Difference between revisions of "Neuropathology tumours"

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The article covers '''CNS tumours''', including '''Brain tumours'''.  They are relatively common and mostly real badness.  Tumours are a large part of [[neuropathology]].   
[[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 also includes '''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====
# [[Pilocytic astrocytoma]].
# [[Medulloblastoma]].
# [[Ependymoma]].
# Pontine glioma, often [[Diffuse midline glioma, H3 K27-altered]].
 
===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>
====Cerebrum====
*Cortical based - [[oligodendroglioma]].
*Grey-white junction - metastases.
*White matter - astrocytoma, [[glioblastoma]].
*Periventricular - CNS lymphoma.
*Cystic - [[ganglioglioma]], [[pilocytic astrocytoma]], [[pleomorphic xanthoastrocytoma]].
====Cerebellum====
*Midline/central - [[medulloblastoma]].
*Cystic lesion - pilocytic astrocytoma (younger individual), [[hemangioblastoma]] (older individual).
*Solid lesion (older individual) - [[metastasis]].
====Sella turcica====
* [[Pituitary adenoma]].
* [[Craniopharyngioma]].
less common:
* [[Pituicytoma]].
* [[Granular cell tumour]].
* [[Germinoma]].
* [[Chordoma]]
* Rathke cleft cyst.
* Hypophysitis.
* Xanthogranuloma.
====Spinal cord====
*[[Ependymoma]]
*[[Glioblastoma]]
*[[Meningioma]]
*Carcinoma metastasis
*[[Hemangioblastoma]]
====Filum terminale====
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].
====Meninges====
* [[Meningioma]].
* [[Solitary fibrous tumour]] / Hemangiopericytoma.
* [[Hemangioblastoma]].
less common:
* [[Melanoma]] / Melanocytoma.
* Lymphoproliferative diseases.
* [[Sarcoidosis]]
* [[Arachnoid cyst]].
* Disseminated oligodendroglial-like leptomeningeal tumour.
* 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 versus secondary===
*[[AKA]] (primary) brain tumour versus metastatic cancer.
====Primary====
[[Glioma|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====
*[[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 neuropathology tumours in a table===
{| class="wikitable"
|'''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.
 
==Brain metastasis==
{{Main|Brain metastasis}}
 


===Children===
===Molecular===
# Astrocytoma.
See also:  [[Molecular_pathology_tests#Neuropathology|Molecular Neuropathology]]
# Medulloblastoma.
# Ependymoma.


==Astrocytomas==  
==Gliomas==
*Pilocytic astrocytomas (WHO Grade I).  
{{Main|Glioma}}
*Dysembryoplastic neuroepithelial tumour (DNT), (WHO Grade I).
 
*Low-grade (diffuse) astrocytomas (Grade II).
Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.
*Anaplastic astrocytomas (Grade III).
 
*Glioblastoma (Grade IV).
===Astrocytic tumours===
{{Main|Astrocytoma}}
 
* [[Astrocytoma]], IDH-mutant.
* [[Glioblastoma]], IDH-wildtype.
** [[Gliosarcoma]] (a glioblastoma subtype)


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>
*Nuclear pleomorphism.  
*Glial processes - '''key feature'''.
*Mitotic figures.  
**Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
*Microvascular proliferation or necrosis with pseudopalisading tumour cells.
*No Rosenthal fibres within the tumour itself.
**Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of pales forming a defense barrier or fortification.
 
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/neurotest/Q05-Ans.htm Endothelial proliferation (ouhse.edu)].
*[http://path.upmc.edu/cases/case368.html Gemistocytic astrocytoma - several images (upmc.edu)].
 
Depreceated:
* Diffuse [[Astrocytoma]]
* [[Anaplastic astrocytoma]]
* [[Gliomatosis cerebri]]
* Spongioblastoma
 
===Oligodendroglial tumours===
* [[Oligodendroglioma]], IDH-mutant and 1p/19q codeleted.
 
Depreceated:
* Anaplastic oligodendroglioma
* [[Oligoastrocytoma]]
* Anaplastic oligoastrocytoma
 
===Pediatric-type diffuse high-grade glioma===
{{Main|Pediatric-type diffuse high-grade glioma}}
* [[Astrocytoma#Diffuse_midline_glioma.2C_H3_K27M_mutant|Diffuse midline glioma H3 K27-mutant]]
 
===Pediatric-type diffuse low-grade glioma===
{{Main|Pediatric-type diffuse low-grade glioma}}
 
 
===Circumscribed astrocytic gliomas===
* [[Pilocytic astrocytoma]] (PA)
** [[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]].
 
====Astroblastoma====
*No WHO grade yet.<ref>{{Ref WHOCNS|88}}</ref>
*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>
 
 
<gallery>
File:Astroblastoma_HE_Specimen.jpg | HE. (WC/jensflorian)
File:Astroblastoma_HE_papillae.jpg | HE. (WC/jensflorian)
File:Astroblastoma.jpg | Astroblastoma (AFIP)
</gallery>
 
====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.<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>
 
<gallery>
File:NP op 20201028 009.jpg | Chordoid Glioma. (WC/jensflorian)
</gallery>
 
 
===Ependymal tumours===
* [[Subependymoma]]
* [[Myxopapillary Ependymoma]]
* [[Ependymoma]]
* Anaplastic ependymoma
 
==Choroid plexus tumours==
* [[Choroid plexus papilloma]]
* Atypical choroid plexus papilloma
* [[Choroid plexus carcinoma]]


==Pilocytic astrocytoma==
==Other neuroepithelial tumours==
*Low-grade astrocytoma.
* [[Neuropathology_tumours#Cribiform_neuroepithelial_tumour|Cribifiorm neuroepithelial tumour]].


===Gross===
*Do NOT smear.


===Microscopic===
===Cribiform neuroepithelial tumour===
*Rosenthal fibres - key feature.
AKA: '''CRINET'''.
**Image: [http://commons.wikimedia.org/wiki/File:Rosenthal_HE_40x.jpg Rosenthal fibres (WC)].
*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>
 
==Neuronal and mixed neuronal/glial tumours==
* [[Desmoplastic infantile astrocytoma]] / ganglioglioma (DIA/DIG)
* [[Dysembryoplastic neuroepithelial tumour]]
* [[Central Neurocytoma]] / Extraventricular [[neurocytoma]]
* Cerebellar liponeurocytoma
* [[Papillary glioneuronal tumour]] (PGNT)
* [[Rosette-forming glioneuronal tumour of the fourth ventricle]] (RGNT)
* Gangliocytoma / Ganglioglioma
* Dysplastic ganglioglioma of the cerebellum ([[Lhermitte-Duclos disease]])
* [[Paraganglioma]]


DDx (of Rosenthal fibers):<ref>MUN. 9 Mar 2009.</ref>
===Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma===
*Chronic reactive gliosis.
* Abbreviated ''DIA'' or ''DIG''.
*Subependymoma.
* ICD-O code: 9412/1
*Ganglioma.
* Large, superficial, cystic tumor of the infancy.
*Alexander's disease (rare leukodystrophy).
* 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>


==Oligodendroglioma==
===Cerebellar liponeurocytoma===
*Arise from oligodendrocytes.
* 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.<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====
*Calcifications.<ref>[http://www.emedicine.com/radio/topic481.htm http://www.emedicine.com/radio/topic481.htm]</ref> - key feature.
* Advanced neuronal and lipomatous differentiation.
*Oligodendrocytes.  
* Neurocytes: round to oval nuclei with clear cytoplasm.
**Cells with clear cytoplasm.
* Quite cellular.
*Abundant delicate vessels (may vagues resemble paraganglioma at low power).
* Mitoses almost absent.  


Images:
====IHC====
*[http://commons.wikimedia.org/wiki/File:Oligodendroglioma1_high_mag.jpg Oligodendroglioma high mag. (WC)].
* [[GFAP]] +/-ve (focal).
*[http://commons.wikimedia.org/wiki/File:Oligodendroglioma1_low_mag.jpg Oligodendroglioma low mag. (WC)].
* [[MAP2]] +ve.
* Synaptophysin +ve.
* NeuN +ve.
* MIB-1: usu 1-3%.


==Peripheral nerve sheath tumours==
====Molecular====
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>
* Distinct methylation profile.
*Benign:
* 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>
**Schwannoma.
**Neurofibroma.
**Perineurioma.
**Traumatic neuroma.
*Malignant:
**Malignant peripheral nerve sheath tumour (MPNST).


==Schwannoma==
<gallery>
*Tumour of tissue surrounding a nerve.
File:Cerebellar liponeurocytoma.jpg | Liponeurocytoma, HE (WC/Marvin101).
**Axons adjacent to the tumour are normal... but may be compressed.
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>


===Histology===
====DDx====
Antoni tissue:<ref name=pmid17893219/>
* [[Medulloblastoma]]
====Antoni A====
* [[Neurocytoma]]
*Cellular.
*'Fibrillary, polar, elongated'.


Comment: May look somewhat like scattered matchsticks.
===Gangliocytoma===
====Antoni B====
* Grade I WHO neuronal tumour.
*Loose microcystic tissue.
** ICD-O code: 9492/0
*Adjacent to Antoni A.
* Groups of irregular large neurons.
* Non-neoplastic, reticulin-rich glial stroma.


Micrographs:
===Ganglioglioma===
*[http://www.pathguy.com/~lulo/lulo0003.htm Antoni A (pathguy.com)].
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
*[http://www.ajnr.org/cgi/content/full/28/9/1633/F8 Antoni A & Antoni B side-by-side (ajnr.org)].
====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.


==Neurofibroma==
====Macroscopic====
General:<ref name=pmid17893219/>
*Circumscribed lesion.
*Composed of Schwann cells, axons, fibrous material.
*Usu. contrast enhancing.
*Solid, but intracortical cysts may be present.
*Little mass effect.


Appearance/morphology:<ref name=pmid17893219/>
*Plexiform growth pattern - "bag of worms".


==Ependymoma==
====Microscopic====
===Microscopy===
Features:
Features:
*Cells have a "tadpole-like" morphology.
*Dysplastic neurons.
**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>
**Out of regular architecture / abnormal location.
*Rosettes - cells arranged in a pseudoglandular fashion.
**Cytomegaly
*"Nucleus free zones" - cells arranged around a blood vessel (pseudorosettes) - vessel not seen, only cytoplasm of tumour cells.
**Clustering
**The nucleus free zone is composed of tumour cell cytoplasm that is adjacent to an unseen blood vessel.
**Binucleated (very occassionally).
*Nuclear feature monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
*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====
<gallery>
File:Ganglioglioma lymphocytic cuffing PAS.jpg | Lymphocytic cuffing in ganglioglioma (WC/jensflorian)
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)].
 
===Lhermitte-Duclos disease===
*Abbreviated ''LDD''.
*[[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>
 
===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.
<gallery>
File:PGNT_HE_stain.jpg | PGNT (HE) (WC/jensflorian)
</gallery>
 
===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%.
<gallery>
File:Histology RGNT HE.jpg | RGNT, HE stain (WC/jensflorian).
File:RGNT HE 2.jpg | RGNT, higher magnification (WC/jensflorian).
</gallery>
 
===Polymorphous low-grade tumor of the young (PLNTY)===
* [[Pediatric-type diffuse low-grade glioma#Diffuse low-grade glioma, MAPK pathway-altered|Polymorphous low-grade tumor of the young (PLNTY)]]
 
==Pineal tumours==
{{Main|Pineal gland}}
 
* [[Pineocytoma]]
* [[Pineal parenchymal tumour of intermediate differentiation]]
* [[Pineoblastoma]]
* [[Papillary tumour of the pineal region]]
 
==Embryonal tumours==
* [[Atypical teratoid/rhabdoid tumour]] (AT/RT) or (AT-RT)
* [[Medulloblastoma]]
* [[Primitive neuroectodermal tumour]] (PNET)
* [[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR)


DDx:
DDx:
*Subependymoma.
* [[Ewing sarcoma]]
* [[Sarcoma with CIC-rearrangement]]
 
==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>
'''Benign:'''
*[[Schwannoma]].
*[[Neurofibroma]].
*[[Perineurioma]].
*Ganglioneuroma.
**[[Traumatic neuroma]].
'''Malignant:'''
*[[Malignant peripheral nerve sheath tumour]] (MPNST).
 
===Ganglioneuroma===
:'''Not''' to be confused with ''[[ganglioglioma]]''.
*[[AKA]] ganglioma.<ref>URL: [http://medical-dictionary.thefreedictionary.com/ganglioma http://medical-dictionary.thefreedictionary.com/ganglioma]. Accessed on: 8 November 2010.</ref>
{{Main|Ganglioneuroma}}
 


==Choroid plexus papilloma==
===Microscopy===
Features:
*Papillae.
*Psammoma bodies.


Image:
==Meningioma==
*[http://commons.wikimedia.org/wiki/File:Choroid_plexus_papilloma_micrograph.jpg Choroid plexus papilloma (WC)].
{{Main|Meningioma}}


==Chordoma==
==Chordoma==
*Location: usually sacrum or clivus.
{{Main|Chordoma}}
 
==Hemangioblastoma==
{{Main|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.<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>DCHH P.184.</ref>
Features:
*Architecture: islands of cells surrounded by fibrous tissue.
*Large cell lymphoma.
**Also described as "lobulated" architecture; may not be apparent.
**Size = 2x diameter normal lymphocyte.
*Myxoid background - grey extracellular material, variable amount present.
**Nucleolus - common.
*Mixed cell population:
*Perivascular clustering.
*#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):
====Images====
*[http://www.surgical-pathology.com/Chordoma4_image.htm Chordoma - crappy quality image (surgical-pathology.com)].
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===
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/>
Common pattern:
*[[CD20]] +ve - key stain.
*CD3 -ve.
*Ki-67 ~40%.
*Bcl-6 +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:
Features:
*S100 +ve.
*Ganglion-like cells with a prominent nucleolus.
*CK +ve.
*Small undifferentiated cells with scant cytoplasm.
*Brachyury +ve.
<gallery>
**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>
Image:Adrenal Ganglioneuroblastoma LP CTR.jpg|thumb|Adrenal Ganglioneuroblastoma  - Low power (SKB)
**''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>
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==
*[[Neuropathology]].
*[[Muscle biopsy]].


==References==
==References==
Line 148: Line 685:


==External links==
==External links==
*[http://www.neuropathologyweb.org/ Neuropathology] - neuropathologyweb.org.
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course] - pathology.vcu.edu.
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-1.html Neuropathology Mini-Course (pathology.vcu.edu)].
*[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html Neuropathology Mini-Course (pathology.vcu.edu)].


[[Category:Neuropathology]]
[[Category:Neuropathology]]

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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