CSF cytopathology

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

This article deals 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.

Cerebrospinal fluid


  • Paucicellular.
  • <12/3 cells
  • 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).



  • Xanthochromatous specimen
    • Can be artificial -> due punctuation injuries or rifampin medication.[1]
    • Can be seen in newborn -> due to increased bilirubin levels.
    • Best seen when looking from top through the tube. [2]
    • pink (free hemoglobin directly after bleeding) to yellow (bilirubin after one day).


  • Mostly RBC.
  • Neutrophils can be increased.
  • +/-Erythro- and Siderophages (usu. after 3-4d).

Acute bacterial meningitis


  • Neutrophils - none should be present normally.[3][4]
    • 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.


  • TBC
  • Fungal meningitis

Viral meningitis


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


  • Pleocytosis (usu. 10-1000 cells/µl).
  • Polymorphous population of lymphocytes.[3]
  • Activated lymphocytes.
  • Plasma cells (sometimes bi- and multinuclear).
  • Occ. mitoses.
  • Activated (vacuolated) monocytes.

Mollaret's meningitis


  • Rare aseptic meningitis.
  • Suspected to be caused by HSV1 and HSV2.[5]


  • Recurrent meningismus, headache, +/-fever.[5]



  • Mollaret cells - described as monocytoid cells[3] (look like monocytes[6] - but do not phagocytose), and large endothelial cells.[5]
    • Features - large cells with: abundant cytoplasm, footprint-shaped" nucleus.
    • Mollaret cells not pathognomonic.[5]
  • Mixed population of inflammatory cells[3] (PMNs, monocytes, plasma cells, lymphocytes); usually lymphocyte predominant.[5]


Meningeosis neoplastica

CNS lymphoma


  • 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.


  • Massive karyorrhexis (nuclear fragmentation) is suggestive of lymphoma[3] - not common.

Meningeal carcinomatosis (Meningeosis carcinomatosa)


  • abnormal cell size / giant multinuclear cells.
  • unusual nuclear/cytoplasm ratio.
  • hyperchromatic nuclei.
  • prominent nucleoli.
  • atypical mitoses.
  • cell clustering.


  • cell count can be normal.
  • accompanied by granulocytes and monocytes.

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.

CNS fungal infections

  • Cryptococcus is the most common.[7]


  • AKA cryptococcus infection


  • Usu. immunocompromised host.


Microscopic appearance:

  • Yeast:[7]
    • 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).


See also


  1. 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.
  2. Bremer, HL. (May 1985). "Identification of xanthochromia.". JAMA 253 (17): 2496. PMID 3981778.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 681 (Q25). ISBN 978-1416025887.
  4. MUN. 4 November 2010.
  5. 5.0 5.1 5.2 5.3 5.4 http://emedicine.medscape.com/article/1169489-overview
  6. http://www.mondofacto.com/facts/dictionary?monocytoid+cell
  7. 7.0 7.1 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 682. ISBN 978-1416025887.