CSF cytopathology

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.

The findings from CSF specimens usually needed speedily; thus, in many institutions these specimens are stat.

Normal

• 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).

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.
  • Can be seen in newborn -> due to increased bilirubin levels.
  • Best seen when looking from top through the tube.
  • 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.
  • 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.

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  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.
• 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.

Clinical:

• Recurrent meningismus, headache, +/-fever.

Cytology

Features:

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

Image:

• Mollaret cells (cmaj.ca).

Meningeosis neoplastica

CNS lymphoma

Histology:

• 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 - 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.

Cryptococcosis

Main article: Cryptococcosis

• AKA cryptococcus infection

General

• Usu. immunocompromised host.

Microscopic

Microscopic appearance:

• Yeast:
  • 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:

• Cryptococcus in lung FNA - Field stain (WC).
• Crytococcosis - mucicarmine stain (WC).
• Crytococcosis - methenamine silver stain (WC).

• 

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

See also

• CNS cytopathology.
• Cytopathology.
• Basics.
• Neuropathology.