Difference between revisions of "CSF cytopathology"

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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''.  ''Lumbar puncture'' redirects here.
==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:
Line 26: Line 28:
*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> none should be present normally.<ref>MUN. 4 November 2010.</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.
**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>
Line 42: Line 101:
*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.
Line 51: Line 111:
*[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''.
Line 62: Line 123:
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>
Line 74: Line 178:
**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:
Line 80: Line 184:
*[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==

Latest revision as of 17:38, 26 June 2024

CSF cytopathology is a subset of CNS cytopathology, which is a subset of cytopathology.

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

In many institutions, CSF specimens get triaged/rapidly assessed as:

  1. They are small specimens ~ usually 1-10 ml.
  2. The procedure to obtain them is non-trivial, i.e. not pleasant for the patient and not risk free.
  3. Lymphoma is a common malignancy of malignancies found in the CSF.

In many institutions, all CSF specimens are stat. Lumbar puncture redirects here.

Cerebrospinal fluid

Normal

  • Paucicellular.
    • Acellular specimens common and considered adequate.[1]
  • protein is around 15-40 mg/dl.

Gobs of anuclear material:

  • Protein vs. white matter.
  • Ocassionally arachnoid cap cell-

Bark-like flaky material:

  • Contaminant.

Fluffy/smudged large cells (~2-3x RBC dia.) with an indistinct nucleus:

  • Degenerated white cells.
    • Should prompt a comment about "degeneration", if the population is dominant.

Routine processing

  • Cytospin - if no abnormality at triage.
    • The cellularity of the cytospin will appear to be increased (artifact).

Images

  • Normal CSF fluid is clear. (WC/James Heilman)

  • Normal CSF cytology Pappenheim specimen. (WC/jensflorian)

Hemorrhage

  • Xanthochromatous specimen
    • Can be artificial -> due punctuation injuries or rifampin medication.[2]
    • Can be seen in newborn -> due to increased bilirubin levels.
    • Best seen when looking from top through the tube. [3]
    • 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).

  • Xanthochromatous CSF (WC/Dschafar)

  • A siderophage (WC/jensflorian)


Acute bacterial meningitis

Main article: Meningitis

Cytology

  • Neutrophils - none should be present normally.[4][5]
    • 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.

  • CSF (Pappenheim stain) with numerous neutrophils indicating a purulent meningitis (WC/jensflorian)

  • Streoptococcal meningitis in a neonate with ventriculoperitoneal shunt (WC/Paulo Henrique Orlandi Mourao)

  • Gram-positive Anthrax bacteria in a CSF specimen (WC/TenOfAllTrades).

DDx:

  • TBC
  • Fungal meningitis

Viral meningitis

Main article: Meningitis

General

  • Positive viral culture.
    • HSV
    • CMV
    • Enterovirus
    • HIV

Cytology

  • Pleocytosis (usu. 10-1000 cells/µl).
  • Polymorphous population of lymphocytes.[4]
  • Activated lymphocytes.
  • Plasma cells (sometimes bi- and multinuclear).
  • Occ. mitoses.
  • Activated (vacuolated) monocytes.

  • Lymphocytic plecoytosis in HIV meningeoencephalitis

  • Activated lymphocytes in HSV1 encephalitis

Mollaret's meningitis

General

  • Rare aseptic meningitis.
  • Suspected to be caused by HSV1 and HSV2.[6]

Clinical:

  • Recurrent meningismus, headache, +/-fever.[6]

Cytology

Features:

  • Mollaret cells - described as monocytoid cells[4] (look like monocytes[7] - but do not phagocytose), and large endothelial cells.[6]
    • Features - large cells with: abundant cytoplasm, footprint-shaped" nucleus.
    • Mollaret cells not pathognomonic.[6]
  • Mixed population of inflammatory cells[4] (PMNs, monocytes, plasma cells, lymphocytes); usually lymphocyte predominant.[6]

Image:

Meningeosis neoplastica

CNS lymphoma

Histology:[4]

  • Too many cells - key feature.
    • Not diagnostic... but should raise suspicion.
  • Single cells (as typical of lymphoma/leukemia).
  • Large lymphocytes - >2x RBC diameter.
  • +/-Nuclear atypia.
    • Radial segmentation - a completely cleaved nucleus/quasi-binucleation.

Notes:

  • Massive karyorrhexis (nuclear fragmentation) is suggestive of lymphoma[4] - not common.

  • CSF cytology of a diffuse large B-cell non hodgkin lymphoma. Atypical cells are larger and have a basophilic cytoplasm (WC/jensflorian).

  • Blastoid cells in a CNS lympoma (WC/Prof. Erhabor Osaro)

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.

  • Lung adenocarcinoma cells in CSF (WC/Marvin101).

  • Atypical mitosis in epithelial cells in CSF (WC/jensflorian).

  • Leptomeningeal carinomatois (WC/jensflorian).

Non-lymphoid, non-epithelial neoplasm

  • Non-lymphoid, non-epithelial neoplasms are rarely found in the CSF.
  • Ependymomas and medulloblastomas 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.

  • GFAP IHC in a CSF specimen highlighting glioma cells (WC/Marvin101).

CNS fungal infections

  • Cryptococcus is the most common.[8]

Cryptococcosis

Main article: Cryptococcosis
  • AKA cryptococcus infection

General

  • Usu. immunocompromised host.

Microscopic

Microscopic appearance:

  • Yeast:[8]
    • Round/ovoid 5-15 micrometres.
    • Thick mucopolysacchardie capsule + refractile centre.
      • "Target-like" shape/"bull's eye" appearance.
    • "Tear drop-shapped" budding pattern (useful to differentiate from Blastomyces, Histoplasma).

Images:

  • Ink preparation of Cryptococcosis (CDC/Dr. Leanor Haley)

See also

References

  1. ↑ Mody, Dina R. (2018). Diagnostic Cytopathology (1st ed.). Elsevier Canada. pp. II-3 2. ISBN 978-1931884556.
  2. ↑ Liggett, SB.; Berger, JR.; Hush, J. (Aug 1982). "Cerebrospinal fluid xanthochromia with rifampin.". Ann Neurol 12 (2): 228-9. doi:10.1002/ana.410120240. PMID 7125611.
  3. ↑ Bremer, HL. (May 1985). "Identification of xanthochromia.". JAMA 253 (17): 2496. PMID 3981778.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 681 (Q25). ISBN 978-1416025887.
  5. ↑ MUN. 4 November 2010.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 http://emedicine.medscape.com/article/1169489-overview
  7. ↑ http://www.mondofacto.com/facts/dictionary?monocytoid+cell
  8. ↑ 8.0 8.1 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 682. ISBN 978-1416025887.
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