Mesothelial cytopathology

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.

An introduction to cytopathology is in the cytopathology article.

Pleural fluid redirects to here.

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

• Adenocarcinoma not otherwise specified (NOS) - most common.
• Reactive mesothelium.
• Malignant mesothelioma.
• Serous carcinoma.
• Lymphoma.

Less common:

• Squamous carcinoma.
• Rheumatoid pleuritis.
• Systemic lupus erythematosus pleurisy.
• Endosalpingiosis.
• Endometriosis.
• Small cell carcinoma.

Peritoneal cavity specific

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

Normal mesothelium

Features:

• "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 an intercellular window. (WC)

Reactive mesothelium

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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:

• Trauma with air in the pleural cavity.
  • Repeated tap in the context of pneumothorax.
• Pulmonary infarct.
• Pneumonia.
• Parasitic infections.
• Hodgkin lymphoma.
• Idiopathic - most common cause.

Cytology

Features:

• Eosinophils >10%.

Rheumatoid pleuritis

General

• History of rheumatoid arthritis.
• Cytologic appearance considered to be pathognomonic.

Cytology

Features:

• 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:
  • Pink blobs (representing a denatured nuclei) - phagocytosed by macrophages or PMNs.

Image:

• LE cell (utah.edu).
• LE cell (tabers.com).

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:

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:

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:

• IHC mesothelioma (acta-cytol.com).
• IHC mesothelioma (nature.com).

• 

  Mesothelioma - 1 (WC)

• 

  Mesothelioma - 2 (WC)

IHC

• Calretin +ve.
• WT-1 +ve.
• D2-40 +ve.
• TTF-1 -ve.
• CEA -ve.

Adenocarcinoma

Cytology

Adenocarcinoma in fluid - features:

• 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:

• Breast.
• Ovary.
• Lung.
• GI.

Images

• 

  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)

Colorectal adenocarcinoma

Main article: Colorectal adenocarcinoma

• May be abbreviated CRA.

General

• Cytology may be distinctive.

Cytology

Features:

• Cannonballs (non-specific).
• Suggestive of CRA:
  • 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.
• Cilia.
• Abnormal architecture:
  • Large clusters of cells / micropapillae (?).
  • Nuclear overlap.
  • +/-True papillae.

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

• Columnar cells.
• Cilia.
• Papillae.
• Psammoma bodies.

DDx of serous carcinoma (found in ascites fluid):

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

Images

www:

• Ascites fluid serous adenocarcinoma (nagoya-u.ac.jp).

• 

  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.
  • The diagnosis of small cell lymphomas relies on architecture and immunostains.

Cytology

Features:

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

DDx:

• Small cell carcinoma.
• Other small round cell tumours.

Images

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  Lymphoma - intermed. mag.

• 

  Lymphoma - high mag.

• 

  Lymphoma - very high mag.

• 

  Lymphoma - high mag.

• 

  Lymphoma - very high mag.

See also

• Cytopathology.
• Urine cytopathology.
• Pulmonary cytopathology.
• Basics.
• Urothelium.

External links

• Mesothelioma (histopathology-india.net).
• Respiratory cytopathology (Australian Society).