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.

Benign mesothelial cells from a pleural fluid specimen. (WC)
Adenocarcinoma (lung) and benign mesothelial cells in a pleural fluid specimen. (WC)

An introduction to cytopathology is in the cytopathology article.

A general differential diagnosis of pleural effusion is given in the pleural effusion article.

Pleural fluid, pleural cytopathology, peritoneal fluid, and peritoneal cytopathology redirect to here.

Overview

Specimen types

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

Note: This distinction is important as wash specimens may have pseudopapillae.

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.

Features of malignancy

Strongly suggestive of malignancy:

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

May be suggestive:

  • High NC ratio.

Differential diagnosis

Less common:

Peritoneal cavity specific

  • Hepatocellular carcinoma (HCC) may be associated with ascites... but it is rarely positive for malignant cells.[2]
    • HCC in ascites fluid is super rare -- I haven't seen a case.[3]

Normal mesothelium

General

Often seen in the context of:

  • Gynecologic surgeries - done to exclude malignancy.
  • Taps for ascites.

Cytology

Features:[4]

  • "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).

Note - abnormal features:

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

Images

  • Peritoneal wash - benign mesothelial cells in sheets (WC)

  • Peritoneal wash - benign mesothelial cells in sheets - high mag. (WC)

  • Pairs of mesothelial cells with an intercellular window. (WC)

Reactive mesothelium

General

Cytology

See mesothelioma.

Images

  • PF - high mag. (WC)

  • PF - very high mag. (WC)

  • PF - very high mag. (WC)

Sign out

Pleural Fluid, Right, Thoracentesis: 
- Negative for malignant cells. 
- Reactive mesothelial cells present in a background of abundant lymphocytes. 

Comment: 
Additional sampling should be considered within the clinical context.

Specific diagnoses - benign

Eosinophilic pleuritis

General

This has a large DDx:

Cytology

Features:

  • Eosinophils >10%.

Rheumatoid pleuritis

General

Cytology

Features:[6]

  • Large (single) multinucleated cells - classically spindled.
    • May have epithelioid morphology.
  • Necrotic debris - fluffy orange-to-blue crap.

Note:

  • Necrotizing granulomatous inflammation.

Systemic lupus erythematosus pleurisy

Main article: Systemic lupus erythematosus
  • AKA systemic lupus erythematosus pleuritis.

General

  • Not common.
  • Distinctive cytology.

Cytology

Features:

  • Lupus erythematosus cells, usually abbreviated LE cells:[7]
    • Pink blobs (representing a denatured nuclei) - phagocytosed by a neutrophil.[8]

Image:

Specific diagnoses - malignant

Malignant mesothelioma

Main article: Malignant 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:[9]

  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).

Notes:

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

Mesothelioma versus reactive mesothelium:[9]

Characteristic 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.

Images

www:

  • Mesothelioma - 1 (WC)

  • Mesothelioma - 2 (WC)

IHC

Adenocarcinoma

General

Cytology

Adenocarcinoma in fluid - features:[11]

  • 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:[11]

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

Images

Case 1

  • Adenocarcinoma - high mag. (WC)

  • Adenocarcinoma - very high mag. (WC)

  • Lung adenocarcinoma - high mag. (WC)

  • Lung adenocarcinoma - very high mag. (WC)

  • Lung adenocarcinoma - high mag. (WC)

  • Lung adenocarcinoma - very high mag. (WC)

Case 2

  • Adenocarcinoma - high mag. (WC)

  • Adenocarcinoma - very high mag. (WC)

  • Adenocarcinoma - very high mag. (WC)

  • Adenocarcinoma - TTF-1 - high mag. (WC)

  • Adenocarcinoma - TTF-1 - very high mag. (WC)

IHC

Breast:

  • ER +ve/-ve.
  • Calretinin -ve.

Colon:

  • CK20 +ve.
  • CDX2 +ve.
  • Calretinin -ve.

Lung:

  • TTF-1 +ve.
  • Calretinin -ve.

Colorectal adenocarcinoma

Main article: Colorectal adenocarcinoma
  • May be abbreviated CRA.

General

  • Cytology may be distinctive.

Cytology

Features:

  • Cannonballs (non-specific).
  • Suggestive of CRA:[11]
    • Pseudostratified cells.
    • Columnar cells.

Note:

  • See adenocarcinoma section above for other types of adenocarcinoma.

Serous carcinoma

Main article: Serous carcinoma

General

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

Microscopic

Features:

  • Large nucleoli.[12]
  • Cilia.[13]
  • Abnormal architecture:[14]
    • Large clusters of cells / micropapillae (?).
    • Nuclear overlap.
    • +/-True papillae.[15]

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.[15]
  • Uterine tube.
  • Ovary.
  • Primary peritoneal.

Images

www:

  • Serous carcinoma - cytology - low mag. (WC)

  • Serous carcinoma - histology - high mag. (WC)

IHC

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

Lymphoma

General

  • Can only be reasonably certain for large cell lymphomas, e.g. DLBCL.

Cytology

Features:

  • Dyscohesive cells ~2x a resting lymphocyte - usually with scant blue cytoplasm.

DDx:

Images

  • Lymphoma - intermed. mag.

  • Lymphoma - high mag.

  • Lymphoma - very high mag.

  • Lymphoma - high mag.

  • Lymphoma - very high mag.

See also

References

  1. ↑ Karoo, RO.; Lloyd, TD.; Garcea, G.; Redway, HD.; Robertson, GS. (May 2003). "How valuable is ascitic cytology in the detection and management of malignancy?". Postgrad Med J 79 (931): 292-4. PMID 12782778.
  2. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 679. ISBN 978-1416025887.
  3. ↑ SB. 8 January 2010.
  4. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 674. ISBN 978-1416025887.
  5. ↑ Selvaggi, SM.; Migdal, S. (1990). "Cytologic features of atypical mesothelial cells in peritoneal dialysis fluid.". Diagn Cytopathol 6 (1): 22-6. PMID 2323293.
  6. ↑ 6.0 6.1 Naylor, B.. "The pathognomonic cytologic picture of rheumatoid pleuritis. The 1989 Maurice Goldblatt Cytology award lecture.". Acta Cytol 34 (4): 465-73. PMID 2197838.
  7. ↑ URL:http://www.tabers.com/tabersonline/ub/view/Tabers/143167/34/L_E__cell. Accessed on: 12 April 2012.
  8. ↑ URL: http://library.med.utah.edu/WebPath/IMMHTML/IMM008.html. Accessed on: 12 April 2012.
  9. ↑ 9.0 9.1 Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 359-60. ISBN 978-0470519035.
  10. ↑ Pu, RT.; Pang, Y.; Michael, CW. (Jan 2008). "Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions.". Diagn Cytopathol 36 (1): 20-5. doi:10.1002/dc.20747. PMID 18064689.
  11. ↑ 11.0 11.1 11.2 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 675. ISBN 978-1416025887.
  12. ↑ Kuebler, DL.; Nikrui, N.; Bell, DA.. "Cytologic features of endometrial papillary serous carcinoma.". Acta Cytol 33 (1): 120-6. PMID 2916358.
  13. ↑ http://www3.interscience.wiley.com/journal/112702002/abstract?CRETRY=1&SRETRY=0
  14. ↑ Weir, MM.; Bell, DA. (Oct 2001). "Cytologic identification of serous neoplasms in peritoneal fluids.". Cancer 93 (5): 309-18. PMID 11668465.
  15. ↑ 15.0 15.1 Boerner, S. 12 January 2010.

External links

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