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CSF cytopathology (view source)

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This article deal only with cerebrospinal fluid (CSF) cytopathology.  An introduction to cytopathology is in the ''[[cytopathology]]'' article.
This article deal only with cerebrospinal fluid (CSF) cytopathology.  An introduction to cytopathology is in the ''[[cytopathology]]'' article.


All CSF specimens get ''triaged'' at UHN as:
In many institutions, CSF specimens get triaged/rapidly assessed as:
#They are small specimens ~ usually 1-10 ml.
#They are small specimens ~ usually 1-10 ml.
#The procedure to obtain them is non-trivial, i.e. not pleasant for the patient and not risk free.
#The procedure to obtain them is non-trivial, i.e. not pleasant for the patient and not risk free.
#Lymphoma is a common malignancy of malignancies found in the CSF.
#Lymphoma is a common malignancy of malignancies found in the CSF.


All CSF specimens are ''stat''.
In many institutions, all CSF specimens are ''stat''.
==Cerebrospinal fluid==
==Cerebrospinal fluid==
==Normal==
==Normal==
*Paucicellular.
*Paucicellular.
 
**Acellular specimens common and considered adequate.<ref>{{cite book |author=Mody, Dina R. |title= [https://www.amazon.ca/Diagnostic-Pathology-Cytopathology-Dina-Mody/dp/1931884552/ Diagnostic Cytopathology] |publisher=Elsevier Canada |location= |year=2018 |pages= {{{1|II-3 2}}} |edition=1st |isbn=978-1931884556 |oclc= |doi= |accessdate=}}</ref>
*protein is around 15-40 mg/dl
Gobs of anuclear material:
Gobs of anuclear material:
*Protein vs. white mater.
*Protein vs. white matter.
*Ocassionally arachnoid cap cell-


Bark-like flaky material:
Bark-like flaky material:
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*Cytospin - if no abnormality at triage.
*Cytospin - if no abnormality at triage.
**The cellularity of the cytospin will appear to be increased (artifact).
**The cellularity of the cytospin will appear to be increased (artifact).
===Images===
<gallery>
File:4 vials of human cerebrospinal fluid.jpg | Normal CSF fluid is clear. (WC/James Heilman)
File:CSF normal cytology.jpg | Normal CSF cytology Pappenheim specimen. (WC/jensflorian)
</gallery>
==Hemorrhage==
*Xanthochromatous specimen
**Can be artificial -> due punctuation injuries or rifampin medication.<ref name="pmid7125611">{{Cite journal  | last1 = Liggett | first1 = SB. | last2 = Berger | first2 = JR. | last3 = Hush | first3 = J. | title = Cerebrospinal fluid xanthochromia with rifampin. | journal = Ann Neurol | volume = 12 | issue = 2 | pages = 228-9 | month = Aug | year = 1982 | doi = 10.1002/ana.410120240 | PMID = 7125611 }}</ref>
**Can be seen in newborn -> due to increased bilirubin levels.
**Best seen when looking from top through the tube. <ref name="pmid3981778">{{Cite journal  | last1 = Bremer | first1 = HL. | title = Identification of xanthochromia. | journal = JAMA | volume = 253 | issue = 17 | pages = 2496 | month = May | year = 1985 | doi =  | PMID = 3981778 }}</ref>
**pink (free hemoglobin directly after bleeding) to yellow (bilirubin after one day).
===Cytology===
*Mostly RBC.
*Neutrophils can be increased.
*+/-Erythro- and Siderophages (usu. after 3-4d).
<gallery>
File:XanthochromeCSF.jpg | Xanthochromatous CSF (WC/Dschafar)
File:Siderophage_CSF_cytology.jpg | A siderophage (WC/jensflorian)
</gallery>


==Acute bacterial meningitis==
==Acute bacterial meningitis==
*Neutrophils.<ref name=Ref_APBR681>{{Ref APBR|681 (Q25)}}</ref>
{{Main|Meningitis}}
===Cytology===
*Neutrophils - none should be present normally.<ref name=Ref_APBR681>{{Ref APBR|681 (Q25)}}</ref><ref>MUN. 4 November 2010.</ref>
**If the tap is traumatic (i.e. fibrin is present) the finding may be uninterpretable.
**Neutrophils may be present in early exsudative phase of viral meningitis.
*Cell count usually above 1000/µl.
<gallery>
File:CSF_pleocytosis_neutrophils.jpg | CSF (Pappenheim stain) with numerous neutrophils indicating a purulent meningitis (WC/jensflorian)
File:CSF S capitis 2013-11-08.JPG | Streoptococcal meningitis in a neonate with ventriculoperitoneal shunt (WC/Paulo Henrique Orlandi Mourao)
File:Gram Stain Anthrax.jpg | Gram-positive Anthrax bacteria in a CSF specimen (WC/TenOfAllTrades).
</gallery>
 
DDx:
*[[TBC]]
*Fungal meningitis


==Viral meningitis==
==Viral meningitis==
{{Main|Meningitis}}
===General===
*Positive viral culture.
**HSV
**CMV
**Enterovirus
**HIV
===Cytology===
*Pleocytosis (usu. 10-1000 cells/µl).
*Polymorphous population of lymphocytes.<ref name=Ref_APBR681/>
*Polymorphous population of lymphocytes.<ref name=Ref_APBR681/>
* Activated lymphocytes.
* Plasma cells (sometimes bi- and multinuclear).
* Occ. mitoses.
* Activated (vacuolated) monocytes.
<gallery>
File:Hiv_meningeoencephalitis_csf_pleocytosis.jpg | Lymphocytic plecoytosis in HIV meningeoencephalitis
File:HSV1_encephalitis_CSF_specimen.jpg | Activated lymphocytes in HSV1 encephalitis
</gallery>


==Mollaret's meningitis==
==Mollaret's meningitis==
General:
===General===
*Rare aseptic meningitis.
*Rare aseptic meningitis.
*Suspected to be caused by HSV1 and HSV2.<ref name=emed1169489>[http://emedicine.medscape.com/article/1169489-overview http://emedicine.medscape.com/article/1169489-overview]</ref>
*Suspected to be caused by HSV1 and HSV2.<ref name=emed1169489>[http://emedicine.medscape.com/article/1169489-overview http://emedicine.medscape.com/article/1169489-overview]</ref>
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*Recurrent meningismus, headache, +/-fever.<ref name=emed1169489/>
*Recurrent meningismus, headache, +/-fever.<ref name=emed1169489/>


Histology:
===Cytology===
Features:
*Mollaret cells - described as ''monocytoid cells''<ref name=Ref_APBR681/> (look like monocytes<ref>[http://www.mondofacto.com/facts/dictionary?monocytoid+cell http://www.mondofacto.com/facts/dictionary?monocytoid+cell]</ref> - but do not phagocytose), and ''large endothelial cells''.<ref name=emed1169489/>  
*Mollaret cells - described as ''monocytoid cells''<ref name=Ref_APBR681/> (look like monocytes<ref>[http://www.mondofacto.com/facts/dictionary?monocytoid+cell http://www.mondofacto.com/facts/dictionary?monocytoid+cell]</ref> - but do not phagocytose), and ''large endothelial cells''.<ref name=emed1169489/>  
**Features - large cells with: abundant cytoplasm, footprint-shaped" nucleus.
**Features - large cells with: abundant cytoplasm, footprint-shaped" nucleus.
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*[http://www.cmaj.ca/cgi/content/full/174/12/1710-a Mollaret cells (cmaj.ca)].
*[http://www.cmaj.ca/cgi/content/full/174/12/1710-a Mollaret cells (cmaj.ca)].


==CNS lymphoma==
==Meningeosis neoplastica==
===CNS lymphoma===
Histology:<ref name=Ref_APBR681>{{Ref APBR|681 (Q25)}}</ref>
Histology:<ref name=Ref_APBR681>{{Ref APBR|681 (Q25)}}</ref>
*Too many cells - ''key feature''.
*Too many cells - ''key feature''.
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Notes:
Notes:
*Massive karyorrhexis (nuclear fragmentation) is suggestive of lymphoma<ref name=Ref_APBR681>{{Ref APBR|681 (Q25)}}</ref> - not common.
*Massive karyorrhexis (nuclear fragmentation) is suggestive of lymphoma<ref name=Ref_APBR681>{{Ref APBR|681 (Q25)}}</ref> - not common.
<gallery>
File:NHL b-cell meningiosis.jpg | CSF cytology of a diffuse large B-cell non hodgkin lymphoma. Atypical cells are larger and have a basophilic cytoplasm (WC/jensflorian).
File:CSF Lymphoma on CSF cytospin cluster of blastoid cells 3.jpg | Blastoid cells in a CNS lympoma (WC/Prof. Erhabor Osaro)
</gallery>
===Meningeal carcinomatosis (Meningeosis carcinomatosa)===
Histology:
*abnormal cell size / giant multinuclear cells.
*unusual nuclear/cytoplasm ratio.
*hyperchromatic nuclei.
*prominent nucleoli.
*atypical mitoses.
*cell clustering.
Notes:
*cell count can be normal.
*accompanied by granulocytes and monocytes.
<gallery>
File:Meningeosis carcinomatosa.jpg | Lung adenocarcinoma cells in CSF (WC/Marvin101).
File:Leptomeningeal metastasis.jpg | Atypical mitosis in epithelial cells in CSF (WC/jensflorian).
File:Meningiosis carcinomatosa.jpg | Leptomeningeal carinomatois (WC/jensflorian).
</gallery>
===Non-lymphoid, non-epithelial neoplasm===
*Non-lymphoid, non-epithelial neoplasms are rarely found in the CSF.
*[[Ependymoma]]s and [[medulloblastoma]]s have a higher rate of dissemination than other primary brain tumors.
Meningeosis gliomatosa ([[Astrocytoma]]/[[Glioblastoma]]):
*May vaguely resemble a neuroendocrine tumour:
**Small cell clusters.
**Nuclear moulding.
**Cells somewhat larger than small cell carcinoma.
**Scant cytoplasm.
<gallery>
File:Bild 01Meningeosis gliomatosa 20x GFAP.jpg | GFAP IHC in a CSF specimen highlighting glioma cells (WC/Marvin101).
</gallery>


==CNS fungal infections==
==CNS fungal infections==
*Cryptococcus is the most common.<ref name=Ref_APBR682>{{Ref APBR|682}}</ref>
*Cryptococcus is the most common.<ref name=Ref_APBR682>{{Ref APBR|682}}</ref>


==Cryptococcus infection==
==Cryptococcosis==
*Immunocompromised host.
{{Main|Cryptococcosis}}
*[[AKA]] cryptococcus infection
 
===General===
*Usu. immunocompromised host.


===Microscopic===
Microscopic appearance:
Microscopic appearance:
*Yeast:<ref name=Ref_APBR682>{{Ref APBR|682}}</ref>
*Yeast:<ref name=Ref_APBR682>{{Ref APBR|682}}</ref>
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**Thick mucopolysacchardie capsule + refractile centre.
**Thick mucopolysacchardie capsule + refractile centre.
***"Target-like" shape/"bull's eye" appearance.
***"Target-like" shape/"bull's eye" appearance.
**"Tear drop-shapped" budding pattern (useful to differentiate from Blastomyces, Histoplasma).
**"Tear drop-shapped" budding pattern (useful to differentiate from Blastomyces, [[Histoplasma]]).


Images:
Images:
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*[http://commons.wikimedia.org/wiki/File:Cryptococcosis_of_lung_in_patient_with_AIDS._Mucicarmine_stain_962_lores.jpg Crytococcosis - mucicarmine stain (WC)].
*[http://commons.wikimedia.org/wiki/File:Cryptococcosis_of_lung_in_patient_with_AIDS._Mucicarmine_stain_962_lores.jpg Crytococcosis - mucicarmine stain (WC)].
*[http://commons.wikimedia.org/wiki/File:Cryptococcosis_of_lung_in_patient_with_AIDS_Methenamine_silver_stain_963_lores.jpg Crytococcosis - methenamine silver stain (WC)].
*[http://commons.wikimedia.org/wiki/File:Cryptococcosis_of_lung_in_patient_with_AIDS_Methenamine_silver_stain_963_lores.jpg Crytococcosis - methenamine silver stain (WC)].
 
<gallery>
{{Main|Microorganisms}}
File:Cryptococcus_neoformans_using_a_light_India_ink_staining_preparation_PHIL_3771_lores.jpg | Ink preparation of Cryptococcosis (CDC/Dr. Leanor Haley)
 
</gallery>
==Non-lymphoid neoplasm==
*Non-lymphoid neoplasms are rarely found in the CSF.
 
Astrocytoma:
*May vaguely resemble a neuroendocrine tumour:
**Small cell clusters.
**Nuclear moulding.
**Cells somewhat larger than small cell carcinoma.
**Scant cytoplasm.


==See also==
==See also==
Michael
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