Mesothelial cytopathology

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Mesothelial cytopathology is a large part of cytopathology. The article deals with cytopathology specimens from spaces lined with mesothelium, i.e. it deals with pericardial fluid, peritoneal fluid and pleural fluid.

An introduction to cytopathology is in the cytopathology article.

Cavity fluids

Basic types

  • Wash, e.g. peritoneal wash: expect sheets of (benign squamous) cells.
  • Spontaneous, e.g. pleural fluid: usually no large sheets.

Approach

Look for:

  1. Two cell populations.
  2. Large dark objects.
  3. Boerner's red flags.

Boerner's red flags:

  1. 3-D clusters.
    • Doublet & triplets common.
    • Quads-to-Quints - sweat breaks-out.
    • Sextuplets... very nervous.
  2. "Busy" slide:
    • Nuclear pleomorphism.
    • Too many "intermediate cells".
    • Mitoses - 1-2/slide is "many".
  3. Vacuolated cytoplasm.
  4. Small cells with high NC ratio.

Main DDx

Peritoneal cavity specific

  • HCC may be assoc. with ascites... but it is rarely positive for malignant cells.[1]
    • HCC in ascites fluid is super rare -- I haven't seen a case.[2]

Malignancy

Strongly suggestive of malignancy:

  • 3-D clusters.
  • Large clusters.
  • Highly cellularity.
  • Irregular nucleoli.
  • Group pleomorphism.

May be suggestive:

  • High NC ratio.

Normal mesothelium

Features:[3]

  • "Window" or "space" between attached cells (due to microvilli).
  • Cytoplasmic blebs.
    • Bleb = "drop" of cytoplasm at cell periphery.
  • +/-Multinucleated.
  • Variable size (normal).
  • Nucleoli (in reactive cells).

Images:

Abnormal features:

  • Large clusters of cells, e.g. 150+ micrometres.

Mesothelioma

General

  • Can be challenging to diagnose.
    • NC ratio may be normal in mesothelioma.
    • Large NC ratios may be seen in reactive mesothelial cells.
    • Focal hyperchromasia is seen in reactive mesothelial cells.
    • Focal macronucleoli are seen in reactive mesothelial cells.

Cytopathology

Features:[4]

  1. Nuclear membrane irregularies (rare).
  2. Hyperchromasia - diffuse.
  3. 3-D clusters of cells (strongly suggestive).
    • Clusters of cells with "knobby" border; border is hobnail-like.
  4. Large clusters of cells; >10 cells in a cluster (rare in benign).
  5. Large NC ratio (common - not specific).
  6. Gigantic cells; cells 2X+ neighbouring mesothelial cell (uncommon - but strong).
  7. Nucleoli:
    • Macronucleoli - must be widespread (not common - strong).
    • Multiple nucleoli.
    • Irregular nucleoli (strong).

Images:

Notes:

  • Single cells/small clusters - suggestive of mesothelioma vs. serous carcinoma. (???)

IHC

  • Calretin.

Mesothelial fluid cytopathology tables

Mesothelioma vs. reactive mesothelium[4]

Reactive mesothelial cells Mesothelioma
Architecture Flat sheets 3-D groups
Group size Small, <10 cells Large, >10 cells
Nuclear atypia - see Note 1. +/-Hyperchromasia, +/-focal atypia +/-Widespread atypia
Large cells +/-Yes No
Nucleoli Common - small, focal large +/-Large widespread, +/-multiple

Note 1:

  • Best assessed on single cells.

Breast carcinoma in fluid

Breast adenocarcinoma in fluid - features:[5]

  • Classically large morules (clusters of cells that are heaped/are "3-dimensional"), known as cannonballs, with "community borders".
    • "Community border" = smooth, low surface area border; should be differentiated from a "knobby" border seen in mesothelioma.
  • Intracytoplasmic "lumens"/inclusions (think lobular carcinoma).

DDx of cannonballs:[5]

  • Breast.
  • Ovary.
  • Lung.
  • GI.

Colorectal adenocarcinoma (CRA)

Features:

  • Cannonballs (non-specific).
  • Suggestive of CRA:[5]
    • Pseudostratified cells.
    • Columnar cells.

Serous carcinoma

General

  • S. Boerner believes one can and ought to separate adenocarcinoma from serous carcinoma.

Microscopic

Features:

  • Large nucleoli.[6]
  • Cilia.[7]
  • Abnormal architecture:[8]
    • Large clusters of cells / micropapillae (?).
    • Nuclear overlap.
    • +/-True papillae.[9]

Images:

Note 1 - classic features of serous (see gynecologic pathology article):

DDx of serous carcinoma (found in ascites fluid):

  • Cervix.
  • Endometrium.
    • Intravacuolar neutrophils are erroneously believed to be indicative of this.[10]
  • Uterine tube.
  • Ovary.
  • Primary peritoneal.

IHC

  • WT-1 +ve.
  • CA-125 +ve.
  • D2-40 +ve.

See also

References

  1. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 679. ISBN 978-1416025887.
  2. ↑ SB. 8 January 2010.
  3. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 674. ISBN 978-1416025887.
  4. ↑ 4.0 4.1 Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 359-60. ISBN 978-0470519035.
  5. ↑ 5.0 5.1 5.2 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 675. ISBN 978-1416025887.
  6. ↑ Kuebler, DL.; Nikrui, N.; Bell, DA.. "Cytologic features of endometrial papillary serous carcinoma.". Acta Cytol 33 (1): 120-6. PMID 2916358.
  7. ↑ http://www3.interscience.wiley.com/journal/112702002/abstract?CRETRY=1&SRETRY=0
  8. ↑ Weir, MM.; Bell, DA. (Oct 2001). "Cytologic identification of serous neoplasms in peritoneal fluids.". Cancer 93 (5): 309-18. PMID 11668465.
  9. ↑ SB. 12 January 2010.
  10. ↑ SB. 12 January 2010.

External links

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