mag.jpg Hemangioblastoma - high mag. (WC)].
*Primary CNS lymphoma.
*Non-primary CNS lymphoma - see ''[[lymphoma]]'' article.
==Medulloblastoma==
===General===
*Mostly paediatric population.  
*May be seen as a component of [[nevoid basal cell carcinoma syndrome]] (NBCCS).


===Gross===
===General - primary CNS===
*Location: cerebellum - '''key feature'''.
*Classically periventicular distribution.
**Morphologically identical supratentorial tumours are called ''primitive neuroepithelial tumour'' (PNET).
*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.<ref name=pmid19925562>{{cite journal |author=Raoux D, Duband S, Forest F, ''et al.'' |title=Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance |journal=Neuropathology |volume=30 |issue=3 |pages=232–40 |year=2010 |month=June |pmid=19925562 |doi=10.1111/j.1440-1789.2009.01074.x |url=}}</ref>


===Microscopic===
===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>
Features:
*Homer-Wright rosettes= 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>
*Large cell lymphoma.
**Size = 2x diameter normal lymphocyte.
**Nucleolus - common.
*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>


Image:
===IHC===
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm Medulloblastoma (ouhsc.edu)].
Can be subclassified in ''GCB (germinal centre B-cell-like)'' and ''non-GCB'' by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.<ref name=pmid19925562/>


====Subtypes====
Common pattern:
*Classic medulloblastoma (~85% of all medulloblastomas).
*[[CD20]] +ve - key stain.
*Variants of medulloblastoma (~15% of all medulloblastomas together):
*CD3 -ve.
*#Anaplastic variant.
*Ki-67 ~40%.
*#Large cell variant.
*Bcl-6 +ve.
*#Desmoplastic/nodular medulloblastoma (DNMB).
*Bcl-1 -ve.
*#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==  
==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
===General===
*Abbreviated ''PNET''.
*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===
===Microscopic===
Features:
Features:
*See ''medulloblastoma''.
*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.


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>
==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


Molecular

See also: Molecular Neuropathology

Gliomas

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

Astrocytic tumours

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

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]


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]


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.

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]

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

Lhermitte-Duclos disease

  • Abbreviated LDD.
  • AKA dysplastic cerebellar gangliocytoma.[25]
  • AKA dysplastic gangliocytoma of the cerebellum.

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.

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%.

Polymorphous low-grade tumor of the young (PLNTY)

Pineal tumours

Embryonal tumours

DDx:

Peripheral nerve sheath tumours

A classification:[26] Benign:

Malignant:

Ganglioneuroma

Not to be confused with ganglioglioma.


Meningioma

Chordoma

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:

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

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.

Images:

IHC

  • NSE +ve -- small cells.

Lesions of the sella turcica

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.
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