Libre Pathology - User contributions [en]

Basics

2014-11-19T22:41:32Z

Laura: /* Strict pathologic definition */

This article serves as an '''introduction''' to [[anatomical pathology]] and discusses the '''basics'''.

==Pathology simplified==
===Blue & pink===
H&E is the standard...
*Too much '''PINK''' = DEAD ([[necrosis]]).
*Too much '''BLUE''' = BAD.

In words:
*''Blue is bad and pink is dead!''<ref>Streutker, C. 8 June 2013.</ref>

Note:
*There is a lengthy list of things that are blue and ''not'' "bad"... that why a pathology residency is years.
**[[Lymph node]]s are very blue... they aren't necessarily bad.
**Reactive processes can be very blue... they aren't bad.

===Three questions===
Pathology can be boiled down to:
#What is it?
#*Biopsies.
#Did I get it all?
#*Resections.
#Did I get the right thing?
#*Most other things.

==Terms==
===Staining===
*Eosinophilic - pink.
*Hyperchromatic - blue.
*Amphophilic - ''bluish-red'' colour when referring to H&E stained section.<ref>URL:[http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref>
**''Amphophilic'' means stains with both acidic & basic dyes.
**Images: [http://pancreaticcancer2000.com/immunoblast1.jpg amphophilic material - arrow (pancreaticcancer2000.com)], [http://www.webpathology.com/image.asp?n=4&Case=20 amphophilic cytoplasm in prostate carcinoma (webpathology.com)].
*''Argyrophilic'' means has an affinity for silver<ref>URL: [http://www.merriam-webster.com/medical/argyrophilic http://www.merriam-webster.com/medical/argyrophilic]. Accessed on: 29 August 2011.</ref><ref>URL: [http://en.wiktionary.org/wiki/argyrophilic http://en.wiktionary.org/wiki/argyrophilic]. Accessed on: 29 August 2011.</ref>/loves silver/stains with silver.
===Morphologic patterns===
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Name of pattern
! Meaning
! DDx (incomplete/abbrev. list)
! Image
|-
| Hobnail
| basement membrane area < area exposed to luminal surface
| [[angiosarcoma]], clear cell carcinoma
| [[Image:Epithelioid_angiosarcoma_-_very_high_mag.jpg |thumb|center|150px| [[Angiosarcoma]] - very high mag. (WC/Nephron)]]
|-
| Storiform
| spiral appearance ''or'' cartwhell pattern<ref>Storiform. dictionary.com. URL: [http://dictionary.reference.com/browse/storiform http://dictionary.reference.com/browse/storiform]. Accessed on: April 24, 2009.</ref>
| [[solitary fibrous tumour]], [[DFSP]], [[dermatofibroma]], [[UPS]]
| [[Image:Storiform_pattern_-_very_high_mag.jpg | thumb| center|150px| [[DFSP]] - very high mag. (WC/Nephron)]]
|-
| Fascicular
| the long axis of the (spindle) cells are perpendicular to one another in adjacent bundles of cells
| [[leiomyoma]], [[leiomyosarcoma]]
| [[Image:Cutaneous_leiomyosarcoma_-_very_high_mag.jpg| thumb | center | 150px | [[Leiomyosarcoma]] - very high mag. (WC/Nephron)]]
|-
| Plexiform
| web-like formation<ref>URL: [http://www.mondofacto.com/facts/dictionary?plexiform http://www.mondofacto.com/facts/dictionary?plexiform]. Accessed on: March 9, 2010.</ref>
| [[plexiform neurofibroma]], [[MPNST]], plexiform lesion of [[pulmonary hypertension]]
| [http://www.flickr.com/photos/bc_the_path/1715728630/ plexiform lesion of Pulm. HTn (flickr.com)]
|-
| Cribriform
| pierced with small holes<ref>URL: [http://dictionary.reference.com/browse/cribriform http://dictionary.reference.com/browse/cribriform]. Accessed on: 8 August 2011.</ref>
| cribriform [[DCIS]], cribriform [[HGPIN]], cribriforming in a [[tubular adenoma of the gastrointestinal tract|tubular adenoma]] with high-grade dysplasia, endometrioid endometrial carcinoma
| [[Image:Atypical_ductal_hyperplasia_-_very_high_mag.jpg|thumb|center|150px|Cribriform architecure ([[ADH]]) - very high mag. (WC/Nephron)]]
|-
| Solid ''or'' Sheeting
| no architecture - back-to-back cells with no pattern apparent / no spaces between cells
| solid DCIS, poorly-differentiated malignancy (carcinoma, sarcoma, lymphoma)
| [[Image:Merkel_cell_carcinoma_-_high_mag.jpg|thumb|center|150px|Sheeting in a [[Merkel cell carcinoma]] - high mag. (WC/Nephron)]]
|-
| Micropapillary
| nipple like projections without a fibrovascular core (papillary = nipple-like<ref>URL: [http://dictionary.reference.com/browse/papillary http://dictionary.reference.com/browse/papillary]. Accessed on: 8 August 2011.</ref>)
| micropapillary [[DCIS]], micropapillary [[HGPIN]]
| [[File:Invasive_micropapillary_carcinoma_of_the_breast.jpg|thumb|center|150px|Micropapillary carcinoma. (WC)]]
|-
| Papillary
| nipple-like projection with a fibrovascular core
| [[papillary thyroid carcinoma]]
| [[Image:Papillary_renal_cell_carcinoma_high_mag.jpg| thumb|center|150px|[[Papillary RCC]] - high mag. (WC/Nephron)]]
|-
| Flat
| board-like, does not have a projection above the surface
| flat DCIS
| [http://www.breastpathology.info/Sloane/Images/dcis/flat1-400.jpg flat DCIS 1 (breastpathology.info)],<ref name=sloane/> [http://www.breastpathology.info/Sloane/Images/dcis/flat2-400.jpg flat DCIS 2 (breastpathology.info)]<ref name=sloane>URL: [http://www.breastpathology.info/Sloane/dcis.html http://www.breastpathology.info/Sloane/dcis.html]. Accessed on: 8 August 2011.</ref>
|-
| Herring bone
| like herring bone (technique) for climbing a hill in cross country skiing; books on a shelf, where they have partially fallen over -- on the one shelf to the left and the one below to the right
| [[fibrosarcoma]], [[synovial sarcoma]], [[MPNST]]
| [[Image:Malignant_peripheral_nerve_sheath_tumour_-_high_mag.jpg|thumb|center|150px| [[MPNST]] - high mag.(WC/Nephron)]]
|-
| [[Trabecular]] ''or'' cords
| trabecula = ''little beam''<ref>URL: [http://dictionary.reference.com/browse/trabecula http://dictionary.reference.com/browse/trabecula]. Accessed on: 26 December 2010.</ref>; quasi-linear arrangement of cells
| normal liver lobule, [[Sertoli cell tumour]]
| [[Image:Papillary thyroid carcinoma tall cell var high mag.jpg|thumb|center|150px|[[PTC]] tall cell variant - high mag. (WC/Nephron)]]
|-
| Nested (nesting)
| islands of cells with a circular outline
| neuroendocrine tumours
| [[Image:Small_intestine_neuroendocrine_tumour_high_mag_cropped.jpg |thumb|center|150px|[[Neuroendocrine tumour]] - low mag. (WC/Nephron)]]
|-
| Biphasic / multiple patterns
| multiple patterns or cell types; e.g. spindle cells and epithelioid cells
| [[synovial sarcoma]], [[malignant melanoma]], [[pleomorphic adenoma]], [[angiomyolipoma]], [[chondroid syringoma]]
| [[Image:Desmoplastic_small_round_cell_tumour_-_high_mag.jpg |thumb|center|150px| [[DSRCT]] - high mag. (WC/Nephron)]]
|}

===Nuclear destruction words===
There are several fancy terms:<ref>[http://upload.wikimedia.org/wikipedia/en/5/51/Nuclear_changes.jpg http://upload.wikimedia.org/wikipedia/en/5/51/Nuclear_changes.jpg]</ref>
*Karyolysis = nuclear fading/dissolution.
*Pyknosis = nuclear shrinkage.
*Karyorrhexis = nuclear fragmentation.

Image:
*[http://en.wikipedia.org/wiki/File:Nuclear_changes.jpg Karyolysis, pyknosis, karyorrhexis (WP)].

===Erosions and ulcers===
*Ulcer = lesion through skin or mucous membrane.
*Erosion = limited to the mucosa - superficial ulceration.
**In dermatopathology - through the epidermis.

Image:
<gallery>
Image:Ulcers,_fissures,_and_erosions.svg | Ulcers and erosions - schematic. (WC)
</gallery>
====Microscopic - erosion====
Features - require 1 and 2:
#Loss of epithelium.
#Vital response at site of lost epithelium.
#*[[Neutrophil]]ic infiltrate.
#*+/-Fibrin.
#*+/-Cellular debris.

Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/figure/f4-cln_67p705/ Mucosal erosion (nih.gov)].<ref name=pmid22892912>{{Cite journal | last1 = Arashiro | first1 = RT. | last2 = Teixeira | first2 = MG. | last3 = Rawet | first3 = V. | last4 = Quintanilha | first4 = AG. | last5 = Paula | first5 = HM. | last6 = Silva | first6 = AZ. | last7 = Nahas | first7 = SC. | last8 = Cecconello | first8 = I. | title = Histopathological evaluation and risk factors related to the development of pouchitis in patients with ileal pouches for ulcerative colitis. | journal = Clinics (Sao Paulo) | volume = 67 | issue = 7 | pages = 705-10 | month = Jul | year = 2012 | doi = | PMID = 22892912 | PMC = 3400158 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400158/}}</ref>

==The general differential diagnosis==
Mnemonic ''CINE-TV-DATE'':
*Congenital.
*Inflammatory.
*Neoplastic.
*Endocrine.
*Trauma.
*Vascular.
*Degenerative.
*Autoimmune.
*Toxic.
*Everything else (iatrogenic, idiopathic, psychiatric).

In diagnostic pathology, most stuff falls into the ''neoplastic'' category.

===Features of malignancy===
====Cytologic features of malignancy====
It is said that:<ref name=boerner>S. Boerner. 12 September 2011.</ref>
#It is the nuclear abnormalities that make a cell malignant.
#The cytoplasm that gives one clues as to the cell of origin.

Nuclear features and malignancy:<ref name=boerner>S. Boerner. 12 September 2011.</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Feature
! Strength in predicting malignancy?
|-
| Large nuclear size
| weak
|-
| [[Nuclear-to-cytoplasmic ratio]]
| strong
|-
| Nuclear pleomorphism
| weak
|-
| Nucleoli shape (angulated, spiked, complex)
| strong
|-
| Nucleoli size
| weak - generally; strong if like in a [[Hodgkin lymphoma|RS cell]]
|-
| High nucleoli number
| weak negative; finding favours benign
|-
| Chromatin hyperchromasia
| weak
|-
| Chromatin granularity
| strong
|-
| Nuclear membrane irregularities
| strong (clefting, flat edges, sharp angles), scalloped (suggests benign)
|-
| Mitoses
| weak §
|-
| Atypical mitoses
| strong
|}

§ mitoses are seen in poorly differentiated tumour and regeneration. High mitotic rate in the context of unremarkable nuclear morphology is usually not malignant.

====Other features====
In the context of [[soft tissue lesions]], it is said that the two most important features of malignancy are:
#[[Necrosis]].
#High vascularity.

Notes:
*Benign soft tissue lesions may have marked [[nuclear atypia]] and abundant mitotic activity.

===General differential diagnosis of malignant lesion===
This should ''always'' be considered:
<center>

{{familytree/start}}
{{familytree | | | |A11| | | | |A11 = Malignancy }}
{{familytree | |,|-|-|^|-|-|.|}}
{{familytree | B11 | | | | B12 |B11=Primary|B12=[[metastasis|Metastatic]] }}
{{familytree/end}}
</center>
Q. Why? 
A. (1) The site of the tumour can considerably change the differential diagnosis. (2) The management is usually totally different. 

===A general clinico-histomorphologically motivated differential diagnosis of malignancy===
<center>

{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Malignancy}}
{{familytree | |,|-|-|-|v|-|-|-|v|-|^|-|v|-|-|-|v|-|-|-|.| |}}
{{familytree | B | | C | | D | | E | | F | |G |B=Epithelial (Carcinoma)|C=Mesenchymal ([[Sarcoma]])|D=[[Germ cell tumours|Germ cell tumour]]|E=[[Neuroendocrine carcinoma|Neuroendocrine carcinoma]]|F=Hematologic|G=[[Melanoma|Malignant melanoma]]}}
{{familytree/end}}
</center>

Notes:
*''[[Malignant melanoma]]'', also ''melanoma'', is a separate category as it can look like almost anything under the microscope.
*''Hematologic'' includes [[lymphoma]], [[leukemia]], [[plasma cell neoplasms]] and others.
*The above is a useful clinical classification. The problem is it isn't that useful for difficult cases as:
**Germ cell tumours are often not distinctive.
**Numerous epithelioid sarcomas can mimic carcinomas.
**Spindle cell carcinomas can mimic sarcomas very well.
**Neuroendocrine differentiation is not always readily apparent.
**The ''[[modified general morphologic DDx of malignancy]]'' is better for approaching difficult tumours.
Memory device ''HMN GEM'': hematologic, melanoma, neuroendocrine carcinoma, germ cell, epithelial, mesenchymal.

====Morphologic categorization====
=====Factors to consider=====
Factors to consider when attempting to group by morphology:
#Cell shape (spindle cell, epithelioid, plasmacytoid, mixed).
#Cell size (small or large) - size in relation to a neutrophil or [[red blood cell]].
#Cell cohesion - dyscohesive vs. cohesive.
#*If one sees several groups of 5+ cells... probably cohesive.
#*Presence of cell cohesion strongly disfavours lymphoma.
#Cytoplasm - abundance (scant, moderate, abundant).
#*Eosinophilic cytoplasm disfavours lymphoma.
#Chromatin - coarseness (fine, granular).
#Nucleoli - number (absent, present, multiple).
#*Large [[nucleoli]] (nucleoli seen with the 10x objective) pretty much exclude neuroendocrine.

======Types of cells======
{| class="wikitable sortable"
! Type
! Morphology
! Significance
|-
| [[Spindle cell]]
| tapered at both ends<ref>URL: [http://www.medterms.com/script/main/art.asp?articlekey=25657 http://www.medterms.com/script/main/art.asp?articlekey=25657]. Accessed on: 18 January 2010.</ref>
| suggestive of sarcoma - compatible with melanoma and some carcinomas
|-
| Epithelioid cell
| cell shape round/oval, nucleus round/oval, looks like epithelium (cell borders touch neighbouring cells - collectively form a barrier)
| suggests epithelial lesion (carcinoma) - compatible with others
|-
| [[Small round blue cell tumour]]/lymphoid:
| small cells with scant cytoplasm - usually round; "small" is classically 2x a "resting lymphocyte" diameter †
| common in children; in adults often lymphoma
|-
| Small lymphoid ([[small cell lymphoma]]).
| "small" in the context of lymphoid is classically ~1x a "resting lymphocyte" diameter; often not malignant by cytology
| suggests [[small cell lymphoma]], reactive changes or infection
|-
| Plasmacytoid cell
| resemble a plasma cell: eccentric nucleus, moderate basophilic cytoplasm, +/-"clockface" chromatin pattern (clumping of chromatin at the periphery of the nucleus), +/-perinuclear hof (crescentic cytoplasmic clearing adjacent to the nucleus; represents abundant Golgi apparatus
| suggests [[plasma cell neoplasm]] or infection
|}

Note:
*† Diameter of a "resting lymphocyte" ~ diameter of a [[red blood cell]] (RBC) ~ 8 micrometres.
**Most carcinoma cells are 3-4x the size of a RBC.

======Dyscohesive versus cohesive======
Deciding cells are dyscohesive vs. cohesive is important, as it is a strong determinant of whether one is dealing with a lymphoid lesion or not.

{| class="wikitable sortable"
!|
!| Cell spacing
!| Cell membrane
!| Cytoplasm, abundance
!| Cytoplasm, staining
|-
| '''Cohesive'''
| equal spacing ''or'' 3-D clusters ''or'' intracellular bridges
| visible & opposed (in >50% of cells)
| scant to abundant
| any
|-
| '''Dyscohesive'''
| unequal spacing, thin space surrounds cell
| not apparent
| usually scant
| usually basophilic
|-
| Value/utility
| equal or 3-D clusters suggests cohesive, pericellular space/rim suggests dyscohesive
| visible opposed membrane r/i cohesive
| abundant usu. cohesive
| eosinophilic usu. cohesive
|}

Strong predictors of ''cohesive'':
*Intracellular bridges.
*3-D clusters.
*Nuclear moulding.

Weak predictors of ''cohesive'':
*Eosinophilic cytoplasm.
*Abundant cytoplasm.
*>2 X RBC diameter (most lymphoma smaller).

Weak predictors of ''dyscohesive'':
*Pericellular space/rim.
*Scant cytoplasm.
*Basophilic cytoplasm.

=====Probable category by morphology=====
*Carcinoma = cohesive, relatively large (>~2X neutrophil), +/-nucleolus, +/-gland formation (circular structures), often moderate to abundant cytoplasm.
*Sarcoma = cohesive, composed of spindle cells (cells taper at both ends, nucleus oval/cigar-shaped).
*Germ cell tumour = appearance often similar to ''carcinoma'', site (location) very useful - esp. gonadal, midline, retroperitoneal.
*[[Neuroendocrine carcinoma]] = cohesive, fine granular chromatin and no [[nucleolus]].
*Lymphoma = dyscohesive, relatively small (usually <=2X neutrophil diameter), usu. scant basophilic (blue) cytoplasm.
*Melanoma = classically pigmented, often a prominent [[red nucleolus]], a mix of spindle cells and epithelioid cells, mix of cohesive and dyscohesive cells.

===A practical histomorphologic differential diagnosis of malignancy===
====General morphologic DDx of malignancy====
{{familytree/start}}
{{familytree | | | | | | | A01 | | | | | | | | A01=Malignancy}}
{{familytree | |,|-|-|-|v|-|^|-|v|-|-|-|.| | |}}
{{familytree | B01 | | B02 | | B03 | | B04 | |B01=[[Large epithelioid tumours]]|B02=[[spindle cell lesions|Spindle cell tumours]]|B03=[[small round cell tumours|Small blue cell tumours]]|B04=[[Pleomorphic tumours]]}}
{{familytree/end}}

====Modified general morphologic DDx of malignancy====
<center>
{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | |A=Malignancy}}
{{familytree | |,|-|-|-|v|-|-|-|v|-|^|-|v|-|-|-|v|-|-|-|.| |}}
{{familytree | B | | C | | D | | E | | F | |G |B=[[Large epithelioid tumours]]|C=[[spindle cell lesions|Spindle cell tumours]]|D=[[small round cell tumours|Small blue cell tumours]]|E=[[Pleomorphic tumours]]|F=[[Clear cell tumours]]|G=[[myxoid lesions|Myxoid tumours]]}}
{{familytree/end}}
</center>

The above is more useful than the ''general clinico-histomorphologically motivated differential diagnosis of malignancy''.

==Differential diagnosis by site==
{{Main|Short power list}}
It is essential to have a concept of what is common. The ''[[short power list]]'' gives a short [[differential diagnosis]] for the common sites.

{{Main|Long power list}}
The ''[[long power list]]'' is a longer list for the common sites.

==Finding the elements==
===Mitoses===
*Nucleus darker (hyperchromatic) - '''key feature'''.
*No nuclear membrane - '''key feature'''.
*In prophase chromatin may have a scalloped border/beaded border.<ref>URL: [http://www.microbehunter.com/wp/wp-content/uploads/2009/lily_prophase.jpg http://www.microbehunter.com/wp/wp-content/uploads/2009/lily_prophase.jpg] and [http://www.microbehunter.com/2009/12/06/mitosis-stages-of-the-lily/ http://www.microbehunter.com/2009/12/06/mitosis-stages-of-the-lily/]. Accessed on: 3 November 2010.</ref>

DDx:
*Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.

====Images====
<gallery>
Image:Atypical_mitosis.jpg| Mitoses and an atypical mitosis. (WC)
Image:Tripolar_Mitosis_-_breast_carcinoma.jpg| Tripolar mitosis. (WC)
</gallery>
www:
*[http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab4/IMAGES/MITOSIS%20IN%20GUT.JPG Mitoses (vetmed.vt.edu)].
*[http://www.flickr.com/photos/euthman/426956752/ Starburst mitosis (flicker.com)].

====Phases of mitosis====
*Prophase - chromatin condenses to chromosomes.
*Metaphase - chromosome aligned.
*Anaphase - spindles separated.
*Telophase - reversal of prophase.

===Neutrophils===
{{Main|Neutrophils}}
*Little dots = the multilobular nucleus - '''key feature'''.
*Neutrophils are often found with friends, i.e. lymphocytes, plasma cells.

DDx of little specs:
*Nuclear debris - apoptotic cell.
**Apoptotic cell -- has nuclear condensation (pyknosis), eosinophilic cytoplasm.

Notes:
*AKA '''PMNs''' - polymorphonuclearcyte, polymorphonuclear cell.
*You find PMNs by their nucleus; on a histologic section don't bother looking for the cell membrane (they are usually impossible to see).
*A collection of PMNs... think about ''necrosis'' and ''abscess''.

===Lymph node metstatsis===
{{Main|Lymph node metastasis}}
*Take a good to look at the tumour first.
*Tumour in a node is often better differentiated than the most poorly differentiated part in the primary site.
*Subcapsular space - the first place to look for mets.
*Lymph node metstasis are usually obvious.
**There are of course exceptions, e.g. [[small cell carcinoma]], [[invasive lobular carcinoma]].
*Histiocytes may be difficult to separate from tumour - especially for the novice.
**Histiocytes may be found in the germinal centres, i.e. the node architecture helps.
**Malignant cells, generally, have to have malignant features, i.e. the [[NC ratio]] is abnormal, there is [[nuclear pleomorphism]].
*Several things can mimic metastases - see ''[[Lymph node metastasis]]''.

See: ''[[Lymph node]]'' article for a detailed description of cell types in a lymph node.

===Signet ring cell carcinoma===
{{Main|Signet ring cell carcinoma}}
*It has been said that there are two types of pathologists... those that have missed SRCs ''and'' those that will miss SRCs.

Microscopic:
*Cells resemble signet rings:
**They contain a large amount of mucin, which pushes the nucleus to the cell periphery.
**The pool of mucin in a signet ring cell mimics the appearance of a finger hole.
**The nucleus mimics the appearance of the face of the ring in profile.
*Cells typically 2-3x the size of a lymphocyte.
**Smaller than the typical adipocyte.
*Often have a crescent-shaped ''or'' ovoid nucleus.
**Capillaries sectioned on their lumen have endothelial cells -- the nuclei of these are more spindled.
*SRCs are usually close to friend -- another SRC.
**This helps differentiate SRCs from capillaries sectioned on their lumen.
*The mucin is often clear on H&E... but maybe eosinophilic.

DDx:
*[[Fat atrophy]].

Stains:
*PAS stain.
*Alican blue-PAS stain.

====Images====
<gallery>
Image:Signet_ring_cells_5.jpg |SRCs - H&E stain. (WC/Nephron)
Image:Gastric_signet_ring_cell_carcinoma_histopatholgy_(2)_PAS_stain.jpg | SRCs - AL-PAS stain. (WC)
Image:Gastric_signet_ring_cell_carcinoma_histopatholgy_(1).jpg | SRC - H&E stain. (WC)
</gallery>
www:
*[http://www.engravingarts.com/sales/LVX2.jpg Signet rings (engravingarts.com)].

===Necrosis===
{{Main|Necrosis}}
Features:
*Dead cells - pink (on H&E).
**Anucleate cells ("Ghost cells")/outlines of cells - usu. subtle.
***Fluffy appearance.
*+/-Neutrophils (very common).

DDx of necrosis:
*Fibrin.

Images (necrosis):
*[http://www0.sun.ac.za/ortho/webct-ortho/tb/tb-histology.html Necrosis at the centre of a granuloma (sun.ac.za)].
*[http://www.biomedical-engineering-online.com/content/9/1/10/figure/F7?highres=y Necrosis (biomedical-engineering-online.com)].
*[http://www.nature.com/bmt/journal/v39/n9/fig_tab/1705646f1.html Necrosis (nature.com)].
*[http://moon.ouhsc.edu/kfung/jty1/Com08/Com08Image/Com801-1-09.gif Necrosis (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com08/Com801-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com08/Com801-1-Diss.htm]. Accessed on: 3 November 2010.</ref>
<gallery>
Image:Cat_scratch_disease_-_very_high_mag.jpg | Necrosis in [[cat scratch disease]]. (WC/Nephron)
Image:Histiocytic_necrotizing_lymphadenitis_-_very_high_mag.jpg | Necrosis in [[histiocytic necrotizing lymphadenitis]]. (WC/Nephron)
Image:Systemic_lupus_erythematosus_lymphadenopathy_-_high_mag.jpg | Necrosis in [[SLE lymphadenopathy]]. (WC/Nephron)
</gallery>

==Granulomas==
*Granulomas can be elusive to the novice.
*Plural of ''granuloma'' was ''granulomata''; ''granulomas'' (an anglicized version) is, however, now generally accepted.

===Definition of granuloma===
*Many definitions exist.
*The term is used rather loosely by clinicans.
**Radiologists occasionally call small lung nodules "granulomas".

====Strict pathologic definition====
Robbins definition:
*Chronic inflammatory reaction characterized by the focal accumulation of activated macrophages, often with an epithelioid appearance.<ref name=Ref_PBoD82>{{Ref PBoD|82}}</ref>
**"Epithelioid" cells = cells whose morphology resembles that of epithelial cells; the cells appear to adhere to one another.

Adams definition - it's short & sweet:
*A compact collection of macrophages.<ref name=pmid937513>{{cite journal |author=Adams DO |title=The granulomatous inflammatory response. A review. |journal=American Journal of Pathology |volume=84 |issue=1 |pages=164–191 |year=1976 |pmid=937513 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032357/?tool=pubmed}}</ref>
**The macrophages must form a small ball/cluster of cells, i.e. touch one another.

Other pathologic definitions include the presence of:<ref name=pmid937513/>
*Plasma cells.
*Lymphocytes.
*Epithelioid macrophages.

Notes:
*The textbook answer for what is a granuloma is: "A collection of epithelioid macrophages."
**Granulomas are often associated with lymphocytes.

===Features that assist one in finding granulomas===
#Collection of cells that have abundant bubbly cytoplasm - '''most useful feature'''.
#'''Multinucleated [[giant cells]]''' - these are easy to identify if you've seen some before.
#*Individual/singular multinucleated giant cells are not diagnostic of a granuloma... but should raise one's suspicion of one being present.
#Necrosis - too much pink (on H&E stained sections).

Notes:
*Small round collection of lymphocytes - without a capsule (as seen in lymph nodes).
**If there are no macrophages... it's a ''lymphoid nodule''.

Images:
<gallery>
Image:Granuloma_20x.jpg |Granulomas showing abundant bubbly cytoplasm. (WC)
Image:Asteroid_body_intermed_mag.jpg |Granulomas with multinucleated giant cells in sarcoidosis. (WC)
Image:Necrogran10x.jpg|Granuloma with necrosis. (WC)
</gallery>
====As a list====
Features:<ref>Santos, G. 26 January 2010.</ref>
#Foamy/bubbly cytoplasm, abundant - '''low power'''.
#Epithelioid morphology - cell borders ''near'' indistinct - '''key feature'''.
#"Footprint" pattern nuclei/bean-shaped nuclei - '''key feature'''.
#*Macrophages usu. have an ovoid nucleus.
#+/-Nucleoli, small.
#+/-Fibrosis.
#+/-Palisading at edge.

====DDx====
*Reactive germinal centre - especially if there are abundant surrounding lymphocytes.<ref name=Ref_GLP170>{{Ref GLP|170}}</ref>

===Classification of granuloma===
====Histologic classification====
#Necrosing (also ''caseating'').
#*More likely to be infectious.
#*Examples: [[Tuberculosis]] (TB).
#Non-necrosing.
#*Less likely to be infectious.
#*Examples: Crohn's disease, sarcoidosis, drug reaction.

Whether necrosis is present in a granuloma is affected by the immune function, e.g. a [[HIV]]/AIDS patient may have non-necrosing granulomata due to TB.

Notes:
*A few people differentiate between ''caseating'' (fragments of recognizable tissue) and ''necrosing'' (dead debris only).<ref name=pmid17257125>{{Cite journal | last1 = El-Zammar | first1 = OA. | last2 = Katzenstein | first2 = AL. | title = Pathological diagnosis of granulomatous lung disease: a review. | journal = Histopathology | volume = 50 | issue = 3 | pages = 289-310 | month = Feb | year = 2007 | doi = 10.1111/j.1365-2559.2006.02546.x | PMID = 17257125 }}</ref>
*Infectious non-necrosing infections: [[Mycobacterium avium complex]] (MAC), [[cryptococcus]], infections in immunosuppressed individuals.<ref name=pmid17257125/>

====Etiologic classification====
#Infectious, e.g. [[tuberculosis]], [[MAC]], [[leprosy]], [[syphilis]], [[cat-scratch disease]], schistosomiasis,<ref name=Ref_PCPBoD8_47>{{Ref PCPBoD8|47}}</ref> fungal infection.
#Neoplastic, e.g. [[seminoma]], Lennert lymphoma,<ref name=pmid19775391>{{Cite journal | last1 = Summers | first1 = TA. | last2 = Rush | first2 = W. | last3 = Aguilera | first3 = N. | last4 = Lupton | first4 = G. | title = Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature. | journal = J Cutan Pathol | volume = 36 Suppl 1 | issue = | pages = 25-30 | month = Oct | year = 2009 | doi = 10.1111/j.1600-0560.2008.01203.x | PMID = 19775391 }}</ref> ruptured ovarian teratoma.<ref name=pmid15526210>{{Cite journal | last1 = Phupong | first1 = V. | last2 = Sueblinvong | first2 = T. | last3 = Triratanachat | first3 = S. | title = Ovarian teratoma with diffused peritoneal reactions mimicking advanced ovarian malignancy. | journal = Arch Gynecol Obstet | volume = 270 | issue = 3 | pages = 189-91 | month = Nov | year = 2004 | doi = 10.1007/s00404-003-0479-8 | PMID = 15526210 }}</ref>
#Autoimmune/inflammatory, e.g. [[Wegener's granulomatosis]], [[Churg-Strauss syndrome]].
#Allergic, e.g. [[hypersensitivity pneumonitis]].
#Foreign body, e.g. [[pulmonary talcosis]], silicosis, berylliosis,<ref name=Ref_PCPBoD8_47>{{Ref PCPBoD8|47}}</ref> [[suture material]].
#Drug reaction.
#Idiopathic, e.g. [[sarcoidosis]].

Notes:
*Memory device: ''DNF AAII'' = drug reaction, neoplasm, foreign body, allergy, autoimmune, idiopathic, infection.
*A long [[DDx]] for granulomas is complied by ''James''.<ref name=pmid10908370>{{Cite journal | last1 = James | first1 = DG. | title = A clinicopathological classification of granulomatous disorders. | journal = Postgrad Med J | volume = 76 | issue = 898 | pages = 457-65 | month = Aug | year = 2000 | doi = | PMID = 10908370 }}</ref>

===Lung granulomata===
There are many causes.<ref name=pmid17257125/>

Infectious:
*Myocbacterial: [[Tuberculosis]], [[MAC]], other.
*Fungal: [[Histoplasmosis]], [[Cryptococcosis]], [[Blastomycosis]], [[Coccidioidomycosis]].
*[[Aspiration pneumonia]].
Non-infectious:
*Pneumoconioses/[[hypersensitivity pneumonitis]]: Talcosis, Berylliosis.
Idiopathic/autoimmune:
*[[Sarcoidosis]].
*[[Wegener's granulomatosis]].
*[[Churg-Strauss disease]].
*[[Rheumatoid nodules]].

===Special granulomas===
====Fibrin ring granuloma====
*Classically associated with ''[[Q fever]]''.
**DDx:<ref name=pmid11881318>{{cite journal |author=Tjwa M, De Hertogh G, Neuville B, Roskams T, Nevens F, Van Steenbergen W |title=Hepatic fibrin-ring granulomas in granulomatous hepatitis: report of four cases and review of the literature |journal=Acta Clin Belg |volume=56 |issue=6 |pages=341–8 |year=2001 |pmid=11881318 |doi= |url=}}</ref> infections (Coxiella burnetii (causes [[Q fever]]), [[CMV]], [[EBV]] + others), drug reaction, malignancy (e.g. Hodgkin lymphoma<ref name=pmid8514044>{{cite journal |author=de Bayser L, Roblot P, Ramassamy A, Silvain C, Levillain P, Becq-Giraudon B |title=Hepatic fibrin-ring granulomas in giant cell arteritis |journal=Gastroenterology |volume=105 |issue=1 |pages=272–3 |year=1993 |month=July |pmid=8514044 |doi= |url=}}</ref>).
*Appearance:
**Epithelioid macrophages (i.e. a granuloma) surrounding a fibrin ring with a clear (lipid-filled) vacuole at its center.
***Images:
****[http://en.gooword.com/picture/864449/ FRG (gooword.com)].
====Naked granuloma====
*Minimal (lymphoid) inflammation.
**Classically [[sarcoidosis]] <ref name=pmid18948765>{{Cite journal | last1 = Brinster | first1 = NK. | title = Dermatopathology for the surgical pathologist: a pattern-based approach to the diagnosis of inflammatory skin disorders (part II). | journal = Adv Anat Pathol | volume = 15 | issue = 6 | pages = 350-69 | month = Nov | year = 2008 | doi = 10.1097/PAP.0b013e31818b1ac6 | PMID = 18948765 }}</ref><ref name=pmid24138972>{{Cite journal | last1 = Noiles | first1 = K. | last2 = Beleznay | first2 = K. | last3 = Crawford | first3 = RI. | last4 = Au | first4 = S. | title = Sarcoidosis can present with necrotizing granulomas histologically: two cases of ulcerated sarcoidosis and review of the literature. | journal = J Cutan Med Surg | volume = 17 | issue = 6 | pages = 377-83 | month = | year = | doi = | PMID = 24138972 }}</ref> - DDx large.

==Common morphologic problems==
===DDx of pink stuff (on H&E)===
The ''ABCs'' of pink:
*'''A'''myloid.
*'''B'''lood clot (organized); fibrin.
*'''C'''ollagen (fibrous tissue).
*'''S'''mooth muscle cells (SMCs).

=====Images=====
<gallery>
Image:Cardiac_amyloidosis_high_mag_he.jpg | Cardiac amyloid. (WC/Nephron)
Image:Laminations_in_a_thrombus_-_high_mag.jpg | Fibrin in a thrombus. (WC/Nephron)
Image:Ovarian_fibroma_-_high_mag.jpg | Collagen in an ovarian fibroma. (WC/Nephron)
Image:Glatte_Muskelzellen.jpg | Smooth muscle. (WC/Polarlys)
</gallery>

====Smooth muscle cells (SMCs) vs. fibrous tissue====
Fibroblasts (fibrous tissue):
*Wavy nuclei with pointy ends.
*Less nuclei.
SMCs:
*Elliptical nuclei.
*More nuclei.

Remembering the above:
*SMCs are stretched; ergo, not wavy.
*Fibrous tissue is fibrous... more protein... less cells; ergo, less nuclei.
*'''F'''ibroblast = '''f'''ootball-like.
*Cigar-shaped nuclei (SMCs) are affected by cigars (smoking causes vascular disease).

Notes:
*Schwann cells (found in nerve): nuclei = wavy appearance, thin. (???)

===Pigmented material===
*[[AKA]] brown/black granular crap.

DDx of granular stuff/pigment:
#Lipofuscin - especially in old people.
#Hemosiderin.
#Bile - found in hepatocytes, yellow.
#Foreign material (tattoo pigment, anthracotic pigment, [[amalgam tattoo]]).
#Melanin.

Notes:
*Granular stuff should prompt consideration of ''malignant melanoma''.
*Memory device ''BH MILF'' = Bile, Homogentisic acid, Melanin, Iron (hemosiderin), Lipofuscin, Foreign material.
*''Homogentisic acid'' found in ''alkaptonuria'',<ref name=Ref_PCPBoD8_20>{{Ref PCPBoD8|20}}</ref>can be considered the sixth (black) pigment.
**Gentisic = jen-TIS-ik.<ref>URL: [http://dictionary.reference.com/browse/gentisic+acid http://dictionary.reference.com/browse/gentisic+acid]. Accessed on: 11 January 2012.</ref>

====[[Stains]] that can help sort it out====
*Prussian blue (iron stain) for hemosiderin.
*[[Fontana-Masson stain]] (or ''Melan A'') for melanin.
*[[PAS stain]]<ref name=pmid5463681 >{{cite journal |author=Kovi J, Leifer C |title=Lipofuscin pigment accumulation in spontaneous mammary carcinoma of A/Jax mouse |journal=J Natl Med Assoc |volume=62 |issue=4 |pages=287–90 |year=1970 |month=July |pmid=5463681 |pmc=2611776 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2611776/pdf/jnma00512-0077.pdf}}</ref> ''or'' Kluver-Barrera for lipofuscin.

==Staining==
{{main|Stains}}
Basic knowledge of stain is important. The above article starts with H&E and goes from there.

==Immunohistochemistry==
{{main|Immunohistochemistry}}
If the special stains don't help... there is immunohistochemistry.

==Food and pathology==
{{main|Pathology and food}}

==Tumour remaining==
{{Main|Surgical margins}}
''R classification'':<ref>URL: [http://www.informedicalcme.com/colon-cancer/tnm-stage-groupings/ http://www.informedicalcme.com/colon-cancer/tnm-stage-groupings/]. Accessed on: 27 March 2012.</ref>
*"RX resection" = residual tumour cannot be assessed.
*"R0 resection" = clean margin macroscopically & microscopically.
*"R1 resection" = microscopic tumour left.
*"R2 resection" = macroscopic tumour left.

Surgeons use this terminology. Essentially, it is the margin status. It is nice when the surgeon's assessment and the pathologist's are in agreement.

Note:
*Generally, positive margins suck. For example, in locally advanced rectal cancer, in one study,<ref name=pmid17614249>{{cite journal |author=Larsen SG, Wiig JN, Dueland S, Giercksky KE |title=Prognostic factors after preoperative irradiation and surgery for locally advanced rectal cancer |journal=Eur J Surg Oncol |volume=34 |issue=4 |pages=410–7 |year=2008 |month=April |pmid=17614249 |doi=10.1016/j.ejso.2007.05.012 |url=}}</ref> five year survival was found to be 60%, 31% and 0% for R0, R1, and R2 resections respectively.

==Clinician talk==
===Performance status===
*ECOG - score from 1-5 for performance status.<ref name=pmid7165009>{{cite journal |author=Oken MM, Creech RH, Tormey DC, ''et al.'' |title=Toxicity and response criteria of the Eastern Cooperative Oncology Group |journal=Am. J. Clin. Oncol. |volume=5 |issue=6 |pages=649–55 |year=1982 |month=December |pmid=7165009 |doi= |url=}}</ref>
**ECOG = Eastern Cooperative Oncology Group.

ECOG score:
*ECOG 0: healthy.
*ECOG 1: ambulatory, no strenuous activity.
*ECOG 2: limited to self-care in bed <50% of time.
*ECOG 3: difficult to care for self in bed >50% of time.
*ECOG 4: bed bound.
*ECOG 5: dead.

==Pathology & pathologists==
===[[Fixation]] & lifestyle===
Pathologist have a great lifestyle 'cause tissue takes long to fix; the penetration of tissue by formalin is 1 mm/hour.<ref>Gross rounds. 14 August 2009.</ref>

===Malignancy & inflammation===
If there is lots of inflammation... and you're thinking cancer you should probably back-off, i.e. tend toward benign. Inflammation can make cells look more malignant than they might be if left alone.

==Miscellaneous==
===Infectious stuffs===
{{main|Microorganisms}}

Images: [http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/Gram3.htm http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/Gram3.htm]

*Staphylococcus - in clusters.
*Streptococcus - in chains.

==Microscopes==
{{main|HPFitis}}
*Pathologists throw around the term ''high power field'' (''HPF'').
**"HPF" has no agreed upon definition and, IMHO, should '''''never''''' be used without a non-ambiguous definition.

''HPF'' generally refers to the area seen with the largest magnification objective (40x), i.e. the field at 400x (as the eye piece magnification is usually 10x). The field size varies significantly from microscope to microscope.

===Estimating ''field of view''===
FOV = Deye piece x 1/Mobj.

Where:
*FOV = field of view.
*Deye piece = diameter of eye piece (this is usually inscribed on the side of the eye piece).
*Mobj = magnification of the objective.

Example:
*Deye piece = 22 mm
*Mobj = 40x (largest magnification objective)

Applying the formula:
*FOV = 22 mm / 40
*FOV = 0.55 mm

Note:
*Most of the resident [[microscope]]s, at U of T, have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.

==Pathology reports==
{{Main|Pathology reports}}
The key point in report writing is that the report should be precise, complete and easy-to-understand.

===Standards===
There is no universal standard; however, there is a push to standardize by the ''Association of Directors of Anatomic and Surgical Pathology'',<ref>URL: [http://www.adasp.org/papers/position/Standardization.htm http://www.adasp.org/papers/position/Standardization.htm]</ref> among others.

====Checklists====
{{Main|CAP checklists}}
The College of American Pathologists (CAP) has checklists for cancer - [http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=committees%2Fcancer%2Fcancer_protocols%2Fprotocols_index.html&_state=maximized&_pageLabel=cntvwr CAP protocols].

Pathologists will probably use more checklists in the future... they are deemed effective in a number of places inside and outside of medicine.
Surgeons know that checklists work and that they save lives.<ref name=pmid19158173>{{cite journal |author=Soar J, Peyton J, Leonard M, Pullyblank AM |title=Surgical safety checklists |journal=BMJ |volume=338 |issue= |pages=b220 |year=2009 |pmid=19158173 |doi= |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=19158173}}</ref>
Pilots have been using checklists since the 1930s.

===Standard diagnostic notation===

Site, operation/procedure: 
- Tissue type diagnosis.

Example:
 
Gallbladder, cholecystectomy: 
- Acute cholecystitis.

==Lab talk==
Tissue cutting terms - these often vary from lab-to-lab:<ref>URL: [http://www.mailman.srv.ualberta.ca/pipermail/patho-l/2002-July/016955.html http://www.mailman.srv.ualberta.ca/pipermail/patho-l/2002-July/016955.html]. Accessed on: 18 October 2011.</ref>
*Recut = cut off the top of the block.
*Serial sections = make several cuts off the top of the block and look at all of 'em.
*Level = trim the block ~30 micrometres --throw away trimmed tissue-- and then cut a section to look at.
*Deeper = trim the block ~100 micrometres --throw away trimmed tissue-- and then cut a section to look at.

==See also==
*[[Granulation tissue]].
*[[No truth in names]].
*[[Blood work]].
*[[Quality]].

==References==
{{reflist|2}}

==External links==
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=committees%2Fcancer%2Fcancer_protocols%2Fprotocols_index.html&_state=maximized&_pageLabel=cntvwr CAP protocols] - cap.org.
*[http://focosi.altervista.org/pathohomoprocess_regressive.html Regressive histopathologic findings (altervista.org)].
*[http://granuloma.homestead.com/ Atlas of Granulomatous Diseases (granuloma.homestead.com)].

[[Category:Basics]]

Neurofibroma

2014-11-16T20:19:14Z

Laura: /* General */

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Neurofibroma_(3).jpg
| Width =
| Caption = Neurofibroma. [[H&E stain]].
| Micro = spindle cells with wavy nuclei without pleomorphism ("shredded carrots"), +/-arranged in fascicles and intermixed with collagen, moderately increased cellularity, poorly ''or'' well-circumscribed, +/-plexiform growth pattern ("bag of worms"), +/-mast cells (useful)
| Subtypes = [[plexiform neurofibroma]]
| LMDDx = [[schwannoma]], [[dermatofibrosarcoma protuberans]], [[ganglioneuroma]], neurotized [[melanocytic nevus]], [[MPNST]]
| Stains = S-100 +ve, CD34 +ve, EMA +ve/-ve, NF +ve/-ve
| IHC =
| EM =
| Molecular =
| IF =
| Gross = "bag of worms" appearance (plexiform neurofibroma)
| Grossing =
| Site = [[soft tissue lesions|soft tissue]] - [[peripheral nerve sheath tumours]]
| Assdx =
| Syndromes = [[neurofibromatosis type 1]]
| Clinicalhx =
| Signs =
| Symptoms = [[painful skin lesion]]
| Prevalence = not common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = benign
| Other =
| ClinDDx =
}}
'''Neurofibroma''' is an uncommon [[skin]] lesion in the [[peripheral nerve sheath tumour]] grouping. This article also includes '''plexiform neurofibroma'''.

==General==
*May be a part of [[neurofibromatosis]] 1 (NF1).
*A [[painful skin lesion]].
*Composed of Schwann cells, axons, fibrous material.<ref name=pmid17893219>{{Cite journal | last1 = Wippold | first1 = FJ. | last2 = Lubner | first2 = M. | last3 = Perrin | first3 = RJ. | last4 = Lämmle | first4 = M. | last5 = Perry | first5 = 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 | month = Oct | year = 2007 | doi = 10.3174/ajnr.A0682 | PMID = 17893219 }}</ref>

Classification:<ref name=pmid15486243>{{Cite journal | last1 = Wilkinson | first1 = LM. | last2 = Manson | first2 = D. | last3 = Smith | first3 = CR. | title = Best cases from the AFIP: plexiform neurofibroma of the bladder. | journal = Radiographics | volume = 24 Suppl 1 | issue = | pages = S237-42 | month = Oct | year = 2004 | doi = 10.1148/rg.24si035170 | PMID = 15486243 }}</ref>
#Localized - sporadic.
#Diffuse - usually poorly defined, young adults and children; sporadic.
#Plexiform - associated with NF1.

==Gross/radiologic==
Gross features (plexiform NF):<ref name=pmid15486243>{{Cite journal | last1 = Wilkinson | first1 = LM. | last2 = Manson | first2 = D. | last3 = Smith | first3 = CR. | title = Best cases from the AFIP: plexiform neurofibroma of the bladder. | journal = Radiographics | volume = 24 Suppl 1 | issue = | pages = S237-42 | month = Oct | year = 2004 | doi = 10.1148/rg.24si035170 | PMID = 15486243 }}</ref>
*"Bag of worms" appearance.

Radiologic:<ref name=pmid15486243/>
*Fusiform mass.

==Microscopic==
Features:
*Spindle cells with wavy nuclei without pleomorphism - '''key feature'''.
**Often described as "shredded carrots".
*May be arranged in fascicles and intermixed with collagen.
**Often no pattern is apparent.
*Moderate increase of cellularity vis-a-vis normal dermis.
*May be poorly or well-circumscribed.
*+/-Plexiform growth pattern - "bag of worms".<ref name=pmid17893219/>
**Multiple well-circumscribed nests.
*Mast cells<ref name=pmid20233971>{{Cite journal | last1 = Staser | first1 = K. | last2 = Yang | first2 = FC. | last3 = Clapp | first3 = DW. | title = Mast cells and the neurofibroma microenvironment. | journal = Blood | volume = 116 | issue = 2 | pages = 157-64 | month = Jul | year = 2010 | doi = 10.1182/blood-2009-09-242875 | PMID = 20233971 }}</ref> - one has to look for them at high power.
**Very useful for confirming the low power suspicion.

DDx:
*[[Plexiform neurofibroma]].
*[[Schwannoma]] - calretinin +ve, CD34 mostly -ve.<ref>URL: [http://www.ihcworld.com/_newsletter/2004/2004-10_NF_vs_schwannoma_v1.pdf http://www.ihcworld.com/_newsletter/2004/2004-10_NF_vs_schwannoma_v1.pdf]. Accessed on: 25 November 2013.</ref>
*[[Dermatofibrosarcoma protuberans]] (DFSP) - S-100 -ve.
*[[Ganglioneuroma]].
*Neurotized [[melanocytic nevus]] - melanocyte nests make the diagnosis, otherwise immunostains are needed to differentiate.<ref name=pmid693815>{{Cite journal | last1 = Gray | first1 = MH. | last2 = Smoller | first2 = BR. | last3 = McNutt | first3 = NS. | last4 = Hsu | first4 = A. | title = Neurofibromas and neurotized melanocytic nevi are immunohistochemically distinct neoplasms. | journal = Am J Dermatopathol | volume = 12 | issue = 3 | pages = 234-41 | month = Jun | year = 1990 | doi = | PMID = 1693815 }}</ref>
**Usually have more [[mast cell]]s than neurofibromas.<ref name=pmid8432898>{{Cite journal | last1 = Carr | first1 = NJ. | last2 = Warren | first2 = AY. | title = Mast cell numbers in melanocytic naevi and cutaneous neurofibromas. | journal = J Clin Pathol | volume = 46 | issue = 1 | pages = 86-7 | month = Jan | year = 1993 | doi = | PMID = 8432898 }}</ref>

===Images===
<gallery>
Image:Neurofibroma_(1).jpg | Neurofibroma - low mag. (WC)
Image:Neurofibroma_(2).jpg | Neurofibroma - intermed. mag. (WC)
Image:Neurofibroma_(3).jpg | Neurofibroma - high mag. (WC)
</gallery>
www:
*[http://radiographics.rsna.org/content/24/suppl_1/S237/F9.expansion.html Plexiform neurofibroma (rsna.org)].
*[http://radiographics.rsna.org/content/24/suppl_1/S237/F10.expansion.html Plexiform neurofibroma (rsna.org)].
*[http://path.upmc.edu/cases/case304/micro.html Plexiform neurofibroma - several images (upmc.edu)].
*[http://eyewiki.aao.org/File:Orbital_Neurofibroma_-_S100.JPG Neurofibroma - S-100 (eyewiki.aao.org)].

==IHC==
Features:<ref name=pmid12692193>{{cite journal |author=Hirose T, Tani T, Shimada T, Ishizawa K, Shimada S, Sano T |title=Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors |journal=Mod. Pathol. |volume=16 |issue=4 |pages=293–8 |year=2003 |month=April |pmid=12692193 |doi=10.1097/01.MP.0000062654.83617.B7 |url=http://www.nature.com/modpathol/journal/v16/n4/full/3880761a.html }}</ref>
*S100 +ve -- wavy pattern.<ref name=pmid22742554>{{Cite journal | last1 = Chen | first1 = Y. | last2 = Klonowski | first2 = PW. | last3 = Lind | first3 = AC. | last4 = Lu | first4 = D. | title = Differentiating neurotized melanocytic nevi from neurofibromas using Melan-A (MART-1) immunohistochemical stain. | journal = Arch Pathol Lab Med | volume = 136 | issue = 7 | pages = 810-5 | month = Jul | year = 2012 | doi = 10.5858/arpa.2011-0335-OA | PMID = 22742554 }}
</ref>
*CD34 +ve.
*Glut1 +ve.
*EMA +ve/-ve.
*NF +ve/-ve.<ref name=pmid22742554/>
*MART-1 -ve.<ref name=pmid22742554/>
**Positive in neurotized melanocytic nevi.

==Sign out==
<pre>
FOURTH TOE, LEFT, EXCISION:
- NEUROFIBROMA.
</pre>

===Micro===
The sections show skin with a lesion composed of irregular-shaped groups of bland dermal spindle cells with wavy nuclei and pale-eosinophilic cytoplasm. Mast cells are seen scattered throughout the lesion. Thick collagen separates the clusters of the spindle
cells. There is no nuclear atypia. Mitotic activity is not appreciated. No melanocytic nests are identified.

The overlying epidermis matures to the surface.

====Alternate====
The sections show skin with an unencapsulated dermal spindle cell lesion with navy nuclei that have a likeness to shredded carrots. Occasional mast cells are present within the lesion. There is no nuclear atypia. Mitotic activity is not appreciated. No melanocytic nests are identified.

==See also==
*[[Peripheral nerve sheath tumours]].
*[[Neurofibromatosis type 1]].

==References==
{{Reflist|2}}

[[Category:Peripheral nerve sheath tumours]]
[[Category:Diagnosis]]

Meningioma

2014-11-16T16:23:10Z

Laura: /* Gross/Radiology */

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Meningioma_high_mag.jpg
| Width =
| Caption = Meningioma. [[HPS stain]].
| Synonyms =
| Micro = whorled appearance, calcification - [[psammoma bodies|psammomatous]], +/-[[nuclear pseudoinclusions]]
| Subtypes = Grade I (meningothelial, fibrous, transistional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic), Grade II (invasive, clear cell, chordoid), Grade III (papillary, rhabdoid)
| LMDDx = [[schwannoma]], [[solitary fibrous tumour]], [[hemangiopericytoma]], others
| Stains =
| IHC = EMA +ve, keratins usu. -ve, CD34 -ve/+ve, S-100 -ve (usu.), PR +ve (-ve in more aggressive ones)
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = see ''[[CNS tumours]]''
| Assdx =
| Syndromes = [[Neurofibromatosis|neurofibromatosis 2]], [[nevoid basal cell carcinoma syndrome]]
| Clinicalhx = +/-radiation
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads = extra-axial, intradural lesion
| Endoscopy =
| Prognosis = usually benign, dependent on grade
| Other =
| ClinDDx = dependent on site - see ''[[CNS tumours]]''
| Tx = surgical removal
}}
'''Meningioma''' a very common [[CNS tumours|tumour]] in [[neuropathology]].

==General==
===Prevalence===
*Most common primary brain tumour.<ref name=pmid25343186>{{Cite journal | last1 = Rogers | first1 = L. | last2 = Barani | first2 = I. | last3 = Chamberlain | first3 = M. | last4 = Kaley | first4 = TJ. | last5 = McDermott | first5 = M. | last6 = Raizer | first6 = J. | last7 = Schiff | first7 = D. | last8 = Weber | first8 = DC. | last9 = Wen | first9 = PY. | title = Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. | journal = J Neurosurg | volume = | issue = | pages = 1-20 | month = Oct | year = 2014 | doi = 10.3171/2014.7.JNS131644 | PMID = 25343186 }}</ref>
*May be caused by prior radiation.<ref name=pmid25249493>{{Cite journal | last1 = Baldi | first1 = I. | last2 = Engelhardt | first2 = J. | last3 = Bonnet | first3 = C. | last4 = Bauchet | first4 = L. | last5 = Berteaud | first5 = E. | last6 = Grüber | first6 = A. | last7 = Loiseau | first7 = H. | title = Epidemiology of meningiomas. | journal = Neurochirurgie | volume = | issue = | pages = | month = Sep | year = 2014 | doi = 10.1016/j.neuchi.2014.05.006 | PMID = 25249493 }}</ref>

===Prognosis===
*Most are benign - usu. a good prognosis.
**May be malignant - bad prognosis.

===Genetics===
*May be seen in genetic disorders such as:
**[[Neurofibromatosis|Neurofibromatosis 2 (NF2)]].<Ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[Nevoid basal cell carcinoma syndrome]] (Gorlin syndrome).<ref name=pmid15545745>{{Cite journal | last1 = Kimonis | first1 = VE. | last2 = Mehta | first2 = SG. | last3 = Digiovanna | first3 = JJ. | last4 = Bale | first4 = SJ. | last5 = Pastakia | first5 = B. | title = Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. | journal = Genet Med | volume = 6 | issue = 6 | pages = 495-502 | month = | year = | doi = 10.109701.GIM.0000145045.17711.1C | PMID = 15545745 }}</ref><ref>{{Cite journal | last1 = Lee | first1 = CW. | last2 = Tan | first2 = TC. | title = Meningioma associated with Gorlin's syndrome. | journal = J Clin Neurosci | volume = 21 | issue = 2 | pages = 349-50 | month = Feb | year = 2014 | doi = 10.1016/j.jocn.2013.02.033 | PMID = 24100109 }}</ref>

==Gross/Radiology==
*Extra-axial, intradural.
**Can be extradural - very rare.<ref name=upmc_case702>URL: [http://path.upmc.edu/cases/case702.html http://path.upmc.edu/cases/case702.html]. Accessed on: 2 February 2012.</ref>
*Classic "dural tail" sign: enhancement of dura adjacent to tumour
*May invade skull causing hyperostosis (no prognostic significance)

==Microscopic==
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, [[psammoma bodies|psammomatous]] (target-like appearance; (tight) onion skin).
*+/-[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Notes:
*May involute into benign sclerotic tissue.<ref>URL: [http://radiographics.rsna.org/content/23/3/785.long http://radiographics.rsna.org/content/23/3/785.long]. Accessed on: 3 November 2010.</ref>
*Thick-walled blood vessels -> think [[schwannoma]].

DDx:
*[[Schwannoma]] - especially at [[CP angle]].
*[[Solitary fibrous tumour]].
*[[Hemangiopericytoma]].
*Others - see subtypes.

===Images===
<Gallery>
Image:Meningioma_high_mag.jpg | Meningioma - high mag. (WC)
Image:Meningioma_intermed_mag.jpg | Meningioma - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_intermed_mag.jpg | Meningioma with brain invasion - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_high_mag.jpg | Meningioma with brain invasion - high mag. (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter7/chapter7dMiscellaneous.html Meningioma (neuropathologyweb.org)].
*[http://path.upmc.edu/cases/case702.html Extra-dural meningioma (upmc.edu)].

===Morphologic subtypes===
*Many subtypes exist.<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*The histologic subtypes generally don't have much prognostic significance.
**Some subtypes are high grade by definition; also see ''histologic grading''.

====Grade I====
=====Meningothelial meningioma=====
*Most common.

Microscopic:
*Syncytial, nuclear clearing ([[pseudoinclusions]]).

=====Fibrous meningioma=====
*[[AKA]] ''fibroblastic meningioma''.
*'''Not''' collagen... but looks like it.
**It is really laminin or fibronectin.

=====Transistional meningioma=====
*Rare.

=====Psammomatous meningioma=====
Microscopic:
*[[Psammoma bodies]].

=====Angiomatous meningioma=====
*AKA vascular.
*May bleed like stink.

=====Microcystic meningioma=====
Microscopic:
*Cystic appearance.

=====Secretory meningioma=====
*Associated with brain edema; may have a worse outcome.

Microscopic:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 12 October 2011.</ref>
*Eosinophilic intracytoplasmic inclusions that are CEA +ve and PAS +ve.

DDx:
*Metastatic [[mucinous adenocarcinoma]].

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Com04/Com04Image/Com405-1-8.gif Secretory meningioma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 3 January 2012.</ref>
*[http://path.upmc.edu/cases/case370.html Secretory meningioma - several images (upmc.edu)].

=====Lymphoplasmacyte-rich meningioma=====
Microscopic:
*Lymphocytes.
*Plasma cells.

Images:
*[http://path.upmc.edu/cases/case225/micro.html Lymphoplasmacyte-rich meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case247/micro.html Lymphoplasmacyte-rich meningioma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case528.html Lymphoplasmacyte-rich meningioma - case 3 - several images (upmc.edu)].

=====Metaplastic meningioma=====
*Much talked about... but very rare.

Microscopic:
*Cartilage or bone formation.

====Grade II====
=====Invasive meningioma=====
*Invades the brain.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE18-Meningioma-Invasion.htm Meningioma with brain invasion (ouhsc.edu)].

=====Clear cell meningioma=====
Epidemiology:
*Usu. spinal cord.<ref>{{Ref PSNP|200}}</ref>

Microscopic:
*Clear cells - contain glycogen (PAS +ve).

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=20080802174938386 Clear cell meningioma (surgicalpathologyatlas.com)].
*[http://blog.lib.umn.edu/santa013/neuropathology/2009/10/meningioma-with-clear-cell-features.html Clear cell meningioma (umn.edu)].

=====Chordoid meningioma=====
*Chordoma-like.

Microscopic:
*[[Myxoid]] appearance.

Image:
*[http://frontalcortex.com/?page=oll&topic=24&qid=914 Chordoid meningioma (frontalcortex.com)].

====Grade III====
=====Papillary meningioma=====
Microscopic:
*discohesive meningothelial tumour cells around a fibrovascular core.
*perivascular pseudorosettes.

=====Rhabdoid meningioma=====
Microscopic:
*Rhabdoid appearance (abundant cytoplasm).
**Cross-striations.

======Images======
<gallery>
Image:Rhabdoid Meningioma Histopathology.jpg | Rhabdoid meningioma. (WC/Marvin 101)
</gallery>
www:
*[http://path.upmc.edu/cases/case373.html Rhabdoid meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case393.html Rhabdoid meningioma - case 2 - several images (upmc.edu)].

===Histologic grading===
Grading:<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*Grade 1:
**Low mitotic rate (< 4 mitoses/10 HPF - for whatever HPF means, see [[HPFitis]]).
**Excludes ''clear cell'', ''chordoid'', ''papillary'', and ''rhabdoid'' subtypes.
*Grade 2 (either #1, #2 or #3):
*#Brain-invasive meningioma.
*#*Invasion of meningioma into brain.
*#**Meninogioma with entraped GFAP +ve tissue.
*#Atypical meningioma (by histomorphology) - either ''A'' or ''B''.
*#* A. Intermediate mitotic rate (>= 4 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
*#* B. Three of the following five features:
*#*#Sheeting architecture.
*#*#High [[NC ratio]] clusters; clusters of "lymphocyte-like" cells.
*#*#Hypercellularity.
*#*#Macronucleoli.
*#*#[[Necrosis]] not caused by treatment, e.g. radiation or embolization.
*#''Clear cell'' or ''chordoid'' subtype.
*Grade 3 (either of the following):
**High mitotic rate (>=20 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
**"Frank anaplasia"; marked nuclear atypia.
**''Papillary'' or ''rhabdoid'' subtype.

Notes:
*Grade II soft criteria memory device ''HMNs'': hypercellular, macronucleoli, NC ratio increased, necrosis, sheeting.

==IHC==
*EMA +ve.<ref name=Ref_PSNP13>{{Ref PSNP|13}}</ref>
*Other CKs usually -ve.

===DDx of meningioma & IHC<ref name=pmid16393681>{{cite journal |author=Hahn HP, Bundock EA, Hornick JL |title=Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics |journal=Am. J. Clin. Pathol. |volume=125 |issue=2 |pages=203–8 |year=2006 |month=February |pmid=16393681 |doi=10.1309/G659-FVVB-MG7U-4RPQ |url=http://ajcp.ascpjournals.org/content/125/2/203.full.pdf}}</ref>===
*S-100 +ve - [[schwannoma]].
**+ve in ~80% of fibrous meningiomas.
*CD34 +ve - [[solitary fibrous tumour]].
**+ve in ~60% of [[fibrous meningioma]]s.
*EMA +ve in ~30% of hemangiopericytoma.
*Claudin-1 - new kid on the block: +ve in meningioma, but low [[sensitivity]].

===Standard work-up (UHN)===
*Ki-67 >5-10% - predicts re-occurrence.<ref>Croul, SE. 8 November 2010.</ref>
*PR (progesterone receptor) +ve in > 80% of meningiomas.<ref>{{Cite journal | last1 = Takei | first1 = H. | last2 = Buckleair | first2 = LW. | last3 = Powell | first3 = SZ. | title = Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas. | journal = Neuropathology | volume = 28 | issue = 1 | pages = 62-8 | month = Feb | year = 2008 | doi = 10.1111/j.1440-1789.2007.00852.x | PMID = 18021195 }}</ref>
**Loss of PR staining predicts recurrence.
**Strong association with tumour grade:<ref name=pmid22616825>{{Cite journal | last1 = Tao | first1 = Y. | last2 = Liang | first2 = G. | last3 = Li | first3 = Z. | last4 = Wang | first4 = Y. | last5 = Wu | first5 = A. | last6 = Wang | first6 = H. | last7 = Lu | first7 = Y. | last8 = Liu | first8 = Z. | last9 = Hu | first9 = G. | title = Clinical features and immunohistochemical expression levels of androgen, estrogen, progesterone and Ki-67 receptors in relationship with gross-total resected meningiomas relapse. | journal = Br J Neurosurg | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.3109/02688697.2012.685780 | PMID = 22616825 }}</ref>
***Low WHO grade tumours usu. +ve.
***High WHO grade tumours usu. -ve.

==See also==
*[[Neuropathology]].
*[[Neurohistology]].
*[[CNS tumours]].

==References==
{{Reflist|2}}

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

Craniopharyngioma

2014-11-15T23:34:25Z

Laura: /* Adamantinomatous */

'''Craniopharyngioma''' is a benign [[neuropathology tumour]].

It is subdivided into '''papillary craniopharyngioma''' and '''adamantinomatous craniopharyngioma'''.

==General==
*Develop from remains of Rathke's pouch or squamous epithelial cell rests.<ref name=pmid17425791>{{Cite journal | last1 = Garnett | first1 = MR. | last2 = Puget | first2 = S. | last3 = Grill | first3 = J. | last4 = Sainte-Rose | first4 = C. | title = Craniopharyngioma. | journal = Orphanet J Rare Dis | volume = 2 | issue = | pages = 18 | month = | year = 2007 | doi = 10.1186/1750-1172-2-18 | PMID = 17425791 }}</ref>

Comes in two flavours:<ref name=pmid17425791/>
*Adamantinomatous type.
**Adults and children.
*Squamous papillary type.
**Adults individuals.<ref name=pmid6696166>{{Cite journal | last1 = Giangaspero | first1 = F. | last2 = Burger | first2 = PC. | last3 = Osborne | first3 = DR. | last4 = Stein | first4 = RB. | title = Suprasellar papillary squamous epithelioma ("papillary craniopharyngioma"). | journal = Am J Surg Pathol | volume = 8 | issue = 1 | pages = 57-64 | month = Jan | year = 1984 | doi = | PMID = 6696166 }}</ref>
**Usually solid.

==Gross==
*Cystic mass filled with motor oil-like fluid.<ref name=pmid21584897>{{Cite journal | last1 = Fernandez-Miranda | first1 = JC. | last2 = Gardner | first2 = PA. | last3 = Snyderman | first3 = CH. | last4 = Devaney | first4 = KO. | last5 = Strojan | first5 = P. | last6 = Suárez | first6 = C. | last7 = Genden | first7 = EM. | last8 = Rinaldo | first8 = A. | last9 = Ferlito | first9 = A. | title = Craniopharyngioma: a pathologic, clinical, and surgical review. | journal = Head Neck | volume = 34 | issue = 7 | pages = 1036-44 | month = Jul | year = 2012 | doi = 10.1002/hed.21771 | PMID = 21584897 }}</ref>
**May not be seen in the papillary variant of craniopharyngioma.

Radiology:<ref name=pmid17425791/>
*Calcified - adamantinomatous type only.
*Solid & cystic.

==Microscopic==
===Adamantinomatous===
Features (adamantinomatous):<ref name=Ref_DCHH184>{{Ref DCHH|184}}</ref>
*Well-circumscribed (or pseudoinvasive border).
*Multicystic.
*Small-to-medium sized cells with moderate amount of basophilic cytoplasm.
*Bland nuclei (with occ. small nucleoli).
*"Wet" keratin - nests of whorled keratin.
*Calcifications (non-psammomatous).
Often contain mutations in CTNNB1, encoding β-catenin<ref>{{Cite journal | last1 = Preda | first1 = V. | last2 = Larkin | first2 = SJ. | last3 = Karavitaki | first3 = N. | last4 = Ansorge | first4 = O. | last5 = Grossman | first5 = AB. | title = The Wnt Signalling Cascade and the Adherens Junction Complex in Craniopharyngioma Tumorigenesis. | journal = Endocr Pathol | volume = | issue = | pages = | month = Oct | year = 2014 | doi = 10.1007/s12022-014-9341-8 | PMID = 25355426 }}
{{Cite web | last = | first = | title = http://www.ncbi.nlm.nih.gov/pubmed/25355426 | url = http://www.ncbi.nlm.nih.gov/pubmed/25355426 | publisher = | date = | accessdate = 15 November 2014 }}</ref> resulting in intranuclear β-catenin immunohistochemical positivity.
====Images====
<gallery>
Image:Adamantinomatous_craniopharyngioma_-_very_low_mag.jpg | Adamantinomatous craniopharyngioma - very low mag. (WC/Nephron)
Image:Adamantinomatous_craniopharyngioma_-_intermed_mag.jpg | Adamantinomatous craniopharyngioma - intermed. mag. (WC/Nephron)
Image:Adamantinomatous_craniopharyngioma_-_very_high_mag.jpg | Adamantinomatous craniopharyngioma - very high mag. (WC/Nephron)
</gallery>

===Papillary===
Features (papillary):<ref name=Ref_PSNP406>{{Ref PSNP|406}}</ref>
*Non-keratinized squamous epithelium (without nuclear atypia).
*Fibrovascular cores (required for ''papillary'').

Notes:
*+/-Cilia (rare).
*+/-Goblet cell-like formations (rare).

====Image====
<gallery>
Image:Papillary_craniopharyngioma_-_intermed_mag.jpg |Papillary craniopharyngioma - intermed. mag. (WC/Nephron)
Image:Papillary_craniopharyngioma_-_very_high_mag.jpg |Papillary craniopharyngioma - very high mag. (WC/Nephron)
</gallery>
www:
*[http://library.med.utah.edu/WebPath/jpeg4/ENDO115.jpg Craniopharyngioma (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/jpeg4/ENDO115.jpg http://library.med.utah.edu/WebPath/jpeg4/ENDO115.jpg]. Accessed on: 6 December 2010.</ref>

==See also==
*[[Pituitary gland]].
*[[Neuropathology tumours]].

==References==
{{Reflist|2}}

[[Category:Neuropathology]]

Craniopharyngioma

2014-11-15T23:25:03Z

Laura: /* Adamantinomatous */

'''Craniopharyngioma''' is a benign [[neuropathology tumour]].

It is subdivided into '''papillary craniopharyngioma''' and '''adamantinomatous craniopharyngioma'''.

==General==
*Develop from remains of Rathke's pouch or squamous epithelial cell rests.<ref name=pmid17425791>{{Cite journal | last1 = Garnett | first1 = MR. | last2 = Puget | first2 = S. | last3 = Grill | first3 = J. | last4 = Sainte-Rose | first4 = C. | title = Craniopharyngioma. | journal = Orphanet J Rare Dis | volume = 2 | issue = | pages = 18 | month = | year = 2007 | doi = 10.1186/1750-1172-2-18 | PMID = 17425791 }}</ref>

Comes in two flavours:<ref name=pmid17425791/>
*Adamantinomatous type.
**Adults and children.
*Squamous papillary type.
**Adults individuals.<ref name=pmid6696166>{{Cite journal | last1 = Giangaspero | first1 = F. | last2 = Burger | first2 = PC. | last3 = Osborne | first3 = DR. | last4 = Stein | first4 = RB. | title = Suprasellar papillary squamous epithelioma ("papillary craniopharyngioma"). | journal = Am J Surg Pathol | volume = 8 | issue = 1 | pages = 57-64 | month = Jan | year = 1984 | doi = | PMID = 6696166 }}</ref>
**Usually solid.

==Gross==
*Cystic mass filled with motor oil-like fluid.<ref name=pmid21584897>{{Cite journal | last1 = Fernandez-Miranda | first1 = JC. | last2 = Gardner | first2 = PA. | last3 = Snyderman | first3 = CH. | last4 = Devaney | first4 = KO. | last5 = Strojan | first5 = P. | last6 = Suárez | first6 = C. | last7 = Genden | first7 = EM. | last8 = Rinaldo | first8 = A. | last9 = Ferlito | first9 = A. | title = Craniopharyngioma: a pathologic, clinical, and surgical review. | journal = Head Neck | volume = 34 | issue = 7 | pages = 1036-44 | month = Jul | year = 2012 | doi = 10.1002/hed.21771 | PMID = 21584897 }}</ref>
**May not be seen in the papillary variant of craniopharyngioma.

Radiology:<ref name=pmid17425791/>
*Calcified - adamantinomatous type only.
*Solid & cystic.

==Microscopic==
===Adamantinomatous===
Features (adamantinomatous):<ref name=Ref_DCHH184>{{Ref DCHH|184}}</ref>
*Well-circumscribed (or pseudoinvasive border).
*Multicystic.
*Small-to-medium sized cells with moderate amount of basophilic cytoplasm.
*Bland nuclei (with occ. small nucleoli).
*"Wet" keratin - nests of whorled keratin.
*Calcifications (non-psammomatous).
Often contain mutations in CTNNB1, encoding β-catenin<ref>{{Cite journal | last1 = Preda | first1 = V. | last2 = Larkin | first2 = SJ. | last3 = Karavitaki | first3 = N. | last4 = Ansorge | first4 = O. | last5 = Grossman | first5 = AB. | title = The Wnt Signalling Cascade and the Adherens Junction Complex in Craniopharyngioma Tumorigenesis. | journal = Endocr Pathol | volume = | issue = | pages = | month = Oct | year = 2014 | doi = 10.1007/s12022-014-9341-8 | PMID = 25355426 }}
{{Cite web | last = | first = | title = http://www.ncbi.nlm.nih.gov/pubmed/25355426 | url = http://www.ncbi.nlm.nih.gov/pubmed/25355426 | publisher = | date = | accessdate = 15 November 2014 }}</ref> resulting in intranuclear β-catenin immunohistochemical positivity
====Images====
<gallery>
Image:Adamantinomatous_craniopharyngioma_-_very_low_mag.jpg | Adamantinomatous craniopharyngioma - very low mag. (WC/Nephron)
Image:Adamantinomatous_craniopharyngioma_-_intermed_mag.jpg | Adamantinomatous craniopharyngioma - intermed. mag. (WC/Nephron)
Image:Adamantinomatous_craniopharyngioma_-_very_high_mag.jpg | Adamantinomatous craniopharyngioma - very high mag. (WC/Nephron)
</gallery>

===Papillary===
Features (papillary):<ref name=Ref_PSNP406>{{Ref PSNP|406}}</ref>
*Non-keratinized squamous epithelium (without nuclear atypia).
*Fibrovascular cores (required for ''papillary'').

Notes:
*+/-Cilia (rare).
*+/-Goblet cell-like formations (rare).

====Image====
<gallery>
Image:Papillary_craniopharyngioma_-_intermed_mag.jpg |Papillary craniopharyngioma - intermed. mag. (WC/Nephron)
Image:Papillary_craniopharyngioma_-_very_high_mag.jpg |Papillary craniopharyngioma - very high mag. (WC/Nephron)
</gallery>
www:
*[http://library.med.utah.edu/WebPath/jpeg4/ENDO115.jpg Craniopharyngioma (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/jpeg4/ENDO115.jpg http://library.med.utah.edu/WebPath/jpeg4/ENDO115.jpg]. Accessed on: 6 December 2010.</ref>

==See also==
*[[Pituitary gland]].
*[[Neuropathology tumours]].

==References==
{{Reflist|2}}

[[Category:Neuropathology]]

Meningioma

2014-11-15T18:03:03Z

Laura: /* Histologic grading */

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Meningioma_high_mag.jpg
| Width =
| Caption = Meningioma. [[HPS stain]].
| Synonyms =
| Micro = whorled appearance, calcification - [[psammoma bodies|psammomatous]], +/-[[nuclear pseudoinclusions]]
| Subtypes = Grade I (meningothelial, fibrous, transistional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic), Grade II (invasive, clear cell, chordoid), Grade III (papillary, rhabdoid)
| LMDDx = [[schwannoma]], [[solitary fibrous tumour]], [[hemangiopericytoma]], others
| Stains =
| IHC = EMA +ve, keratins usu. -ve, CD34 -ve/+ve, S-100 -ve (usu.), PR +ve (-ve in more aggressive ones)
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = see ''[[CNS tumours]]''
| Assdx =
| Syndromes = [[Neurofibromatosis|neurofibromatosis 2]], [[nevoid basal cell carcinoma syndrome]]
| Clinicalhx = +/-radiation
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads = extra-axial, intradural lesion
| Endoscopy =
| Prognosis = usually benign, dependent on grade
| Other =
| ClinDDx = dependent on site - see ''[[CNS tumours]]''
| Tx = surgical removal
}}
'''Meningioma''' a very common [[CNS tumours|tumour]] in [[neuropathology]].

==General==
===Prevalence===
*Most common primary brain tumour.<ref name=pmid25343186>{{Cite journal | last1 = Rogers | first1 = L. | last2 = Barani | first2 = I. | last3 = Chamberlain | first3 = M. | last4 = Kaley | first4 = TJ. | last5 = McDermott | first5 = M. | last6 = Raizer | first6 = J. | last7 = Schiff | first7 = D. | last8 = Weber | first8 = DC. | last9 = Wen | first9 = PY. | title = Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. | journal = J Neurosurg | volume = | issue = | pages = 1-20 | month = Oct | year = 2014 | doi = 10.3171/2014.7.JNS131644 | PMID = 25343186 }}</ref>
*May be caused by prior radiation.<ref name=pmid25249493>{{Cite journal | last1 = Baldi | first1 = I. | last2 = Engelhardt | first2 = J. | last3 = Bonnet | first3 = C. | last4 = Bauchet | first4 = L. | last5 = Berteaud | first5 = E. | last6 = Grüber | first6 = A. | last7 = Loiseau | first7 = H. | title = Epidemiology of meningiomas. | journal = Neurochirurgie | volume = | issue = | pages = | month = Sep | year = 2014 | doi = 10.1016/j.neuchi.2014.05.006 | PMID = 25249493 }}</ref>

===Prognosis===
*Most are benign - usu. a good prognosis.
**May be malignant - bad prognosis.

===Genetics===
*May be seen in genetic disorders such as:
**[[Neurofibromatosis|Neurofibromatosis 2 (NF2)]].<Ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[Nevoid basal cell carcinoma syndrome]] (Gorlin syndrome).<ref name=pmid15545745>{{Cite journal | last1 = Kimonis | first1 = VE. | last2 = Mehta | first2 = SG. | last3 = Digiovanna | first3 = JJ. | last4 = Bale | first4 = SJ. | last5 = Pastakia | first5 = B. | title = Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. | journal = Genet Med | volume = 6 | issue = 6 | pages = 495-502 | month = | year = | doi = 10.109701.GIM.0000145045.17711.1C | PMID = 15545745 }}</ref><ref>{{Cite journal | last1 = Lee | first1 = CW. | last2 = Tan | first2 = TC. | title = Meningioma associated with Gorlin's syndrome. | journal = J Clin Neurosci | volume = 21 | issue = 2 | pages = 349-50 | month = Feb | year = 2014 | doi = 10.1016/j.jocn.2013.02.033 | PMID = 24100109 }}</ref>

==Gross/Radiology==
*Extra-axial, intradural.
**Can be extradural - very rare.<ref name=upmc_case702>URL: [http://path.upmc.edu/cases/case702.html http://path.upmc.edu/cases/case702.html]. Accessed on: 2 February 2012.</ref>

==Microscopic==
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, [[psammoma bodies|psammomatous]] (target-like appearance; (tight) onion skin).
*+/-[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Notes:
*May involute into benign sclerotic tissue.<ref>URL: [http://radiographics.rsna.org/content/23/3/785.long http://radiographics.rsna.org/content/23/3/785.long]. Accessed on: 3 November 2010.</ref>
*Thick-walled blood vessels -> think [[schwannoma]].

DDx:
*[[Schwannoma]] - especially at [[CP angle]].
*[[Solitary fibrous tumour]].
*[[Hemangiopericytoma]].
*Others - see subtypes.

===Images===
<Gallery>
Image:Meningioma_high_mag.jpg | Meningioma - high mag. (WC)
Image:Meningioma_intermed_mag.jpg | Meningioma - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_intermed_mag.jpg | Meningioma with brain invasion - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_high_mag.jpg | Meningioma with brain invasion - high mag. (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter7/chapter7dMiscellaneous.html Meningioma (neuropathologyweb.org)].
*[http://path.upmc.edu/cases/case702.html Extra-dural meningioma (upmc.edu)].

===Morphologic subtypes===
*Many subtypes exist.<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*The histologic subtypes generally don't have much prognostic significance.
**Some subtypes are high grade by definition; also see ''histologic grading''.

====Grade I====
=====Meningothelial meningioma=====
*Most common.

Microscopic:
*Syncytial, nuclear clearing ([[pseudoinclusions]]).

=====Fibrous meningioma=====
*[[AKA]] ''fibroblastic meningioma''.
*'''Not''' collagen... but looks like it.
**It is really laminin or fibronectin.

=====Transistional meningioma=====
*Rare.

=====Psammomatous meningioma=====
Microscopic:
*[[Psammoma bodies]].

=====Angiomatous meningioma=====
*AKA vascular.
*May bleed like stink.

=====Microcystic meningioma=====
Microscopic:
*Cystic appearance.

=====Secretory meningioma=====
*Associated with brain edema; may have a worse outcome.

Microscopic:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 12 October 2011.</ref>
*Eosinophilic intracytoplasmic inclusions that are CEA +ve and PAS +ve.

DDx:
*Metastatic [[mucinous adenocarcinoma]].

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Com04/Com04Image/Com405-1-8.gif Secretory meningioma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 3 January 2012.</ref>
*[http://path.upmc.edu/cases/case370.html Secretory meningioma - several images (upmc.edu)].

=====Lymphoplasmacyte-rich meningioma=====
Microscopic:
*Lymphocytes.
*Plasma cells.

Images:
*[http://path.upmc.edu/cases/case225/micro.html Lymphoplasmacyte-rich meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case247/micro.html Lymphoplasmacyte-rich meningioma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case528.html Lymphoplasmacyte-rich meningioma - case 3 - several images (upmc.edu)].

=====Metaplastic meningioma=====
*Much talked about... but very rare.

Microscopic:
*Cartilage or bone formation.

====Grade II====
=====Invasive meningioma=====
*Invades the brain.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE18-Meningioma-Invasion.htm Meningioma with brain invasion (ouhsc.edu)].

=====Clear cell meningioma=====
Epidemiology:
*Usu. spinal cord.<ref>{{Ref PSNP|200}}</ref>

Microscopic:
*Clear cells - contain glycogen (PAS +ve).

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=20080802174938386 Clear cell meningioma (surgicalpathologyatlas.com)].
*[http://blog.lib.umn.edu/santa013/neuropathology/2009/10/meningioma-with-clear-cell-features.html Clear cell meningioma (umn.edu)].

=====Chordoid meningioma=====
*Chordoma-like.

Microscopic:
*[[Myxoid]] appearance.

Image:
*[http://frontalcortex.com/?page=oll&topic=24&qid=914 Chordoid meningioma (frontalcortex.com)].

====Grade III====
=====Papillary meningioma=====
Microscopic:
*discohesive meningothelial tumour cells around a fibrovascular core.
*perivascular pseudorosettes.

=====Rhabdoid meningioma=====
Microscopic:
*Rhabdoid appearance (abundant cytoplasm).
**Cross-striations.

======Images======
<gallery>
Image:Rhabdoid Meningioma Histopathology.jpg | Rhabdoid meningioma. (WC/Marvin 101)
</gallery>
www:
*[http://path.upmc.edu/cases/case373.html Rhabdoid meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case393.html Rhabdoid meningioma - case 2 - several images (upmc.edu)].

===Histologic grading===
Grading:<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*Grade 1:
**Low mitotic rate (< 4 mitoses/10 HPF - for whatever HPF means, see [[HPFitis]]).
**Excludes ''clear cell'', ''chordoid'', ''papillary'', and ''rhabdoid'' subtypes.
*Grade 2 (either #1, #2 or #3):
*#Brain-invasive meningioma.
*#*Invasion of meningioma into brain.
*#**Meninogioma with entraped GFAP +ve tissue.
*#Atypical meningioma (by histomorphology) - either ''A'' or ''B''.
*#* A. Intermediate mitotic rate (>= 4 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
*#* B. Three of the following five features:
*#*#Sheeting architecture.
*#*#High [[NC ratio]] clusters; clusters of "lymphocyte-like" cells.
*#*#Hypercellularity.
*#*#Macronucleoli.
*#*#[[Necrosis]] not caused by treatment, e.g. radiation or embolization.
*#''Clear cell'' or ''chordoid'' subtype.
*Grade 3 (either of the following):
**High mitotic rate (>=20 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
**"Frank anaplasia"; marked nuclear atypia.
**''Papillary'' or ''rhabdoid'' subtype.

Notes:
*Grade II soft criteria memory device ''HMNs'': hypercellular, macronucleoli, NC ratio increased, necrosis, sheeting.

==IHC==
*EMA +ve.<ref name=Ref_PSNP13>{{Ref PSNP|13}}</ref>
*Other CKs usually -ve.

===DDx of meningioma & IHC<ref name=pmid16393681>{{cite journal |author=Hahn HP, Bundock EA, Hornick JL |title=Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics |journal=Am. J. Clin. Pathol. |volume=125 |issue=2 |pages=203–8 |year=2006 |month=February |pmid=16393681 |doi=10.1309/G659-FVVB-MG7U-4RPQ |url=http://ajcp.ascpjournals.org/content/125/2/203.full.pdf}}</ref>===
*S-100 +ve - [[schwannoma]].
**+ve in ~80% of fibrous meningiomas.
*CD34 +ve - [[solitary fibrous tumour]].
**+ve in ~60% of [[fibrous meningioma]]s.
*EMA +ve in ~30% of hemangiopericytoma.
*Claudin-1 - new kid on the block: +ve in meningioma, but low [[sensitivity]].

===Standard work-up (UHN)===
*Ki-67 >5-10% - predicts re-occurrence.<ref>Croul, SE. 8 November 2010.</ref>
*PR (progesterone receptor) +ve in > 80% of meningiomas.<ref>{{Cite journal | last1 = Takei | first1 = H. | last2 = Buckleair | first2 = LW. | last3 = Powell | first3 = SZ. | title = Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas. | journal = Neuropathology | volume = 28 | issue = 1 | pages = 62-8 | month = Feb | year = 2008 | doi = 10.1111/j.1440-1789.2007.00852.x | PMID = 18021195 }}</ref>
**Loss of PR staining predicts recurrence.
**Strong association with tumour grade:<ref name=pmid22616825>{{Cite journal | last1 = Tao | first1 = Y. | last2 = Liang | first2 = G. | last3 = Li | first3 = Z. | last4 = Wang | first4 = Y. | last5 = Wu | first5 = A. | last6 = Wang | first6 = H. | last7 = Lu | first7 = Y. | last8 = Liu | first8 = Z. | last9 = Hu | first9 = G. | title = Clinical features and immunohistochemical expression levels of androgen, estrogen, progesterone and Ki-67 receptors in relationship with gross-total resected meningiomas relapse. | journal = Br J Neurosurg | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.3109/02688697.2012.685780 | PMID = 22616825 }}</ref>
***Low WHO grade tumours usu. +ve.
***High WHO grade tumours usu. -ve.

==See also==
*[[Neuropathology]].
*[[Neurohistology]].
*[[CNS tumours]].

==References==
{{Reflist|2}}

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

Meningioma

2014-11-15T17:59:17Z

Laura: /* Papillary meningioma */

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Meningioma_high_mag.jpg
| Width =
| Caption = Meningioma. [[HPS stain]].
| Synonyms =
| Micro = whorled appearance, calcification - [[psammoma bodies|psammomatous]], +/-[[nuclear pseudoinclusions]]
| Subtypes = Grade I (meningothelial, fibrous, transistional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic), Grade II (invasive, clear cell, chordoid), Grade III (papillary, rhabdoid)
| LMDDx = [[schwannoma]], [[solitary fibrous tumour]], [[hemangiopericytoma]], others
| Stains =
| IHC = EMA +ve, keratins usu. -ve, CD34 -ve/+ve, S-100 -ve (usu.), PR +ve (-ve in more aggressive ones)
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = see ''[[CNS tumours]]''
| Assdx =
| Syndromes = [[Neurofibromatosis|neurofibromatosis 2]], [[nevoid basal cell carcinoma syndrome]]
| Clinicalhx = +/-radiation
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads = extra-axial, intradural lesion
| Endoscopy =
| Prognosis = usually benign, dependent on grade
| Other =
| ClinDDx = dependent on site - see ''[[CNS tumours]]''
| Tx = surgical removal
}}
'''Meningioma''' a very common [[CNS tumours|tumour]] in [[neuropathology]].

==General==
===Prevalence===
*Most common primary brain tumour.<ref name=pmid25343186>{{Cite journal | last1 = Rogers | first1 = L. | last2 = Barani | first2 = I. | last3 = Chamberlain | first3 = M. | last4 = Kaley | first4 = TJ. | last5 = McDermott | first5 = M. | last6 = Raizer | first6 = J. | last7 = Schiff | first7 = D. | last8 = Weber | first8 = DC. | last9 = Wen | first9 = PY. | title = Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review. | journal = J Neurosurg | volume = | issue = | pages = 1-20 | month = Oct | year = 2014 | doi = 10.3171/2014.7.JNS131644 | PMID = 25343186 }}</ref>
*May be caused by prior radiation.<ref name=pmid25249493>{{Cite journal | last1 = Baldi | first1 = I. | last2 = Engelhardt | first2 = J. | last3 = Bonnet | first3 = C. | last4 = Bauchet | first4 = L. | last5 = Berteaud | first5 = E. | last6 = Grüber | first6 = A. | last7 = Loiseau | first7 = H. | title = Epidemiology of meningiomas. | journal = Neurochirurgie | volume = | issue = | pages = | month = Sep | year = 2014 | doi = 10.1016/j.neuchi.2014.05.006 | PMID = 25249493 }}</ref>

===Prognosis===
*Most are benign - usu. a good prognosis.
**May be malignant - bad prognosis.

===Genetics===
*May be seen in genetic disorders such as:
**[[Neurofibromatosis|Neurofibromatosis 2 (NF2)]].<Ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q13-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[Nevoid basal cell carcinoma syndrome]] (Gorlin syndrome).<ref name=pmid15545745>{{Cite journal | last1 = Kimonis | first1 = VE. | last2 = Mehta | first2 = SG. | last3 = Digiovanna | first3 = JJ. | last4 = Bale | first4 = SJ. | last5 = Pastakia | first5 = B. | title = Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. | journal = Genet Med | volume = 6 | issue = 6 | pages = 495-502 | month = | year = | doi = 10.109701.GIM.0000145045.17711.1C | PMID = 15545745 }}</ref><ref>{{Cite journal | last1 = Lee | first1 = CW. | last2 = Tan | first2 = TC. | title = Meningioma associated with Gorlin's syndrome. | journal = J Clin Neurosci | volume = 21 | issue = 2 | pages = 349-50 | month = Feb | year = 2014 | doi = 10.1016/j.jocn.2013.02.033 | PMID = 24100109 }}</ref>

==Gross/Radiology==
*Extra-axial, intradural.
**Can be extradural - very rare.<ref name=upmc_case702>URL: [http://path.upmc.edu/cases/case702.html http://path.upmc.edu/cases/case702.html]. Accessed on: 2 February 2012.</ref>

==Microscopic==
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, [[psammoma bodies|psammomatous]] (target-like appearance; (tight) onion skin).
*+/-[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Notes:
*May involute into benign sclerotic tissue.<ref>URL: [http://radiographics.rsna.org/content/23/3/785.long http://radiographics.rsna.org/content/23/3/785.long]. Accessed on: 3 November 2010.</ref>
*Thick-walled blood vessels -> think [[schwannoma]].

DDx:
*[[Schwannoma]] - especially at [[CP angle]].
*[[Solitary fibrous tumour]].
*[[Hemangiopericytoma]].
*Others - see subtypes.

===Images===
<Gallery>
Image:Meningioma_high_mag.jpg | Meningioma - high mag. (WC)
Image:Meningioma_intermed_mag.jpg | Meningioma - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_intermed_mag.jpg | Meningioma with brain invasion - intermed. mag. (WC)
Image:Meningioma_-_brain_invasion_-_high_mag.jpg | Meningioma with brain invasion - high mag. (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter7/chapter7dMiscellaneous.html Meningioma (neuropathologyweb.org)].
*[http://path.upmc.edu/cases/case702.html Extra-dural meningioma (upmc.edu)].

===Morphologic subtypes===
*Many subtypes exist.<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*The histologic subtypes generally don't have much prognostic significance.
**Some subtypes are high grade by definition; also see ''histologic grading''.

====Grade I====
=====Meningothelial meningioma=====
*Most common.

Microscopic:
*Syncytial, nuclear clearing ([[pseudoinclusions]]).

=====Fibrous meningioma=====
*[[AKA]] ''fibroblastic meningioma''.
*'''Not''' collagen... but looks like it.
**It is really laminin or fibronectin.

=====Transistional meningioma=====
*Rare.

=====Psammomatous meningioma=====
Microscopic:
*[[Psammoma bodies]].

=====Angiomatous meningioma=====
*AKA vascular.
*May bleed like stink.

=====Microcystic meningioma=====
Microscopic:
*Cystic appearance.

=====Secretory meningioma=====
*Associated with brain edema; may have a worse outcome.

Microscopic:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 12 October 2011.</ref>
*Eosinophilic intracytoplasmic inclusions that are CEA +ve and PAS +ve.

DDx:
*Metastatic [[mucinous adenocarcinoma]].

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Com04/Com04Image/Com405-1-8.gif Secretory meningioma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com04/Com405-1-Diss.htm]. Accessed on: 3 January 2012.</ref>
*[http://path.upmc.edu/cases/case370.html Secretory meningioma - several images (upmc.edu)].

=====Lymphoplasmacyte-rich meningioma=====
Microscopic:
*Lymphocytes.
*Plasma cells.

Images:
*[http://path.upmc.edu/cases/case225/micro.html Lymphoplasmacyte-rich meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case247/micro.html Lymphoplasmacyte-rich meningioma - case 2 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case528.html Lymphoplasmacyte-rich meningioma - case 3 - several images (upmc.edu)].

=====Metaplastic meningioma=====
*Much talked about... but very rare.

Microscopic:
*Cartilage or bone formation.

====Grade II====
=====Invasive meningioma=====
*Invades the brain.

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE18-Meningioma-Invasion.htm Meningioma with brain invasion (ouhsc.edu)].

=====Clear cell meningioma=====
Epidemiology:
*Usu. spinal cord.<ref>{{Ref PSNP|200}}</ref>

Microscopic:
*Clear cells - contain glycogen (PAS +ve).

Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&sort=0&s=20080802174938386 Clear cell meningioma (surgicalpathologyatlas.com)].
*[http://blog.lib.umn.edu/santa013/neuropathology/2009/10/meningioma-with-clear-cell-features.html Clear cell meningioma (umn.edu)].

=====Chordoid meningioma=====
*Chordoma-like.

Microscopic:
*[[Myxoid]] appearance.

Image:
*[http://frontalcortex.com/?page=oll&topic=24&qid=914 Chordoid meningioma (frontalcortex.com)].

====Grade III====
=====Papillary meningioma=====
Microscopic:
*discohesive meningothelial tumour cells around a fibrovascular core.
*perivascular pseudorosettes.

=====Rhabdoid meningioma=====
Microscopic:
*Rhabdoid appearance (abundant cytoplasm).
**Cross-striations.

======Images======
<gallery>
Image:Rhabdoid Meningioma Histopathology.jpg | Rhabdoid meningioma. (WC/Marvin 101)
</gallery>
www:
*[http://path.upmc.edu/cases/case373.html Rhabdoid meningioma - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case393.html Rhabdoid meningioma - case 2 - several images (upmc.edu)].

===Histologic grading===
Grading:<ref name=Ref_PSNP194>{{Ref PSNP|194}}</ref>
*Grade 1:
**Low mitotic rate (< 4 mitoses/10 HPF - for whatever HPF means, see [[HPFitis]]).
**Excludes ''clear cell'', ''chordoid'', ''papillary'', and ''rhabdoid'' subtypes.
*Grade 2 (either #1, #2 or #3):
*#Brain-invasive meningioma.
*#*Protrusion of meningioma into brain.
*#**Meninogioma with entraped GFAP +ve tissue.
*#Atypical meningioma (by histomorphology) - either ''A'' or ''B''.
*#* A. Intermediate mitotic rate (>= 4 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
*#* B. Three of the following five features:
*#*#Sheeting architecture.
*#*#High [[NC ratio]] clusters; clusters of "lymphocyte-like" cells.
*#*#Hypercellularity.
*#*#Macronucleoli.
*#*#[[Necrosis]] not caused by treatment, e.g. radiation or embolization.
*#''Clear cell'' or ''chordoid'' subtype.
*Grade 3 (either of the following):
**High mitotic rate (>=20 mitoses/10 HPF - for whatever ''HPF'' means, see [[HPFitis]].)
**"Frank anaplasia"; marked nuclear atypia.
**''Papillary'' or ''rhabdoid'' subtype.

Notes:
*Grade II soft criteria memory device ''HMNs'': hypercellular, macronucleoli, NC ratio increased, necrosis, sheeting.

==IHC==
*EMA +ve.<ref name=Ref_PSNP13>{{Ref PSNP|13}}</ref>
*Other CKs usually -ve.

===DDx of meningioma & IHC<ref name=pmid16393681>{{cite journal |author=Hahn HP, Bundock EA, Hornick JL |title=Immunohistochemical staining for claudin-1 can help distinguish meningiomas from histologic mimics |journal=Am. J. Clin. Pathol. |volume=125 |issue=2 |pages=203–8 |year=2006 |month=February |pmid=16393681 |doi=10.1309/G659-FVVB-MG7U-4RPQ |url=http://ajcp.ascpjournals.org/content/125/2/203.full.pdf}}</ref>===
*S-100 +ve - [[schwannoma]].
**+ve in ~80% of fibrous meningiomas.
*CD34 +ve - [[solitary fibrous tumour]].
**+ve in ~60% of [[fibrous meningioma]]s.
*EMA +ve in ~30% of hemangiopericytoma.
*Claudin-1 - new kid on the block: +ve in meningioma, but low [[sensitivity]].

===Standard work-up (UHN)===
*Ki-67 >5-10% - predicts re-occurrence.<ref>Croul, SE. 8 November 2010.</ref>
*PR (progesterone receptor) +ve in > 80% of meningiomas.<ref>{{Cite journal | last1 = Takei | first1 = H. | last2 = Buckleair | first2 = LW. | last3 = Powell | first3 = SZ. | title = Immunohistochemical expression of apoptosis regulating proteins and sex hormone receptors in meningiomas. | journal = Neuropathology | volume = 28 | issue = 1 | pages = 62-8 | month = Feb | year = 2008 | doi = 10.1111/j.1440-1789.2007.00852.x | PMID = 18021195 }}</ref>
**Loss of PR staining predicts recurrence.
**Strong association with tumour grade:<ref name=pmid22616825>{{Cite journal | last1 = Tao | first1 = Y. | last2 = Liang | first2 = G. | last3 = Li | first3 = Z. | last4 = Wang | first4 = Y. | last5 = Wu | first5 = A. | last6 = Wang | first6 = H. | last7 = Lu | first7 = Y. | last8 = Liu | first8 = Z. | last9 = Hu | first9 = G. | title = Clinical features and immunohistochemical expression levels of androgen, estrogen, progesterone and Ki-67 receptors in relationship with gross-total resected meningiomas relapse. | journal = Br J Neurosurg | volume = | issue = | pages = | month = May | year = 2012 | doi = 10.3109/02688697.2012.685780 | PMID = 22616825 }}</ref>
***Low WHO grade tumours usu. +ve.
***High WHO grade tumours usu. -ve.

==See also==
*[[Neuropathology]].
*[[Neurohistology]].
*[[CNS tumours]].

==References==
{{Reflist|2}}

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

Pilocytic astrocytoma

2014-11-15T17:31:18Z

Laura: /* Gross */

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Pilocytic_astrocytoma_-_smear_-_very_high_mag.jpg
| Width =
| Caption = Pilocytic astrocytoma. Smear. [[H&E stain]].
| Synonyms =
| Micro =
| Subtypes =
| LMDDx = piloid gliosis, [[oligodendroglioma]], [[glioblastoma]]
| Stains = PAS-D +ve (eosinophilic granular bodies)
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross = usually cerebellar +/-cystic
| Grossing =
| Site = brain - usu. [[cerebellum]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = common - esp. in children
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good (WHO Grade I)
| Other =
| ClinDDx =
| Tx =
}}
'''Pilocytic astrocytoma''' is a low-grade [[astrocytoma]]. It the most common glioma in children.

==General==
*Low-grade [[astrocytoma]] - ''WHO Grade I'' by definition.
*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==
Features:<ref name=Ref_PSNP82>{{Ref PSNP|82}}</ref>
*Usually well-circumscribed.
*Often cystic with mural nodule.

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

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

DDx (of Rosenthal fibers):<ref>Munoz D. 9 Mar 2009.</ref>
*Chronic reactive gliosis.
*Subependymoma.
*Ganglioma.
*Alexander's disease (rare leukodystrophy).

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

===Images===
====Smears====
<gallery>
Image:Pilocytic_astrocytoma_-_smear_-_very_high_mag.jpg | Bipolar cells with hair-like processes - smear - very high mag. (WC)
Image:Pilocytic_Micro.jpg | EGBs - smear. (WC/AFIP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear. (WC/AFIP)
</gallery>
====Sections====
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WC)
</gallery>
www:
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q19-Ans.htm Rosenthal fibre (ouhsc.edu)].
*[http://path.upmc.edu/cases/case162.html Pilocytic astrocytoma (upmc.edu)].
*[http://path.upmc.edu/cases/case90.html Pilocytic astrocytoma - another case (upmc.edu)].
*[http://path.upmc.edu/cases/case195/images/figure3b.jpg Pilocytic astrocytoma - pennies on a plate (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case195.html http://path.upmc.edu/cases/case195.html]. Accessed on: 8 January 2012.</ref>
*[http://path.upmc.edu/cases/case397.html Pilocytic astrocytoma (upmc.edu)].

==Stains==
*PAS-D: eosinophilic granular bodies +ve.

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

==See also==
*[[Neuropathology tumours]].
*[[Astrocytoma]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Pilocytic astrocytoma

2014-11-15T17:30:16Z

Laura: /* Gross */

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Pilocytic_astrocytoma_-_smear_-_very_high_mag.jpg
| Width =
| Caption = Pilocytic astrocytoma. Smear. [[H&E stain]].
| Synonyms =
| Micro =
| Subtypes =
| LMDDx = piloid gliosis, [[oligodendroglioma]], [[glioblastoma]]
| Stains = PAS-D +ve (eosinophilic granular bodies)
| IHC = GFAP +ve
| EM =
| Molecular =
| IF =
| Gross = usually cerebellar +/-cystic
| Grossing =
| Site = brain - usu. [[cerebellum]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = common - esp. in children
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good (WHO Grade I)
| Other =
| ClinDDx =
| Tx =
}}
'''Pilocytic astrocytoma''' is a low-grade [[astrocytoma]]. It the most common glioma in children.

==General==
*Low-grade [[astrocytoma]] - ''WHO Grade I'' by definition.
*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==
Features:<ref name=Ref_PSNP82>{{Ref PSNP|82}}</ref>
*Usually well-circumscribed.
*Cystic ''or'' solid.

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

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

DDx (of Rosenthal fibers):<ref>Munoz D. 9 Mar 2009.</ref>
*Chronic reactive gliosis.
*Subependymoma.
*Ganglioma.
*Alexander's disease (rare leukodystrophy).

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

===Images===
====Smears====
<gallery>
Image:Pilocytic_astrocytoma_-_smear_-_very_high_mag.jpg | Bipolar cells with hair-like processes - smear - very high mag. (WC)
Image:Pilocytic_Micro.jpg | EGBs - smear. (WC/AFIP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear. (WC/AFIP)
</gallery>
====Sections====
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WC)
</gallery>
www:
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/Q19-Ans.htm Rosenthal fibre (ouhsc.edu)].
*[http://path.upmc.edu/cases/case162.html Pilocytic astrocytoma (upmc.edu)].
*[http://path.upmc.edu/cases/case90.html Pilocytic astrocytoma - another case (upmc.edu)].
*[http://path.upmc.edu/cases/case195/images/figure3b.jpg Pilocytic astrocytoma - pennies on a plate (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case195.html http://path.upmc.edu/cases/case195.html]. Accessed on: 8 January 2012.</ref>
*[http://path.upmc.edu/cases/case397.html Pilocytic astrocytoma (upmc.edu)].

==Stains==
*PAS-D: eosinophilic granular bodies +ve.

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

==See also==
*[[Neuropathology tumours]].
*[[Astrocytoma]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Neuropathology tumours]]

Neuropathology tumours

2014-11-15T17:26:46Z

Laura: /* IHC */

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 gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===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>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]] (previously known as ''glioblastoma multiforme'').
# [[Anaplastic astrocytoma]].
# [[Meningioma]].

===Children===
# Astrocytoma.
# [[Medulloblastoma]].
# [[Ependymoma]].

===Location (most common)===
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]].
*Spinal cord:
**[[Ependymoma]], glioblastoma.
**Filum terminale - [[myxopapillary ependymoma]], [[paraganglioma]].

====Filum terminale====
*Filum terminale = bottom end of the spinal cord - has a limited differential.

DDx:<ref>JLK. 31 May 2010.</ref>
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].

====Cerebellopontine angle====
*Abbreviated ''CP angle''.

DDx:<ref>R. Kiehl. 8 November 2010.</ref>
*[[Schwannoma]].
*[[Meningioma]].
*[[Dermoid cyst]]/epidermoid cyst.
*[[Ependymoma]].
*[[Choroid plexus papilloma]].

===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>

===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.

[[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.

===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
|nil
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Astrocytoma]] (grade II or worse)
|glial processes (esp. on smear), nuclear atypia (size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|Astrocytoma. (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)]]
|-
|[[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)]]
|-
|[[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
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (Grade II).
*Anaplastic astrocytomas (Grade III).
*Glioblastoma (Grade IV).

Notes:
*Non-infiltrative gliomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
**[[Dysembryoplastic neuroepithelial tumour]] (DNT), (WHO Grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*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:
*[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)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[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.

Images:
*Glioblastoma:
**[http://commons.wikimedia.org/wiki/File:Glioblastoma_%281%29.jpg Glioblastoma - pseudopalisading of tumour cells (WC)].
**[http://commons.wikimedia.org/wiki/File:Glioblastoma_-_high_mag.jpg Glioblastoma with fragment of near-normal white matter - high mag. (WC)].
*Anaplastic astrocytoma:
**[http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg Anaplastic astrocytoma - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg Anaplastic astrocytoma - GFAP - very high mag. (WC)].

=====Table of common gliomas - grading=====
Histomorphologic comparison of common gliomas:
{| class="wikitable"
|'''Entity''' || '''Rosenthal fibres / EGBs''' ||'''Nuclear atypia''' ||'''Mitoses''' || '''Necrosis or MVP''' || '''Infiltrative''' || '''Image'''
|-
|Pilocytic astrocytoma || yes || usu. no || usu. no || usu. no || no || [http://commons.wikimedia.org/wiki/File:Rosenthal_HE_40x.jpg]
|-
|Low-grade astrocytoma || no || yes || no || no || yes || image?
|-
|Anaplastic astrocytoma || no || yes || yes || no || yes || [http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_high_mag.jpg]
|-
|Glioblastoma || no || yes || yes || yes || yes || [http://commons.wikimedia.org/wiki/File:Glioblastoma_-_high_mag.jpg]
|}
Notes:
*''MVP'' = microvascular proliferation.
*''EGBs'' = eosinophilic granular bodies.

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

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

==Pilocytic astrocytoma==
{{Main|Pilocytic astrocytoma}}

==Pleomorphic xanthoastrocytoma==
*Abbreviated ''PXA''.
===General===
Features:
*Classically in the temporal lobe in children and young adults.
*Associated with seizures.
*Moderately aggressive (WHO Grade II).<ref name=pmid11465399>{{Cite journal | last1 = Fouladi | first1 = M. | last2 = Jenkins | first2 = J. | last3 = Burger | first3 = P. | last4 = Langston | first4 = J. | last5 = Merchant | first5 = T. | last6 = Heideman | first6 = R. | last7 = Thompson | first7 = S. | last8 = Sanford | first8 = A. | last9 = Kun | first9 = L. | title = Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection. | journal = Neuro Oncol | volume = 3 | issue = 3 | pages = 184-92 | month = Jul | year = 2001 | doi = | PMID = 11465399 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920613/pdf/11465399.pdf}}</ref>

===Gross===
*Temporal lobe - classic.
*Usually assoc. with the leptomeninges,<ref name=pmid11465399/> i.e. superficial.

===Microscopic===
Features:<ref name=Ref_PBoD8_1333>{{Ref PBoD8|1333}}</ref>
*Marked nuclear atypia.
*Eosinophilic granular bodies - very common.<ref name=pmid11465399/>
*Inflammation (chronic).

Notes:
*No mitoses.
*No [[necrosis]].

Images:
*[http://path.upmc.edu/cases/case499.html Pleomorphic xanthoastrocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case511.html Pleomorphic xanthoastrocytoma with anaplasia - another case - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case578.html Pleomorphic xanthoastrocytoma with anaplasia - case 3 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case579.html Cerebellar pleomorphic xanthoastrocytoma - case 4 - several image (upmc.edu)].

===Stains===
*[[Reticulin stain]] - intercellular, prominent.<ref name=pmid21479234>{{Cite journal | last1 = Dias-Santagata | first1 = D. | last2 = Lam | first2 = Q. | last3 = Vernovsky | first3 = K. | last4 = Vena | first4 = N. | last5 = Lennerz | first5 = JK. | last6 = Borger | first6 = DR. | last7 = Batchelor | first7 = TT. | last8 = Ligon | first8 = KL. | last9 = Iafrate | first9 = AJ. | title = BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. | journal = PLoS One | volume = 6 | issue = 3 | pages = e17948 | month = | year = 2011 | doi = 10.1371/journal.pone.0017948 | PMID = 21479234 }}</ref>

Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066220/figure/pone-0017948-g001/ PXA - several images (nih.gov)].<ref name=pmid21479234/>

===IHC===
*GFAP +ve.
*CD68 +ve.

==Dysembryoplastic neuroepithelial tumour==
*Abbreviated ''DNT''.

===General===
*Common tumour cause of drug resistant epilepsy.<ref name=pmid15881751>{{Cite journal | last1 = Cataltepe | first1 = O. | last2 = Turanli | first2 = G. | last3 = Yalnizoglu | first3 = D. | last4 = Topçu | first4 = M. | last5 = Akalan | first5 = N. | title = Surgical management of temporal lobe tumor-related epilepsy in children. | journal = J Neurosurg | volume = 102 | issue = 3 Suppl | pages = 280-7 | month = Apr | year = 2005 | doi = 10.3171/ped.2005.102.3.0280 | PMID = 15881751 }}</ref>
*Paediatric population.

===Gross/radiology===
*Temporal lobe.
*Variable architecture:<ref name=pmid18071981/> cystic, solitary nodular, multinodular.

===Microscopic===
Features:<ref name=pmid18071981>{{Cite journal | last1 = O'Brien | first1 = DF. | last2 = Farrell | first2 = M. | last3 = Delanty | first3 = N. | last4 = Traunecker | first4 = H. | last5 = Perrin | first5 = R. | last6 = Smyth | first6 = MD. | last7 = Park | first7 = TS. | title = The Children's Cancer and Leukaemia Group guidelines for the diagnosis and management of dysembryoplastic neuroepithelial tumours. | journal = Br J Neurosurg | volume = 21 | issue = 6 | pages = 539-49 | month = Dec | year = 2007 | doi = 10.1080/02688690701594817 | PMID = 18071981 }}</ref>
*Cells similar to oligodendrocytes:
**Large central nuclei with indentations.
**Multiple small nucleoli (common).
**Clear cytoplasm.

DDx:
*[[Oligodendroglioma]].
**These have rounder, smaller nuclei with occasional nucleoli.<ref name=pmid18071981/>

Images:
*[http://commons.wikimedia.org/wiki/File:DNET_HE.jpg DNT (WC)].
*[http://path.upmc.edu/cases/case106.html DNT - several images (upmc.edu)].

==Subependymal giant cell astrocytoma==
*Abbreviated ''SEGA''.

===General===
*Associated with [[tuberous sclerosis complex]] (TSC).<ref name=pmid21455842>{{Cite journal | last1 = Grajkowska | first1 = W. | last2 = Kotulska | first2 = K. | last3 = Jurkiewicz | first3 = E. | last4 = Roszkowski | first4 = M. | last5 = Daszkiewicz | first5 = P. | last6 = Jóźwiak | first6 = S. | last7 = Matyja | first7 = E. | title = Subependymal giant cell astrocytomas with atypical histological features mimicking malignant gliomas. | journal = Folia Neuropathol | volume = 49 | issue = 1 | pages = 39-46 | month = | year = 2011 | doi = | PMID = 21455842 }}</ref>
*WHO Grade I.

===Gross/radiology===
*Well-demarcated.

===Microscopic===
Features:<ref name=upmc_case179/><ref name=pmid9595853>{{Cite journal | last1 = Taraszewska | first1 = A. | last2 = Kroh | first2 = H. | last3 = Majchrowski | first3 = A. | title = Subependymal giant cell astrocytoma: clinical, histologic and immunohistochemical characteristic of 3 cases. | journal = Folia Neuropathol | volume = 35 | issue = 3 | pages = 181-6 | month = | year = 1997 | doi = | PMID = 9595853 }}</ref>
*Giant cells with nuclear atypia ("bizarre cells").
**Vesicular nuclei.
**[[Nuclear pseudoinclusions]].<ref name=upmc179>URL: [http://path.upmc.edu/cases/case179/micro.html http://path.upmc.edu/cases/case179/micro.html]. Accessed on: 8 January 2012.</ref>
*Glassy eosinophilic cytoplasm.
*Abundant [[mast cell]]s.<ref name=upmc179>URL: [http://path.upmc.edu/cases/case179/micro.html http://path.upmc.edu/cases/case179/micro.html]. Accessed on: 8 January 2012.</ref>

Images:
*[http://path.upmc.edu/cases/case179/micro.html SEGA (upmc.edu)].<ref name=upmc_case179>URL: [http://path.upmc.edu/cases/case179.html http://path.upmc.edu/cases/case179.html]. Accessed on: 29 July 2011.</ref>
*[http://path.upmc.edu/cases/case500.html SEGA - another case (upmc.edu)].

===IHC===
Features:<ref name=pmid9595853/>
*GFAP +ve. (???)
*Vimentin +ve. (???)
*S100 +ve. (???)

==Pilomyxoid astrocytoma==
===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===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*Classically - hypothalamic location/suprasellar location; may involve the sella turcica.<ref name=pmid19766001>{{cite journal |author=Alimohamadi M, Bidabadi MS, Ayan Z, Ketabchi E, Amirjamshidi A |title=Pilomyxoid astrocytoma with involvement of the sella turcica in an adolescent |journal=J Clin Neurosci |volume=16 |issue=12 |pages=1648–9 |year=2009 |month=December |pmid=19766001 |doi=10.1016/j.jocn.2009.01.035 |url=}}</ref>
*Solid.
*Well-circumscribed.

===Microscopic===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*Consists of small round/ovoid bland cells in a [[myxoid stroma]].
*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>
*Rosenthal fibres are absent - '''key negative'''.
*Monophasic (unlike classical pilocytic astrocytomas) - '''key negative'''.
*May rarely have eosinophilic granular bodies.

<gallery>
Image:Pilomyxoid Astrocytoma HE20x.jpg | Pilomyxoid astrocytoma. (WC/Marvin 101)
</gallery>

===Grading===
*''WHO Grade II'' by definition.<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>

==Atypical teratoid/rhabdoid tumour==
:See also: ''[[Extrarenal malignant rhabdoid tumour]]''.
*Commonly abbreviated ''AT/RT''.
*May be written ''atypical teratoid rhabdoid tumour'', i.e. without the forward slash, or ''atypical teratoid-rhabdoid tumour'' (AT-RT).
{{Main|Atypical teratoid/rhabdoid tumour}}

==Oligodendroglioma==
{{Main|Oligodendroglioma}}

==Oligoastrocytoma==
===General===
*Mixed tumour.

===Microscopic===
Features:
*Astrocytoma-like and oligodendroglioma-like:
*#Oligodendroglioma-like cells = round nucleus, peri-nuclear clearing.
*#Astrocytoma-like cells = non-ovoid/elongated nucleus.

DDx:
*Anaplastic astrocytoma.
*Oligodendroglioma. (???)

===IHC===
*Oligodendroglioma-like cells: MAP-2 +ve (cytoplasm).
*Astrocytoma-like cells: GFAP +ve (cytoplasm, nuclear membrane).

Others:
*Ki-67 ~10%. (???)
*p53 - focally +ve. (???)
*IDH-1 +ve. (85%)

==Meningioma==
{{Main|Meningioma}}
===General===
*Very common.
*May be part of a syndrome.

===Microscopic===
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, psammomatous.
*[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Grading: see ''[[meningioma]]''.

==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]].
**[[Traumatic neuroma]].
*Malignant:
**[[Malignant peripheral nerve sheath tumour]] (MPNST).

==Schwannoma==

{{Main|Schwannoma}}
===General===
*Tumour of tissue surrounding a nerve.
**Axons adjacent to the tumour are normal... but may be compressed.

===Microscopic===
Features:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Antoni A:
**Cellular.
**'Fibrillary, polar, elongated'.
*Antoni B:
**Pauci-cellular.
**Loose microcystic tissue.
*Verocay bodies - paucinuclear area surrounded by palisaded nuclei.
*In the GI tract: classically have a ''peripheral lymphoid cuff''.<ref name=pmid15728600>{{cite journal |author=Levy AD, Quiles AM, Miettinen M, Sobin LH |title=Gastrointestinal schwannomas: CT features with clinicopathologic correlation |journal=AJR Am J Roentgenol |volume=184 |issue=3 |pages=797–802 |year=2005 |month=March |pmid=15728600 |doi= |url=http://www.ajronline.org/cgi/content/full/184/3/797}}</ref>

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

Notes:
*Several subtypes exist.

==Neurofibroma==
{{Main|Peripheral nerve sheath tumours#Neurofibroma}}
===General===
*May be a part of [[neurofibromatosis]] 1.
*Composed of Schwann cells, axons, fibrous material.<ref name=pmid17893219/>

===Microscopic===
Features:
*Spindle cells lesion.
**See ''[[Neurofibroma]]'' article for details.

Image:
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(1).jpg Neurofibroma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(2).jpg Neurofibroma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(3).jpg Neurofibroma - high mag. (WC)].

==Ganglioneuroma==
:'''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>
===General===
*May be retroperitoneal.
*Occasionally found in the GI tract - may form [[Gastrointestinal_tract_polyps#Ganglioneuroma|colonic polyp]].
*Multiple ganglioneuromas may be due to [[multiple endocrine neoplasia IIb]].

Classification:
*In a grouping known as ''neuroblastic tumours'' 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).

===Gross===
*Solid.
*White.
*Firm.
*Well-circumscribed.
*May be nodular.

Images:
*[http://commons.wikimedia.org/wiki/File:Adrenal_ganglioneuroma_02.JPG Adrenal ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?case=84&n=1 Ganglioneuroma (webpathology.com)].

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

Images:
*[http://it.wikipedia.org/wiki/File:Ganglioneuroma_(1).jpg Ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?n=4&Case=84 Ganglioneuroma (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=412&n=4 Ganglioneuroma (webpathology.com)].
*[http://en.wikipedia.org/wiki/File:Ganglion_high_mag.jpg Normal ganglion - high mag. (WC)] .

See: ''[[adrenal ganglioneuroma]]'', ''[[Gastrointestinal tract polyps#Ganglioneuroma|colonic ganglioneuroma]]''.

===IHC===
Features:<ref>{{Ref GLP|217}}</ref>
*Spindle cells: S-100 +ve.
*Ganglion cells: NSE, synaptophysin, NF.

==Ependymoma==
===General===
*Called the forgotten glial tumour.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usu. spinal cord.
**Children: usu. posterior fossa.
*May be assoc. with [[neurofibromatosis]] 2.

Comes in two main flavours:
#Ependymoma (not otherwise specified).
#Myxopapillary ependymoma.
#*Classically at filum terminale.

Other flavours:<ref>URL: [http://emedicine.medscape.com/article/1744030-overview http://emedicine.medscape.com/article/1744030-overview]. Accessed on: 17 January 2012.</ref>
*Papillary ependymoma.
*Clear cell ependymoma.

===Microscopic===
====Classic ependymoma====
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''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); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.

DDx (classic ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
**Invasive border = GBM; circumscribed border of lesion = ependymoma.

Images:
*www:
**[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
**[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
**[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
**[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
*WC:
**[http://commons.wikimedia.org/wiki/File:Ependymoma_intermed_mag.jpg Ependymoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Ependymoma_low_intermed_mag.jpg Ependymoma - low mag. (WC)].

====Myxopapillary ependymoma====
Features:
*Perivascular pseudorosettes:
**Myxoid material surround blood vessels.
***[[Myxoid]] material surrounded by tumour cells.

Images:
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma_-_high_mag.jpg Myxopapillary ependymoma - high mag. (WC)].
*[http://careers.bmj.com/article-images/cf0708.f2_default.gif Myxopapillary ependymoma (bmj.com)] - part of [http://careers.bmj.com/careers/advice/view-article.html?id=351 careers.bmj.com article on paediatric pathology].
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma.jpg Myxopapillary ependymoma - cytology (WC)].
*[http://path.upmc.edu/cases/case626.html Myxopapillary ependymoma - several images (upmc.edu)].

====Grading====
Easy:
*Subependymoma = WHO grade I.
*Myxopapillary ependymoma = WHO grade I.
Not-so-easy:
*Classic ependymoma = WHO grade II.
*Anaplastic ependymoma = WHO grade III.

Grade II vs. Grade III:
*Cellular density.
*Mitoses.
*Necrosis.
*Microvascular proliferation.

Notes:
*Many tumours fall between grade II and grade III. These are called "indeterminate" by many.

===IHC===
*Reticulin.
*GFAP.
*MIB1.

==Subependymoma==
{{Main|Subependymoma}}

==Choroid plexus papilloma==
{{Main|Choroid plexus papilloma}}

==Choroid plexus carcinoma==
===General===
*Usually pediatric population.
*Malignant counterpart of ''[[choroid plexus papilloma]]''.<ref name=pmid19679976>{{Cite journal | last1 = Singh | first1 = A. | last2 = Vermani | first2 = S. | last3 = Shruti | first3 = S. | title = Choroid plexus carcinoma: report of two cases. | journal = Indian J Pathol Microbiol | volume = 52 | issue = 3 | pages = 405-7 | month = | year = | doi = 10.4103/0377-4929.55009 | PMID = 19679976 }}</ref>
*Poor prognosis - WHO grade III.<ref name=pmid20644273>{{Cite journal | last1 = Menon | first1 = G. | last2 = Nair | first2 = SN. | last3 = Baldawa | first3 = SS. | last4 = Rao | first4 = RB. | last5 = Krishnakumar | first5 = KP. | last6 = Gopalakrishnan | first6 = CV. | title = Choroid plexus tumors: an institutional series of 25 patients. | journal = Neurol India | volume = 58 | issue = 3 | pages = 429-35 | month = | year = | doi = 10.4103/0028-3886.66455 | PMID = 20644273 |URL = http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2010;volume=58;issue=3;spage=429;epage=435;aulast=Menon }}</ref>
*Classically posterior fossa.
*Intraventricular mass.

===Microscopic===
Features:<ref name=pmid19679976/>
*Choroid plexus epithelium with [[nuclear pleomorphism]] & high [[NC ratio]].
*Mitoses.
*Necrosis.
*+/-Brain invasion.

DDx:
*[[Choroid plexus papilloma]].
*Atypical plexus papilloma - has features intermediate between ''choroid plexus papilloma'' and ''choroid plexus carcinoma''.<ref name=pmid20644273/>
*[[Atypical teratoid/rhabdoid tumour]].

Images:
*[http://path.upmc.edu/cases/case198/micro.html Choroid plexus carcinoma - several images (upmc.edu)].

===IHC===
Features:<ref name=pmid20644273/>
*Cytokeratins +ve.
*EMA usu. -ve.
*GFAP -ve (~20% +ve).
*Ki-67 high.
**Useful to diff. from benign counterpart.
*INI1 +ve.

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==Medulloblastoma==
{{Main|Medulloblastoma}}
*Tumour of cerebellum - key feature.
*Morphologically identical supratentorial tumours are called [[primitive neuroectodermal tumour]] (PNET).

==Primitive neuroectodermal tumour==
*[[AKA]] ''primitive neuroepithelial tumour''. (???)

===General===
*Abbreviated ''PNET''.
*Should not be confused with ''peripheral primitive neuroectodermal tumour'' (abbreviated ''[[pPNET]]''<ref name=PST14feb11>PST. 14 February 2011.</ref>), [[AKA]] ''[[Ewing sarcoma]]''.

===Microscopic===
Features:
*[[Small round blue cell tumour]] - see ''[[medulloblastoma]]''.

DDx:
*[[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR).<ref name=pmid19563506>{{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>

Images:
*[http://path.upmc.edu/cases/case414.html Primitive neuroectodermal tumour - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case649.html GBM with PNET component - several images (upmc.edu)].

==Embryonal tumour with abundant neuropil and true rosettes==
*Abbreviated ''ETANTR''.
===General===
*Super rare.
*Reported only in children <4 years old.<ref name=pmid16551982/>

===Microscopic===
Features:<ref name=pmid20499240>{{Cite journal | last1 = Ferri Niguez | first1 = B. | last2 = Martínez-Lage | first2 = JF. | last3 = Almagro | first3 = MJ. | last4 = Fuster | first4 = JL. | last5 = Serrano | first5 = C. | last6 = Torroba | first6 = MA. | last7 = Sola | first7 = J. | title = Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update. | journal = Childs Nerv Syst | volume = 26 | issue = 8 | pages = 1003-8 | month = Aug | year = 2010 | doi = 10.1007/s00381-010-1179-x | PMID = 20499240 }}</ref>
*[[Small round blue cell tumour]].
*True rosettes = flower-like cluster of cells that surrounds a space.<ref name=pmid16551982>{{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>
*Fibrillary neuropil.
**Meshwork of fibers.

DDx:
*[[Primitive neuroectodermal tumour]].
*[[Medulloblastoma]]. (???)

Images:
*[http://path.upmc.edu/cases/case585.html ETANTR - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case666.html ETANTR - another case (upmc.edu)].

==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===
Features:
*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>

===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.

==Neurocytoma==
===General===
*Rare.

===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm]. Accessed on: 12 October 2011.</ref>
*[[Pineocytoma|Pineocytomatous]]/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Similar to Homer-Wright rosette.
*Perinuclear clearing.
*Well-defined cell borders.

DDx:
*[[Oligodendroglioma]] - do not have the characteristic rosettes.
*[[Ganglioglioma]].
*[[Ependymoma]].

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm Neurocytoma (ouhsc.edu)].
*[http://path.upmc.edu/cases/case383.html Neurocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case561.html Neurocytoma - cerebellar - several images (upmc.edu)].
===IHC===
*Synaptophysin +ve.
**Most glial tumour -ve.<ref>URL: [http://path.upmc.edu/cases/case383/dx.html http://path.upmc.edu/cases/case383/dx.html]. Accessed on: 15 January 2012.</ref>

==Central neurocytoma==
*Abbreviated ''CNC''.
===General===
*Rare - less than 1% of brain tumours.<ref name=pmid16163043>{{Cite journal | last1 = Chuang | first1 = MT. | last2 = Lin | first2 = WC. | last3 = Tsai | first3 = HY. | last4 = Liu | first4 = GC. | last5 = Hu | first5 = SW. | last6 = Chiang | first6 = IC. | title = 3-T proton magnetic resonance spectroscopy of central neurocytoma: 3 case reports and review of the literature. | journal = J Comput Assist Tomogr | volume = 29 | issue = 5 | pages = 683-8 | month = | year = | doi = | PMID = 16163043 }}</ref>
*Benign.
*First described in 1982.<ref name=pmid16163043/>

===Gross/radiology===
*Intraventricular.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm]. Accessed on: 12 January 2012.</ref>
**Characteristically attached to the ''septum pellucidum''.<ref name=pmid20692674>{{Cite journal | last1 = Kerkeni | first1 = A. | last2 = Ben Lakhdher | first2 = Z. | last3 = Rkhami | first3 = M. | last4 = Sebai | first4 = R. | last5 = Belguith | first5 = L. | last6 = Khaldi | first6 = M. | last7 = Ben Hamouda | first7 = M. | title = [Central neurocytoma: Study of 32 cases and review of the literature]. | journal = Neurochirurgie | volume = 56 | issue = 5 | pages = 408-14 | month = Oct | year = 2010 | doi = 10.1016/j.neuchi.2010.07.001 | PMID = 20692674 }}</ref>

===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm]. Accessed on: 27 May 2011.</ref>
*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{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>
*Islands of neuropil.
*Polygonal cells with a perinuclear halo.

DDx:
*[[Oligodendroglioma]].

DDx of perivascular pseudorosette:
*Ependymoma.
*[[Medulloblastoma]], PNET.
*[[Glioblastoma]]s.

====Images====
<gallery>
Image:Central_neurocytoma_-_intermed_mag.jpg | Central neurocytoma - intermed. mag. (WC)
Image:Central_neurocytoma_-_high_mag.jpg | Central neurocytoma - oligodendrogllioma-like area - high mag. (WC)
Image:Central_neurocytoma_-_2_-_high_mag.jpg | Central neurocytoma - pseudorosettes - high mag. (WC)
Image:Central_neurocytoma_-_2_-_very_high_mag.jpg | Central neurocytoma - pseudorossettes - very high mag. (WC)
</gallery>
[[www]]:
*[http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm Central neurocytoma - several images (ouhsc.edu)].
*[http://frontalcortex.com/?page=image&topic=1&qid=1203 Central neurocytoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case74/micro.html Central neurocytoma - crappy images (upmc.edu)].

===IHC===
*MIB1 - high may predict re-occurance.<ref name=pmid15015671>{{Cite journal | last1 = Schmidt | first1 = MH. | last2 = Gottfried | first2 = ON. | last3 = von Koch | first3 = CS. | last4 = Chang | first4 = SM. | last5 = McDermott | first5 = MW. | title = Central neurocytoma: a review. | journal = J Neurooncol | volume = 66 | issue = 3 | pages = 377-84 | month = Feb | year = 2004 | doi = | PMID = 15015671 }}</ref>

==Ganglioglioma==
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
===General===
*Rare.
*Usu. temporal lobe.
*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>

===Microscopic===
Features:
*Atypical neurons.
*Atypical glia.

Images:
*[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}}

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.

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==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[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]]

Oligodendroglioma

2014-11-15T17:24:16Z

Laura: /* IHC */

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Oligodendroglioma1_high_mag.jpg
| Width =
| Caption = Oligodendroglioma. [[H&E stain]].
| Synonyms =
| Micro = highly cellular lesion composed of cells resembling ''fried eggs'' (oligodendrocytes) with a round nucleus (important), distinct cell borders, +/-clear cytoplasm - useful feature (if present), acutely branched capillary sized vessels ("chicken-wire" like appearance), calcifications
| Subtypes =
| LMDDx = [[neurocytoma]], clear cell variant of [[ependymoma]], [[seminoma]] / [[dysgerminoma]] / [[germinoma]]
| Stains =
| IHC =
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[neuropathology tumours]] - cerebral hemispheres, posterior fossa (rare), spinal cord (very rare)
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = moderate - dependent on grade
| Other =
| ClinDDx =
| Tx =
}}
'''Oligodendroglioma''' is [[CNS tumour]] that is typically in the cerebral hemispheres.

==General==
*Do ''not'' arise from oligodendrocytes.
**Arise from ''glial precursor cells''.

Usual location:
*Cerebral hemispheres- most often frontal lobe.
*Posterior fossa (rare)
*Intramedullary spinal cord (very rare).

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==
Features:
*Highly cellular lesion composed of:
**Cells resembling ''fried eggs'' (oligodendrocytes) with:
***Round nucleus - '''key feature'''.
***Distinct cell borders.
***Moderate-to-marked nuclear atypia.
***Clear cytoplasm - useful feature (if present).
****Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing.
**Acutely branched capillary sized vessels - "chicken-wire" like appearance.
***Abundant, delicate appearing; may vaguely resemble a paraganglioma at low power.
*Calcifications - important feature.<ref>URL: [http://www.emedicine.com/radio/topic481.htm http://www.emedicine.com/radio/topic481.htm].</ref>

Note:
*Tumour cells may be plasmacytoid, i.e. have a [[plasma cell]]-like appearance.<ref name=pmid17284109>{{Cite journal | last1 = Aldape | first1 = K. | last2 = Burger | first2 = PC. | last3 = Perry | first3 = A. | title = Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. | journal = Arch Pathol Lab Med | volume = 131 | issue = 2 | pages = 242-51 | month = Feb | year = 2007 | doi = 10.1043/1543-2165(2007)131[242:CAOQLA]2.0.CO;2 | PMID = 17284109 | URL = http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2007)131%5B242:CAOQLA%5D2.0.CO;2 }}</ref>

DDx:
*[[Neurocytoma]] also have perinuclear clearing and well-defined cellular borders.
**Pineocytomatous/neurocytic rosettes = (irregular) rosette with a large meshwork of fibers (neuropil) at the centre.

Notes:
*Few neural tumours have round nuclei - DDx:
**Oligodendroglioma.
**[[Lymphoma]].
**Clear cell variant of [[ependymoma]].
**[[Germ cell tumour]] (germinoma/dysgerminoma/seminoma).

===Images===
<gallery>
Image:Oligodendroglioma1_high_mag.jpg | Oligodendroglioma high mag. (WC)
Image:Oligodendroglioma1_low_mag.jpg | Oligodendroglioma low mag. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case713.html Oligodendroglioma - several images (upmc.edu)].
*[http://frontalcortex.com/?page=oll&topic=24&qid=864 Oligodendroglioma with plasmacytoid cells (frontalcortex.com)].

===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==
Features:
*MAP-2 +ve.<reF name=pmid12025943>{{cite journal |author=Suzuki SO, Kitai R, Llena J, Lee SC, Goldman JE, Shafit-Zagardo B |title=MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration |journal=J. Neuropathol. Exp. Neurol. |volume=61 |issue=5 |pages=403–12 |year=2002 |month=May |pmid=12025943 |doi= |url=}}</ref>
*GFAP +ve (variable).
**Some subtypes +ve - should not be used to distinguish.<ref name=Ref_PSNP>{{Ref PSNP|98}}</ref>
*EMA +ve.
*IDH-1 +ve. (80%).
*p53 -ve.
**Useful for differentiating ''astrocytoma'' vs. ''oligodendroglioma''.
*Ki-67.

==Molecular pathology==
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>
*Greater chemosensitivity
*Better prognosis.

==See also==
*[[Neuropathology tumours]].
*[[Neuropathology]].

==References==
{{Reflist|2}}

[[Category:Neuropathology tumours]]
[[Category:Diagnosis]]

Oligodendroglioma

2014-11-15T16:07:22Z

Laura:

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Oligodendroglioma1_high_mag.jpg
| Width =
| Caption = Oligodendroglioma. [[H&E stain]].
| Synonyms =
| Micro = highly cellular lesion composed of cells resembling ''fried eggs'' (oligodendrocytes) with a round nucleus (important), distinct cell borders, +/-clear cytoplasm - useful feature (if present), acutely branched capillary sized vessels ("chicken-wire" like appearance), calcifications
| Subtypes =
| LMDDx = [[neurocytoma]], clear cell variant of [[ependymoma]], [[seminoma]] / [[dysgerminoma]] / [[germinoma]]
| Stains =
| IHC =
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[neuropathology tumours]] - cerebral hemispheres, posterior fossa (rare), spinal cord (very rare)
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = moderate - dependent on grade
| Other =
| ClinDDx =
| Tx =
}}
'''Oligodendroglioma''' is [[CNS tumour]] that is typically in the cerebral hemispheres.

==General==
*Do ''not'' arise from oligodendrocytes.
**Arise from ''glial precursor cells''.

Usual location:
*Cerebral hemispheres- most often frontal lobe.
*Posterior fossa (rare)
*Intramedullary spinal cord (very rare).

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==
Features:
*Highly cellular lesion composed of:
**Cells resembling ''fried eggs'' (oligodendrocytes) with:
***Round nucleus - '''key feature'''.
***Distinct cell borders.
***Moderate-to-marked nuclear atypia.
***Clear cytoplasm - useful feature (if present).
****Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing.
**Acutely branched capillary sized vessels - "chicken-wire" like appearance.
***Abundant, delicate appearing; may vaguely resemble a paraganglioma at low power.
*Calcifications - important feature.<ref>URL: [http://www.emedicine.com/radio/topic481.htm http://www.emedicine.com/radio/topic481.htm].</ref>

Note:
*Tumour cells may be plasmacytoid, i.e. have a [[plasma cell]]-like appearance.<ref name=pmid17284109>{{Cite journal | last1 = Aldape | first1 = K. | last2 = Burger | first2 = PC. | last3 = Perry | first3 = A. | title = Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma. | journal = Arch Pathol Lab Med | volume = 131 | issue = 2 | pages = 242-51 | month = Feb | year = 2007 | doi = 10.1043/1543-2165(2007)131[242:CAOQLA]2.0.CO;2 | PMID = 17284109 | URL = http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2007)131%5B242:CAOQLA%5D2.0.CO;2 }}</ref>

DDx:
*[[Neurocytoma]] also have perinuclear clearing and well-defined cellular borders.
**Pineocytomatous/neurocytic rosettes = (irregular) rosette with a large meshwork of fibers (neuropil) at the centre.

Notes:
*Few neural tumours have round nuclei - DDx:
**Oligodendroglioma.
**[[Lymphoma]].
**Clear cell variant of [[ependymoma]].
**[[Germ cell tumour]] (germinoma/dysgerminoma/seminoma).

===Images===
<gallery>
Image:Oligodendroglioma1_high_mag.jpg | Oligodendroglioma high mag. (WC)
Image:Oligodendroglioma1_low_mag.jpg | Oligodendroglioma low mag. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case713.html Oligodendroglioma - several images (upmc.edu)].
*[http://frontalcortex.com/?page=oll&topic=24&qid=864 Oligodendroglioma with plasmacytoid cells (frontalcortex.com)].

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

==Molecular pathology==
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>
*Greater chemosensitivity
*Better prognosis.

==See also==
*[[Neuropathology tumours]].
*[[Neuropathology]].

==References==
{{Reflist|2}}

[[Category:Neuropathology tumours]]
[[Category:Diagnosis]]

Neuropathology tumours

2014-11-15T15:43:25Z

Laura: /* Grading */

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 gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===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>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]] (previously known as ''glioblastoma multiforme'').
# [[Anaplastic astrocytoma]].
# [[Meningioma]].

===Children===
# Astrocytoma.
# [[Medulloblastoma]].
# [[Ependymoma]].

===Location (most common)===
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]].
*Spinal cord:
**[[Ependymoma]], glioblastoma.
**Filum terminale - [[myxopapillary ependymoma]], [[paraganglioma]].

====Filum terminale====
*Filum terminale = bottom end of the spinal cord - has a limited differential.

DDx:<ref>JLK. 31 May 2010.</ref>
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].

====Cerebellopontine angle====
*Abbreviated ''CP angle''.

DDx:<ref>R. Kiehl. 8 November 2010.</ref>
*[[Schwannoma]].
*[[Meningioma]].
*[[Dermoid cyst]]/epidermoid cyst.
*[[Ependymoma]].
*[[Choroid plexus papilloma]].

===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>

===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.

[[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.

===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
|nil
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Astrocytoma]] (grade II or worse)
|glial processes (esp. on smear), nuclear atypia (size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|Astrocytoma. (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)]]
|-
|[[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)]]
|-
|[[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
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (Grade II).
*Anaplastic astrocytomas (Grade III).
*Glioblastoma (Grade IV).

Notes:
*Non-infiltrative gliomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
**[[Dysembryoplastic neuroepithelial tumour]] (DNT), (WHO Grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*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:
*[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)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[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.

Images:
*Glioblastoma:
**[http://commons.wikimedia.org/wiki/File:Glioblastoma_%281%29.jpg Glioblastoma - pseudopalisading of tumour cells (WC)].
**[http://commons.wikimedia.org/wiki/File:Glioblastoma_-_high_mag.jpg Glioblastoma with fragment of near-normal white matter - high mag. (WC)].
*Anaplastic astrocytoma:
**[http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg Anaplastic astrocytoma - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg Anaplastic astrocytoma - GFAP - very high mag. (WC)].

=====Table of common gliomas - grading=====
Histomorphologic comparison of common gliomas:
{| class="wikitable"
|'''Entity''' || '''Rosenthal fibres / EGBs''' ||'''Nuclear atypia''' ||'''Mitoses''' || '''Necrosis or MVP''' || '''Infiltrative''' || '''Image'''
|-
|Pilocytic astrocytoma || yes || usu. no || usu. no || usu. no || no || [http://commons.wikimedia.org/wiki/File:Rosenthal_HE_40x.jpg]
|-
|Low-grade astrocytoma || no || yes || no || no || yes || image?
|-
|Anaplastic astrocytoma || no || yes || yes || no || yes || [http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_high_mag.jpg]
|-
|Glioblastoma || no || yes || yes || yes || yes || [http://commons.wikimedia.org/wiki/File:Glioblastoma_-_high_mag.jpg]
|}
Notes:
*''MVP'' = microvascular proliferation.
*''EGBs'' = eosinophilic granular bodies.

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

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

==Pilocytic astrocytoma==
{{Main|Pilocytic astrocytoma}}

==Pleomorphic xanthoastrocytoma==
*Abbreviated ''PXA''.
===General===
Features:
*Classically in the temporal lobe in children and young adults.
*Associated with seizures.
*Moderately aggressive (WHO Grade II).<ref name=pmid11465399>{{Cite journal | last1 = Fouladi | first1 = M. | last2 = Jenkins | first2 = J. | last3 = Burger | first3 = P. | last4 = Langston | first4 = J. | last5 = Merchant | first5 = T. | last6 = Heideman | first6 = R. | last7 = Thompson | first7 = S. | last8 = Sanford | first8 = A. | last9 = Kun | first9 = L. | title = Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection. | journal = Neuro Oncol | volume = 3 | issue = 3 | pages = 184-92 | month = Jul | year = 2001 | doi = | PMID = 11465399 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920613/pdf/11465399.pdf}}</ref>

===Gross===
*Temporal lobe - classic.
*Usually assoc. with the leptomeninges,<ref name=pmid11465399/> i.e. superficial.

===Microscopic===
Features:<ref name=Ref_PBoD8_1333>{{Ref PBoD8|1333}}</ref>
*Marked nuclear atypia.
*Eosinophilic granular bodies - very common.<ref name=pmid11465399/>
*Inflammation (chronic).

Notes:
*No mitoses.
*No [[necrosis]].

Images:
*[http://path.upmc.edu/cases/case499.html Pleomorphic xanthoastrocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case511.html Pleomorphic xanthoastrocytoma with anaplasia - another case - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case578.html Pleomorphic xanthoastrocytoma with anaplasia - case 3 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case579.html Cerebellar pleomorphic xanthoastrocytoma - case 4 - several image (upmc.edu)].

===Stains===
*[[Reticulin stain]] - intercellular, prominent.<ref name=pmid21479234>{{Cite journal | last1 = Dias-Santagata | first1 = D. | last2 = Lam | first2 = Q. | last3 = Vernovsky | first3 = K. | last4 = Vena | first4 = N. | last5 = Lennerz | first5 = JK. | last6 = Borger | first6 = DR. | last7 = Batchelor | first7 = TT. | last8 = Ligon | first8 = KL. | last9 = Iafrate | first9 = AJ. | title = BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. | journal = PLoS One | volume = 6 | issue = 3 | pages = e17948 | month = | year = 2011 | doi = 10.1371/journal.pone.0017948 | PMID = 21479234 }}</ref>

Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066220/figure/pone-0017948-g001/ PXA - several images (nih.gov)].<ref name=pmid21479234/>

===IHC===
*GFAP +ve.
*CD68 +ve.

==Dysembryoplastic neuroepithelial tumour==
*Abbreviated ''DNT''.

===General===
*Common tumour cause of drug resistant epilepsy.<ref name=pmid15881751>{{Cite journal | last1 = Cataltepe | first1 = O. | last2 = Turanli | first2 = G. | last3 = Yalnizoglu | first3 = D. | last4 = Topçu | first4 = M. | last5 = Akalan | first5 = N. | title = Surgical management of temporal lobe tumor-related epilepsy in children. | journal = J Neurosurg | volume = 102 | issue = 3 Suppl | pages = 280-7 | month = Apr | year = 2005 | doi = 10.3171/ped.2005.102.3.0280 | PMID = 15881751 }}</ref>
*Paediatric population.

===Gross/radiology===
*Temporal lobe.
*Variable architecture:<ref name=pmid18071981/> cystic, solitary nodular, multinodular.

===Microscopic===
Features:<ref name=pmid18071981>{{Cite journal | last1 = O'Brien | first1 = DF. | last2 = Farrell | first2 = M. | last3 = Delanty | first3 = N. | last4 = Traunecker | first4 = H. | last5 = Perrin | first5 = R. | last6 = Smyth | first6 = MD. | last7 = Park | first7 = TS. | title = The Children's Cancer and Leukaemia Group guidelines for the diagnosis and management of dysembryoplastic neuroepithelial tumours. | journal = Br J Neurosurg | volume = 21 | issue = 6 | pages = 539-49 | month = Dec | year = 2007 | doi = 10.1080/02688690701594817 | PMID = 18071981 }}</ref>
*Cells similar to oligodendrocytes:
**Large central nuclei with indentations.
**Multiple small nucleoli (common).
**Clear cytoplasm.

DDx:
*[[Oligodendroglioma]].
**These have rounder, smaller nuclei with occasional nucleoli.<ref name=pmid18071981/>

Images:
*[http://commons.wikimedia.org/wiki/File:DNET_HE.jpg DNT (WC)].
*[http://path.upmc.edu/cases/case106.html DNT - several images (upmc.edu)].

==Subependymal giant cell astrocytoma==
*Abbreviated ''SEGA''.

===General===
*Associated with [[tuberous sclerosis complex]] (TSC).<ref name=pmid21455842>{{Cite journal | last1 = Grajkowska | first1 = W. | last2 = Kotulska | first2 = K. | last3 = Jurkiewicz | first3 = E. | last4 = Roszkowski | first4 = M. | last5 = Daszkiewicz | first5 = P. | last6 = Jóźwiak | first6 = S. | last7 = Matyja | first7 = E. | title = Subependymal giant cell astrocytomas with atypical histological features mimicking malignant gliomas. | journal = Folia Neuropathol | volume = 49 | issue = 1 | pages = 39-46 | month = | year = 2011 | doi = | PMID = 21455842 }}</ref>
*WHO Grade I.

===Gross/radiology===
*Well-demarcated.

===Microscopic===
Features:<ref name=upmc_case179/><ref name=pmid9595853>{{Cite journal | last1 = Taraszewska | first1 = A. | last2 = Kroh | first2 = H. | last3 = Majchrowski | first3 = A. | title = Subependymal giant cell astrocytoma: clinical, histologic and immunohistochemical characteristic of 3 cases. | journal = Folia Neuropathol | volume = 35 | issue = 3 | pages = 181-6 | month = | year = 1997 | doi = | PMID = 9595853 }}</ref>
*Giant cells with nuclear atypia ("bizarre cells").
**Vesicular nuclei.
**[[Nuclear pseudoinclusions]].<ref name=upmc179>URL: [http://path.upmc.edu/cases/case179/micro.html http://path.upmc.edu/cases/case179/micro.html]. Accessed on: 8 January 2012.</ref>
*Glassy eosinophilic cytoplasm.
*Abundant [[mast cell]]s.<ref name=upmc179>URL: [http://path.upmc.edu/cases/case179/micro.html http://path.upmc.edu/cases/case179/micro.html]. Accessed on: 8 January 2012.</ref>

Images:
*[http://path.upmc.edu/cases/case179/micro.html SEGA (upmc.edu)].<ref name=upmc_case179>URL: [http://path.upmc.edu/cases/case179.html http://path.upmc.edu/cases/case179.html]. Accessed on: 29 July 2011.</ref>
*[http://path.upmc.edu/cases/case500.html SEGA - another case (upmc.edu)].

===IHC===
Features:<ref name=pmid9595853/>
*GFAP +ve. (???)
*Vimentin +ve. (???)
*S100 +ve. (???)

==Pilomyxoid astrocytoma==
===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===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*Classically - hypothalamic location/suprasellar location; may involve the sella turcica.<ref name=pmid19766001>{{cite journal |author=Alimohamadi M, Bidabadi MS, Ayan Z, Ketabchi E, Amirjamshidi A |title=Pilomyxoid astrocytoma with involvement of the sella turcica in an adolescent |journal=J Clin Neurosci |volume=16 |issue=12 |pages=1648–9 |year=2009 |month=December |pmid=19766001 |doi=10.1016/j.jocn.2009.01.035 |url=}}</ref>
*Solid.
*Well-circumscribed.

===Microscopic===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*Consists of small round/ovoid bland cells in a [[myxoid stroma]].
*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>
*Rosenthal fibres are absent - '''key negative'''.
*Monophasic (unlike classical pilocytic astrocytomas) - '''key negative'''.
*May rarely have eosinophilic granular bodies.

<gallery>
Image:Pilomyxoid Astrocytoma HE20x.jpg | Pilomyxoid astrocytoma. (WC/Marvin 101)
</gallery>

===Grading===
*''WHO Grade II'' by definition.<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>

==Atypical teratoid/rhabdoid tumour==
:See also: ''[[Extrarenal malignant rhabdoid tumour]]''.
*Commonly abbreviated ''AT/RT''.
*May be written ''atypical teratoid rhabdoid tumour'', i.e. without the forward slash, or ''atypical teratoid-rhabdoid tumour'' (AT-RT).
{{Main|Atypical teratoid/rhabdoid tumour}}

==Oligodendroglioma==
{{Main|Oligodendroglioma}}

==Oligoastrocytoma==
===General===
*Mixed tumour.

===Microscopic===
Features:
*Astrocytoma-like and oligodendroglioma-like:
*#Oligodendroglioma-like cells = round nucleus, peri-nuclear clearing.
*#Astrocytoma-like cells = non-ovoid/elongated nucleus.

DDx:
*Anaplastic astrocytoma.
*Oligodendroglioma. (???)

===IHC===
*Oligodendroglioma-like cells: MAP-2 +ve (cytoplasm).
*Astrocytoma-like cells: GFAP +ve (cytoplasm, nuclear membrane).

Others:
*Ki-67 ~10%. (???)
*p53 - focally +ve. (???)
*IDH-1 -ve. (???)

==Meningioma==
{{Main|Meningioma}}
===General===
*Very common.
*May be part of a syndrome.

===Microscopic===
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, psammomatous.
*[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Grading: see ''[[meningioma]]''.

==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]].
**[[Traumatic neuroma]].
*Malignant:
**[[Malignant peripheral nerve sheath tumour]] (MPNST).

==Schwannoma==

{{Main|Schwannoma}}
===General===
*Tumour of tissue surrounding a nerve.
**Axons adjacent to the tumour are normal... but may be compressed.

===Microscopic===
Features:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Antoni A:
**Cellular.
**'Fibrillary, polar, elongated'.
*Antoni B:
**Pauci-cellular.
**Loose microcystic tissue.
*Verocay bodies - paucinuclear area surrounded by palisaded nuclei.
*In the GI tract: classically have a ''peripheral lymphoid cuff''.<ref name=pmid15728600>{{cite journal |author=Levy AD, Quiles AM, Miettinen M, Sobin LH |title=Gastrointestinal schwannomas: CT features with clinicopathologic correlation |journal=AJR Am J Roentgenol |volume=184 |issue=3 |pages=797–802 |year=2005 |month=March |pmid=15728600 |doi= |url=http://www.ajronline.org/cgi/content/full/184/3/797}}</ref>

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

Notes:
*Several subtypes exist.

==Neurofibroma==
{{Main|Peripheral nerve sheath tumours#Neurofibroma}}
===General===
*May be a part of [[neurofibromatosis]] 1.
*Composed of Schwann cells, axons, fibrous material.<ref name=pmid17893219/>

===Microscopic===
Features:
*Spindle cells lesion.
**See ''[[Neurofibroma]]'' article for details.

Image:
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(1).jpg Neurofibroma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(2).jpg Neurofibroma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(3).jpg Neurofibroma - high mag. (WC)].

==Ganglioneuroma==
:'''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>
===General===
*May be retroperitoneal.
*Occasionally found in the GI tract - may form [[Gastrointestinal_tract_polyps#Ganglioneuroma|colonic polyp]].
*Multiple ganglioneuromas may be due to [[multiple endocrine neoplasia IIb]].

Classification:
*In a grouping known as ''neuroblastic tumours'' 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).

===Gross===
*Solid.
*White.
*Firm.
*Well-circumscribed.
*May be nodular.

Images:
*[http://commons.wikimedia.org/wiki/File:Adrenal_ganglioneuroma_02.JPG Adrenal ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?case=84&n=1 Ganglioneuroma (webpathology.com)].

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

Images:
*[http://it.wikipedia.org/wiki/File:Ganglioneuroma_(1).jpg Ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?n=4&Case=84 Ganglioneuroma (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=412&n=4 Ganglioneuroma (webpathology.com)].
*[http://en.wikipedia.org/wiki/File:Ganglion_high_mag.jpg Normal ganglion - high mag. (WC)] .

See: ''[[adrenal ganglioneuroma]]'', ''[[Gastrointestinal tract polyps#Ganglioneuroma|colonic ganglioneuroma]]''.

===IHC===
Features:<ref>{{Ref GLP|217}}</ref>
*Spindle cells: S-100 +ve.
*Ganglion cells: NSE, synaptophysin, NF.

==Ependymoma==
===General===
*Called the forgotten glial tumour.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usu. spinal cord.
**Children: usu. posterior fossa.
*May be assoc. with [[neurofibromatosis]] 2.

Comes in two main flavours:
#Ependymoma (not otherwise specified).
#Myxopapillary ependymoma.
#*Classically at filum terminale.

Other flavours:<ref>URL: [http://emedicine.medscape.com/article/1744030-overview http://emedicine.medscape.com/article/1744030-overview]. Accessed on: 17 January 2012.</ref>
*Papillary ependymoma.
*Clear cell ependymoma.

===Microscopic===
====Classic ependymoma====
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''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); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.

DDx (classic ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
**Invasive border = GBM; circumscribed border of lesion = ependymoma.

Images:
*www:
**[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
**[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
**[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
**[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
*WC:
**[http://commons.wikimedia.org/wiki/File:Ependymoma_intermed_mag.jpg Ependymoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Ependymoma_low_intermed_mag.jpg Ependymoma - low mag. (WC)].

====Myxopapillary ependymoma====
Features:
*Perivascular pseudorosettes:
**Myxoid material surround blood vessels.
***[[Myxoid]] material surrounded by tumour cells.

Images:
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma_-_high_mag.jpg Myxopapillary ependymoma - high mag. (WC)].
*[http://careers.bmj.com/article-images/cf0708.f2_default.gif Myxopapillary ependymoma (bmj.com)] - part of [http://careers.bmj.com/careers/advice/view-article.html?id=351 careers.bmj.com article on paediatric pathology].
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma.jpg Myxopapillary ependymoma - cytology (WC)].
*[http://path.upmc.edu/cases/case626.html Myxopapillary ependymoma - several images (upmc.edu)].

====Grading====
Easy:
*Subependymoma = WHO grade I.
*Myxopapillary ependymoma = WHO grade I.
Not-so-easy:
*Classic ependymoma = WHO grade II.
*Anaplastic ependymoma = WHO grade III.

Grade II vs. Grade III:
*Cellular density.
*Mitoses.
*Necrosis.
*Microvascular proliferation.

Notes:
*Many tumours fall between grade II and grade III. These are called "indeterminate" by many.

===IHC===
*Reticulin.
*GFAP.
*MIB1.

==Subependymoma==
{{Main|Subependymoma}}

==Choroid plexus papilloma==
{{Main|Choroid plexus papilloma}}

==Choroid plexus carcinoma==
===General===
*Usually pediatric population.
*Malignant counterpart of ''[[choroid plexus papilloma]]''.<ref name=pmid19679976>{{Cite journal | last1 = Singh | first1 = A. | last2 = Vermani | first2 = S. | last3 = Shruti | first3 = S. | title = Choroid plexus carcinoma: report of two cases. | journal = Indian J Pathol Microbiol | volume = 52 | issue = 3 | pages = 405-7 | month = | year = | doi = 10.4103/0377-4929.55009 | PMID = 19679976 }}</ref>
*Poor prognosis - WHO grade III.<ref name=pmid20644273>{{Cite journal | last1 = Menon | first1 = G. | last2 = Nair | first2 = SN. | last3 = Baldawa | first3 = SS. | last4 = Rao | first4 = RB. | last5 = Krishnakumar | first5 = KP. | last6 = Gopalakrishnan | first6 = CV. | title = Choroid plexus tumors: an institutional series of 25 patients. | journal = Neurol India | volume = 58 | issue = 3 | pages = 429-35 | month = | year = | doi = 10.4103/0028-3886.66455 | PMID = 20644273 |URL = http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2010;volume=58;issue=3;spage=429;epage=435;aulast=Menon }}</ref>
*Classically posterior fossa.
*Intraventricular mass.

===Microscopic===
Features:<ref name=pmid19679976/>
*Choroid plexus epithelium with [[nuclear pleomorphism]] & high [[NC ratio]].
*Mitoses.
*Necrosis.
*+/-Brain invasion.

DDx:
*[[Choroid plexus papilloma]].
*Atypical plexus papilloma - has features intermediate between ''choroid plexus papilloma'' and ''choroid plexus carcinoma''.<ref name=pmid20644273/>
*[[Atypical teratoid/rhabdoid tumour]].

Images:
*[http://path.upmc.edu/cases/case198/micro.html Choroid plexus carcinoma - several images (upmc.edu)].

===IHC===
Features:<ref name=pmid20644273/>
*Cytokeratins +ve.
*EMA usu. -ve.
*GFAP -ve (~20% +ve).
*Ki-67 high.
**Useful to diff. from benign counterpart.
*INI1 +ve.

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==Medulloblastoma==
{{Main|Medulloblastoma}}
*Tumour of cerebellum - key feature.
*Morphologically identical supratentorial tumours are called [[primitive neuroectodermal tumour]] (PNET).

==Primitive neuroectodermal tumour==
*[[AKA]] ''primitive neuroepithelial tumour''. (???)

===General===
*Abbreviated ''PNET''.
*Should not be confused with ''peripheral primitive neuroectodermal tumour'' (abbreviated ''[[pPNET]]''<ref name=PST14feb11>PST. 14 February 2011.</ref>), [[AKA]] ''[[Ewing sarcoma]]''.

===Microscopic===
Features:
*[[Small round blue cell tumour]] - see ''[[medulloblastoma]]''.

DDx:
*[[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR).<ref name=pmid19563506>{{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>

Images:
*[http://path.upmc.edu/cases/case414.html Primitive neuroectodermal tumour - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case649.html GBM with PNET component - several images (upmc.edu)].

==Embryonal tumour with abundant neuropil and true rosettes==
*Abbreviated ''ETANTR''.
===General===
*Super rare.
*Reported only in children <4 years old.<ref name=pmid16551982/>

===Microscopic===
Features:<ref name=pmid20499240>{{Cite journal | last1 = Ferri Niguez | first1 = B. | last2 = Martínez-Lage | first2 = JF. | last3 = Almagro | first3 = MJ. | last4 = Fuster | first4 = JL. | last5 = Serrano | first5 = C. | last6 = Torroba | first6 = MA. | last7 = Sola | first7 = J. | title = Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update. | journal = Childs Nerv Syst | volume = 26 | issue = 8 | pages = 1003-8 | month = Aug | year = 2010 | doi = 10.1007/s00381-010-1179-x | PMID = 20499240 }}</ref>
*[[Small round blue cell tumour]].
*True rosettes = flower-like cluster of cells that surrounds a space.<ref name=pmid16551982>{{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>
*Fibrillary neuropil.
**Meshwork of fibers.

DDx:
*[[Primitive neuroectodermal tumour]].
*[[Medulloblastoma]]. (???)

Images:
*[http://path.upmc.edu/cases/case585.html ETANTR - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case666.html ETANTR - another case (upmc.edu)].

==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===
Features:
*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>

===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.

==Neurocytoma==
===General===
*Rare.

===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm]. Accessed on: 12 October 2011.</ref>
*[[Pineocytoma|Pineocytomatous]]/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Similar to Homer-Wright rosette.
*Perinuclear clearing.
*Well-defined cell borders.

DDx:
*[[Oligodendroglioma]] - do not have the characteristic rosettes.
*[[Ganglioglioma]].
*[[Ependymoma]].

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm Neurocytoma (ouhsc.edu)].
*[http://path.upmc.edu/cases/case383.html Neurocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case561.html Neurocytoma - cerebellar - several images (upmc.edu)].
===IHC===
*Synaptophysin +ve.
**Most glial tumour -ve.<ref>URL: [http://path.upmc.edu/cases/case383/dx.html http://path.upmc.edu/cases/case383/dx.html]. Accessed on: 15 January 2012.</ref>

==Central neurocytoma==
*Abbreviated ''CNC''.
===General===
*Rare - less than 1% of brain tumours.<ref name=pmid16163043>{{Cite journal | last1 = Chuang | first1 = MT. | last2 = Lin | first2 = WC. | last3 = Tsai | first3 = HY. | last4 = Liu | first4 = GC. | last5 = Hu | first5 = SW. | last6 = Chiang | first6 = IC. | title = 3-T proton magnetic resonance spectroscopy of central neurocytoma: 3 case reports and review of the literature. | journal = J Comput Assist Tomogr | volume = 29 | issue = 5 | pages = 683-8 | month = | year = | doi = | PMID = 16163043 }}</ref>
*Benign.
*First described in 1982.<ref name=pmid16163043/>

===Gross/radiology===
*Intraventricular.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm]. Accessed on: 12 January 2012.</ref>
**Characteristically attached to the ''septum pellucidum''.<ref name=pmid20692674>{{Cite journal | last1 = Kerkeni | first1 = A. | last2 = Ben Lakhdher | first2 = Z. | last3 = Rkhami | first3 = M. | last4 = Sebai | first4 = R. | last5 = Belguith | first5 = L. | last6 = Khaldi | first6 = M. | last7 = Ben Hamouda | first7 = M. | title = [Central neurocytoma: Study of 32 cases and review of the literature]. | journal = Neurochirurgie | volume = 56 | issue = 5 | pages = 408-14 | month = Oct | year = 2010 | doi = 10.1016/j.neuchi.2010.07.001 | PMID = 20692674 }}</ref>

===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm]. Accessed on: 27 May 2011.</ref>
*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{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>
*Islands of neuropil.
*Polygonal cells with a perinuclear halo.

DDx:
*[[Oligodendroglioma]].

DDx of perivascular pseudorosette:
*Ependymoma.
*[[Medulloblastoma]], PNET.
*[[Glioblastoma]]s.

====Images====
<gallery>
Image:Central_neurocytoma_-_intermed_mag.jpg | Central neurocytoma - intermed. mag. (WC)
Image:Central_neurocytoma_-_high_mag.jpg | Central neurocytoma - oligodendrogllioma-like area - high mag. (WC)
Image:Central_neurocytoma_-_2_-_high_mag.jpg | Central neurocytoma - pseudorosettes - high mag. (WC)
Image:Central_neurocytoma_-_2_-_very_high_mag.jpg | Central neurocytoma - pseudorossettes - very high mag. (WC)
</gallery>
[[www]]:
*[http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm Central neurocytoma - several images (ouhsc.edu)].
*[http://frontalcortex.com/?page=image&topic=1&qid=1203 Central neurocytoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case74/micro.html Central neurocytoma - crappy images (upmc.edu)].

===IHC===
*MIB1 - high may predict re-occurance.<ref name=pmid15015671>{{Cite journal | last1 = Schmidt | first1 = MH. | last2 = Gottfried | first2 = ON. | last3 = von Koch | first3 = CS. | last4 = Chang | first4 = SM. | last5 = McDermott | first5 = MW. | title = Central neurocytoma: a review. | journal = J Neurooncol | volume = 66 | issue = 3 | pages = 377-84 | month = Feb | year = 2004 | doi = | PMID = 15015671 }}</ref>

==Ganglioglioma==
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
===General===
*Rare.
*Usu. temporal lobe.
*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>

===Microscopic===
Features:
*Atypical neurons.
*Atypical glia.

Images:
*[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}}

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.

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==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[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]]

Neuropathology tumours

2014-11-15T15:42:29Z

Laura: /* Grading */

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 gland|pituitary/peri-pituitary lesions]]''.

==Brain tumours - overview==
===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>
# Metastatic brain tumours (barely edges out primary tumours)
#*[[Lung cancer|Lung]] (most common).
#*[[Invasive breast cancer|Breast]].
#*[[Melanoma]].
#*[[Renal cell carcinoma]] (RCC).
# [[Glioblastoma]] (previously known as ''glioblastoma multiforme'').
# [[Anaplastic astrocytoma]].
# [[Meningioma]].

===Children===
# Astrocytoma.
# [[Medulloblastoma]].
# [[Ependymoma]].

===Location (most common)===
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]].
*Spinal cord:
**[[Ependymoma]], glioblastoma.
**Filum terminale - [[myxopapillary ependymoma]], [[paraganglioma]].

====Filum terminale====
*Filum terminale = bottom end of the spinal cord - has a limited differential.

DDx:<ref>JLK. 31 May 2010.</ref>
*[[Meningioma]].
*[[Myxopapillary ependymoma]].
*[[Neurofibroma]].
*[[Schwannoma]].
*[[Paraganglioma]].

====Cerebellopontine angle====
*Abbreviated ''CP angle''.

DDx:<ref>R. Kiehl. 8 November 2010.</ref>
*[[Schwannoma]].
*[[Meningioma]].
*[[Dermoid cyst]]/epidermoid cyst.
*[[Ependymoma]].
*[[Choroid plexus papilloma]].

===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>

===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.

[[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.

===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
|nil
|[[Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg|thumb|center|150px|Reactive astrocytes. (WC)]]
|-
|[[Astrocytoma]] (grade II or worse)
|glial processes (esp. on smear), nuclear atypia (size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †
|often enhancing (suggests high grade), usu. supratentorial, usu. white matter
|usu. old, occ. young
|very common, esp. glioblastoma
|IDH-1+/-, GFAP+
| [[Image:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg | thumb| center| 150px|Astrocytoma. (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)]]
|-
|[[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)]]
|-
|[[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
|[[Image:Schwannoma_-_Antoni_A_and_B_-_very_high_mag.jpg|thumb|center|150px|Schwannoma. (WC)]]
|}
† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

==Brain metastasis==
{{Main|Brain metastasis}}

==Infiltrative astrocytomas==
{{Main|Astrocytoma}}

===Overview===
*Low-grade (diffuse) astrocytomas (Grade II).
*Anaplastic astrocytomas (Grade III).
*Glioblastoma (Grade IV).

Notes:
*Non-infiltrative gliomas:
**[[Pilocytic astrocytoma]] (WHO Grade I).
**[[Dysembryoplastic neuroepithelial tumour]] (DNT), (WHO Grade I).

===Microscopic===
Features:<ref name=pmid>{{cite journal |author=Rong Y, Durden DL, Van Meir EG, Brat DJ |title='Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis |journal=J. Neuropathol. Exp. Neurol. |volume=65 |issue=6 |pages=529–39 |year=2006 |month=June |pmid=16783163 |doi= |url=}}</ref><ref>[http://dictionary.reference.com/browse/palisading http://dictionary.reference.com/browse/palisading]</ref>
*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:
*[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)].

Notes:
*Glial vs. non-glial tumours:
**Glial: "blends into brain"/gradual transition to non-tumour brain.
**Non-glial: no glial processes.
*Rosenthal fibres within the tumour... make it into a [[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 defense barrier or fortification.

Images:
*Glioblastoma:
**[http://commons.wikimedia.org/wiki/File:Glioblastoma_%281%29.jpg Glioblastoma - pseudopalisading of tumour cells (WC)].
**[http://commons.wikimedia.org/wiki/File:Glioblastoma_-_high_mag.jpg Glioblastoma with fragment of near-normal white matter - high mag. (WC)].
*Anaplastic astrocytoma:
**[http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_very_high_mag_-_cropped.jpg Anaplastic astrocytoma - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_gfap_-_very_high_mag.jpg Anaplastic astrocytoma - GFAP - very high mag. (WC)].

=====Table of common gliomas - grading=====
Histomorphologic comparison of common gliomas:
{| class="wikitable"
|'''Entity''' || '''Rosenthal fibres / EGBs''' ||'''Nuclear atypia''' ||'''Mitoses''' || '''Necrosis or MVP''' || '''Infiltrative''' || '''Image'''
|-
|Pilocytic astrocytoma || yes || usu. no || usu. no || usu. no || no || [http://commons.wikimedia.org/wiki/File:Rosenthal_HE_40x.jpg]
|-
|Low-grade astrocytoma || no || yes || no || no || yes || image?
|-
|Anaplastic astrocytoma || no || yes || yes || no || yes || [http://commons.wikimedia.org/wiki/File:Anaplastic_astrocytoma_-_high_mag.jpg]
|-
|Glioblastoma || no || yes || yes || yes || yes || [http://commons.wikimedia.org/wiki/File:Glioblastoma_-_high_mag.jpg]
|}
Notes:
*''MVP'' = microvascular proliferation.
*''EGBs'' = eosinophilic granular bodies.

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

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

==Pilocytic astrocytoma==
{{Main|Pilocytic astrocytoma}}

==Pleomorphic xanthoastrocytoma==
*Abbreviated ''PXA''.
===General===
Features:
*Classically in the temporal lobe in children and young adults.
*Associated with seizures.
*Moderately aggressive (WHO Grade II).<ref name=pmid11465399>{{Cite journal | last1 = Fouladi | first1 = M. | last2 = Jenkins | first2 = J. | last3 = Burger | first3 = P. | last4 = Langston | first4 = J. | last5 = Merchant | first5 = T. | last6 = Heideman | first6 = R. | last7 = Thompson | first7 = S. | last8 = Sanford | first8 = A. | last9 = Kun | first9 = L. | title = Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection. | journal = Neuro Oncol | volume = 3 | issue = 3 | pages = 184-92 | month = Jul | year = 2001 | doi = | PMID = 11465399 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920613/pdf/11465399.pdf}}</ref>

===Gross===
*Temporal lobe - classic.
*Usually assoc. with the leptomeninges,<ref name=pmid11465399/> i.e. superficial.

===Microscopic===
Features:<ref name=Ref_PBoD8_1333>{{Ref PBoD8|1333}}</ref>
*Marked nuclear atypia.
*Eosinophilic granular bodies - very common.<ref name=pmid11465399/>
*Inflammation (chronic).

Notes:
*No mitoses.
*No [[necrosis]].

Images:
*[http://path.upmc.edu/cases/case499.html Pleomorphic xanthoastrocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case511.html Pleomorphic xanthoastrocytoma with anaplasia - another case - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case578.html Pleomorphic xanthoastrocytoma with anaplasia - case 3 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case579.html Cerebellar pleomorphic xanthoastrocytoma - case 4 - several image (upmc.edu)].

===Stains===
*[[Reticulin stain]] - intercellular, prominent.<ref name=pmid21479234>{{Cite journal | last1 = Dias-Santagata | first1 = D. | last2 = Lam | first2 = Q. | last3 = Vernovsky | first3 = K. | last4 = Vena | first4 = N. | last5 = Lennerz | first5 = JK. | last6 = Borger | first6 = DR. | last7 = Batchelor | first7 = TT. | last8 = Ligon | first8 = KL. | last9 = Iafrate | first9 = AJ. | title = BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. | journal = PLoS One | volume = 6 | issue = 3 | pages = e17948 | month = | year = 2011 | doi = 10.1371/journal.pone.0017948 | PMID = 21479234 }}</ref>

Image:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3066220/figure/pone-0017948-g001/ PXA - several images (nih.gov)].<ref name=pmid21479234/>

===IHC===
*GFAP +ve.
*CD68 +ve.

==Dysembryoplastic neuroepithelial tumour==
*Abbreviated ''DNT''.

===General===
*Common tumour cause of drug resistant epilepsy.<ref name=pmid15881751>{{Cite journal | last1 = Cataltepe | first1 = O. | last2 = Turanli | first2 = G. | last3 = Yalnizoglu | first3 = D. | last4 = Topçu | first4 = M. | last5 = Akalan | first5 = N. | title = Surgical management of temporal lobe tumor-related epilepsy in children. | journal = J Neurosurg | volume = 102 | issue = 3 Suppl | pages = 280-7 | month = Apr | year = 2005 | doi = 10.3171/ped.2005.102.3.0280 | PMID = 15881751 }}</ref>
*Paediatric population.

===Gross/radiology===
*Temporal lobe.
*Variable architecture:<ref name=pmid18071981/> cystic, solitary nodular, multinodular.

===Microscopic===
Features:<ref name=pmid18071981>{{Cite journal | last1 = O'Brien | first1 = DF. | last2 = Farrell | first2 = M. | last3 = Delanty | first3 = N. | last4 = Traunecker | first4 = H. | last5 = Perrin | first5 = R. | last6 = Smyth | first6 = MD. | last7 = Park | first7 = TS. | title = The Children's Cancer and Leukaemia Group guidelines for the diagnosis and management of dysembryoplastic neuroepithelial tumours. | journal = Br J Neurosurg | volume = 21 | issue = 6 | pages = 539-49 | month = Dec | year = 2007 | doi = 10.1080/02688690701594817 | PMID = 18071981 }}</ref>
*Cells similar to oligodendrocytes:
**Large central nuclei with indentations.
**Multiple small nucleoli (common).
**Clear cytoplasm.

DDx:
*[[Oligodendroglioma]].
**These have rounder, smaller nuclei with occasional nucleoli.<ref name=pmid18071981/>

Images:
*[http://commons.wikimedia.org/wiki/File:DNET_HE.jpg DNT (WC)].
*[http://path.upmc.edu/cases/case106.html DNT - several images (upmc.edu)].

==Subependymal giant cell astrocytoma==
*Abbreviated ''SEGA''.

===General===
*Associated with [[tuberous sclerosis complex]] (TSC).<ref name=pmid21455842>{{Cite journal | last1 = Grajkowska | first1 = W. | last2 = Kotulska | first2 = K. | last3 = Jurkiewicz | first3 = E. | last4 = Roszkowski | first4 = M. | last5 = Daszkiewicz | first5 = P. | last6 = Jóźwiak | first6 = S. | last7 = Matyja | first7 = E. | title = Subependymal giant cell astrocytomas with atypical histological features mimicking malignant gliomas. | journal = Folia Neuropathol | volume = 49 | issue = 1 | pages = 39-46 | month = | year = 2011 | doi = | PMID = 21455842 }}</ref>
*WHO Grade I.

===Gross/radiology===
*Well-demarcated.

===Microscopic===
Features:<ref name=upmc_case179/><ref name=pmid9595853>{{Cite journal | last1 = Taraszewska | first1 = A. | last2 = Kroh | first2 = H. | last3 = Majchrowski | first3 = A. | title = Subependymal giant cell astrocytoma: clinical, histologic and immunohistochemical characteristic of 3 cases. | journal = Folia Neuropathol | volume = 35 | issue = 3 | pages = 181-6 | month = | year = 1997 | doi = | PMID = 9595853 }}</ref>
*Giant cells with nuclear atypia ("bizarre cells").
**Vesicular nuclei.
**[[Nuclear pseudoinclusions]].<ref name=upmc179>URL: [http://path.upmc.edu/cases/case179/micro.html http://path.upmc.edu/cases/case179/micro.html]. Accessed on: 8 January 2012.</ref>
*Glassy eosinophilic cytoplasm.
*Abundant [[mast cell]]s.<ref name=upmc179>URL: [http://path.upmc.edu/cases/case179/micro.html http://path.upmc.edu/cases/case179/micro.html]. Accessed on: 8 January 2012.</ref>

Images:
*[http://path.upmc.edu/cases/case179/micro.html SEGA (upmc.edu)].<ref name=upmc_case179>URL: [http://path.upmc.edu/cases/case179.html http://path.upmc.edu/cases/case179.html]. Accessed on: 29 July 2011.</ref>
*[http://path.upmc.edu/cases/case500.html SEGA - another case (upmc.edu)].

===IHC===
Features:<ref name=pmid9595853/>
*GFAP +ve. (???)
*Vimentin +ve. (???)
*S100 +ve. (???)

==Pilomyxoid astrocytoma==
===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===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*Classically - hypothalamic location/suprasellar location; may involve the sella turcica.<ref name=pmid19766001>{{cite journal |author=Alimohamadi M, Bidabadi MS, Ayan Z, Ketabchi E, Amirjamshidi A |title=Pilomyxoid astrocytoma with involvement of the sella turcica in an adolescent |journal=J Clin Neurosci |volume=16 |issue=12 |pages=1648–9 |year=2009 |month=December |pmid=19766001 |doi=10.1016/j.jocn.2009.01.035 |url=}}</ref>
*Solid.
*Well-circumscribed.

===Microscopic===
Features:<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>
*Consists of small round/ovoid bland cells in a [[myxoid stroma]].
*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>
*Rosenthal fibres are absent - '''key negative'''.
*Monophasic (unlike classical pilocytic astrocytomas) - '''key negative'''.
*May rarely have eosinophilic granular bodies.

<gallery>
Image:Pilomyxoid Astrocytoma HE20x.jpg | Pilomyxoid astrocytoma. (WC/Marvin 101)
</gallery>

===Grading===
*''WHO Grade II'' by definition.<ref name=Ref_PSNP86>{{Ref PSNP|86}}</ref>

==Atypical teratoid/rhabdoid tumour==
:See also: ''[[Extrarenal malignant rhabdoid tumour]]''.
*Commonly abbreviated ''AT/RT''.
*May be written ''atypical teratoid rhabdoid tumour'', i.e. without the forward slash, or ''atypical teratoid-rhabdoid tumour'' (AT-RT).
{{Main|Atypical teratoid/rhabdoid tumour}}

==Oligodendroglioma==
{{Main|Oligodendroglioma}}

==Oligoastrocytoma==
===General===
*Mixed tumour.

===Microscopic===
Features:
*Astrocytoma-like and oligodendroglioma-like:
*#Oligodendroglioma-like cells = round nucleus, peri-nuclear clearing.
*#Astrocytoma-like cells = non-ovoid/elongated nucleus.

DDx:
*Anaplastic astrocytoma.
*Oligodendroglioma. (???)

===IHC===
*Oligodendroglioma-like cells: MAP-2 +ve (cytoplasm).
*Astrocytoma-like cells: GFAP +ve (cytoplasm, nuclear membrane).

Others:
*Ki-67 ~10%. (???)
*p53 - focally +ve. (???)
*IDH-1 -ve. (???)

==Meningioma==
{{Main|Meningioma}}
===General===
*Very common.
*May be part of a syndrome.

===Microscopic===
Features (memory device ''WCN''):
*Whorled appearance - '''key feature'''.
*Calcification, psammomatous.
*[[Nuclear pseudoinclusions]] - focal nuclear clearing with a sharp interface to unremarkable chromatin.

Grading: see ''[[meningioma]]''.

==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]].
**[[Traumatic neuroma]].
*Malignant:
**[[Malignant peripheral nerve sheath tumour]] (MPNST).

==Schwannoma==

{{Main|Schwannoma}}
===General===
*Tumour of tissue surrounding a nerve.
**Axons adjacent to the tumour are normal... but may be compressed.

===Microscopic===
Features:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Antoni A:
**Cellular.
**'Fibrillary, polar, elongated'.
*Antoni B:
**Pauci-cellular.
**Loose microcystic tissue.
*Verocay bodies - paucinuclear area surrounded by palisaded nuclei.
*In the GI tract: classically have a ''peripheral lymphoid cuff''.<ref name=pmid15728600>{{cite journal |author=Levy AD, Quiles AM, Miettinen M, Sobin LH |title=Gastrointestinal schwannomas: CT features with clinicopathologic correlation |journal=AJR Am J Roentgenol |volume=184 |issue=3 |pages=797–802 |year=2005 |month=March |pmid=15728600 |doi= |url=http://www.ajronline.org/cgi/content/full/184/3/797}}</ref>

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

Notes:
*Several subtypes exist.

==Neurofibroma==
{{Main|Peripheral nerve sheath tumours#Neurofibroma}}
===General===
*May be a part of [[neurofibromatosis]] 1.
*Composed of Schwann cells, axons, fibrous material.<ref name=pmid17893219/>

===Microscopic===
Features:
*Spindle cells lesion.
**See ''[[Neurofibroma]]'' article for details.

Image:
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(1).jpg Neurofibroma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(2).jpg Neurofibroma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Neurofibroma_(3).jpg Neurofibroma - high mag. (WC)].

==Ganglioneuroma==
:'''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>
===General===
*May be retroperitoneal.
*Occasionally found in the GI tract - may form [[Gastrointestinal_tract_polyps#Ganglioneuroma|colonic polyp]].
*Multiple ganglioneuromas may be due to [[multiple endocrine neoplasia IIb]].

Classification:
*In a grouping known as ''neuroblastic tumours'' 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).

===Gross===
*Solid.
*White.
*Firm.
*Well-circumscribed.
*May be nodular.

Images:
*[http://commons.wikimedia.org/wiki/File:Adrenal_ganglioneuroma_02.JPG Adrenal ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?case=84&n=1 Ganglioneuroma (webpathology.com)].

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

Images:
*[http://it.wikipedia.org/wiki/File:Ganglioneuroma_(1).jpg Ganglioneuroma (WC)].
*[http://www.webpathology.com/image.asp?n=4&Case=84 Ganglioneuroma (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=412&n=4 Ganglioneuroma (webpathology.com)].
*[http://en.wikipedia.org/wiki/File:Ganglion_high_mag.jpg Normal ganglion - high mag. (WC)] .

See: ''[[adrenal ganglioneuroma]]'', ''[[Gastrointestinal tract polyps#Ganglioneuroma|colonic ganglioneuroma]]''.

===IHC===
Features:<ref>{{Ref GLP|217}}</ref>
*Spindle cells: S-100 +ve.
*Ganglion cells: NSE, synaptophysin, NF.

==Ependymoma==
===General===
*Called the forgotten glial tumour.

Epidemiology:<ref name=Ref_PBoD8_1334>{{Ref PBoD8|1334}}</ref>
*Usual site:
**Adults: usu. spinal cord.
**Children: usu. posterior fossa.
*May be assoc. with [[neurofibromatosis]] 2.

Comes in two main flavours:
#Ependymoma (not otherwise specified).
#Myxopapillary ependymoma.
#*Classically at filum terminale.

Other flavours:<ref>URL: [http://emedicine.medscape.com/article/1744030-overview http://emedicine.medscape.com/article/1744030-overview]. Accessed on: 17 January 2012.</ref>
*Papillary ependymoma.
*Clear cell ependymoma.

===Microscopic===
====Classic ependymoma====
Features:
*Cells have a "tadpole-like" morphology.
**May also be described as ''ice cream cone-shaped''.<ref>[http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html]</ref>
*'''Rosettes''' = circular nuclear free zones/cells arranged in a pseudoglandular fashion; comes in two flavours in ependymoma:
**''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); more common than ependymal rosette... but less specific.
**''Ependymal rosette'' ([[AKA]] ''true ependymal rosette'') = rosette has an empty space at the centre - '''key feature'''.
*Nuclear features monotonous, i.e. "boring".<ref>MUN. 6 Oct 2009.</ref>
**There is little variation in size, shape and staining.

DDx (classic ependymoma):
*[[Subependymoma]].
*[[Glioblastoma]] (GBM).
**Invasive border = GBM; circumscribed border of lesion = ependymoma.

Images:
*www:
**[http://www.flickr.com/photos/ckrishnan/3862487821/in/photostream Ependymoma (flickr.com)].
**[http://www.ajnr.org/cgi/content-nw/full/27/3/488/F10 Ependymoma - ependymal rosettes (ajnr.org)].
**[http://path.upmc.edu/cases/case95/micro.html Anaplastic ependymoma - case 1 (upmc.edu)].
**[http://path.upmc.edu/cases/case324.html Anaplastic ependymoma - case 2 (upmc.edu)].
*WC:
**[http://commons.wikimedia.org/wiki/File:Ependymoma_intermed_mag.jpg Ependymoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Ependymoma_low_intermed_mag.jpg Ependymoma - low mag. (WC)].

====Myxopapillary ependymoma====
Features:
*Perivascular pseudorosettes:
**Myxoid material surround blood vessels.
***[[Myxoid]] material surrounded by tumour cells.

Images:
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma_-_high_mag.jpg Myxopapillary ependymoma - high mag. (WC)].
*[http://careers.bmj.com/article-images/cf0708.f2_default.gif Myxopapillary ependymoma (bmj.com)] - part of [http://careers.bmj.com/careers/advice/view-article.html?id=351 careers.bmj.com article on paediatric pathology].
*[http://commons.wikimedia.org/wiki/File:Myxopapillary_ependymoma.jpg Myxopapillary ependymoma - cytology (WC)].
*[http://path.upmc.edu/cases/case626.html Myxopapillary ependymoma - several images (upmc.edu)].

====Grading====
Easy:
*Subependymoma = WHO grade I.
*Myxopapillary ependymoma = WHO grade I.
Not-so-easy:
*Classic ependymoma = WHO grade II.
*Anaplastic ependymoma = WHO grade III.

Grade II vs. Grade III:
*Cellular density.
*Mitoses.
*Necrosis.
*Microvascular proliferation.

Notes:
*Many tumours fall between grade II and grade III. These are called "indeterminate" by many.

===IHC===
*Reticulin.
*GFAP.
*MIB1.

==Subependymoma==
{{Main|Subependymoma}}

==Choroid plexus papilloma==
{{Main|Choroid plexus papilloma}}

==Choroid plexus carcinoma==
===General===
*Usually pediatric population.
*Malignant counterpart of ''[[choroid plexus papilloma]]''.<ref name=pmid19679976>{{Cite journal | last1 = Singh | first1 = A. | last2 = Vermani | first2 = S. | last3 = Shruti | first3 = S. | title = Choroid plexus carcinoma: report of two cases. | journal = Indian J Pathol Microbiol | volume = 52 | issue = 3 | pages = 405-7 | month = | year = | doi = 10.4103/0377-4929.55009 | PMID = 19679976 }}</ref>
*Poor prognosis - WHO grade III.<ref name=pmid20644273>{{Cite journal | last1 = Menon | first1 = G. | last2 = Nair | first2 = SN. | last3 = Baldawa | first3 = SS. | last4 = Rao | first4 = RB. | last5 = Krishnakumar | first5 = KP. | last6 = Gopalakrishnan | first6 = CV. | title = Choroid plexus tumors: an institutional series of 25 patients. | journal = Neurol India | volume = 58 | issue = 3 | pages = 429-35 | month = | year = | doi = 10.4103/0028-3886.66455 | PMID = 20644273 |URL = http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2010;volume=58;issue=3;spage=429;epage=435;aulast=Menon }}</ref>
*Classically posterior fossa.
*Intraventricular mass.

===Microscopic===
Features:<ref name=pmid19679976/>
*Choroid plexus epithelium with [[nuclear pleomorphism]] & high [[NC ratio]].
*Mitoses.
*Necrosis.
*+/-Brain invasion.

DDx:
*[[Choroid plexus papilloma]].
*Atypical plexus papilloma - has features intermediate between ''choroid plexus papilloma'' and ''choroid plexus carcinoma''.<ref name=pmid20644273/>
*[[Atypical teratoid/rhabdoid tumour]].

Images:
*[http://path.upmc.edu/cases/case198/micro.html Choroid plexus carcinoma - several images (upmc.edu)].

===IHC===
Features:<ref name=pmid20644273/>
*Cytokeratins +ve.
*EMA usu. -ve.
*GFAP -ve (~20% +ve).
*Ki-67 high.
**Useful to diff. from benign counterpart.
*INI1 +ve.

==Chordoma==
{{Main|Chordoma}}

==Hemangioblastoma==
{{Main|Hemangioblastoma}}

==Medulloblastoma==
{{Main|Medulloblastoma}}
*Tumour of cerebellum - key feature.
*Morphologically identical supratentorial tumours are called [[primitive neuroectodermal tumour]] (PNET).

==Primitive neuroectodermal tumour==
*[[AKA]] ''primitive neuroepithelial tumour''. (???)

===General===
*Abbreviated ''PNET''.
*Should not be confused with ''peripheral primitive neuroectodermal tumour'' (abbreviated ''[[pPNET]]''<ref name=PST14feb11>PST. 14 February 2011.</ref>), [[AKA]] ''[[Ewing sarcoma]]''.

===Microscopic===
Features:
*[[Small round blue cell tumour]] - see ''[[medulloblastoma]]''.

DDx:
*[[Embryonal tumour with abundant neuropil and true rosettes]] (ETANTR).<ref name=pmid19563506>{{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>

Images:
*[http://path.upmc.edu/cases/case414.html Primitive neuroectodermal tumour - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case649.html GBM with PNET component - several images (upmc.edu)].

==Embryonal tumour with abundant neuropil and true rosettes==
*Abbreviated ''ETANTR''.
===General===
*Super rare.
*Reported only in children <4 years old.<ref name=pmid16551982/>

===Microscopic===
Features:<ref name=pmid20499240>{{Cite journal | last1 = Ferri Niguez | first1 = B. | last2 = Martínez-Lage | first2 = JF. | last3 = Almagro | first3 = MJ. | last4 = Fuster | first4 = JL. | last5 = Serrano | first5 = C. | last6 = Torroba | first6 = MA. | last7 = Sola | first7 = J. | title = Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update. | journal = Childs Nerv Syst | volume = 26 | issue = 8 | pages = 1003-8 | month = Aug | year = 2010 | doi = 10.1007/s00381-010-1179-x | PMID = 20499240 }}</ref>
*[[Small round blue cell tumour]].
*True rosettes = flower-like cluster of cells that surrounds a space.<ref name=pmid16551982>{{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>
*Fibrillary neuropil.
**Meshwork of fibers.

DDx:
*[[Primitive neuroectodermal tumour]].
*[[Medulloblastoma]]. (???)

Images:
*[http://path.upmc.edu/cases/case585.html ETANTR - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case666.html ETANTR - another case (upmc.edu)].

==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===
Features:
*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>

===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.

==Neurocytoma==
===General===
*Rare.

===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm]. Accessed on: 12 October 2011.</ref>
*[[Pineocytoma|Pineocytomatous]]/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Similar to Homer-Wright rosette.
*Perinuclear clearing.
*Well-defined cell borders.

DDx:
*[[Oligodendroglioma]] - do not have the characteristic rosettes.
*[[Ganglioglioma]].
*[[Ependymoma]].

Images:
*[http://moon.ouhsc.edu/kfung/jty1/Composites/FNA0IE14-Neurocytoma-Micro.htm Neurocytoma (ouhsc.edu)].
*[http://path.upmc.edu/cases/case383.html Neurocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case561.html Neurocytoma - cerebellar - several images (upmc.edu)].
===IHC===
*Synaptophysin +ve.
**Most glial tumour -ve.<ref>URL: [http://path.upmc.edu/cases/case383/dx.html http://path.upmc.edu/cases/case383/dx.html]. Accessed on: 15 January 2012.</ref>

==Central neurocytoma==
*Abbreviated ''CNC''.
===General===
*Rare - less than 1% of brain tumours.<ref name=pmid16163043>{{Cite journal | last1 = Chuang | first1 = MT. | last2 = Lin | first2 = WC. | last3 = Tsai | first3 = HY. | last4 = Liu | first4 = GC. | last5 = Hu | first5 = SW. | last6 = Chiang | first6 = IC. | title = 3-T proton magnetic resonance spectroscopy of central neurocytoma: 3 case reports and review of the literature. | journal = J Comput Assist Tomogr | volume = 29 | issue = 5 | pages = 683-8 | month = | year = | doi = | PMID = 16163043 }}</ref>
*Benign.
*First described in 1982.<ref name=pmid16163043/>

===Gross/radiology===
*Intraventricular.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm]. Accessed on: 12 January 2012.</ref>
**Characteristically attached to the ''septum pellucidum''.<ref name=pmid20692674>{{Cite journal | last1 = Kerkeni | first1 = A. | last2 = Ben Lakhdher | first2 = Z. | last3 = Rkhami | first3 = M. | last4 = Sebai | first4 = R. | last5 = Belguith | first5 = L. | last6 = Khaldi | first6 = M. | last7 = Ben Hamouda | first7 = M. | title = [Central neurocytoma: Study of 32 cases and review of the literature]. | journal = Neurochirurgie | volume = 56 | issue = 5 | pages = 408-14 | month = Oct | year = 2010 | doi = 10.1016/j.neuchi.2010.07.001 | PMID = 20692674 }}</ref>

===Microscopic===
Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm]. Accessed on: 27 May 2011.</ref>
*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{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>
*Islands of neuropil.
*Polygonal cells with a perinuclear halo.

DDx:
*[[Oligodendroglioma]].

DDx of perivascular pseudorosette:
*Ependymoma.
*[[Medulloblastoma]], PNET.
*[[Glioblastoma]]s.

====Images====
<gallery>
Image:Central_neurocytoma_-_intermed_mag.jpg | Central neurocytoma - intermed. mag. (WC)
Image:Central_neurocytoma_-_high_mag.jpg | Central neurocytoma - oligodendrogllioma-like area - high mag. (WC)
Image:Central_neurocytoma_-_2_-_high_mag.jpg | Central neurocytoma - pseudorosettes - high mag. (WC)
Image:Central_neurocytoma_-_2_-_very_high_mag.jpg | Central neurocytoma - pseudorossettes - very high mag. (WC)
</gallery>
[[www]]:
*[http://moon.ouhsc.edu/kfung/jty1/Com/Com307-1-Diss.htm Central neurocytoma - several images (ouhsc.edu)].
*[http://frontalcortex.com/?page=image&topic=1&qid=1203 Central neurocytoma (frontalcortex.com)].
*[http://path.upmc.edu/cases/case74/micro.html Central neurocytoma - crappy images (upmc.edu)].

===IHC===
*MIB1 - high may predict re-occurance.<ref name=pmid15015671>{{Cite journal | last1 = Schmidt | first1 = MH. | last2 = Gottfried | first2 = ON. | last3 = von Koch | first3 = CS. | last4 = Chang | first4 = SM. | last5 = McDermott | first5 = MW. | title = Central neurocytoma: a review. | journal = J Neurooncol | volume = 66 | issue = 3 | pages = 377-84 | month = Feb | year = 2004 | doi = | PMID = 15015671 }}</ref>

==Ganglioglioma==
:'''Not''' to be confused with ''[[ganglioneuroma]]''.
===General===
*Rare.
*Usu. temporal lobe.
*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>

===Microscopic===
Features:
*Atypical neurons.
*Atypical glia.

Images:
*[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}}

==Ganglioneuroblastoma==
{{Main|Neuroblastoma}}
===General===
*Uncommon.
*Part of the ''neuroblastic tumours'' group which includes:<ref name=pmid10421272>{{cite journal |author=Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B |title=Terminology and morphologic criteria of neuroblastic tumors: recommendations by the International Neuroblastoma Pathology Committee |journal=Cancer |volume=86 |issue=2 |pages=349–63 |year=1999 |month=July |pmid=10421272 |doi= |url=}}</ref>
**[[Ganglioneuroma]] (benign).
**Ganglioneuroblastoma (intermediate).
**[[Neuroblastoma]] (aggressive).

===Microscopic===
Features:
*Ganglion-like cells with a prominent nucleolus.
*Small undifferentiated cells with scant cytoplasm.

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==
{{reflist|2}}

==External links==
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
*[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]]

Neuropathology

2014-11-15T01:20:54Z

Laura: /* Acute disseminated encephalomyelitis */

'''Neuropathology''' is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

This article is an introduction to neuropathology. There are separate articles for [[brain tumours]], the [[pituitary gland]], the [[spine]], the [[eye]], [[muscle pathologies]], [[neurohistology]] and [[neuroanatomy]].

==Neuroanatomy==
{{Main|Neuroanatomy}}
This is a large topic. It covered in a separate article, that also covers grossing.

==Neuroradiology==
Enhancing vs. non-enhancing:
*If it is tumour... enhancing usu. high grade, non-enhancing usu. low grade.

===Ring enhancing lesions===
In [[HIV]]/AIDS patients... mass on CT if infection:
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>

Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
*Metstasis.
*Abscess.
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.

==Grossing==
This is covered in the ''[[neuroanatomy]]'' article.

===Gross pathology===
The gross usually useless for arriving at a definitive diagnosis.

Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
*Soft & tan colour = [[pituitary adenoma]].

==Normal histology==
{{main|Neurohistology}}
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.

==Histopathology==
===Neuronal changes===
====Anoxic neurons====
*[[AKA]] ''red neurons''.

Features:
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.

=====Images=====
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter2/images2/2-1HIE.jpg Anoxic neurons (neuropathologyweb.org)].
*[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>

====Central chromatolysis====
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*Central clearing.
**Nucleus and Nissl substance are pushed to cell periphery.

DDx:
*Axonal injury (traumatic).<ref name=pmid8909880>{{cite journal |author=Holland GR |title=Experimental trigeminal nerve injury |journal=Crit. Rev. Oral Biol. Med. |volume=7 |issue=3 |pages=237–58 |year=1996 |pmid=8909880 |doi= |url=}}</ref>
*Vitamin deficiency ([[pellagra]]).<ref name=pmid15577526>{{cite journal |author=Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF |title=Pellagra: a rare disease observed in a victim of mental and physical abuse |journal=Am J Forensic Med Pathol |volume=25 |issue=4 |pages=342–4 |year=2004 |month=December |pmid=15577526 |doi= |url=}}</ref>

=====Images=====
<gallery>
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
</gallery>
====Axonal swellings====
H&E:
*Eosinophilic (light pink) - ground glass-like appearance.
*Shape:
**Round if sectioned perpendicular to axis of axon.
***Bound by cell membrane.
***Large ~ typically 2-4x RBC diameter.
**Sausage-shaped if cut in along axis.

Images:
*[http://frontalcortex.com/gallery/pics/gliageek_VWMDx200.jpg Axonal swelling (frontalcortex.com)].<ref>URL: [http://frontalcortex.com/?page=oll&topic=24&qid=602 http://frontalcortex.com/?page=oll&topic=24&qid=602]. Accessed on: 3 November 2010.</ref>
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].

=====IHC=====
*APP.

Image:
*[http://vet.sagepub.com/content/37/6/677/F7.expansion.html Axonal swelling - APP (sagepub.com)].<ref>{{cite journal |author=Finnie JW, Manavis J, Blumbergs PC, Kuchel TR |title=Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin |journal=Vet. Pathol. |volume=37 |issue=6 |pages=677–80 |year=2000 |month=November |pmid=11105962 |doi= |url=http://vet.sagepub.com/content/37/6/677.full}}</ref>

===Glial changes===
====Astrocyte changes====
Reactive astrocytes:
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
*Well-defined cell border.
*Eosinophilic cytoplasm with many branching processes.
**Classically described as "funnel-shaped" in benign astrocytes.<ref>MUN. 15 November 2010.</ref>
*Peripheral nucleus.
<gallery>
Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg | Reactive astrocytes - high mag. (WC)
</gallery>

Alzheimer type II astrocyte:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[http://www.neuropathologyweb.org/chapter10/images10/10-AlzIIl.jpg Alzheimer type II astrocytes (neuropathologyweb.org)] .
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag.jpg| Alzheimer type II astrocytes. (WC)
</gallery>

Creutzfeldt cell:<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
*Finding associated with demyelinating disease.
*Image: [http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>

Gemistocytic astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 7 November 2010.</ref>
*Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:<ref name=Ref_MBNP173>{{Ref MBNP|173}}</ref>
*Cellular processes loaded with tau protein (as may be seen with tau [[IHC]] or Gallyas silver stain); Parisian-star-like appearance with special stain.
*+/-Multinucleated.
*A classic feature of ''[[progressive supranuclear palsy]]''.

====Other glial====
Bergmann gliosis (in the cerebellum):<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

<gallery>
Image:Bergmann_gliosis_-_intermed_mag.jpg | Bergmann gliosis - intermed. mag. (WC)
Image:Bergmann_gliosis_-_high_mag.jpg | Bergmann gliosis - high mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_intermed_mag.jpg | Bergmann gliosis due to compression by metastasis - intermed mag. (WC)
</gallery>
Image:
*[http://tpx.sagepub.com/content/35/5/676/F5.expansion.html Bergmann gliosis (sagepub.com)].

====Reactive change vs. malignancy====
Reactive changes vs. malignancy (mnemonic ''MIMICS''):<ref name=Ref_TPoSP254>{{Ref TPoSP|254}}</ref>
*'''MI'''crovesicular pattern.
*'''M'''itoses.
*'''I'''rregular spacing.
*'''C'''alcifications.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.

===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].

====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.

=====Gross=====
*Frontal and temporal lobe - most common for HSV encephalitis.<ref>{{Ref APBR|416 Q47}}</ref>

=====Microscopic=====
Features:<ref name=pmid20051019>{{Cite journal | last1 = Takei | first1 = H. | last2 = Wilfong | first2 = A. | last3 = Malphrus | first3 = A. | last4 = Yoshor | first4 = D. | last5 = Hunter | first5 = JV. | last6 = Armstrong | first6 = DL. | last7 = Bhattacharjee | first7 = MB. | title = Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature. | journal = Neuropathology | volume = 30 | issue = 4 | pages = 381-91 | month = Aug | year = 2010 | doi = 10.1111/j.1440-1789.2009.01079.x | PMID = 20051019 }}</ref>
*Perivascular inflammation.
*Microglia.
*+/-Neuronophagia.
**Phagocytosis of neurons.<ref>URL: [http://medical-dictionary.thefreedictionary.com/neuronophagia http://medical-dictionary.thefreedictionary.com/neuronophagia]. Accessed on: 11 April 2012.</ref>
*+/-Viral cytopathic changes.
*+/-Perineuronal inflammation.

Notes:
*Hemorrhage<ref name=pmid18246335>{{Cite journal | last1 = Vossough | first1 = A. | last2 = Zimmerman | first2 = RA. | last3 = Bilaniuk | first3 = LT. | last4 = Schwartz | first4 = EM. | title = Imaging findings of neonatal herpes simplex virus type 2 encephalitis. | journal = Neuroradiology | volume = 50 | issue = 4 | pages = 355-66 | month = Apr | year = 2008 | doi = 10.1007/s00234-007-0349-3 | PMID = 18246335 }}</ref> and necrosis - characteristic of HSV encephalitis.

Image:
*[http://neuropathology-web.org/chapter5/images5/5-21l.jpg HSV encephalitis (neuropathology-web.org)].<ref>URL: [http://neuropathology-web.org/chapter5/chapter5dViruses.html http://neuropathology-web.org/chapter5/chapter5dViruses.html]. Accessed on: 27 January 2012.</ref>

=====IHC=====
IHC stains for:
*Viral etiologies, e.g. [[HSV]], [[CMV]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.

===Architecture===
====Rosettes====
*Rosette = circular/flower-like arrangement of cells.<ref name=pmid16551982>{{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>

*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{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>
**[[Ependymoma]].
**[[Medulloblastoma]], PNET.
**[[Central neurocytoma]].
**[[Glioblastoma]]s.

*Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Medulloblastoma.
***Image: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-TU-01-17.gif Medulloblastoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17 http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17]. Accessed on: 3 December 2010.</ref>
**PNET (can be thought of as a supratentorial medulloblastoma) .

*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**Pineoblastomas.
**Medulloepitheliomas.

*True ependymal rosette = surrounds a space.<ref name=pmid16551982/>
**[[Ependymoma]].

*Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Similar to Homer-Wright rosette.
**[[Pineocytoma]].
**[[Neurocytoma]].

====Other====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Well-seen on trichrome stains.
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
*Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
**Pseudopalisading of tumour cells (around necrotic regions) is seen in [[glioblastoma]].

Note:
*Good set of articles: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist Neuropathology for radiologists (ncbi.nlm.nih.gov)].

===Inclusion bodies===
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**[[Rabies]].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>

*Lewy bodies.
**Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.<ref name=pmid15235805>{{cite journal |author=Marui W, Iseki E, Kato M, Akatsu H, Kosaka K |title=Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease |journal=Acta Neuropathol. |volume=108 |issue=2 |pages=121–8 |year=2004 |month=August |pmid=15235805 |doi=10.1007/s00401-004-0869-4 |url=}}</ref>
<gallery>
Image:Lewy_Koerperchen.JPG | Lewy body. (WC)
</gallery>
====Table of inclusions====
{| class="wikitable sortable"
! Feature
! Appearance
! Associated disease
! Comment
! Image
|-
| Grumous bodies [[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1 AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on location in brain; +ve for alpha-synuclein, alpha-B crystallin, ubiquitin
| [[Image:Lewy_Koerperchen.JPG |thumb|center|150px|]], [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| Lafora body
| round
| myoclonic [[epilepsy]]
| look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands
| ?Image
|-
| Lipofuscin
| yellow & granular
| aging
| olive, dendate
| ?Image
|-
| Negri body
| small eosinophic bodies
| rabies
| found in hippocampal neurons and Purkinje cells
| [[Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg|thumb|center|150px|]]
|-
| Hirano body
| concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron
| Alzheimer disease, Pick disease<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| actin crystals, may look like capillaries; location: CA1 of hippocampus
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adhirano.jpg]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>
|-
| Neurofibrillary tangles
| flame-shaped cytoplasmic thingy ~30 micrometers
| aging, Alzheimer's disease
| seen with silver stain
| [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg Schematic]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Granulovacuolar degeneration
| cytoplasmic vacuoles 4-5 micrometers
| ageing, [[Alzheimer's disease]], Pick's disease
| main found in Ammon horn<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adgvd.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Pick bodies
| round, homogenous, intracytoplasmic, ~10 micrometers
| [[Pick's disease]]
| pyramidal neurons, dentate granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
| [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?action=view&current=Picks60x.jpg&mediafilter=images]
|-
| Bunina body
| size of Nissl granules, eosinophilic
| [[amyotrophic lateral sclerosis]] (ALS)
| EM: membrane-bound bodies; ubiquitin +ve
| [http://pathol.umin.ac.jp/gakubu/exam/2006jpg/19.jpg]
|-

|}

Image collection: [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?mediafilter=images Inclusion bodies (photobucket.com)].

==Immunohistochemistry==
{{Main|Immunohistochemistry}}
===General===
*S-100.
**Sensitive... but non-specific, e.g. also stains [[melanoma]].

===Glial===
*GFAP (glial fibrillary acidic protein) - should stain perikaryon.

====Glial tumours====
Standard work-up:
*GFAP.
*p53.
*Ki-67.

===Neuronal===
*Synaptophysin.
*Chromogranin.

===Carcinoma vs. glial tumours===
*AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.<ref name=Ref_PSNP_12>{{Ref PSNP|12}}</ref>

===Others===
*APP (amyloid precursor protein) - detects axonal swellings.
*NF (neurofilament) - detects axonal swellings.

=Brain tumours=
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology. The most common brain tumour is a metastasis. The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.

=Non-tumour=
==Cerebral hemorrhage==
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds

Includes discussion of:
*[[Epidural hematoma]].
*[[Subdural hematoma]].
*[[Subarachnoid hematoma]].
*[[Intracerebral hematoma]]s.

==Duret hematoma==
*[[AKA]] Duret hemorrhage.
===General===
*Bleed in the upper brainstem (midbrain and pons).
**Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, [[intracranial hemorrhage]]).<ref name=pmid11819006>{{Cite journal | last1 = Parizel | first1 = PM. | last2 = Makkat | first2 = S. | last3 = Jorens | first3 = PG. | last4 = Ozsarlak | first4 = O. | last5 = Cras | first5 = P. | last6 = Van Goethem | first6 = JW. | last7 = van den Hauwe | first7 = L. | last8 = Verlooy | first8 = J. | last9 = De Schepper | first9 = AM. | title = Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage). | journal = Intensive Care Med | volume = 28 | issue = 1 | pages = 85-8 | month = Jan | year = 2002 | doi = 10.1007/s00134-001-1160-y | PMID = 11819006 }}</ref>
*Often fatal.<ref name=pmid11098635>{{Cite journal | last1 = Fujimoto | first1 = Y. | last2 = Aguiar | first2 = PH. | last3 = Freitas | first3 = AB. | last4 = de Andrade | first4 = AF. | last5 = Marino Júnior | first5 = R. | title = Recovery from Duret hemorrhage: a rare complication after craniotomy--case report. | journal = Neurol Med Chir (Tokyo) | volume = 40 | issue = 10 | pages = 508-10 | month = Oct | year = 2000 | doi = | PMID = 11098635 }}</ref>
===Gross===
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>

Image:
*[http://library.med.utah.edu/WebPath/jpeg5/CNS037.jpg Duret hemorrhage (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 4 December 2011.</ref>

===Microscopic===
Features:
*RBC extravasation.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.

==Alcohol & CNS==
===Clinical===
*Wernicke's encephalopathy
**Mnemonic ''WACO'':
***Wernicke's.
***Ataxia.
***Confusion, confabulation -- Korsakoff.
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.

===Pathology===
Features:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
*Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex<ref>URL: [http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939 http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939]. Accessed on: 22 September 2010.</ref> usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>
*Central pontine myelinolysis (CPM).<ref name=pmid21085565>{{cite journal |author=Campbell MC |title=Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report |journal=Prim Care Companion J Clin Psychiatry |volume=12 |issue=4 |pages= |year=2010 |pmid=21085565 |pmc=2983455 |doi=10.4088/PCC.09l00936ecr |url=}}</ref>
**Just what it sound like - myelin loss in the central pons.
**Classically associated with rapid correction of hyponatremia.<ref>{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref>
*Mammillary body shrinkage.<ref name=pmid8947329>{{cite journal |author=Shear PK, Sullivan EV, Lane B, Pfefferbaum A |title=Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia |journal=Alcohol. Clin. Exp. Res. |volume=20 |issue=8 |pages=1489-95 |year=1996 |month=November |pmid=8947329 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489}}</ref>
*Anterior cerebellar vermis atrophy; weak finding - as also age-related.<ref name=pmid3478969>{{cite journal |author=Torvik A |title=Brain lesions in alcoholics: neuropathological observations |journal=Acta Med. Scand. Suppl. |volume=717 |issue= |pages=47–54 |year=1987 |pmid=3478969 |doi= |url=}}</ref>
**Vermis atrophy is also seen in schizophrenia.<ref name=pmid1938163>{{cite journal |author=Sandyk R, Kay SR, Merriam AE |title=Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia |journal=Int. J. Neurosci. |volume=57 |issue=3-4 |pages=205–12 |year=1991 |month=April |pmid=1938163 |doi= |url=}}</ref>

====Marchiafava-Bignami Disease====
*Rare.
*Demyelination of the corpus callosum.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>

====Wernicke's encephalopathy====
General:
*Due to thiamine deficiency.
**Malnourishment often accompanies [[alcoholism]].

Features:<ref name=pmid3929155>{{Cite journal | last1 = Torvik | first1 = A. | title = Two types of brain lesions in Wernicke's encephalopathy. | journal = Neuropathol Appl Neurobiol | volume = 11 | issue = 3 | pages = 179-90 | month = | year = | doi = | PMID = 3929155 }}</ref>
*Neurons of mammillary bodies preserved - '''key'''.
*Loss of myelin.
*Hemorrhage.
*Edema.
*Reactive blood vessels.

Note:
*The thalamus and inferior olives show neuronal loss.<ref name=pmid3929155/>

====Common non-specific findings====
*[[Intracranial haemorrhage]] - due to trauma.

==Meningitis==
===General===
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.

CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
|-
| Bacterial, acute
| low
| high
| neutrophils
|-
| Viral
| normal
| slight elevation
| lymphocytes
|}

====Etiology====
*Infectious.
**Bacterial.
**Viral.
**Parasitic
*Autoimmune.
*Toxic.
*Aseptic - see ''[[Mollaret's meningitis]]''.

Bacterial meningitis - most probably cause by age:<ref>{{Ref PCPBoD8|666-7}}</ref>
{| class="wikitable sortable"
! Age
! Organism
|-
| Neonate
| ''Escherichia coli'', Group B Streptococcus
|-
| Infants, children
| ''Streptococcus pneumoniae''
|-
| Adolescents, young adults
| ''Neisseria meningitidis''
|-
| Elderly
| ''Streptococcus pneumoniae'', ''Listeria monocytogenes''
|}

===Gross===
Features:
*+/-Clouded appearance of the meninges.
*+/-Pus.
*+/-Petechiae.
*+/-Cerebral edema.

====Image====
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
</gallery>

===Microscopic===
Features:
*Inflammation of the meninges:
**+/-[[Neutrophil]]s.
**+/-Lymphocytes.
**+/-[[Plasma cell]]s.
*+/-Microorganisms (infectious meningitis):
**Bacteria.
**[[Fungi]], e.g. [[aspergillosis]] (may be intravascular).

Main DDx:
*[[Lymphoma]].

====Image====
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC)
</gallery>

==Cerebral abscess==
===General===
*May mimic malignancy clinically.

===Microscopic===
Features:
*Sheets of neutrophils surrounded by fibrosing brain.
**Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Images:
*[http://pathology.class.kmu.edu.tw/ch01/4-1.jpg Cerebral abscess - very low mag. (kmu.edu.tw)].<ref>URL: [http://pathology.class.kmu.edu.tw/ch01/Slide4.htm http://pathology.class.kmu.edu.tw/ch01/Slide4.htm]. Accessed on: 1 January 2012.</ref>
*[http://pathology.class.kmu.edu.tw/ch01/4-5.jpg Cerebral abscess - low mag. (kmu.edu.tw)].

==Neurodegenerative diseases==
{{Main|Neurodegenerative diseases}}
This is a hueueuge topic. It is covered in its own article and includes a general discussion of dementia.

==Epilepsy==
{{Main|Epilepsy}}

==Cerebrovascular accident==
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.

===General===
*Very common.
*Leading cause of morbidity and mortality.

Clinical classification:
# Hemorrhagic stroke.
# Ischemic stroke.

===Gross===
*Soft/mushy brain.
*Older [[infarct]]s.
**A "roof" is present - a thin submeningeal layer is preserved by the CSF.<ref>MUN. 16 December 2009.</ref>
***"Roof" is absent in trauma.
**Cavity - in older infarcts.
***''[[Multiple sclerosis]]'' does not cavitate.
*Laminar necrosis = (thin) chalky line replaces grey mater.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q03-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q03-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[AKA]] ''pseudolaminar necrosis'' - as it is not localized to a specific layer of the cortex.<ref>MUN. 26 November 2010.</ref>

DDx:
*[[Cerebral contusion]].

===Microscopic===
Features:
*Ischemic neurons.
*+/-Neuronal loss.
*+/-Microglial.
*+/-[[Thrombosis]].
*+/-[[Atherosclerosis]].

==Hypoxic-ischemic encephalopathy==
*Abbreviated ''HIE''.
===General===
*Often due to ''cardiac arrest'', i.e. global ischemia.
*Triple watershed area = parieto-occipital cortex, extrastriate occipital cortex.

Note:
*''Hypoxia'' = blood decreased oxygen carrying capacity,<ref name=Ref_PCPBoD8_10>{{Ref PCPBoD8|10}}</ref> e.g. [[anemia]].
*''Ischemia'' = decreased blood flow.<ref name=Ref_PCPBoD8_10>{{Ref PCPBoD8|10}}</ref>
*Either ''or'' both = less oxygen delivery to tissue.
===Microscopic===
Features:
*Hippocampal ischemic changes (in adults):
**Loss of neurons in CA1, CA3 and CA4 +/- "cavitation".
***Neuronal loss: No blue (nuclei) where there should be some.
***Cavitation: bubbles/clear spaces where there should be none.
**CA2 neurons preserved/resistant.
*Purkinje cell loss in the cerebellum and [[Bergmann gliosis]].
*"Anoxic neurons".<ref>URL: [http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html]. Accessed on: 12 July 2010.</ref>
**Shrunken neurons with intensely eosinophilic cytoplasm and pyknotic (shrunken) nuclei.
*Pseudolaminar necrosis - (uncontrolled) cell death in the cerebral cortex in a band-like pattern,<ref>Hypoxic and Ischemic Encephalopathy. neuropathology.neoucom.edu. Accessed on: 29 December 2010.</ref> with a relative preservation of cells immediately adjacent to the meninges.

Notes:
*Neurons of ''subiculum'' in adults - usu. normal (as they are resistant to ischemic changes).
====Images====
*Anoxic neurons:
**[http://www.neuropathologyweb.org/chapter2/images2/2-1HIE.jpg Anoxic neurons (neuropathologyweb.org)].
**[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons. (WC)
</gallery>
*Hippocampal ischemic changes:
**[http://www.neuropathologyweb.org/chapter2/images2/2-hippoHIE.jpg Hippocampus in HIE (neuropathologyweb.org)].<ref>URL: [http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html]. Accessed on: 14 January 2011.</ref>
*Pseudolaminar necrosis:
<gallery>
Image:Cortical_pseudolaminar_necrosis_-_lfb_-_very_low_mag.jpg | Pseudolaminar necrosis - very low mag. (WC)
Image:Cortical_pseudolaminar_necrosis_-_lfb_-_intermed_mag.jpg | Pseudolaminar necrosis - intermed. mag. (WC)
</gallery>

==Multiple sclerosis==
*Abbreviated ''MS''.
===General===
*A bread 'n butter disease of neurology in Canada.

Clinical:
*CSF: oligoclonal bands of immunoglobulin.<ref>{{Ref PBoD8|1311}}</ref>

Classification of MS lesions:
*Early active.
*Inactive.
*Early remyelinating.
*Late remyelinating.

===Radiologic/Gross===
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*White matter lesions.
**Cerebrum (classically): periventricular distribution.
**Optic nerves (optic neuritis) - classic presentation.

===Microscopic===
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*Perivascular inflammation.
**Esp. lymphocytes.
*Demyelination.
**Subcortical myelinated fibers are often spared.

Chronic lesions - specific features:<ref>{{Ref APBR|425 Q43}}</ref>
#Macrophages.
#Astrocyte enlargement.

DDx:
*[[ADEM]].
*[[Neuromyelitis optica]].
*[[Lymphoma]].
*[[Diffuse astrocytoma]].

Images:
*[http://path.upmc.edu/cases/case79.html Multiple sclerosis masquerading as a diffuse astrocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case636.html Tumefactive multiple sclerosis - several images (upmc.edu)].

===IHC===
*HAM-56 - macrophages.
*CD8 - lymphocytes.

==Cerebral amyloid angiopathy==
===General===
*Abbreviated ''CAA''.
*Disease of the old.
*Strong association with ''[[lobar haemorrhage]]'' (bleeds of the cerebellar cortex and cerebral cortex).<ref name=pmid16982664>{{cite journal |author=Thanvi B, Robinson T |title=Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people |journal=Age Ageing |volume=35 |issue=6 |pages=565–71 |year=2006 |month=November |pmid=16982664 |doi=10.1093/ageing/afl108 |url=}}</ref>

Etiology:
*[[Amyloid]] deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

===Gross===
*Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.<ref name=pmid17297004>{{Cite journal | last1 = Haacke | first1 = EM. | last2 = DelProposto | first2 = ZS. | last3 = Chaturvedi | first3 = S. | last4 = Sehgal | first4 = V. | last5 = Tenzer | first5 = M. | last6 = Neelavalli | first6 = J. | last7 = Kido | first7 = D. | title = Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. | journal = AJNR Am J Neuroradiol | volume = 28 | issue = 2 | pages = 316-7 | month = Feb | year = 2007 | doi = | PMID = 17297004 | URL = http://www.ajnr.org/content/28/2/316.long }}</ref>

===Microscopic===
Features:
*Amorphous, acellular eosinophilic material within walls of small arteries.
**This is a high power diagnosis with congo red staining.

Notes:
*Amyloidosis is seen in all individuals with [[Alzheimer's disease]]; the amount of amyloid is what differs -- in CAA it is lots and lots.
*The white matter is typically spared by CAA.<ref name=pmid19225408>{{Cite journal | last1 = Schröder | first1 = R. | last2 = Deckert | first2 = M. | last3 = Linke | first3 = RP. | title = Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 3 | pages = 286-99 | month = Mar | year = 2009 | doi = 10.1097/NEN.0b013e31819a87f9 | PMID = 19225408 }}
</ref>

====Images====
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
===Stains===
*[[Congo red]].

===IHC===
*Abeta-amyloid (AKA beta-amyloid).

==Central pontine myelinolysis==
*Abbreviated ''CPM''.
*[[AKA]] ''pontine myelinolysis''.
===General===
*Classically in the pons, ergo "pontine" is in the name.
*Classically midline, ergo "central" is in the name.
**May occur elsewhere -- known as ''extrapontine myelinolysis''.

Etiology:
*Rapid correction of hyponatremia.<ref name=pmid22080394>{{Cite journal | last1 = Chang | first1 = Y. | last2 = An | first2 = DH. | last3 = Xing | first3 = Y. | last4 = Qi | first4 = X. | title = Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. | journal = Neurol Sci | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1007/s10072-011-0838-3 | PMID = 22080394 }}</ref>
*Tacrolimus post-liver transplant.<ref name=pmid21959523>{{Cite journal | last1 = Fukazawa | first1 = K. | last2 = Nishida | first2 = S. | last3 = Aguina | first3 = L. | last4 = Pretto | first4 = E. | title = Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation. | journal = Ann Transplant | volume = 16 | issue = 3 | pages = 139-42 | month = Sep | year = 2011 | doi = | PMID = 21959523 }}</ref>
*Associated with [[alcoholism]] and malnourishment.

Clinical:<ref>{{Cite journal | last1 = Lai | first1 = CC. | last2 = Tan | first2 = CK. | last3 = Lin | first3 = SH. | last4 = Chen | first4 = HW. | title = Central pontine myelinolysis. | journal = CMAJ | volume = 183 | issue = 9 | pages = E605 | month = Jun | year = 2011 | doi = 10.1503/cmaj.090186 | PMID = 21543311 | PMC = 3114939 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114939/?tool=pubmed }}</ref>
*Decreased level of consciousness - most common.
*Quadriplegia.
*Poor prognosis.

===Microscopic===
Features:<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*Myelin loss.
*No inflammation.
*Relative preservation of neurons.

Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].

==Vascular malformations==
{{Main|Vascular malformations}}
Types:<ref name=pmid17076525>{{cite journal |author=Prayson RA, Kleinschmidt-DeMasters BK |title=An algorithmic approach to the brain biopsy--part II |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1639–48 |year=2006 |month=November |pmid=17076525 |doi= |url=}}</ref>
#Arteriovenous malformation.
#*Most important clinically - highest risk of bleeding.
#Varix.
#*One large (dilated) vein.
#Venous angioma.
#*Many small veins.
#Cavernous malformation.
#*Vessels are back-to-back (no intervening parenchyma).

Also see: ''[[Sturge-Weber syndrome]]''.

=Cysts=
===General===
*All are "benign", but some may be fatal due to spatial constraints.

===List of cysts===
*[[Colloid cyst]].
**Columnar epithelium.
*Arachnoid cyst - considered precursor of [[meningioma]].
**[[Psammoma bodies]].
**Clumps of cells.
**Whorled pattern.
*[[Dermoid cyst]].
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid cyst.
*Choroid plexus cyst.
*Neuroenteric cyst.
**Foregut cyst with connection to dura.<ref>URL: [http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm]. Accessed on: 19 December 2011.</ref>
***Gastrointestinal tract epithelium.
***Usually seen with vertebral anomalies.
*Epithelial cyst.
*Others.

==Colloid cyst==
===General===
Classic presentation:<ref name=pmid15228889>{{Cite journal | last1 = Spears | first1 = RC. | title = Colloid cyst headache. | journal = Curr Pain Headache Rep | volume = 8 | issue = 4 | pages = 297-300 | month = Aug | year = 2004 | doi = | PMID = 15228889 }}</ref>
*Headache - may be relieved by lying down.
*Can cause [[sudden natural death]].<ref name=pmid14716130>{{Cite journal | last1 = Kava | first1 = MP. | last2 = Tullu | first2 = MS. | last3 = Deshmukh | first3 = CT. | last4 = Shenoy | first4 = A. | title = Colloid cyst of the third ventricle: a cause of sudden death in a child. | journal = Indian J Cancer | volume = 40 | issue = 1 | pages = 31-3 | month = | year = | doi = | PMID = 14716130 }}</ref>

===Gross===
*Fluid filled cyst - classically in the third ventricle.

Image:
*[http://www.ajnr.org/content/21/8/1470/F3.expansion.html Colloid cyst of third ventricle (ajnr.org)].<ref name=pmid11003281/>

===Microscopic===
Features:<ref name=pmid11003281>{{Cite journal | last1 = Armao | first1 = D. | last2 = Castillo | first2 = M. | last3 = Chen | first3 = H. | last4 = Kwock | first4 = L. | title = Colloid cyst of the third ventricle: imaging-pathologic correlation. | journal = AJNR Am J Neuroradiol | volume = 21 | issue = 8 | pages = 1470-7 | month = Sep | year = 2000 | doi = | PMID = 11003281 }}</ref>
*Simple epithelium with ciliated cells and goblet cells.

====Images====
<gallery>
Image:Colloid_Cyst_HE_40x.jpg | Colloid cyst. (WC)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F4.expansion.html Colloid cyst (ajnr.org)].<ref name=pmid11003281/>

=Paediatric pathology=
==Kernicterus==
===General===
*Due to hyperbilirubinemia.<ref name=pmid7063283>{{Cite journal | last1 = Turkel | first1 = SB. | last2 = Miller | first2 = CA. | last3 = Guttenberg | first3 = ME. | last4 = Moynes | first4 = DR. | last5 = Godgman | first5 = JE. | title = A clinical pathologic reappraisal of kernicterus. | journal = Pediatrics | volume = 69 | issue = 3 | pages = 267-72 | month = Mar | year = 1982 | doi = | PMID = 7063283 }}</ref>

===Gross===
*Yellow staining:<ref name=npw>URL: [http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html]. Accessed on: 30 May 2012.</ref>
**Basal ganglia.<ref name=pmid10920171>{{Cite journal | last1 = Hansen | first1 = TW. | last2 = Hervieux | first2 = JF. | last3 = Orth | first3 = J. | last4 = Schmorl | first4 = CG. | last5 = Baumes | first5 = JB. | title = Pioneers in the scientific study of neonatal jaundice and kernicterus. | journal = Pediatrics | volume = 106 | issue = 2 | pages = E15 | month = Aug | year = 2000 | doi = | PMID = 10920171 }}</ref>
**Hippocampus.<ref name=pmid15091133>{{Cite journal | last1 = Paksoy | first1 = Y. | last2 = Koç | first2 = H. | last3 = Genç | first3 = BO. | title = Bilateral mesial temporal sclerosis and kernicterus. | journal = J Comput Assist Tomogr | volume = 28 | issue = 2 | pages = 269-72 | month = | year = | doi = | PMID = 15091133 }}</ref>
**Subthalamic nucleus.

Note:
*May not be specific.<ref name=pmid7063283/>

Image:
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].

===Microscopic===
Features - similar to [[HIE]]:<ref name=npw/>
*+/-Red neurons.
*+/-Gliosis.

==Joubert syndrome==
*Malformation of the cerebellar vermis.<ref name=ninds_joubert>[http://www.ninds.nih.gov/disorders/joubert/joubert.htm http://www.ninds.nih.gov/disorders/joubert/joubert.htm]</ref>

===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>

=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
===General===
*Thought to be autoimmune; often associated with/preceded by viral illness.<ref name=pmid17438235>{{cite journal |author=Tenembaum S, Chitnis T, Ness J, Hahn JS |title=Acute disseminated encephalomyelitis |journal=Neurology |volume=68 |issue=16 Suppl 2 |pages=S23–36 |year=2007 |month=April |pmid=17438235 |doi=10.1212/01.wnl.0000259404.51352.7f |url=}}</ref>
*May mimic [[multiple sclerosis]].

Treatment:
*Steroids.
*Plasmapheresis.

Diagnosis:
*Need to r/o infection (with lumbar puncture).
*No old plaques on imaging (MRI).

An acute form exists known as ''acute hemorrhagic leukoencephalitis''<ref>URL: [http://path.upmc.edu/cases/case102/dx.html http://path.upmc.edu/cases/case102/dx.html]. Accessed on: 2 January 2012.</ref> (AKA ''acute necrotizing hemorrhagic encephalomyelitis'').

===Microscopic===
Features:<ref>{{Ref PBoD8|1312}}</ref>
*Myelin loss with sparing of axons.
*Inflammation:
**Early: [[neutrophil]]s.
**Late: mononuclear cells (lymphocytes, plasma cells).
*Lipid-laden macrophages.

DDx:
*[[Multiple sclerosis]].
**Tend to be larger, more lymphocytes,<ref>{{Ref APBR|423}}</ref> age of the lesions differ.
*Acute necrotizing hemorrhagic encephalomyelitis (ANHE) - if one considers this a separate entity.
*Acute necrotizing encephalopathy.<ref>URL: [http://path.upmc.edu/cases/case619/dx.html http://path.upmc.edu/cases/case619/dx.html]. Accessed on: 26 January 2012.</ref>

==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>

Diagnosis:
*NMO-IgG.

Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).

===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.

Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].

===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.

==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
===General===
*Autosomal dominant disorder - as the name implies.<ref name=pmid19174371>{{Cite journal | last1 = Tikka | first1 = S. | last2 = Mykkänen | first2 = K. | last3 = Ruchoux | first3 = MM. | last4 = Bergholm | first4 = R. | last5 = Junna | first5 = M. | last6 = Pöyhönen | first6 = M. | last7 = Yki-Järvinen | first7 = H. | last8 = Joutel | first8 = A. | last9 = Viitanen | first9 = M. | title = Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. | journal = Brain | volume = 132 | issue = Pt 4 | pages = 933-9 | month = Apr | year = 2009 | doi = 10.1093/brain/awn364 | PMID = 19174371 }}
</ref>
*Causes strokes in 40-50 year-old.
*Cerebral microbleeds - common.
**Associated with increased risk of [[intracerebral hemorrhage]].<ref name=pmid17135568>{{Cite journal | last1 = Choi | first1 = JC. | last2 = Kang | first2 = SY. | last3 = Kang | first3 = JH. | last4 = Park | first4 = JK. | title = Intracerebral hemorrhages in CADASIL. | journal = Neurology | volume = 67 | issue = 11 | pages = 2042-4 | month = Dec | year = 2006 | doi = 10.1212/01.wnl.0000246601.70918.06 | PMID = 17135568 }}</ref>
*Characteristic MRI findings - present in asymptomatic individuals with mutation.
*Increased risk of [[heart|myocardial infarction]].<ref name=pmid12861102>{{cite journal |author=Lesnik Oberstein SA, Jukema JW, Van Duinen SG, ''et al.'' |title=Myocardial infarction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) |journal=Medicine (Baltimore) |volume=82 |issue=4 |pages=251–6 |year=2003 |month=July |pmid=12861102 |doi=10.1097/01.md.0000085054.63483.40 |url=}}</ref>

Note:
*There is also an autosomal recessive form - CARASIL.<ref name=pmid21215656>{{Cite journal | last1 = Fukutake | first1 = T. | title = Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. | journal = J Stroke Cerebrovasc Dis | volume = 20 | issue = 2 | pages = 85-93 | month = | year = | doi = 10.1016/j.jstrokecerebrovasdis.2010.11.008 | PMID = 21215656 }}</ref>
====Etiology====
*Mutation of ''Notch 3'' gene.<ref name=pmid15537516>{{Cite journal | last1 = Kalaria | first1 = RN. | last2 = Viitanen | first2 = M. | last3 = Kalimo | first3 = H. | last4 = Dichgans | first4 = M. | last5 = Tabira | first5 = T. | title = The pathogenesis of CADASIL: an update. | journal = J Neurol Sci | volume = 226 | issue = 1-2 | pages = 35-9 | month = Nov | year = 2004 | doi = 10.1016/j.jns.2004.09.008 | PMID = 15537516 }}</ref>
**Diagnosis: proven ''Notch 3'' mutation.

===Microscopic===
Features:
*+/-Subcortical infarcts.
**Patches of (non-myelinated) tissue within the white matter deep to the cortex with abundant macrophages.
*Blood vessels typically have a basophilic granularity.<ref name=pmid17076524>{{cite journal |author=Kleinschmidt-DeMasters BK, Prayson RA |title=An algorithmic approach to the brain biopsy--part I |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1630–8 |year=2006 |month=November |pmid=17076524 |doi= |url=}}</ref>

====IHC====
*Notch 3: smooth muscle and pericytes punctate +ve.<ref name=pmid12861102/>

Notes:
*No cortical involvement -- this is unlike ''multiple sclerosis''.

DDx:
*[[Amyloidosis]].
*[[Binswanger's disease]] - multi-infarct dementia affecting subcortical white matter.
**Often diagnosed as ''Alzheimer's disease'' in the past.

<gallery>
Image:CADASIL_-_very_high_mag.jpg | Notch 3 staining in CADASIL. (WC/Nephron)
</gallery>
====Skin biopsy diagnosis====
*Can be diagnosed on a skin biopsy.<ref name=pmid11755616 >{{cite journal |author=Joutel A, Favrole P, Labauge P, ''et al.'' |title=Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis |journal=Lancet |volume=358 |issue=9298 |pages=2049–51 |year=2001 |month=December |pmid=11755616 |doi=10.1016/S0140-6736(01)07142-2 |url=}}</ref>

===Electron microscopy===
*Granular osmiophilic material (GOM).

==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
===General===
*Caused by ''JC virus'' (a type of [[polyomavirus]]<ref name=pmid21499097>{{Cite journal | last1 = Berger | first1 = JR. | title = The basis for modeling progressive multifocal leukoencephalopathy pathogenesis. | journal = Curr Opin Neurol | volume = 24 | issue = 3 | pages = 262-7 | month = Jun | year = 2011 | doi = 10.1097/WCO.0b013e328346d2a3 | PMID = 21499097 }}</ref>) in the context of immunodeficiency; usu. in the setting of [[HIV]] infection.<ref name=pmid12709870>{{Cite journal | last1 = Berger | first1 = JR. | title = Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions. | journal = J Neurovirol | volume = 9 Suppl 1 | issue = | pages = 38-41 | month = | year = 2003 | doi = 10.1080/13550280390195261 | PMID = 12709870 }}</ref>
**Approximately 5% of HIV patients develop PML.<ref name=pmid12709870/>
**Virus destroys oligodendrocytes -> demyelination results.<ref name=pmid21823157>{{Cite journal | last1 = Mateen | first1 = FJ. | last2 = Muralidharan | first2 = R. | last3 = Carone | first3 = M. | last4 = van de Beek | first4 = D. | last5 = Harrison | first5 = DM. | last6 = Aksamit | first6 = AJ. | last7 = Gould | first7 = MS. | last8 = Clifford | first8 = DB. | last9 = Nath | first9 = A. | title = Progressive multifocal leukoencephalopathy in transplant recipients. | journal = Ann Neurol | volume = 70 | issue = 2 | pages = 305-22 | month = Aug | year = 2011 | doi = 10.1002/ana.22408 | PMID = 21823157 }}
</ref>
*Suspected cases are biopsied - unlike other demyelinating diseases.<ref>URL: [http://path.upmc.edu/cases/case336/dx.html http://path.upmc.edu/cases/case336/dx.html]. Accessed on: 15 January 2012.</ref>
===Gross===
*Multifocal - as the name suggests.

DDx:
*[[Multiple sclerosis]].

===Microscopic===
Features:<ref>URL: [http://path.upmc.edu/cases/case120/dx.html http://path.upmc.edu/cases/case120/dx.html]. Accessed on: 3 January 2012.</ref>
*Perivascular inflammatory cells.
*Foamy histiocytes.
*Abnormal appearing glial cells:<ref name=uscf_pml>URL: [http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm]. Accessed on: 3 January 2012.</ref>
**Reactive astrocytes.
**Oligodendrocytes with nuclear enlargement and glassy magenta chromatin - '''key feature'''.
**Atypical mitoses - known as ''[[Creutzfeldt cell]]''.

Note:
*The chromatin changes remind me of [[Urine_cytopathology#Human_polyomavirus_infection|polyomavirus]] in [[urine cytology]]... perhaps ''not'' surprising as they are related.

Images:
*[http://path.upmc.edu/cases/case120/micro.html PML - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case120/dx.html PML - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell - case 2 (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>
*[http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Figures/PMLHandE.jpg PML oligodendrocyte (ucsf.edu)].<ref name=uscf_pml>URL: [http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm]. Accessed on: 3 January 2012.</ref>
*[http://neuro.psychiatryonline.org/data/Journals/NP/3923/RA4831F2.jpeg PML oligodendrocyte (psychiatryonline.org)].<ref>{{Cite journal | last1 = Hurley | first1 = RA. | last2 = Ernst | first2 = T. | last3 = Khalili | first3 = K. | last4 = Del Valle | first4 = L. | last5 = Simone | first5 = IL. | last6 = Taber | first6 = KH. | title = Identification of HIV-associated progressive multifocal leukoencephalopathy: magnetic resonance imaging and spectroscopy. | journal = J Neuropsychiatry Clin Neurosci | volume = 15 | issue = 1 | pages = 1-6 | month = | year = 2003 | doi = | PMID = 12556565 }}</ref>

===IHC===
*SV40 +ve.<ref name=pmid15581180>{{Cite journal | last1 = Muñoz-Mármol | first1 = AM. | last2 = Mola | first2 = G. | last3 = Fernández-Vasalo | first3 = A. | last4 = Vela | first4 = E. | last5 = Mate | first5 = JL. | last6 = Ariza | first6 = A. | title = JC virus early protein detection by immunohistochemistry in progressive multifocal leukoencephalopathy: a comparative study with in situ hybridization and polymerase chain reaction. | journal = J Neuropathol Exp Neurol | volume = 63 | issue = 11 | pages = 1124-30 | month = Nov | year = 2004 | doi = | PMID = 15581180 }}</ref>

=See also=
*[[Brain tumours]].
*[[Pituitary gland]].
*[[Histiocytoses]].
*[[Intracranial hematomas]].
*[[Spine]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
**[http://www.neuropathologyweb.org/test6/6test.html Quiz (neuropathologyweb.org)].
*[http://blog.lib.umn.edu/santa013/neuropathology/ Neuropathology cases (lib.umn.edu)].
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/AAQuestion-41-60.htm Neurocytopathology quiz (ouhsc.edu)].
*[http://wiki.cns.org/wiki/index.php/Main_Page WikiCNS (wiki.cns.org)].

[[Category:Neuropathology]]

Neuropathology

2014-11-15T01:17:13Z

Laura: /* List of cysts */

'''Neuropathology''' is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

This article is an introduction to neuropathology. There are separate articles for [[brain tumours]], the [[pituitary gland]], the [[spine]], the [[eye]], [[muscle pathologies]], [[neurohistology]] and [[neuroanatomy]].

==Neuroanatomy==
{{Main|Neuroanatomy}}
This is a large topic. It covered in a separate article, that also covers grossing.

==Neuroradiology==
Enhancing vs. non-enhancing:
*If it is tumour... enhancing usu. high grade, non-enhancing usu. low grade.

===Ring enhancing lesions===
In [[HIV]]/AIDS patients... mass on CT if infection:
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>

Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
*Metstasis.
*Abscess.
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.

==Grossing==
This is covered in the ''[[neuroanatomy]]'' article.

===Gross pathology===
The gross usually useless for arriving at a definitive diagnosis.

Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
*Soft & tan colour = [[pituitary adenoma]].

==Normal histology==
{{main|Neurohistology}}
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.

==Histopathology==
===Neuronal changes===
====Anoxic neurons====
*[[AKA]] ''red neurons''.

Features:
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.

=====Images=====
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter2/images2/2-1HIE.jpg Anoxic neurons (neuropathologyweb.org)].
*[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>

====Central chromatolysis====
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*Central clearing.
**Nucleus and Nissl substance are pushed to cell periphery.

DDx:
*Axonal injury (traumatic).<ref name=pmid8909880>{{cite journal |author=Holland GR |title=Experimental trigeminal nerve injury |journal=Crit. Rev. Oral Biol. Med. |volume=7 |issue=3 |pages=237–58 |year=1996 |pmid=8909880 |doi= |url=}}</ref>
*Vitamin deficiency ([[pellagra]]).<ref name=pmid15577526>{{cite journal |author=Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF |title=Pellagra: a rare disease observed in a victim of mental and physical abuse |journal=Am J Forensic Med Pathol |volume=25 |issue=4 |pages=342–4 |year=2004 |month=December |pmid=15577526 |doi= |url=}}</ref>

=====Images=====
<gallery>
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
</gallery>
====Axonal swellings====
H&E:
*Eosinophilic (light pink) - ground glass-like appearance.
*Shape:
**Round if sectioned perpendicular to axis of axon.
***Bound by cell membrane.
***Large ~ typically 2-4x RBC diameter.
**Sausage-shaped if cut in along axis.

Images:
*[http://frontalcortex.com/gallery/pics/gliageek_VWMDx200.jpg Axonal swelling (frontalcortex.com)].<ref>URL: [http://frontalcortex.com/?page=oll&topic=24&qid=602 http://frontalcortex.com/?page=oll&topic=24&qid=602]. Accessed on: 3 November 2010.</ref>
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].

=====IHC=====
*APP.

Image:
*[http://vet.sagepub.com/content/37/6/677/F7.expansion.html Axonal swelling - APP (sagepub.com)].<ref>{{cite journal |author=Finnie JW, Manavis J, Blumbergs PC, Kuchel TR |title=Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin |journal=Vet. Pathol. |volume=37 |issue=6 |pages=677–80 |year=2000 |month=November |pmid=11105962 |doi= |url=http://vet.sagepub.com/content/37/6/677.full}}</ref>

===Glial changes===
====Astrocyte changes====
Reactive astrocytes:
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
*Well-defined cell border.
*Eosinophilic cytoplasm with many branching processes.
**Classically described as "funnel-shaped" in benign astrocytes.<ref>MUN. 15 November 2010.</ref>
*Peripheral nucleus.
<gallery>
Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg | Reactive astrocytes - high mag. (WC)
</gallery>

Alzheimer type II astrocyte:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[http://www.neuropathologyweb.org/chapter10/images10/10-AlzIIl.jpg Alzheimer type II astrocytes (neuropathologyweb.org)] .
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag.jpg| Alzheimer type II astrocytes. (WC)
</gallery>

Creutzfeldt cell:<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
*Finding associated with demyelinating disease.
*Image: [http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>

Gemistocytic astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 7 November 2010.</ref>
*Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:<ref name=Ref_MBNP173>{{Ref MBNP|173}}</ref>
*Cellular processes loaded with tau protein (as may be seen with tau [[IHC]] or Gallyas silver stain); Parisian-star-like appearance with special stain.
*+/-Multinucleated.
*A classic feature of ''[[progressive supranuclear palsy]]''.

====Other glial====
Bergmann gliosis (in the cerebellum):<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

<gallery>
Image:Bergmann_gliosis_-_intermed_mag.jpg | Bergmann gliosis - intermed. mag. (WC)
Image:Bergmann_gliosis_-_high_mag.jpg | Bergmann gliosis - high mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_intermed_mag.jpg | Bergmann gliosis due to compression by metastasis - intermed mag. (WC)
</gallery>
Image:
*[http://tpx.sagepub.com/content/35/5/676/F5.expansion.html Bergmann gliosis (sagepub.com)].

====Reactive change vs. malignancy====
Reactive changes vs. malignancy (mnemonic ''MIMICS''):<ref name=Ref_TPoSP254>{{Ref TPoSP|254}}</ref>
*'''MI'''crovesicular pattern.
*'''M'''itoses.
*'''I'''rregular spacing.
*'''C'''alcifications.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.

===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].

====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.

=====Gross=====
*Frontal and temporal lobe - most common for HSV encephalitis.<ref>{{Ref APBR|416 Q47}}</ref>

=====Microscopic=====
Features:<ref name=pmid20051019>{{Cite journal | last1 = Takei | first1 = H. | last2 = Wilfong | first2 = A. | last3 = Malphrus | first3 = A. | last4 = Yoshor | first4 = D. | last5 = Hunter | first5 = JV. | last6 = Armstrong | first6 = DL. | last7 = Bhattacharjee | first7 = MB. | title = Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature. | journal = Neuropathology | volume = 30 | issue = 4 | pages = 381-91 | month = Aug | year = 2010 | doi = 10.1111/j.1440-1789.2009.01079.x | PMID = 20051019 }}</ref>
*Perivascular inflammation.
*Microglia.
*+/-Neuronophagia.
**Phagocytosis of neurons.<ref>URL: [http://medical-dictionary.thefreedictionary.com/neuronophagia http://medical-dictionary.thefreedictionary.com/neuronophagia]. Accessed on: 11 April 2012.</ref>
*+/-Viral cytopathic changes.
*+/-Perineuronal inflammation.

Notes:
*Hemorrhage<ref name=pmid18246335>{{Cite journal | last1 = Vossough | first1 = A. | last2 = Zimmerman | first2 = RA. | last3 = Bilaniuk | first3 = LT. | last4 = Schwartz | first4 = EM. | title = Imaging findings of neonatal herpes simplex virus type 2 encephalitis. | journal = Neuroradiology | volume = 50 | issue = 4 | pages = 355-66 | month = Apr | year = 2008 | doi = 10.1007/s00234-007-0349-3 | PMID = 18246335 }}</ref> and necrosis - characteristic of HSV encephalitis.

Image:
*[http://neuropathology-web.org/chapter5/images5/5-21l.jpg HSV encephalitis (neuropathology-web.org)].<ref>URL: [http://neuropathology-web.org/chapter5/chapter5dViruses.html http://neuropathology-web.org/chapter5/chapter5dViruses.html]. Accessed on: 27 January 2012.</ref>

=====IHC=====
IHC stains for:
*Viral etiologies, e.g. [[HSV]], [[CMV]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.

===Architecture===
====Rosettes====
*Rosette = circular/flower-like arrangement of cells.<ref name=pmid16551982>{{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>

*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{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>
**[[Ependymoma]].
**[[Medulloblastoma]], PNET.
**[[Central neurocytoma]].
**[[Glioblastoma]]s.

*Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Medulloblastoma.
***Image: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-TU-01-17.gif Medulloblastoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17 http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17]. Accessed on: 3 December 2010.</ref>
**PNET (can be thought of as a supratentorial medulloblastoma) .

*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**Pineoblastomas.
**Medulloepitheliomas.

*True ependymal rosette = surrounds a space.<ref name=pmid16551982/>
**[[Ependymoma]].

*Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Similar to Homer-Wright rosette.
**[[Pineocytoma]].
**[[Neurocytoma]].

====Other====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Well-seen on trichrome stains.
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
*Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
**Pseudopalisading of tumour cells (around necrotic regions) is seen in [[glioblastoma]].

Note:
*Good set of articles: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist Neuropathology for radiologists (ncbi.nlm.nih.gov)].

===Inclusion bodies===
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**[[Rabies]].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>

*Lewy bodies.
**Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.<ref name=pmid15235805>{{cite journal |author=Marui W, Iseki E, Kato M, Akatsu H, Kosaka K |title=Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease |journal=Acta Neuropathol. |volume=108 |issue=2 |pages=121–8 |year=2004 |month=August |pmid=15235805 |doi=10.1007/s00401-004-0869-4 |url=}}</ref>
<gallery>
Image:Lewy_Koerperchen.JPG | Lewy body. (WC)
</gallery>
====Table of inclusions====
{| class="wikitable sortable"
! Feature
! Appearance
! Associated disease
! Comment
! Image
|-
| Grumous bodies [[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1 AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on location in brain; +ve for alpha-synuclein, alpha-B crystallin, ubiquitin
| [[Image:Lewy_Koerperchen.JPG |thumb|center|150px|]], [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| Lafora body
| round
| myoclonic [[epilepsy]]
| look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands
| ?Image
|-
| Lipofuscin
| yellow & granular
| aging
| olive, dendate
| ?Image
|-
| Negri body
| small eosinophic bodies
| rabies
| found in hippocampal neurons and Purkinje cells
| [[Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg|thumb|center|150px|]]
|-
| Hirano body
| concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron
| Alzheimer disease, Pick disease<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| actin crystals, may look like capillaries; location: CA1 of hippocampus
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adhirano.jpg]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>
|-
| Neurofibrillary tangles
| flame-shaped cytoplasmic thingy ~30 micrometers
| aging, Alzheimer's disease
| seen with silver stain
| [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg Schematic]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Granulovacuolar degeneration
| cytoplasmic vacuoles 4-5 micrometers
| ageing, [[Alzheimer's disease]], Pick's disease
| main found in Ammon horn<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adgvd.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Pick bodies
| round, homogenous, intracytoplasmic, ~10 micrometers
| [[Pick's disease]]
| pyramidal neurons, dentate granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
| [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?action=view&current=Picks60x.jpg&mediafilter=images]
|-
| Bunina body
| size of Nissl granules, eosinophilic
| [[amyotrophic lateral sclerosis]] (ALS)
| EM: membrane-bound bodies; ubiquitin +ve
| [http://pathol.umin.ac.jp/gakubu/exam/2006jpg/19.jpg]
|-

|}

Image collection: [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?mediafilter=images Inclusion bodies (photobucket.com)].

==Immunohistochemistry==
{{Main|Immunohistochemistry}}
===General===
*S-100.
**Sensitive... but non-specific, e.g. also stains [[melanoma]].

===Glial===
*GFAP (glial fibrillary acidic protein) - should stain perikaryon.

====Glial tumours====
Standard work-up:
*GFAP.
*p53.
*Ki-67.

===Neuronal===
*Synaptophysin.
*Chromogranin.

===Carcinoma vs. glial tumours===
*AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.<ref name=Ref_PSNP_12>{{Ref PSNP|12}}</ref>

===Others===
*APP (amyloid precursor protein) - detects axonal swellings.
*NF (neurofilament) - detects axonal swellings.

=Brain tumours=
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology. The most common brain tumour is a metastasis. The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.

=Non-tumour=
==Cerebral hemorrhage==
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds

Includes discussion of:
*[[Epidural hematoma]].
*[[Subdural hematoma]].
*[[Subarachnoid hematoma]].
*[[Intracerebral hematoma]]s.

==Duret hematoma==
*[[AKA]] Duret hemorrhage.
===General===
*Bleed in the upper brainstem (midbrain and pons).
**Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, [[intracranial hemorrhage]]).<ref name=pmid11819006>{{Cite journal | last1 = Parizel | first1 = PM. | last2 = Makkat | first2 = S. | last3 = Jorens | first3 = PG. | last4 = Ozsarlak | first4 = O. | last5 = Cras | first5 = P. | last6 = Van Goethem | first6 = JW. | last7 = van den Hauwe | first7 = L. | last8 = Verlooy | first8 = J. | last9 = De Schepper | first9 = AM. | title = Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage). | journal = Intensive Care Med | volume = 28 | issue = 1 | pages = 85-8 | month = Jan | year = 2002 | doi = 10.1007/s00134-001-1160-y | PMID = 11819006 }}</ref>
*Often fatal.<ref name=pmid11098635>{{Cite journal | last1 = Fujimoto | first1 = Y. | last2 = Aguiar | first2 = PH. | last3 = Freitas | first3 = AB. | last4 = de Andrade | first4 = AF. | last5 = Marino Júnior | first5 = R. | title = Recovery from Duret hemorrhage: a rare complication after craniotomy--case report. | journal = Neurol Med Chir (Tokyo) | volume = 40 | issue = 10 | pages = 508-10 | month = Oct | year = 2000 | doi = | PMID = 11098635 }}</ref>
===Gross===
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>

Image:
*[http://library.med.utah.edu/WebPath/jpeg5/CNS037.jpg Duret hemorrhage (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 4 December 2011.</ref>

===Microscopic===
Features:
*RBC extravasation.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.

==Alcohol & CNS==
===Clinical===
*Wernicke's encephalopathy
**Mnemonic ''WACO'':
***Wernicke's.
***Ataxia.
***Confusion, confabulation -- Korsakoff.
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.

===Pathology===
Features:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
*Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex<ref>URL: [http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939 http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939]. Accessed on: 22 September 2010.</ref> usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>
*Central pontine myelinolysis (CPM).<ref name=pmid21085565>{{cite journal |author=Campbell MC |title=Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report |journal=Prim Care Companion J Clin Psychiatry |volume=12 |issue=4 |pages= |year=2010 |pmid=21085565 |pmc=2983455 |doi=10.4088/PCC.09l00936ecr |url=}}</ref>
**Just what it sound like - myelin loss in the central pons.
**Classically associated with rapid correction of hyponatremia.<ref>{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref>
*Mammillary body shrinkage.<ref name=pmid8947329>{{cite journal |author=Shear PK, Sullivan EV, Lane B, Pfefferbaum A |title=Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia |journal=Alcohol. Clin. Exp. Res. |volume=20 |issue=8 |pages=1489-95 |year=1996 |month=November |pmid=8947329 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489}}</ref>
*Anterior cerebellar vermis atrophy; weak finding - as also age-related.<ref name=pmid3478969>{{cite journal |author=Torvik A |title=Brain lesions in alcoholics: neuropathological observations |journal=Acta Med. Scand. Suppl. |volume=717 |issue= |pages=47–54 |year=1987 |pmid=3478969 |doi= |url=}}</ref>
**Vermis atrophy is also seen in schizophrenia.<ref name=pmid1938163>{{cite journal |author=Sandyk R, Kay SR, Merriam AE |title=Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia |journal=Int. J. Neurosci. |volume=57 |issue=3-4 |pages=205–12 |year=1991 |month=April |pmid=1938163 |doi= |url=}}</ref>

====Marchiafava-Bignami Disease====
*Rare.
*Demyelination of the corpus callosum.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>

====Wernicke's encephalopathy====
General:
*Due to thiamine deficiency.
**Malnourishment often accompanies [[alcoholism]].

Features:<ref name=pmid3929155>{{Cite journal | last1 = Torvik | first1 = A. | title = Two types of brain lesions in Wernicke's encephalopathy. | journal = Neuropathol Appl Neurobiol | volume = 11 | issue = 3 | pages = 179-90 | month = | year = | doi = | PMID = 3929155 }}</ref>
*Neurons of mammillary bodies preserved - '''key'''.
*Loss of myelin.
*Hemorrhage.
*Edema.
*Reactive blood vessels.

Note:
*The thalamus and inferior olives show neuronal loss.<ref name=pmid3929155/>

====Common non-specific findings====
*[[Intracranial haemorrhage]] - due to trauma.

==Meningitis==
===General===
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.

CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
|-
| Bacterial, acute
| low
| high
| neutrophils
|-
| Viral
| normal
| slight elevation
| lymphocytes
|}

====Etiology====
*Infectious.
**Bacterial.
**Viral.
**Parasitic
*Autoimmune.
*Toxic.
*Aseptic - see ''[[Mollaret's meningitis]]''.

Bacterial meningitis - most probably cause by age:<ref>{{Ref PCPBoD8|666-7}}</ref>
{| class="wikitable sortable"
! Age
! Organism
|-
| Neonate
| ''Escherichia coli'', Group B Streptococcus
|-
| Infants, children
| ''Streptococcus pneumoniae''
|-
| Adolescents, young adults
| ''Neisseria meningitidis''
|-
| Elderly
| ''Streptococcus pneumoniae'', ''Listeria monocytogenes''
|}

===Gross===
Features:
*+/-Clouded appearance of the meninges.
*+/-Pus.
*+/-Petechiae.
*+/-Cerebral edema.

====Image====
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
</gallery>

===Microscopic===
Features:
*Inflammation of the meninges:
**+/-[[Neutrophil]]s.
**+/-Lymphocytes.
**+/-[[Plasma cell]]s.
*+/-Microorganisms (infectious meningitis):
**Bacteria.
**[[Fungi]], e.g. [[aspergillosis]] (may be intravascular).

Main DDx:
*[[Lymphoma]].

====Image====
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC)
</gallery>

==Cerebral abscess==
===General===
*May mimic malignancy clinically.

===Microscopic===
Features:
*Sheets of neutrophils surrounded by fibrosing brain.
**Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Images:
*[http://pathology.class.kmu.edu.tw/ch01/4-1.jpg Cerebral abscess - very low mag. (kmu.edu.tw)].<ref>URL: [http://pathology.class.kmu.edu.tw/ch01/Slide4.htm http://pathology.class.kmu.edu.tw/ch01/Slide4.htm]. Accessed on: 1 January 2012.</ref>
*[http://pathology.class.kmu.edu.tw/ch01/4-5.jpg Cerebral abscess - low mag. (kmu.edu.tw)].

==Neurodegenerative diseases==
{{Main|Neurodegenerative diseases}}
This is a hueueuge topic. It is covered in its own article and includes a general discussion of dementia.

==Epilepsy==
{{Main|Epilepsy}}

==Cerebrovascular accident==
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.

===General===
*Very common.
*Leading cause of morbidity and mortality.

Clinical classification:
# Hemorrhagic stroke.
# Ischemic stroke.

===Gross===
*Soft/mushy brain.
*Older [[infarct]]s.
**A "roof" is present - a thin submeningeal layer is preserved by the CSF.<ref>MUN. 16 December 2009.</ref>
***"Roof" is absent in trauma.
**Cavity - in older infarcts.
***''[[Multiple sclerosis]]'' does not cavitate.
*Laminar necrosis = (thin) chalky line replaces grey mater.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q03-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q03-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[AKA]] ''pseudolaminar necrosis'' - as it is not localized to a specific layer of the cortex.<ref>MUN. 26 November 2010.</ref>

DDx:
*[[Cerebral contusion]].

===Microscopic===
Features:
*Ischemic neurons.
*+/-Neuronal loss.
*+/-Microglial.
*+/-[[Thrombosis]].
*+/-[[Atherosclerosis]].

==Hypoxic-ischemic encephalopathy==
*Abbreviated ''HIE''.
===General===
*Often due to ''cardiac arrest'', i.e. global ischemia.
*Triple watershed area = parieto-occipital cortex, extrastriate occipital cortex.

Note:
*''Hypoxia'' = blood decreased oxygen carrying capacity,<ref name=Ref_PCPBoD8_10>{{Ref PCPBoD8|10}}</ref> e.g. [[anemia]].
*''Ischemia'' = decreased blood flow.<ref name=Ref_PCPBoD8_10>{{Ref PCPBoD8|10}}</ref>
*Either ''or'' both = less oxygen delivery to tissue.
===Microscopic===
Features:
*Hippocampal ischemic changes (in adults):
**Loss of neurons in CA1, CA3 and CA4 +/- "cavitation".
***Neuronal loss: No blue (nuclei) where there should be some.
***Cavitation: bubbles/clear spaces where there should be none.
**CA2 neurons preserved/resistant.
*Purkinje cell loss in the cerebellum and [[Bergmann gliosis]].
*"Anoxic neurons".<ref>URL: [http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html]. Accessed on: 12 July 2010.</ref>
**Shrunken neurons with intensely eosinophilic cytoplasm and pyknotic (shrunken) nuclei.
*Pseudolaminar necrosis - (uncontrolled) cell death in the cerebral cortex in a band-like pattern,<ref>Hypoxic and Ischemic Encephalopathy. neuropathology.neoucom.edu. Accessed on: 29 December 2010.</ref> with a relative preservation of cells immediately adjacent to the meninges.

Notes:
*Neurons of ''subiculum'' in adults - usu. normal (as they are resistant to ischemic changes).
====Images====
*Anoxic neurons:
**[http://www.neuropathologyweb.org/chapter2/images2/2-1HIE.jpg Anoxic neurons (neuropathologyweb.org)].
**[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons. (WC)
</gallery>
*Hippocampal ischemic changes:
**[http://www.neuropathologyweb.org/chapter2/images2/2-hippoHIE.jpg Hippocampus in HIE (neuropathologyweb.org)].<ref>URL: [http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html]. Accessed on: 14 January 2011.</ref>
*Pseudolaminar necrosis:
<gallery>
Image:Cortical_pseudolaminar_necrosis_-_lfb_-_very_low_mag.jpg | Pseudolaminar necrosis - very low mag. (WC)
Image:Cortical_pseudolaminar_necrosis_-_lfb_-_intermed_mag.jpg | Pseudolaminar necrosis - intermed. mag. (WC)
</gallery>

==Multiple sclerosis==
*Abbreviated ''MS''.
===General===
*A bread 'n butter disease of neurology in Canada.

Clinical:
*CSF: oligoclonal bands of immunoglobulin.<ref>{{Ref PBoD8|1311}}</ref>

Classification of MS lesions:
*Early active.
*Inactive.
*Early remyelinating.
*Late remyelinating.

===Radiologic/Gross===
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*White matter lesions.
**Cerebrum (classically): periventricular distribution.
**Optic nerves (optic neuritis) - classic presentation.

===Microscopic===
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*Perivascular inflammation.
**Esp. lymphocytes.
*Demyelination.
**Subcortical myelinated fibers are often spared.

Chronic lesions - specific features:<ref>{{Ref APBR|425 Q43}}</ref>
#Macrophages.
#Astrocyte enlargement.

DDx:
*[[ADEM]].
*[[Neuromyelitis optica]].
*[[Lymphoma]].
*[[Diffuse astrocytoma]].

Images:
*[http://path.upmc.edu/cases/case79.html Multiple sclerosis masquerading as a diffuse astrocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case636.html Tumefactive multiple sclerosis - several images (upmc.edu)].

===IHC===
*HAM-56 - macrophages.
*CD8 - lymphocytes.

==Cerebral amyloid angiopathy==
===General===
*Abbreviated ''CAA''.
*Disease of the old.
*Strong association with ''[[lobar haemorrhage]]'' (bleeds of the cerebellar cortex and cerebral cortex).<ref name=pmid16982664>{{cite journal |author=Thanvi B, Robinson T |title=Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people |journal=Age Ageing |volume=35 |issue=6 |pages=565–71 |year=2006 |month=November |pmid=16982664 |doi=10.1093/ageing/afl108 |url=}}</ref>

Etiology:
*[[Amyloid]] deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

===Gross===
*Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.<ref name=pmid17297004>{{Cite journal | last1 = Haacke | first1 = EM. | last2 = DelProposto | first2 = ZS. | last3 = Chaturvedi | first3 = S. | last4 = Sehgal | first4 = V. | last5 = Tenzer | first5 = M. | last6 = Neelavalli | first6 = J. | last7 = Kido | first7 = D. | title = Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. | journal = AJNR Am J Neuroradiol | volume = 28 | issue = 2 | pages = 316-7 | month = Feb | year = 2007 | doi = | PMID = 17297004 | URL = http://www.ajnr.org/content/28/2/316.long }}</ref>

===Microscopic===
Features:
*Amorphous, acellular eosinophilic material within walls of small arteries.
**This is a high power diagnosis with congo red staining.

Notes:
*Amyloidosis is seen in all individuals with [[Alzheimer's disease]]; the amount of amyloid is what differs -- in CAA it is lots and lots.
*The white matter is typically spared by CAA.<ref name=pmid19225408>{{Cite journal | last1 = Schröder | first1 = R. | last2 = Deckert | first2 = M. | last3 = Linke | first3 = RP. | title = Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 3 | pages = 286-99 | month = Mar | year = 2009 | doi = 10.1097/NEN.0b013e31819a87f9 | PMID = 19225408 }}
</ref>

====Images====
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
===Stains===
*[[Congo red]].

===IHC===
*Abeta-amyloid (AKA beta-amyloid).

==Central pontine myelinolysis==
*Abbreviated ''CPM''.
*[[AKA]] ''pontine myelinolysis''.
===General===
*Classically in the pons, ergo "pontine" is in the name.
*Classically midline, ergo "central" is in the name.
**May occur elsewhere -- known as ''extrapontine myelinolysis''.

Etiology:
*Rapid correction of hyponatremia.<ref name=pmid22080394>{{Cite journal | last1 = Chang | first1 = Y. | last2 = An | first2 = DH. | last3 = Xing | first3 = Y. | last4 = Qi | first4 = X. | title = Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. | journal = Neurol Sci | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1007/s10072-011-0838-3 | PMID = 22080394 }}</ref>
*Tacrolimus post-liver transplant.<ref name=pmid21959523>{{Cite journal | last1 = Fukazawa | first1 = K. | last2 = Nishida | first2 = S. | last3 = Aguina | first3 = L. | last4 = Pretto | first4 = E. | title = Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation. | journal = Ann Transplant | volume = 16 | issue = 3 | pages = 139-42 | month = Sep | year = 2011 | doi = | PMID = 21959523 }}</ref>
*Associated with [[alcoholism]] and malnourishment.

Clinical:<ref>{{Cite journal | last1 = Lai | first1 = CC. | last2 = Tan | first2 = CK. | last3 = Lin | first3 = SH. | last4 = Chen | first4 = HW. | title = Central pontine myelinolysis. | journal = CMAJ | volume = 183 | issue = 9 | pages = E605 | month = Jun | year = 2011 | doi = 10.1503/cmaj.090186 | PMID = 21543311 | PMC = 3114939 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114939/?tool=pubmed }}</ref>
*Decreased level of consciousness - most common.
*Quadriplegia.
*Poor prognosis.

===Microscopic===
Features:<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*Myelin loss.
*No inflammation.
*Relative preservation of neurons.

Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].

==Vascular malformations==
{{Main|Vascular malformations}}
Types:<ref name=pmid17076525>{{cite journal |author=Prayson RA, Kleinschmidt-DeMasters BK |title=An algorithmic approach to the brain biopsy--part II |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1639–48 |year=2006 |month=November |pmid=17076525 |doi= |url=}}</ref>
#Arteriovenous malformation.
#*Most important clinically - highest risk of bleeding.
#Varix.
#*One large (dilated) vein.
#Venous angioma.
#*Many small veins.
#Cavernous malformation.
#*Vessels are back-to-back (no intervening parenchyma).

Also see: ''[[Sturge-Weber syndrome]]''.

=Cysts=
===General===
*All are "benign", but some may be fatal due to spatial constraints.

===List of cysts===
*[[Colloid cyst]].
**Columnar epithelium.
*Arachnoid cyst - considered precursor of [[meningioma]].
**[[Psammoma bodies]].
**Clumps of cells.
**Whorled pattern.
*[[Dermoid cyst]].
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid cyst.
*Choroid plexus cyst.
*Neuroenteric cyst.
**Foregut cyst with connection to dura.<ref>URL: [http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm]. Accessed on: 19 December 2011.</ref>
***Gastrointestinal tract epithelium.
***Usually seen with vertebral anomalies.
*Epithelial cyst.
*Others.

==Colloid cyst==
===General===
Classic presentation:<ref name=pmid15228889>{{Cite journal | last1 = Spears | first1 = RC. | title = Colloid cyst headache. | journal = Curr Pain Headache Rep | volume = 8 | issue = 4 | pages = 297-300 | month = Aug | year = 2004 | doi = | PMID = 15228889 }}</ref>
*Headache - may be relieved by lying down.
*Can cause [[sudden natural death]].<ref name=pmid14716130>{{Cite journal | last1 = Kava | first1 = MP. | last2 = Tullu | first2 = MS. | last3 = Deshmukh | first3 = CT. | last4 = Shenoy | first4 = A. | title = Colloid cyst of the third ventricle: a cause of sudden death in a child. | journal = Indian J Cancer | volume = 40 | issue = 1 | pages = 31-3 | month = | year = | doi = | PMID = 14716130 }}</ref>

===Gross===
*Fluid filled cyst - classically in the third ventricle.

Image:
*[http://www.ajnr.org/content/21/8/1470/F3.expansion.html Colloid cyst of third ventricle (ajnr.org)].<ref name=pmid11003281/>

===Microscopic===
Features:<ref name=pmid11003281>{{Cite journal | last1 = Armao | first1 = D. | last2 = Castillo | first2 = M. | last3 = Chen | first3 = H. | last4 = Kwock | first4 = L. | title = Colloid cyst of the third ventricle: imaging-pathologic correlation. | journal = AJNR Am J Neuroradiol | volume = 21 | issue = 8 | pages = 1470-7 | month = Sep | year = 2000 | doi = | PMID = 11003281 }}</ref>
*Simple epithelium with ciliated cells and goblet cells.

====Images====
<gallery>
Image:Colloid_Cyst_HE_40x.jpg | Colloid cyst. (WC)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F4.expansion.html Colloid cyst (ajnr.org)].<ref name=pmid11003281/>

=Paediatric pathology=
==Kernicterus==
===General===
*Due to hyperbilirubinemia.<ref name=pmid7063283>{{Cite journal | last1 = Turkel | first1 = SB. | last2 = Miller | first2 = CA. | last3 = Guttenberg | first3 = ME. | last4 = Moynes | first4 = DR. | last5 = Godgman | first5 = JE. | title = A clinical pathologic reappraisal of kernicterus. | journal = Pediatrics | volume = 69 | issue = 3 | pages = 267-72 | month = Mar | year = 1982 | doi = | PMID = 7063283 }}</ref>

===Gross===
*Yellow staining:<ref name=npw>URL: [http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html]. Accessed on: 30 May 2012.</ref>
**Basal ganglia.<ref name=pmid10920171>{{Cite journal | last1 = Hansen | first1 = TW. | last2 = Hervieux | first2 = JF. | last3 = Orth | first3 = J. | last4 = Schmorl | first4 = CG. | last5 = Baumes | first5 = JB. | title = Pioneers in the scientific study of neonatal jaundice and kernicterus. | journal = Pediatrics | volume = 106 | issue = 2 | pages = E15 | month = Aug | year = 2000 | doi = | PMID = 10920171 }}</ref>
**Hippocampus.<ref name=pmid15091133>{{Cite journal | last1 = Paksoy | first1 = Y. | last2 = Koç | first2 = H. | last3 = Genç | first3 = BO. | title = Bilateral mesial temporal sclerosis and kernicterus. | journal = J Comput Assist Tomogr | volume = 28 | issue = 2 | pages = 269-72 | month = | year = | doi = | PMID = 15091133 }}</ref>
**Subthalamic nucleus.

Note:
*May not be specific.<ref name=pmid7063283/>

Image:
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].

===Microscopic===
Features - similar to [[HIE]]:<ref name=npw/>
*+/-Red neurons.
*+/-Gliosis.

==Joubert syndrome==
*Malformation of the cerebellar vermis.<ref name=ninds_joubert>[http://www.ninds.nih.gov/disorders/joubert/joubert.htm http://www.ninds.nih.gov/disorders/joubert/joubert.htm]</ref>

===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>

=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
===General===
*Thought to be autoimmune; often associated with/preceded by by viral illness.<ref name=pmid17438235>{{cite journal |author=Tenembaum S, Chitnis T, Ness J, Hahn JS |title=Acute disseminated encephalomyelitis |journal=Neurology |volume=68 |issue=16 Suppl 2 |pages=S23–36 |year=2007 |month=April |pmid=17438235 |doi=10.1212/01.wnl.0000259404.51352.7f |url=}}</ref>
*May mimic [[multiple sclerosis]].

Treatment:
*Steroids.
*Plasmapheresis.

Diagnosis:
*Need to r/o infection (with lumbar puncture).
*No old plaques on imaging (MRI).

An acute form exists known as ''acute hemorrhagic leukoencephalitis''<ref>URL: [http://path.upmc.edu/cases/case102/dx.html http://path.upmc.edu/cases/case102/dx.html]. Accessed on: 2 January 2012.</ref> (AKA ''acute necrotizing hemorrhagic encephalomyelitis'').

===Microscopic===
Features:<ref>{{Ref PBoD8|1312}}</ref>
*Myelin loss with sparing of axons.
*Inflammation:
**Early: [[neutrophil]]s.
**Late: mononuclear cells (lymphocytes, plasma cells).
*Lipid-laden macrophages.

DDx:
*[[Multiple sclerosis]].
**Tend to be larger, more lymphocytes,<ref>{{Ref APBR|423}}</ref> age of the lesions differ.
*Acute necrotizing hemorrhagic encephalomyelitis (ANHE) - if one considers this a separate entity.
*Acute necrotizing encephalopathy.<ref>URL: [http://path.upmc.edu/cases/case619/dx.html http://path.upmc.edu/cases/case619/dx.html]. Accessed on: 26 January 2012.</ref>

==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>

Diagnosis:
*NMO-IgG.

Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).

===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.

Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].

===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.

==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
===General===
*Autosomal dominant disorder - as the name implies.<ref name=pmid19174371>{{Cite journal | last1 = Tikka | first1 = S. | last2 = Mykkänen | first2 = K. | last3 = Ruchoux | first3 = MM. | last4 = Bergholm | first4 = R. | last5 = Junna | first5 = M. | last6 = Pöyhönen | first6 = M. | last7 = Yki-Järvinen | first7 = H. | last8 = Joutel | first8 = A. | last9 = Viitanen | first9 = M. | title = Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. | journal = Brain | volume = 132 | issue = Pt 4 | pages = 933-9 | month = Apr | year = 2009 | doi = 10.1093/brain/awn364 | PMID = 19174371 }}
</ref>
*Causes strokes in 40-50 year-old.
*Cerebral microbleeds - common.
**Associated with increased risk of [[intracerebral hemorrhage]].<ref name=pmid17135568>{{Cite journal | last1 = Choi | first1 = JC. | last2 = Kang | first2 = SY. | last3 = Kang | first3 = JH. | last4 = Park | first4 = JK. | title = Intracerebral hemorrhages in CADASIL. | journal = Neurology | volume = 67 | issue = 11 | pages = 2042-4 | month = Dec | year = 2006 | doi = 10.1212/01.wnl.0000246601.70918.06 | PMID = 17135568 }}</ref>
*Characteristic MRI findings - present in asymptomatic individuals with mutation.
*Increased risk of [[heart|myocardial infarction]].<ref name=pmid12861102>{{cite journal |author=Lesnik Oberstein SA, Jukema JW, Van Duinen SG, ''et al.'' |title=Myocardial infarction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) |journal=Medicine (Baltimore) |volume=82 |issue=4 |pages=251–6 |year=2003 |month=July |pmid=12861102 |doi=10.1097/01.md.0000085054.63483.40 |url=}}</ref>

Note:
*There is also an autosomal recessive form - CARASIL.<ref name=pmid21215656>{{Cite journal | last1 = Fukutake | first1 = T. | title = Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. | journal = J Stroke Cerebrovasc Dis | volume = 20 | issue = 2 | pages = 85-93 | month = | year = | doi = 10.1016/j.jstrokecerebrovasdis.2010.11.008 | PMID = 21215656 }}</ref>
====Etiology====
*Mutation of ''Notch 3'' gene.<ref name=pmid15537516>{{Cite journal | last1 = Kalaria | first1 = RN. | last2 = Viitanen | first2 = M. | last3 = Kalimo | first3 = H. | last4 = Dichgans | first4 = M. | last5 = Tabira | first5 = T. | title = The pathogenesis of CADASIL: an update. | journal = J Neurol Sci | volume = 226 | issue = 1-2 | pages = 35-9 | month = Nov | year = 2004 | doi = 10.1016/j.jns.2004.09.008 | PMID = 15537516 }}</ref>
**Diagnosis: proven ''Notch 3'' mutation.

===Microscopic===
Features:
*+/-Subcortical infarcts.
**Patches of (non-myelinated) tissue within the white matter deep to the cortex with abundant macrophages.
*Blood vessels typically have a basophilic granularity.<ref name=pmid17076524>{{cite journal |author=Kleinschmidt-DeMasters BK, Prayson RA |title=An algorithmic approach to the brain biopsy--part I |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1630–8 |year=2006 |month=November |pmid=17076524 |doi= |url=}}</ref>

====IHC====
*Notch 3: smooth muscle and pericytes punctate +ve.<ref name=pmid12861102/>

Notes:
*No cortical involvement -- this is unlike ''multiple sclerosis''.

DDx:
*[[Amyloidosis]].
*[[Binswanger's disease]] - multi-infarct dementia affecting subcortical white matter.
**Often diagnosed as ''Alzheimer's disease'' in the past.

<gallery>
Image:CADASIL_-_very_high_mag.jpg | Notch 3 staining in CADASIL. (WC/Nephron)
</gallery>
====Skin biopsy diagnosis====
*Can be diagnosed on a skin biopsy.<ref name=pmid11755616 >{{cite journal |author=Joutel A, Favrole P, Labauge P, ''et al.'' |title=Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis |journal=Lancet |volume=358 |issue=9298 |pages=2049–51 |year=2001 |month=December |pmid=11755616 |doi=10.1016/S0140-6736(01)07142-2 |url=}}</ref>

===Electron microscopy===
*Granular osmiophilic material (GOM).

==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
===General===
*Caused by ''JC virus'' (a type of [[polyomavirus]]<ref name=pmid21499097>{{Cite journal | last1 = Berger | first1 = JR. | title = The basis for modeling progressive multifocal leukoencephalopathy pathogenesis. | journal = Curr Opin Neurol | volume = 24 | issue = 3 | pages = 262-7 | month = Jun | year = 2011 | doi = 10.1097/WCO.0b013e328346d2a3 | PMID = 21499097 }}</ref>) in the context of immunodeficiency; usu. in the setting of [[HIV]] infection.<ref name=pmid12709870>{{Cite journal | last1 = Berger | first1 = JR. | title = Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions. | journal = J Neurovirol | volume = 9 Suppl 1 | issue = | pages = 38-41 | month = | year = 2003 | doi = 10.1080/13550280390195261 | PMID = 12709870 }}</ref>
**Approximately 5% of HIV patients develop PML.<ref name=pmid12709870/>
**Virus destroys oligodendrocytes -> demyelination results.<ref name=pmid21823157>{{Cite journal | last1 = Mateen | first1 = FJ. | last2 = Muralidharan | first2 = R. | last3 = Carone | first3 = M. | last4 = van de Beek | first4 = D. | last5 = Harrison | first5 = DM. | last6 = Aksamit | first6 = AJ. | last7 = Gould | first7 = MS. | last8 = Clifford | first8 = DB. | last9 = Nath | first9 = A. | title = Progressive multifocal leukoencephalopathy in transplant recipients. | journal = Ann Neurol | volume = 70 | issue = 2 | pages = 305-22 | month = Aug | year = 2011 | doi = 10.1002/ana.22408 | PMID = 21823157 }}
</ref>
*Suspected cases are biopsied - unlike other demyelinating diseases.<ref>URL: [http://path.upmc.edu/cases/case336/dx.html http://path.upmc.edu/cases/case336/dx.html]. Accessed on: 15 January 2012.</ref>
===Gross===
*Multifocal - as the name suggests.

DDx:
*[[Multiple sclerosis]].

===Microscopic===
Features:<ref>URL: [http://path.upmc.edu/cases/case120/dx.html http://path.upmc.edu/cases/case120/dx.html]. Accessed on: 3 January 2012.</ref>
*Perivascular inflammatory cells.
*Foamy histiocytes.
*Abnormal appearing glial cells:<ref name=uscf_pml>URL: [http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm]. Accessed on: 3 January 2012.</ref>
**Reactive astrocytes.
**Oligodendrocytes with nuclear enlargement and glassy magenta chromatin - '''key feature'''.
**Atypical mitoses - known as ''[[Creutzfeldt cell]]''.

Note:
*The chromatin changes remind me of [[Urine_cytopathology#Human_polyomavirus_infection|polyomavirus]] in [[urine cytology]]... perhaps ''not'' surprising as they are related.

Images:
*[http://path.upmc.edu/cases/case120/micro.html PML - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case120/dx.html PML - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell - case 2 (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>
*[http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Figures/PMLHandE.jpg PML oligodendrocyte (ucsf.edu)].<ref name=uscf_pml>URL: [http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm]. Accessed on: 3 January 2012.</ref>
*[http://neuro.psychiatryonline.org/data/Journals/NP/3923/RA4831F2.jpeg PML oligodendrocyte (psychiatryonline.org)].<ref>{{Cite journal | last1 = Hurley | first1 = RA. | last2 = Ernst | first2 = T. | last3 = Khalili | first3 = K. | last4 = Del Valle | first4 = L. | last5 = Simone | first5 = IL. | last6 = Taber | first6 = KH. | title = Identification of HIV-associated progressive multifocal leukoencephalopathy: magnetic resonance imaging and spectroscopy. | journal = J Neuropsychiatry Clin Neurosci | volume = 15 | issue = 1 | pages = 1-6 | month = | year = 2003 | doi = | PMID = 12556565 }}</ref>

===IHC===
*SV40 +ve.<ref name=pmid15581180>{{Cite journal | last1 = Muñoz-Mármol | first1 = AM. | last2 = Mola | first2 = G. | last3 = Fernández-Vasalo | first3 = A. | last4 = Vela | first4 = E. | last5 = Mate | first5 = JL. | last6 = Ariza | first6 = A. | title = JC virus early protein detection by immunohistochemistry in progressive multifocal leukoencephalopathy: a comparative study with in situ hybridization and polymerase chain reaction. | journal = J Neuropathol Exp Neurol | volume = 63 | issue = 11 | pages = 1124-30 | month = Nov | year = 2004 | doi = | PMID = 15581180 }}</ref>

=See also=
*[[Brain tumours]].
*[[Pituitary gland]].
*[[Histiocytoses]].
*[[Intracranial hematomas]].
*[[Spine]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
**[http://www.neuropathologyweb.org/test6/6test.html Quiz (neuropathologyweb.org)].
*[http://blog.lib.umn.edu/santa013/neuropathology/ Neuropathology cases (lib.umn.edu)].
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/AAQuestion-41-60.htm Neurocytopathology quiz (ouhsc.edu)].
*[http://wiki.cns.org/wiki/index.php/Main_Page WikiCNS (wiki.cns.org)].

[[Category:Neuropathology]]

Neuropathology

2014-11-15T01:07:43Z

Laura: /* Vascular malformations */

'''Neuropathology''' is the bane of many anatomical pathologists in teaching hospitals... 'cause they have to fill in for the neuropathologist when he or she is on vacation.

This article is an introduction to neuropathology. There are separate articles for [[brain tumours]], the [[pituitary gland]], the [[spine]], the [[eye]], [[muscle pathologies]], [[neurohistology]] and [[neuroanatomy]].

==Neuroanatomy==
{{Main|Neuroanatomy}}
This is a large topic. It covered in a separate article, that also covers grossing.

==Neuroradiology==
Enhancing vs. non-enhancing:
*If it is tumour... enhancing usu. high grade, non-enhancing usu. low grade.

===Ring enhancing lesions===
In [[HIV]]/AIDS patients... mass on CT if infection:
*[[Toxoplasmosis]] - most common.<ref>MUN. Feb 3, 2009.</ref>

Ring enhancing lesion (DDx) - mnemonic ''MAGICAL DR'':<ref>{{Ref TN2005 |NS7}}</ref>
*Metstasis.
*Abscess.
*[[Glioblastoma]].
*[[Infarct]].
*Contusion.
*AIDS-related.
*[[Lymphoma]] + [[HIV]] assoc. disease (toxoplasma).
*Demyelination (e.g. [[multiple sclerosis]]).
*Resolving hematoma.

==Grossing==
This is covered in the ''[[neuroanatomy]]'' article.

===Gross pathology===
The gross usually useless for arriving at a definitive diagnosis.

Exceptions:<ref>R. Kiehl. 8 November 2010.</ref>
*Sausage shape lesion of filum terminale = [[myxopapillary ependymoma]].
*Soft & tan colour = [[pituitary adenoma]].

==Normal histology==
{{main|Neurohistology}}
This is a big topic. It is covered in a separate article called ''[[neurohistology]]''.

==Histopathology==
===Neuronal changes===
====Anoxic neurons====
*[[AKA]] ''red neurons''.

Features:
*Intensely red cytoplasm.
*Pyknosis = nuclear shrinkage + darker staining.

=====Images=====
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons (WC)
</gallery>
www:
*[http://www.neuropathologyweb.org/chapter2/images2/2-1HIE.jpg Anoxic neurons (neuropathologyweb.org)].
*[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>

====Central chromatolysis====
Features:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html http://www.neuropathologyweb.org/chapter1/chapter1aNeurons.html]. Accessed on: 22 December 2010.</ref>
*Central clearing.
**Nucleus and Nissl substance are pushed to cell periphery.

DDx:
*Axonal injury (traumatic).<ref name=pmid8909880>{{cite journal |author=Holland GR |title=Experimental trigeminal nerve injury |journal=Crit. Rev. Oral Biol. Med. |volume=7 |issue=3 |pages=237–58 |year=1996 |pmid=8909880 |doi= |url=}}</ref>
*Vitamin deficiency ([[pellagra]]).<ref name=pmid15577526>{{cite journal |author=Piercecchi-Marti MD, Pélissier-Alicot AL, Leonetti G, Tervé JP, Cianfarani F, Pellissier JF |title=Pellagra: a rare disease observed in a victim of mental and physical abuse |journal=Am J Forensic Med Pathol |volume=25 |issue=4 |pages=342–4 |year=2004 |month=December |pmid=15577526 |doi= |url=}}</ref>

=====Images=====
<gallery>
Image:Central_chromatolysis_-_intermed_mag_-_cropped.jpg | Central chromatolysis - intermed. mag. (WC)
Image:Central_chromatolysis_-_nf_-_very_high_mag.jpg | Central chromatolysis - NF stain - very high mag. (WC)
</gallery>
====Axonal swellings====
H&E:
*Eosinophilic (light pink) - ground glass-like appearance.
*Shape:
**Round if sectioned perpendicular to axis of axon.
***Bound by cell membrane.
***Large ~ typically 2-4x RBC diameter.
**Sausage-shaped if cut in along axis.

Images:
*[http://frontalcortex.com/gallery/pics/gliageek_VWMDx200.jpg Axonal swelling (frontalcortex.com)].<ref>URL: [http://frontalcortex.com/?page=oll&topic=24&qid=602 http://frontalcortex.com/?page=oll&topic=24&qid=602]. Accessed on: 3 November 2010.</ref>
*[http://www.neuropathologyweb.org/chapter3/images3/3-pvlaxonsweling.jpg Axonal swelling (neuropathologyweb.org)].

=====IHC=====
*APP.

Image:
*[http://vet.sagepub.com/content/37/6/677/F7.expansion.html Axonal swelling - APP (sagepub.com)].<ref>{{cite journal |author=Finnie JW, Manavis J, Blumbergs PC, Kuchel TR |title=Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin |journal=Vet. Pathol. |volume=37 |issue=6 |pages=677–80 |year=2000 |month=November |pmid=11105962 |doi= |url=http://vet.sagepub.com/content/37/6/677.full}}</ref>

===Glial changes===
====Astrocyte changes====
Reactive astrocytes:
*Approximately equally-spaced; distance between neighbouring astrocytes is ~2x (or more) the cell size.
*Well-defined cell border.
*Eosinophilic cytoplasm with many branching processes.
**Classically described as "funnel-shaped" in benign astrocytes.<ref>MUN. 15 November 2010.</ref>
*Peripheral nucleus.
<gallery>
Image:Reactive_astrocytes_-_lfb_-_high_mag.jpg | Reactive astrocytes - high mag. (WC)
</gallery>

Alzheimer type II astrocyte:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 2 July 2010.</ref>
*Large cleared nucleus - '''key feature'''.
*Indistinct cytoplasm.
*Found in the context of ''hepatic encephalopathy'' in basal ganglia and lower layers of cortex.<ref name=Ref_Klatt202>{{Ref Klatt|202}}</ref>
*Images:
**[http://neuroquiz.com/?page=image&topic=1&qid=2714 Alzheimer type II astrocytes (neuroquiz.com)].
**[http://www.neuropathologyweb.org/chapter10/images10/10-AlzIIl.jpg Alzheimer type II astrocytes (neuropathologyweb.org)] .
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag.jpg| Alzheimer type II astrocytes. (WC)
</gallery>

Creutzfeldt cell:<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Astrocyte that mimics a mitoses; has moderate (identifiable) cytoplasm.
*Finding associated with demyelinating disease.
*Image: [http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>

Gemistocytic astrocytes:<ref>URL: [http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html http://www.neuropathologyweb.org/chapter1/chapter1bAstrocytes.html]. Accessed on: 7 November 2010.</ref>
*Distinct eosinophilic cytoplasm - with ground-glass appearance.

Tufted astrocytes:<ref name=Ref_MBNP173>{{Ref MBNP|173}}</ref>
*Cellular processes loaded with tau protein (as may be seen with tau [[IHC]] or Gallyas silver stain); Parisian-star-like appearance with special stain.
*+/-Multinucleated.
*A classic feature of ''[[progressive supranuclear palsy]]''.

====Other glial====
Bergmann gliosis (in the cerebellum):<ref name=Ref_PSNP18>{{Ref PSNP|18}}</ref>
*Thin layer of cells (2-3 cells) with open nuclei that are larger than granular cell layer nuclei; seen with Purkinje cell loss.

<gallery>
Image:Bergmann_gliosis_-_intermed_mag.jpg | Bergmann gliosis - intermed. mag. (WC)
Image:Bergmann_gliosis_-_high_mag.jpg | Bergmann gliosis - high mag. (WC)
Image:Metastatic_adenocarcinoma_-_cerebellum_-_intermed_mag.jpg | Bergmann gliosis due to compression by metastasis - intermed mag. (WC)
</gallery>
Image:
*[http://tpx.sagepub.com/content/35/5/676/F5.expansion.html Bergmann gliosis (sagepub.com)].

====Reactive change vs. malignancy====
Reactive changes vs. malignancy (mnemonic ''MIMICS''):<ref name=Ref_TPoSP254>{{Ref TPoSP|254}}</ref>
*'''MI'''crovesicular pattern.
*'''M'''itoses.
*'''I'''rregular spacing.
*'''C'''alcifications.
*'''S'''atellitosis, perineuronal.
**Large "crowds" of glial cells associated with nuclei.

===Inflammatory===
DDx:
*Autoimmune - [[Multiple sclerosis]].
*Neoplastic - [[Neuropathology tumours#CNS lymphoma|CNS lymphoma]].
*Infectious - [[HSV]].

====Encephalitis====
=====General=====
DDx:
*Viral encephalitis.
*Paraneoplastic syndromes.

=====Gross=====
*Frontal and temporal lobe - most common for HSV encephalitis.<ref>{{Ref APBR|416 Q47}}</ref>

=====Microscopic=====
Features:<ref name=pmid20051019>{{Cite journal | last1 = Takei | first1 = H. | last2 = Wilfong | first2 = A. | last3 = Malphrus | first3 = A. | last4 = Yoshor | first4 = D. | last5 = Hunter | first5 = JV. | last6 = Armstrong | first6 = DL. | last7 = Bhattacharjee | first7 = MB. | title = Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of the literature. | journal = Neuropathology | volume = 30 | issue = 4 | pages = 381-91 | month = Aug | year = 2010 | doi = 10.1111/j.1440-1789.2009.01079.x | PMID = 20051019 }}</ref>
*Perivascular inflammation.
*Microglia.
*+/-Neuronophagia.
**Phagocytosis of neurons.<ref>URL: [http://medical-dictionary.thefreedictionary.com/neuronophagia http://medical-dictionary.thefreedictionary.com/neuronophagia]. Accessed on: 11 April 2012.</ref>
*+/-Viral cytopathic changes.
*+/-Perineuronal inflammation.

Notes:
*Hemorrhage<ref name=pmid18246335>{{Cite journal | last1 = Vossough | first1 = A. | last2 = Zimmerman | first2 = RA. | last3 = Bilaniuk | first3 = LT. | last4 = Schwartz | first4 = EM. | title = Imaging findings of neonatal herpes simplex virus type 2 encephalitis. | journal = Neuroradiology | volume = 50 | issue = 4 | pages = 355-66 | month = Apr | year = 2008 | doi = 10.1007/s00234-007-0349-3 | PMID = 18246335 }}</ref> and necrosis - characteristic of HSV encephalitis.

Image:
*[http://neuropathology-web.org/chapter5/images5/5-21l.jpg HSV encephalitis (neuropathology-web.org)].<ref>URL: [http://neuropathology-web.org/chapter5/chapter5dViruses.html http://neuropathology-web.org/chapter5/chapter5dViruses.html]. Accessed on: 27 January 2012.</ref>

=====IHC=====
IHC stains for:
*Viral etiologies, e.g. [[HSV]], [[CMV]].
*Parasites, e.g. [[toxoplasma]].
*[[Fungi]], e.g. PASD.

===Architecture===
====Rosettes====
*Rosette = circular/flower-like arrangement of cells.<ref name=pmid16551982>{{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>

*Perivascular pseudorosette = circular/flower-like arrangement of cells with blood vessel at the centre.<ref name=pmid16551982>{{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>
**[[Ependymoma]].
**[[Medulloblastoma]], PNET.
**[[Central neurocytoma]].
**[[Glioblastoma]]s.

*Homer-Wright rosette = (circular) rosette with a small (~100 micrometers ???) meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Medulloblastoma.
***Image: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Images/N1-TU-01-17.gif Medulloblastoma (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17 http://moon.ouhsc.edu/kfung/IACP-OLP/APAQ-Text/N1-TU-01.htm#17]. Accessed on: 3 December 2010.</ref>
**PNET (can be thought of as a supratentorial medulloblastoma) .

*Flexner-Wintersteiner rosette = rosette with empty centre (donut hole).<ref name=pmid16551982/>
**[[Retinoblastoma]]s.
**Pineoblastomas.
**Medulloepitheliomas.

*True ependymal rosette = surrounds a space.<ref name=pmid16551982/>
**[[Ependymoma]].

*Pineocytomatous/neurocytic rosette = irregular rosette with a large meshwork of fibers (neuropil) at the centre.<ref name=pmid16551982>{{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>
**Similar to Homer-Wright rosette.
**[[Pineocytoma]].
**[[Neurocytoma]].

====Other====
*Rosenthal fibres = worm-like or corkscrew-like (brightly) eosinophilic bodies; 10-40 micrometers.
**Key feature: variable thickness; helps separate from RBCs.
**Well-seen on trichrome stains.
<gallery>
Image:Rosenthal_HE_40x.jpg | Rosenthal fibres. (WP)
Image:Rosenthal_fibers.jpg | Rosenthal fibres - smear (WC/AFIP)
</gallery>
*Eosinophilic granular bodies = related to Rosenthal fibres; round cytoplasmic hyaline droplets in astrocytes.<ref>{{Ref MBNP|11}}</ref>
**Image: [Image:Pilocytic_Micro.jpg EGBs (WC/AFIP)].
*Pseudopalisading - picket fence-like alignment of cells; long axis of cells perpendicular to interface with other structures/cells.
**Pseudopalisading of tumour cells (around necrotic regions) is seen in [[glioblastoma]].

Note:
*Good set of articles: [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=PureSearch&db=PubMed&details_term=Neuropathology%20for%20the%20neuroradiologist Neuropathology for radiologists (ncbi.nlm.nih.gov)].

===Inclusion bodies===
*Negri bodies.
**Cytoplasmic inclusions; classically in Purkinje cells of the cerebellum, pyramidal cells of Ammon's horn.
**[[Rabies]].
<gallery>
Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg | Negri bodies. (WC/CDC)
</gallery>

*Lewy bodies.
**Eosinophilic cytoplasmic inclusion - composed mostly of alpha-synuclein.<ref name=pmid15235805>{{cite journal |author=Marui W, Iseki E, Kato M, Akatsu H, Kosaka K |title=Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease |journal=Acta Neuropathol. |volume=108 |issue=2 |pages=121–8 |year=2004 |month=August |pmid=15235805 |doi=10.1007/s00401-004-0869-4 |url=}}</ref>
<gallery>
Image:Lewy_Koerperchen.JPG | Lewy body. (WC)
</gallery>
====Table of inclusions====
{| class="wikitable sortable"
! Feature
! Appearance
! Associated disease
! Comment
! Image
|-
| Grumous bodies [[AKA]] granular bodies
| granular and eosinophilic ~50 micrometers
| neurodegenerative disease, neuroaxonal dystrophies, aging
| ?Comment
| ?Image
|-
| Cowdry type 1 AKA Cowdry type A
| eosinophilic & round + halo
| [[herpes simplex virus]]
| can be confused with Lewy body, Marinesco body
| ?Image
|-
| Lewy body
| round cytoplasmic eosinophilic body +/- pale halo
| [[Parkinson disease]], dementia with Lewy bodies
| morphology dependent on location in brain; +ve for alpha-synuclein, alpha-B crystallin, ubiquitin
| [[Image:Lewy_Koerperchen.JPG |thumb|center|150px|]], [http://firstaidteam.com/usmlerximages/v/USMLERxLewy+bodies.gif.html]
|-
| Lafora body
| round
| myoclonic [[epilepsy]]
| look like corpora amylacea; location: dentate nucleus, liver, skeletal muscle, sweat glands
| ?Image
|-
| Lipofuscin
| yellow & granular
| aging
| olive, dendate
| ?Image
|-
| Negri body
| small eosinophic bodies
| rabies
| found in hippocampal neurons and Purkinje cells
| [[Image:Rabies_encephalitis_Negri_bodies_PHIL_3377_lores.jpg|thumb|center|150px|]]
|-
| Hirano body
| concentric calcification/rod-shaped bright eosinophilic; overlap edge of neuron
| Alzheimer disease, Pick disease<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| actin crystals, may look like capillaries; location: CA1 of hippocampus
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adhirano.jpg]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>
|-
| Neurofibrillary tangles
| flame-shaped cytoplasmic thingy ~30 micrometers
| aging, Alzheimer's disease
| seen with silver stain
| [http://www.pakmed.net/academic/age/alz/plaques_tanglesBorder.jpg Schematic]<ref name=pakmednet>URL: [http://www.pakmed.net/academic/age/alz/alz030.htm http://www.pakmed.net/academic/age/alz/alz030.htm]. Accessed on: 12 November 2010.</ref>, [http://faculty.washington.edu/alexbert/MEDEX/Fall/adtangle.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Granulovacuolar degeneration
| cytoplasmic vacuoles 4-5 micrometers
| ageing, [[Alzheimer's disease]], Pick's disease
| main found in Ammon horn<ref name=Ref_MBNP5>{{Ref MBNP|5}}</ref>
| [http://faculty.washington.edu/alexbert/MEDEX/Fall/adgvd.jpg]<ref name=alexbert>URL: [http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm http://faculty.washington.edu/alexbert/MEDEX/Fall/NeuroPath_Obj.htm]. Accessed on: 13 November 2010.</ref>
|-
| Pick bodies
| round, homogenous, intracytoplasmic, ~10 micrometers
| [[Pick's disease]]
| pyramidal neurons, dentate granule cells (hippocampus); +ve for tau, tubulin, ubiquitin
| [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?action=view&current=Picks60x.jpg&mediafilter=images]
|-
| Bunina body
| size of Nissl granules, eosinophilic
| [[amyotrophic lateral sclerosis]] (ALS)
| EM: membrane-bound bodies; ubiquitin +ve
| [http://pathol.umin.ac.jp/gakubu/exam/2006jpg/19.jpg]
|-

|}

Image collection: [http://s212.photobucket.com/albums/cc74/cat_at_uw/Osler%20-%20Neuropath/?mediafilter=images Inclusion bodies (photobucket.com)].

==Immunohistochemistry==
{{Main|Immunohistochemistry}}
===General===
*S-100.
**Sensitive... but non-specific, e.g. also stains [[melanoma]].

===Glial===
*GFAP (glial fibrillary acidic protein) - should stain perikaryon.

====Glial tumours====
Standard work-up:
*GFAP.
*p53.
*Ki-67.

===Neuronal===
*Synaptophysin.
*Chromogranin.

===Carcinoma vs. glial tumours===
*AE1/AE3 often +ve in glial tumours (e.g. astrocytomas, oligodendrogliomas); CAM5.2 is usu. -ve in glial tumours.<ref name=Ref_PSNP_12>{{Ref PSNP|12}}</ref>

===Others===
*APP (amyloid precursor protein) - detects axonal swellings.
*NF (neurofilament) - detects axonal swellings.

=Brain tumours=
{{main|Neuropathology tumours}}
Tumours are a big part of neuropathology. The most common brain tumour is a metastasis. The most common primary tumour (in adults) is glioblastoma which has a horrible prognosis.

=Non-tumour=
==Cerebral hemorrhage==
:See: ''[[Intracranial hematoma]]'' for intracranial bleeds

Includes discussion of:
*[[Epidural hematoma]].
*[[Subdural hematoma]].
*[[Subarachnoid hematoma]].
*[[Intracerebral hematoma]]s.

==Duret hematoma==
*[[AKA]] Duret hemorrhage.
===General===
*Bleed in the upper brainstem (midbrain and pons).
**Thought to be due to transtentorial herniation secondary to supratentorial mass effect (e.g. supratentorial tumour, [[intracranial hemorrhage]]).<ref name=pmid11819006>{{Cite journal | last1 = Parizel | first1 = PM. | last2 = Makkat | first2 = S. | last3 = Jorens | first3 = PG. | last4 = Ozsarlak | first4 = O. | last5 = Cras | first5 = P. | last6 = Van Goethem | first6 = JW. | last7 = van den Hauwe | first7 = L. | last8 = Verlooy | first8 = J. | last9 = De Schepper | first9 = AM. | title = Brainstem hemorrhage in descending transtentorial herniation (Duret hemorrhage). | journal = Intensive Care Med | volume = 28 | issue = 1 | pages = 85-8 | month = Jan | year = 2002 | doi = 10.1007/s00134-001-1160-y | PMID = 11819006 }}</ref>
*Often fatal.<ref name=pmid11098635>{{Cite journal | last1 = Fujimoto | first1 = Y. | last2 = Aguiar | first2 = PH. | last3 = Freitas | first3 = AB. | last4 = de Andrade | first4 = AF. | last5 = Marino Júnior | first5 = R. | title = Recovery from Duret hemorrhage: a rare complication after craniotomy--case report. | journal = Neurol Med Chir (Tokyo) | volume = 40 | issue = 10 | pages = 508-10 | month = Oct | year = 2000 | doi = | PMID = 11098635 }}</ref>
===Gross===
*Extravasated blood in midbrain and pons - usu. ventral (anterior) and paramedian (adjacent to the midline).<ref name=pmid11819006/>

Image:
*[http://library.med.utah.edu/WebPath/jpeg5/CNS037.jpg Duret hemorrhage (med.utah.edu)].<ref>URL: [http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/npfrm.html]. Accessed on: 4 December 2011.</ref>

===Microscopic===
Features:
*RBC extravasation.
*+/-Hemosiderin-laden macrophages.
*+/-Ischemic neurons.

==Alcohol & CNS==
===Clinical===
*Wernicke's encephalopathy
**Mnemonic ''WACO'':
***Wernicke's.
***Ataxia.
***Confusion, confabulation -- Korsakoff.
***Ocular Sx (CN IV palsy).
**Cause: thiamine deficiency.

===Pathology===
Features:<ref>http://www.journals.elsevierhealth.com/periodicals/ycdip/article/S0968-6053(07)00035-X/abstract</ref>
*Morel's laminar sclerosis = spongy degeneration and gliosis of the cerebral cortex<ref>URL: [http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939 http://content.karger.com/ProdukteDB/produkte.asp?Doi=114939]. Accessed on: 22 September 2010.</ref> usu. prominent in the third layer of the cortex (outer pyramidal layer) and especially in the lateral-frontal cortex.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>
*Central pontine myelinolysis (CPM).<ref name=pmid21085565>{{cite journal |author=Campbell MC |title=Hyponatremia and central pontine myelinolysis as a result of beer potomania: a case report |journal=Prim Care Companion J Clin Psychiatry |volume=12 |issue=4 |pages= |year=2010 |pmid=21085565 |pmc=2983455 |doi=10.4088/PCC.09l00936ecr |url=}}</ref>
**Just what it sound like - myelin loss in the central pons.
**Classically associated with rapid correction of hyponatremia.<ref>{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref>
*Mammillary body shrinkage.<ref name=pmid8947329>{{cite journal |author=Shear PK, Sullivan EV, Lane B, Pfefferbaum A |title=Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia |journal=Alcohol. Clin. Exp. Res. |volume=20 |issue=8 |pages=1489-95 |year=1996 |month=November |pmid=8947329 |doi= |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0145-6008&date=1996&volume=20&issue=8&spage=1489}}</ref>
*Anterior cerebellar vermis atrophy; weak finding - as also age-related.<ref name=pmid3478969>{{cite journal |author=Torvik A |title=Brain lesions in alcoholics: neuropathological observations |journal=Acta Med. Scand. Suppl. |volume=717 |issue= |pages=47–54 |year=1987 |pmid=3478969 |doi= |url=}}</ref>
**Vermis atrophy is also seen in schizophrenia.<ref name=pmid1938163>{{cite journal |author=Sandyk R, Kay SR, Merriam AE |title=Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia |journal=Int. J. Neurosci. |volume=57 |issue=3-4 |pages=205–12 |year=1991 |month=April |pmid=1938163 |doi= |url=}}</ref>

====Marchiafava-Bignami Disease====
*Rare.
*Demyelination of the corpus callosum.<ref name=pmid15760886>{{cite journal |author=Johkura K, Naito M, Naka T |title=Cortical involvement in Marchiafava-Bignami disease |journal=AJNR Am J Neuroradiol |volume=26 |issue=3 |pages=670–3 |year=2005 |month=March |pmid=15760886 |doi= |url=http://www.ajnr.org/cgi/content/full/26/3/670}}</ref>

====Wernicke's encephalopathy====
General:
*Due to thiamine deficiency.
**Malnourishment often accompanies [[alcoholism]].

Features:<ref name=pmid3929155>{{Cite journal | last1 = Torvik | first1 = A. | title = Two types of brain lesions in Wernicke's encephalopathy. | journal = Neuropathol Appl Neurobiol | volume = 11 | issue = 3 | pages = 179-90 | month = | year = | doi = | PMID = 3929155 }}</ref>
*Neurons of mammillary bodies preserved - '''key'''.
*Loss of myelin.
*Hemorrhage.
*Edema.
*Reactive blood vessels.

Note:
*The thalamus and inferior olives show neuronal loss.<ref name=pmid3929155/>

====Common non-specific findings====
*[[Intracranial haemorrhage]] - due to trauma.

==Meningitis==
===General===
*Definition: inflammation of the meninges (pia mater, arachnoid membranes, dura mater).

Classic clinical presentation:
*Neck stiffness.
*Fever.
*+/-Headache.
*+/-Decreased level of consciousness.

CSF findings:
{| class="wikitable sortable"
! Type
! Glucose
! Protein
! Cells
|-
| Bacterial, acute
| low
| high
| neutrophils
|-
| Viral
| normal
| slight elevation
| lymphocytes
|}

====Etiology====
*Infectious.
**Bacterial.
**Viral.
**Parasitic
*Autoimmune.
*Toxic.
*Aseptic - see ''[[Mollaret's meningitis]]''.

Bacterial meningitis - most probably cause by age:<ref>{{Ref PCPBoD8|666-7}}</ref>
{| class="wikitable sortable"
! Age
! Organism
|-
| Neonate
| ''Escherichia coli'', Group B Streptococcus
|-
| Infants, children
| ''Streptococcus pneumoniae''
|-
| Adolescents, young adults
| ''Neisseria meningitidis''
|-
| Elderly
| ''Streptococcus pneumoniae'', ''Listeria monocytogenes''
|}

===Gross===
Features:
*+/-Clouded appearance of the meninges.
*+/-Pus.
*+/-Petechiae.
*+/-Cerebral edema.

====Image====
<gallery>
Image:Streptococcus_pneumoniae_meningitis,_gross_pathology_33_lores.jpg | Meningitis. (WC)
</gallery>

===Microscopic===
Features:
*Inflammation of the meninges:
**+/-[[Neutrophil]]s.
**+/-Lymphocytes.
**+/-[[Plasma cell]]s.
*+/-Microorganisms (infectious meningitis):
**Bacteria.
**[[Fungi]], e.g. [[aspergillosis]] (may be intravascular).

Main DDx:
*[[Lymphoma]].

====Image====
<gallery>
Image:Meningitis_Histopathology.jpg | Bacterial meningitis. (WC)
</gallery>

==Cerebral abscess==
===General===
*May mimic malignancy clinically.

===Microscopic===
Features:
*Sheets of neutrophils surrounded by fibrosing brain.
**Fibrosing brain: pale (lighter pink than normal brain tissue), dense.

Images:
*[http://pathology.class.kmu.edu.tw/ch01/4-1.jpg Cerebral abscess - very low mag. (kmu.edu.tw)].<ref>URL: [http://pathology.class.kmu.edu.tw/ch01/Slide4.htm http://pathology.class.kmu.edu.tw/ch01/Slide4.htm]. Accessed on: 1 January 2012.</ref>
*[http://pathology.class.kmu.edu.tw/ch01/4-5.jpg Cerebral abscess - low mag. (kmu.edu.tw)].

==Neurodegenerative diseases==
{{Main|Neurodegenerative diseases}}
This is a hueueuge topic. It is covered in its own article and includes a general discussion of dementia.

==Epilepsy==
{{Main|Epilepsy}}

==Cerebrovascular accident==
*Abbreviated ''CVA''.
*[[AKA]] ''stroke''.

===General===
*Very common.
*Leading cause of morbidity and mortality.

Clinical classification:
# Hemorrhagic stroke.
# Ischemic stroke.

===Gross===
*Soft/mushy brain.
*Older [[infarct]]s.
**A "roof" is present - a thin submeningeal layer is preserved by the CSF.<ref>MUN. 16 December 2009.</ref>
***"Roof" is absent in trauma.
**Cavity - in older infarcts.
***''[[Multiple sclerosis]]'' does not cavitate.
*Laminar necrosis = (thin) chalky line replaces grey mater.<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q03-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q03-Ans.htm]. Accessed on: 26 October 2010.</ref>
**[[AKA]] ''pseudolaminar necrosis'' - as it is not localized to a specific layer of the cortex.<ref>MUN. 26 November 2010.</ref>

DDx:
*[[Cerebral contusion]].

===Microscopic===
Features:
*Ischemic neurons.
*+/-Neuronal loss.
*+/-Microglial.
*+/-[[Thrombosis]].
*+/-[[Atherosclerosis]].

==Hypoxic-ischemic encephalopathy==
*Abbreviated ''HIE''.
===General===
*Often due to ''cardiac arrest'', i.e. global ischemia.
*Triple watershed area = parieto-occipital cortex, extrastriate occipital cortex.

Note:
*''Hypoxia'' = blood decreased oxygen carrying capacity,<ref name=Ref_PCPBoD8_10>{{Ref PCPBoD8|10}}</ref> e.g. [[anemia]].
*''Ischemia'' = decreased blood flow.<ref name=Ref_PCPBoD8_10>{{Ref PCPBoD8|10}}</ref>
*Either ''or'' both = less oxygen delivery to tissue.
===Microscopic===
Features:
*Hippocampal ischemic changes (in adults):
**Loss of neurons in CA1, CA3 and CA4 +/- "cavitation".
***Neuronal loss: No blue (nuclei) where there should be some.
***Cavitation: bubbles/clear spaces where there should be none.
**CA2 neurons preserved/resistant.
*Purkinje cell loss in the cerebellum and [[Bergmann gliosis]].
*"Anoxic neurons".<ref>URL: [http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html]. Accessed on: 12 July 2010.</ref>
**Shrunken neurons with intensely eosinophilic cytoplasm and pyknotic (shrunken) nuclei.
*Pseudolaminar necrosis - (uncontrolled) cell death in the cerebral cortex in a band-like pattern,<ref>Hypoxic and Ischemic Encephalopathy. neuropathology.neoucom.edu. Accessed on: 29 December 2010.</ref> with a relative preservation of cells immediately adjacent to the meninges.

Notes:
*Neurons of ''subiculum'' in adults - usu. normal (as they are resistant to ischemic changes).
====Images====
*Anoxic neurons:
**[http://www.neuropathologyweb.org/chapter2/images2/2-1HIE.jpg Anoxic neurons (neuropathologyweb.org)].
**[http://moon.ouhsc.edu/kfung/iacp-olp/APAQ-Images/N1-MS-01-16.gif Anoxic neurons (ouhsc.edu)].<ref>URL: [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-16-Ans.htm] and [http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm]. Accessed on: 31 October 2010.</ref>
<gallery>
Image:Alzheimer_type_II_astrocyte_high_mag_cropped.jpg | Anoxic neurons. (WC)
</gallery>
*Hippocampal ischemic changes:
**[http://www.neuropathologyweb.org/chapter2/images2/2-hippoHIE.jpg Hippocampus in HIE (neuropathologyweb.org)].<ref>URL: [http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html http://www.neuropathologyweb.org/chapter2/chapter2aHIE.html]. Accessed on: 14 January 2011.</ref>
*Pseudolaminar necrosis:
<gallery>
Image:Cortical_pseudolaminar_necrosis_-_lfb_-_very_low_mag.jpg | Pseudolaminar necrosis - very low mag. (WC)
Image:Cortical_pseudolaminar_necrosis_-_lfb_-_intermed_mag.jpg | Pseudolaminar necrosis - intermed. mag. (WC)
</gallery>

==Multiple sclerosis==
*Abbreviated ''MS''.
===General===
*A bread 'n butter disease of neurology in Canada.

Clinical:
*CSF: oligoclonal bands of immunoglobulin.<ref>{{Ref PBoD8|1311}}</ref>

Classification of MS lesions:
*Early active.
*Inactive.
*Early remyelinating.
*Late remyelinating.

===Radiologic/Gross===
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*White matter lesions.
**Cerebrum (classically): periventricular distribution.
**Optic nerves (optic neuritis) - classic presentation.

===Microscopic===
Features:<ref>URL: [http://library.med.utah.edu/kw/ms/path.html http://library.med.utah.edu/kw/ms/path.html]. Accessed on: 12 July 2010.</ref>
*Perivascular inflammation.
**Esp. lymphocytes.
*Demyelination.
**Subcortical myelinated fibers are often spared.

Chronic lesions - specific features:<ref>{{Ref APBR|425 Q43}}</ref>
#Macrophages.
#Astrocyte enlargement.

DDx:
*[[ADEM]].
*[[Neuromyelitis optica]].
*[[Lymphoma]].
*[[Diffuse astrocytoma]].

Images:
*[http://path.upmc.edu/cases/case79.html Multiple sclerosis masquerading as a diffuse astrocytoma - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case636.html Tumefactive multiple sclerosis - several images (upmc.edu)].

===IHC===
*HAM-56 - macrophages.
*CD8 - lymphocytes.

==Cerebral amyloid angiopathy==
===General===
*Abbreviated ''CAA''.
*Disease of the old.
*Strong association with ''[[lobar haemorrhage]]'' (bleeds of the cerebellar cortex and cerebral cortex).<ref name=pmid16982664>{{cite journal |author=Thanvi B, Robinson T |title=Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people |journal=Age Ageing |volume=35 |issue=6 |pages=565–71 |year=2006 |month=November |pmid=16982664 |doi=10.1093/ageing/afl108 |url=}}</ref>

Etiology:
*[[Amyloid]] deposition in the basal lamina of smooth muscle (in the cerebellar cortex and cerebral cortex).

===Gross===
*Bleeds typically superficial (cortex and subcortical white matter) and in the frontal lobe or parietal lobe.<ref name=pmid17297004>{{Cite journal | last1 = Haacke | first1 = EM. | last2 = DelProposto | first2 = ZS. | last3 = Chaturvedi | first3 = S. | last4 = Sehgal | first4 = V. | last5 = Tenzer | first5 = M. | last6 = Neelavalli | first6 = J. | last7 = Kido | first7 = D. | title = Imaging cerebral amyloid angiopathy with susceptibility-weighted imaging. | journal = AJNR Am J Neuroradiol | volume = 28 | issue = 2 | pages = 316-7 | month = Feb | year = 2007 | doi = | PMID = 17297004 | URL = http://www.ajnr.org/content/28/2/316.long }}</ref>

===Microscopic===
Features:
*Amorphous, acellular eosinophilic material within walls of small arteries.
**This is a high power diagnosis with congo red staining.

Notes:
*Amyloidosis is seen in all individuals with [[Alzheimer's disease]]; the amount of amyloid is what differs -- in CAA it is lots and lots.
*The white matter is typically spared by CAA.<ref name=pmid19225408>{{Cite journal | last1 = Schröder | first1 = R. | last2 = Deckert | first2 = M. | last3 = Linke | first3 = RP. | title = Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy. | journal = J Neuropathol Exp Neurol | volume = 68 | issue = 3 | pages = 286-99 | month = Mar | year = 2009 | doi = 10.1097/NEN.0b013e31819a87f9 | PMID = 19225408 }}
</ref>

====Images====
<gallery>
Image:Cerebral_amyloid_angiopathy_-_very_high_mag.jpg |CAA - congo red - very high mag. (WC)
Image:Cerebral_amyloid_angiopathy_-_low_mag.jpg |CAA - congo red - low mag. (WC)
Image:Cerebral_amyloid_angiopathy_-2b-_amyloid_beta_-_high_mag.jpg |CAA - beta-amyloid - high mag. (WC)
</gallery>
===Stains===
*[[Congo red]].

===IHC===
*Abeta-amyloid (AKA beta-amyloid).

==Central pontine myelinolysis==
*Abbreviated ''CPM''.
*[[AKA]] ''pontine myelinolysis''.
===General===
*Classically in the pons, ergo "pontine" is in the name.
*Classically midline, ergo "central" is in the name.
**May occur elsewhere -- known as ''extrapontine myelinolysis''.

Etiology:
*Rapid correction of hyponatremia.<ref name=pmid22080394>{{Cite journal | last1 = Chang | first1 = Y. | last2 = An | first2 = DH. | last3 = Xing | first3 = Y. | last4 = Qi | first4 = X. | title = Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. | journal = Neurol Sci | volume = | issue = | pages = | month = Nov | year = 2011 | doi = 10.1007/s10072-011-0838-3 | PMID = 22080394 }}</ref>
*Tacrolimus post-liver transplant.<ref name=pmid21959523>{{Cite journal | last1 = Fukazawa | first1 = K. | last2 = Nishida | first2 = S. | last3 = Aguina | first3 = L. | last4 = Pretto | first4 = E. | title = Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation. | journal = Ann Transplant | volume = 16 | issue = 3 | pages = 139-42 | month = Sep | year = 2011 | doi = | PMID = 21959523 }}</ref>
*Associated with [[alcoholism]] and malnourishment.

Clinical:<ref>{{Cite journal | last1 = Lai | first1 = CC. | last2 = Tan | first2 = CK. | last3 = Lin | first3 = SH. | last4 = Chen | first4 = HW. | title = Central pontine myelinolysis. | journal = CMAJ | volume = 183 | issue = 9 | pages = E605 | month = Jun | year = 2011 | doi = 10.1503/cmaj.090186 | PMID = 21543311 | PMC = 3114939 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114939/?tool=pubmed }}</ref>
*Decreased level of consciousness - most common.
*Quadriplegia.
*Poor prognosis.

===Microscopic===
Features:<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*Myelin loss.
*No inflammation.
*Relative preservation of neurons.

Images:
*[http://neuropathology-web.org/chapter6/images6/6-9l.jpg CPM (neuropathology-web.org)].<ref name=npw_ch6>URL: [http://neuropathology-web.org/chapter6/chapter6dCPM.html http://neuropathology-web.org/chapter6/chapter6dCPM.html]. Accessed on: 20 December 2011.</ref>
*[http://dartmed.dartmouth.edu/spring09/html/virtual_microscopy_we/ CPM (dartmouth.edu)].

==Vascular malformations==
{{Main|Vascular malformations}}
Types:<ref name=pmid17076525>{{cite journal |author=Prayson RA, Kleinschmidt-DeMasters BK |title=An algorithmic approach to the brain biopsy--part II |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1639–48 |year=2006 |month=November |pmid=17076525 |doi= |url=}}</ref>
#Arteriovenous malformation.
#*Most important clinically - highest risk of bleeding.
#Varix.
#*One large (dilated) vein.
#Venous angioma.
#*Many small veins.
#Cavernous malformation.
#*Vessels are back-to-back (no intervening parenchyma).

Also see: ''[[Sturge-Weber syndrome]]''.

=Cysts=
===General===
*All are "benign", but some may be fatal due to spatial constraints.

===List of cysts===
*[[Colloid cyst]].
**Columnar epithelium.
*Arachnoid cyst - considered precursor of [[meningioma]].
**[[Psammoma bodies]].
**Clumps of cells.
**Whorled pattern.
*[[Dermoid cyst]].
**Skin + adnexal structures.
**... think of ovarian dermoid.
*Epidermoid cyst.
*Choriod cyst.
*Neuroenteric cyst.
**Foregut cyst with connection to dura.<ref>URL: [http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm http://bhj.org/journal/2003_4502_april/neurentericcyst_373.htm]. Accessed on: 19 December 2011.</ref>
***Gastrointestinal tract epithelium.
***Usually seen with vertebral anomalies.
*Epithelial cyst.
*Others.

==Colloid cyst==
===General===
Classic presentation:<ref name=pmid15228889>{{Cite journal | last1 = Spears | first1 = RC. | title = Colloid cyst headache. | journal = Curr Pain Headache Rep | volume = 8 | issue = 4 | pages = 297-300 | month = Aug | year = 2004 | doi = | PMID = 15228889 }}</ref>
*Headache - may be relieved by lying down.
*Can cause [[sudden natural death]].<ref name=pmid14716130>{{Cite journal | last1 = Kava | first1 = MP. | last2 = Tullu | first2 = MS. | last3 = Deshmukh | first3 = CT. | last4 = Shenoy | first4 = A. | title = Colloid cyst of the third ventricle: a cause of sudden death in a child. | journal = Indian J Cancer | volume = 40 | issue = 1 | pages = 31-3 | month = | year = | doi = | PMID = 14716130 }}</ref>

===Gross===
*Fluid filled cyst - classically in the third ventricle.

Image:
*[http://www.ajnr.org/content/21/8/1470/F3.expansion.html Colloid cyst of third ventricle (ajnr.org)].<ref name=pmid11003281/>

===Microscopic===
Features:<ref name=pmid11003281>{{Cite journal | last1 = Armao | first1 = D. | last2 = Castillo | first2 = M. | last3 = Chen | first3 = H. | last4 = Kwock | first4 = L. | title = Colloid cyst of the third ventricle: imaging-pathologic correlation. | journal = AJNR Am J Neuroradiol | volume = 21 | issue = 8 | pages = 1470-7 | month = Sep | year = 2000 | doi = | PMID = 11003281 }}</ref>
*Simple epithelium with ciliated cells and goblet cells.

====Images====
<gallery>
Image:Colloid_Cyst_HE_40x.jpg | Colloid cyst. (WC)
</gallery>
www:
*[http://www.ajnr.org/content/21/8/1470/F4.expansion.html Colloid cyst (ajnr.org)].<ref name=pmid11003281/>

=Paediatric pathology=
==Kernicterus==
===General===
*Due to hyperbilirubinemia.<ref name=pmid7063283>{{Cite journal | last1 = Turkel | first1 = SB. | last2 = Miller | first2 = CA. | last3 = Guttenberg | first3 = ME. | last4 = Moynes | first4 = DR. | last5 = Godgman | first5 = JE. | title = A clinical pathologic reappraisal of kernicterus. | journal = Pediatrics | volume = 69 | issue = 3 | pages = 267-72 | month = Mar | year = 1982 | doi = | PMID = 7063283 }}</ref>

===Gross===
*Yellow staining:<ref name=npw>URL: [http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html http://neuropathology-web.org/chapter3/chapter3eBilirubinencephalopathy.html]. Accessed on: 30 May 2012.</ref>
**Basal ganglia.<ref name=pmid10920171>{{Cite journal | last1 = Hansen | first1 = TW. | last2 = Hervieux | first2 = JF. | last3 = Orth | first3 = J. | last4 = Schmorl | first4 = CG. | last5 = Baumes | first5 = JB. | title = Pioneers in the scientific study of neonatal jaundice and kernicterus. | journal = Pediatrics | volume = 106 | issue = 2 | pages = E15 | month = Aug | year = 2000 | doi = | PMID = 10920171 }}</ref>
**Hippocampus.<ref name=pmid15091133>{{Cite journal | last1 = Paksoy | first1 = Y. | last2 = Koç | first2 = H. | last3 = Genç | first3 = BO. | title = Bilateral mesial temporal sclerosis and kernicterus. | journal = J Comput Assist Tomogr | volume = 28 | issue = 2 | pages = 269-72 | month = | year = | doi = | PMID = 15091133 }}</ref>
**Subthalamic nucleus.

Note:
*May not be specific.<ref name=pmid7063283/>

Image:
*[http://www.flickr.com/photos/neonatal-box/6275988844/ Kernicterus (flickr.com)].

===Microscopic===
Features - similar to [[HIE]]:<ref name=npw/>
*+/-Red neurons.
*+/-Gliosis.

==Joubert syndrome==
*Malformation of the cerebellar vermis.<ref name=ninds_joubert>[http://www.ninds.nih.gov/disorders/joubert/joubert.htm http://www.ninds.nih.gov/disorders/joubert/joubert.htm]</ref>

===Epidemiology===
*Autosomal recessive - mutation in a number of genes including NPHP1, AHI1, and CEP290.<ref name=ninds_joubert/>

=Weird stuff=
==Acute disseminated encephalomyelitis==
*Abbreviated ''ADEM''.
===General===
*Thought to be autoimmune; often associated with/preceded by by viral illness.<ref name=pmid17438235>{{cite journal |author=Tenembaum S, Chitnis T, Ness J, Hahn JS |title=Acute disseminated encephalomyelitis |journal=Neurology |volume=68 |issue=16 Suppl 2 |pages=S23–36 |year=2007 |month=April |pmid=17438235 |doi=10.1212/01.wnl.0000259404.51352.7f |url=}}</ref>
*May mimic [[multiple sclerosis]].

Treatment:
*Steroids.
*Plasmapheresis.

Diagnosis:
*Need to r/o infection (with lumbar puncture).
*No old plaques on imaging (MRI).

An acute form exists known as ''acute hemorrhagic leukoencephalitis''<ref>URL: [http://path.upmc.edu/cases/case102/dx.html http://path.upmc.edu/cases/case102/dx.html]. Accessed on: 2 January 2012.</ref> (AKA ''acute necrotizing hemorrhagic encephalomyelitis'').

===Microscopic===
Features:<ref>{{Ref PBoD8|1312}}</ref>
*Myelin loss with sparing of axons.
*Inflammation:
**Early: [[neutrophil]]s.
**Late: mononuclear cells (lymphocytes, plasma cells).
*Lipid-laden macrophages.

DDx:
*[[Multiple sclerosis]].
**Tend to be larger, more lymphocytes,<ref>{{Ref APBR|423}}</ref> age of the lesions differ.
*Acute necrotizing hemorrhagic encephalomyelitis (ANHE) - if one considers this a separate entity.
*Acute necrotizing encephalopathy.<ref>URL: [http://path.upmc.edu/cases/case619/dx.html http://path.upmc.edu/cases/case619/dx.html]. Accessed on: 26 January 2012.</ref>

==Neuromyelitis optica==
*Abbreviated ''NMO''.
===General===
*Rare autoimmune disease - once considered a variant of [[multiple sclerosis]].
**Autoantibodies directed at aquaporin-4.<ref name=pmid22087205>{{Cite journal | last1 = Kim | first1 = W. | last2 = Kim | first2 = SH. | last3 = Kim | first3 = HJ. | title = New insights into neuromyelitis optica. | journal = J Clin Neurol | volume = 7 | issue = 3 | pages = 115-27 | month = Sep | year = 2011 | doi = 10.3988/jcn.2011.7.3.115 | PMID = 22087205 }}</ref>

Diagnosis:
*NMO-IgG.

Clinical - preferentially:
*Eye (optic neuritis).
*Spinal cord (myelitis).

===Microscopic===
Features:
*Inflammation - lymphocytes, macrophages.
*Reactive astrocytes.

Images:
*[http://path.upmc.edu/cases/case637.html Neuromyelitis optica - several images (upmc.edu)].

===IHC===
*Mixed lymphocyte population with CD3 > CD20.
*Aquaporin-4 loss.

==Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy==
*Commonly abbreviated ''CADASIL''.
===General===
*Autosomal dominant disorder - as the name implies.<ref name=pmid19174371>{{Cite journal | last1 = Tikka | first1 = S. | last2 = Mykkänen | first2 = K. | last3 = Ruchoux | first3 = MM. | last4 = Bergholm | first4 = R. | last5 = Junna | first5 = M. | last6 = Pöyhönen | first6 = M. | last7 = Yki-Järvinen | first7 = H. | last8 = Joutel | first8 = A. | last9 = Viitanen | first9 = M. | title = Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. | journal = Brain | volume = 132 | issue = Pt 4 | pages = 933-9 | month = Apr | year = 2009 | doi = 10.1093/brain/awn364 | PMID = 19174371 }}
</ref>
*Causes strokes in 40-50 year-old.
*Cerebral microbleeds - common.
**Associated with increased risk of [[intracerebral hemorrhage]].<ref name=pmid17135568>{{Cite journal | last1 = Choi | first1 = JC. | last2 = Kang | first2 = SY. | last3 = Kang | first3 = JH. | last4 = Park | first4 = JK. | title = Intracerebral hemorrhages in CADASIL. | journal = Neurology | volume = 67 | issue = 11 | pages = 2042-4 | month = Dec | year = 2006 | doi = 10.1212/01.wnl.0000246601.70918.06 | PMID = 17135568 }}</ref>
*Characteristic MRI findings - present in asymptomatic individuals with mutation.
*Increased risk of [[heart|myocardial infarction]].<ref name=pmid12861102>{{cite journal |author=Lesnik Oberstein SA, Jukema JW, Van Duinen SG, ''et al.'' |title=Myocardial infarction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) |journal=Medicine (Baltimore) |volume=82 |issue=4 |pages=251–6 |year=2003 |month=July |pmid=12861102 |doi=10.1097/01.md.0000085054.63483.40 |url=}}</ref>

Note:
*There is also an autosomal recessive form - CARASIL.<ref name=pmid21215656>{{Cite journal | last1 = Fukutake | first1 = T. | title = Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. | journal = J Stroke Cerebrovasc Dis | volume = 20 | issue = 2 | pages = 85-93 | month = | year = | doi = 10.1016/j.jstrokecerebrovasdis.2010.11.008 | PMID = 21215656 }}</ref>
====Etiology====
*Mutation of ''Notch 3'' gene.<ref name=pmid15537516>{{Cite journal | last1 = Kalaria | first1 = RN. | last2 = Viitanen | first2 = M. | last3 = Kalimo | first3 = H. | last4 = Dichgans | first4 = M. | last5 = Tabira | first5 = T. | title = The pathogenesis of CADASIL: an update. | journal = J Neurol Sci | volume = 226 | issue = 1-2 | pages = 35-9 | month = Nov | year = 2004 | doi = 10.1016/j.jns.2004.09.008 | PMID = 15537516 }}</ref>
**Diagnosis: proven ''Notch 3'' mutation.

===Microscopic===
Features:
*+/-Subcortical infarcts.
**Patches of (non-myelinated) tissue within the white matter deep to the cortex with abundant macrophages.
*Blood vessels typically have a basophilic granularity.<ref name=pmid17076524>{{cite journal |author=Kleinschmidt-DeMasters BK, Prayson RA |title=An algorithmic approach to the brain biopsy--part I |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1630–8 |year=2006 |month=November |pmid=17076524 |doi= |url=}}</ref>

====IHC====
*Notch 3: smooth muscle and pericytes punctate +ve.<ref name=pmid12861102/>

Notes:
*No cortical involvement -- this is unlike ''multiple sclerosis''.

DDx:
*[[Amyloidosis]].
*[[Binswanger's disease]] - multi-infarct dementia affecting subcortical white matter.
**Often diagnosed as ''Alzheimer's disease'' in the past.

<gallery>
Image:CADASIL_-_very_high_mag.jpg | Notch 3 staining in CADASIL. (WC/Nephron)
</gallery>
====Skin biopsy diagnosis====
*Can be diagnosed on a skin biopsy.<ref name=pmid11755616 >{{cite journal |author=Joutel A, Favrole P, Labauge P, ''et al.'' |title=Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis |journal=Lancet |volume=358 |issue=9298 |pages=2049–51 |year=2001 |month=December |pmid=11755616 |doi=10.1016/S0140-6736(01)07142-2 |url=}}</ref>

===Electron microscopy===
*Granular osmiophilic material (GOM).

==Progressive multifocal leukoencephalopathy==
*Abbreviated ''PML''.
===General===
*Caused by ''JC virus'' (a type of [[polyomavirus]]<ref name=pmid21499097>{{Cite journal | last1 = Berger | first1 = JR. | title = The basis for modeling progressive multifocal leukoencephalopathy pathogenesis. | journal = Curr Opin Neurol | volume = 24 | issue = 3 | pages = 262-7 | month = Jun | year = 2011 | doi = 10.1097/WCO.0b013e328346d2a3 | PMID = 21499097 }}</ref>) in the context of immunodeficiency; usu. in the setting of [[HIV]] infection.<ref name=pmid12709870>{{Cite journal | last1 = Berger | first1 = JR. | title = Progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome: explaining the high incidence and disproportionate frequency of the illness relative to other immunosuppressive conditions. | journal = J Neurovirol | volume = 9 Suppl 1 | issue = | pages = 38-41 | month = | year = 2003 | doi = 10.1080/13550280390195261 | PMID = 12709870 }}</ref>
**Approximately 5% of HIV patients develop PML.<ref name=pmid12709870/>
**Virus destroys oligodendrocytes -> demyelination results.<ref name=pmid21823157>{{Cite journal | last1 = Mateen | first1 = FJ. | last2 = Muralidharan | first2 = R. | last3 = Carone | first3 = M. | last4 = van de Beek | first4 = D. | last5 = Harrison | first5 = DM. | last6 = Aksamit | first6 = AJ. | last7 = Gould | first7 = MS. | last8 = Clifford | first8 = DB. | last9 = Nath | first9 = A. | title = Progressive multifocal leukoencephalopathy in transplant recipients. | journal = Ann Neurol | volume = 70 | issue = 2 | pages = 305-22 | month = Aug | year = 2011 | doi = 10.1002/ana.22408 | PMID = 21823157 }}
</ref>
*Suspected cases are biopsied - unlike other demyelinating diseases.<ref>URL: [http://path.upmc.edu/cases/case336/dx.html http://path.upmc.edu/cases/case336/dx.html]. Accessed on: 15 January 2012.</ref>
===Gross===
*Multifocal - as the name suggests.

DDx:
*[[Multiple sclerosis]].

===Microscopic===
Features:<ref>URL: [http://path.upmc.edu/cases/case120/dx.html http://path.upmc.edu/cases/case120/dx.html]. Accessed on: 3 January 2012.</ref>
*Perivascular inflammatory cells.
*Foamy histiocytes.
*Abnormal appearing glial cells:<ref name=uscf_pml>URL: [http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm]. Accessed on: 3 January 2012.</ref>
**Reactive astrocytes.
**Oligodendrocytes with nuclear enlargement and glassy magenta chromatin - '''key feature'''.
**Atypical mitoses - known as ''[[Creutzfeldt cell]]''.

Note:
*The chromatin changes remind me of [[Urine_cytopathology#Human_polyomavirus_infection|polyomavirus]] in [[urine cytology]]... perhaps ''not'' surprising as they are related.

Images:
*[http://path.upmc.edu/cases/case120/micro.html PML - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case120/dx.html PML - case 1 (upmc.edu)].
*[http://path.upmc.edu/cases/case336/images/fig03.jpg Crutzfeldt cell - case 2 (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case336.html http://path.upmc.edu/cases/case336.html]. Accessed on: 15 January 2012.</ref>
*[http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Figures/PMLHandE.jpg PML oligodendrocyte (ucsf.edu)].<ref name=uscf_pml>URL: [http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm http://missinglink.ucsf.edu/lm/ids_104_Demyelination/Didactic/Pml.htm]. Accessed on: 3 January 2012.</ref>
*[http://neuro.psychiatryonline.org/data/Journals/NP/3923/RA4831F2.jpeg PML oligodendrocyte (psychiatryonline.org)].<ref>{{Cite journal | last1 = Hurley | first1 = RA. | last2 = Ernst | first2 = T. | last3 = Khalili | first3 = K. | last4 = Del Valle | first4 = L. | last5 = Simone | first5 = IL. | last6 = Taber | first6 = KH. | title = Identification of HIV-associated progressive multifocal leukoencephalopathy: magnetic resonance imaging and spectroscopy. | journal = J Neuropsychiatry Clin Neurosci | volume = 15 | issue = 1 | pages = 1-6 | month = | year = 2003 | doi = | PMID = 12556565 }}</ref>

===IHC===
*SV40 +ve.<ref name=pmid15581180>{{Cite journal | last1 = Muñoz-Mármol | first1 = AM. | last2 = Mola | first2 = G. | last3 = Fernández-Vasalo | first3 = A. | last4 = Vela | first4 = E. | last5 = Mate | first5 = JL. | last6 = Ariza | first6 = A. | title = JC virus early protein detection by immunohistochemistry in progressive multifocal leukoencephalopathy: a comparative study with in situ hybridization and polymerase chain reaction. | journal = J Neuropathol Exp Neurol | volume = 63 | issue = 11 | pages = 1124-30 | month = Nov | year = 2004 | doi = | PMID = 15581180 }}</ref>

=See also=
*[[Brain tumours]].
*[[Pituitary gland]].
*[[Histiocytoses]].
*[[Intracranial hematomas]].
*[[Spine]].

=References=
{{reflist|2}}

=External links=
*[http://www.neuropathologyweb.org/ Neuropathology (neuropathologyweb.org)].
**[http://www.neuropathologyweb.org/test6/6test.html Quiz (neuropathologyweb.org)].
*[http://blog.lib.umn.edu/santa013/neuropathology/ Neuropathology cases (lib.umn.edu)].
*[http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1 Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org)].
*[http://moon.ouhsc.edu/kfung/jty1/neurotest/AAQuestion-41-60.htm Neurocytopathology quiz (ouhsc.edu)].
*[http://wiki.cns.org/wiki/index.php/Main_Page WikiCNS (wiki.cns.org)].

[[Category:Neuropathology]]