Pleural fluid: cytology

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  • Pleural fluid occurs within the thoracic cavity. Very little or no fluid can be aspirated unless effusion is present.
  • Normal fluid is clear and colorless to slightly yellow and is of low cellularity (<1000 nucleated cells/ml) and low protein (</-2.5 g/dl).
  • Four mechanisms result in cavity effusions:
    • Transudate - low specific gravity fluid crosses membrane barrier.
    • Exudate - inflammation allows fluid with high cellular and protein component ot cross vessel walls.
    • Vessel or viscous rupture.
    • Neoplastic proliferation.
  • Examination of cell morphology helps to distinguish sterile and septic exudates.
  • Sometimes neoplastic cells are recognized (especially in lymphoma    )   →   a non-invasive technique for diagnosing intrathoracic neoplasia.
  • Cytology enables finer differentiation of type of pleural effusion.
  • Use in combination with cell count and differential    , protein    , culture    .



  • Classification or diagnosis of cause of pleural effusion    .
  • Differentiate transudate from effusion.
  • Differentiate septic from sterile effusion.
  • Diagnosis of lymphoma    or mast cell tumor  [Mastocytoma]  when neoplastic cells are exfoliated into the effusion.
  • Diagnosis of other forms of neoplasia, eg carcinoma    , mesothelioma    .
    Reactive mesothelial cells may resemble neoplastic mesothelial cells or carcinoma cells.

In combination

  • With:
    • Other laboratory measures of pleural fluid to diagnose the type of pleural effusion.
    • Cell count and differential    .
    • Protein    .

Other points

Many intrathoracic tumors may result in pleural effusion due to inflammation, eg if tumor is necrotic, or increased hydrostatic pressure but tumor cells are not necessarily exfoliated into the effusion.

Result data

Normal (reference) values

  • Reference values may vary slightly with laboratory.
  • 2 cells per x40 field in normal fluid.
  • Nucleated cell counts typically <1000/ml, refractometer total protein typically <2.5 g/dl (25 g/l).

Abnormal values

  • Small numbers of cells, mainly mononuclear - macrophages and mesothelial cells, lymphocytes and a few non-degenerate neutrophils.
  • Due to hypoproteinemia  [Blood biochemistry: total protein]  , early right cardiac failure    .

Modified transudate

  • Cells similar to transudate but more cellular, possibly more neutrophils. May also be red cells and possibly neoplastic cells.
  • Due to some neoplasia, chronic cardiac failure    , occasionally FIP  [Feline infectious peritonitis]  .
  • Early viscous rupture.


  • Very cellular.
  • Mostly neutrophils.
  • Smaller numbers of mesothelial cells, lymphocytes and macrophages.
  • Septic exudate   →   degenerate neutrophils which are swollen, pale-staining and have a ragged outline. Due to release of toxins from bacteria.
    Not all bacteria release toxins. Actinomyces spp    and Norcardia spp    do not cause much/any degenerative change.
    If sample is not prepared quickly, the cells may take in water and swell up giving the appearance of degenerative change.
  • Non-septic exudate   →   non-degenerate neutrophils which look like blood neutrophils, eg FIP, necrotic tumor, walled-off abscess.
  • In FIP may see numerous fine pink granules which are protein precipitates.
    Do not confuse with bacteria.
  • FIP effusion usually mostly neutrophils, but may be more mononuclear cells (mesothelial cells/macrophages/lymphocytes).


  • Lymphoma    : lymphoblasts which are x1.5-3 diameter of small lymphocytes with large nuclei containing multiple nucleoli. These cells are round and discrete.
    Small lymphocytes are not necessarily indicative of lymphoma and may be seen in many effusions, eg cardiac disease  [Heart: congestive heart failure]  , thymoma, FIP  [Feline infectious peritonitis]  , any modified transudate.
  • Carcinoma cells are often large cohesive epithelial cells seen in clusters/balls.
    Easily confused with reactive mesothelial cells. Best to send for expert analysis.

Mesothelial cells

  • Line the pleural thoracic, pericardial and scrotal cavities.
  • Present in most effusions
  • Single cells or in clusters (if reactive).
  • Round shape with a single round nucleus or may be multinucleate.
  • Cytoplasm may contain phagocytic vacuoles.
  • May have a pink corona/fringe around the edge of the cytoplasm.
  • Reactive mesothelial cells may be multinucleate, may have multiple nucleoli and increased nuclear:cytoplasmic ratio.
    May look neoplastic.

Hemorrhagic effusions

  • Acute hemorrhage: resembles blood. Variable erythrophagocytosis and platelets are present.
  • Chronic hemorrhage/hemorrhage of more than one day's duration: PCV lower than peripheral blood. Do not see platelets. May see erythrophagocytosis   →   red cells or blue/black hemosiderin or golden hematoidin in cytoplasmic vacuoles in macrophages.

Chylous effusions

  • Small lymphocytes usually predominate, although this can be very variable and sometimes neutrophils and/or macrophages predominate (particularly if chronic condition).

Errors and Artifacts

  • Delay in sample preparation   →   neutrophils may look degenerate.
  • Previous antibiotic treatment in septic effusions   →   neutrophils may not look degenerate, bacteria may not be visible.
  • Reactive mesothelial cells may look neoplastic.
  • Clumping and fragmentation can distort nucleated count and appearance of cells.
  • If smears not prepared immediately cells may degenerate.
  • Samples can be preserved in cytologic fixative (40-50% ethanol, 10% formalin or other types) but special preparatory and/or staining techniques may be needed, depending on type of fixative used.
  • Contact laboratory for preferred specifics of sample submission.
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