CSF cytopathology

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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.

Cerebrospinal fluid

Normal

  • Paucicellular.
  • <12/3 cells

Gobs of anuclear material:

  • Protein vs. white mater.

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.


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.[1][2]
    • 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).

Viral meningitis

Main article: Meningitis

General

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

Cytology

  • Pleocytosis (usu. 10-1000 cells/µl).
  • Polymorphous population of lymphocytes.[1]
  • Activated lymphocytes.
  • Plasma cells (sometimes bi- and multinuclear).
  • Occ. mitoses.
  • Activated (vacuolated) monocytes.

  • Lymphocytic plecoytosis in HIV meningeoencephalitis

Mollaret's meningitis

General

  • Rare aseptic meningitis.
  • Suspected to be caused by HSV1 and HSV2.[3]

Clinical:

  • Recurrent meningismus, headache, +/-fever.[3]

Cytology

Features:

  • Mollaret cells - described as monocytoid cells[1] (look like monocytes[4] - but do not phagocytose), and large endothelial cells.[3]
    • Features - large cells with: abundant cytoplasm, footprint-shaped" nucleus.
    • Mollaret cells not pathognomonic.[3]
  • Mixed population of inflammatory cells[1] (PMNs, monocytes, plasma cells, lymphocytes); usually lymphocyte predominant.[3]

Image:

Meningeosis neoplastica

CNS lymphoma

Histology:[1]

  • 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[1] - 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.[5]

Cryptococcosis

Main article: Cryptococcosis
  • AKA cryptococcus infection

General

  • Usu. immunocompromised host.

Microscopic

Microscopic appearance:

  • Yeast:[5]
    • 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. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 681 (Q25). ISBN 978-1416025887.
  2. ↑ MUN. 4 November 2010.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 http://emedicine.medscape.com/article/1169489-overview
  4. ↑ http://www.mondofacto.com/facts/dictionary?monocytoid+cell
  5. ↑ 5.0 5.1 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 682. ISBN 978-1416025887.
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