Malignant mesothelioma

Malignant mesothelioma
Diagnosis in short
Malignant mesothelioma. H&E stain.
LM	infiltrative atypical cells (epithelioid, spindled or both)
Subtypes	biphasic mesothelioma, epithelioid mesothelioma, desmoplastic mesothelioma, sarcomatoid mesothelioma.
LM DDx	mesothelial hyperplasia, fibrosing pleuritis, adenocarcinoma - esp. lung, serous carcinoma
IHC	calretinin +ve, D2-40 +ve, CK5/6 +ve, WT-1 +ve, CK7 +ve, CEA -ve, TTF-1 -ve, MTAP -ve (pleural mesothelioma), BAP1 -ve
Molecular	+/-p16 deletion
Site	lung, peritoneum, omentum, pericardium
Associated Dx	asbestosis
Clinical history	+/-asbestos exposure
Prevalence	rare
Prognosis	very poor

Malignant mesothelioma, also mesothelioma, is a form of cancer. It arises from the mesothelium.

It should not be confused with benign multicystic mesothelioma and benign papillary mesothelioma.

General

• Incidence
  • Rare tumor accounting for 4-7 cases per million individuals.
  • More common in men in 5th and 6th decades of life.
• Poor prognosis - median survival <12 months.

Locations:

• Lung.
• Primary peritoneal.
• Primary pericardial.

Epidemiology:

• Strong association with asbestos exposure.

Treatment:

• +/-Surgical debulking (cytoreduction) with heated chemotherapy - for intraperitoneal mesothelioma.

Note:

• No association with smoking.^{[citation needed]}

Asbestos

Conditions associated with asbestos exposure (mnemonic PALM):

• Pleural plaques.
• Asbestosis.
• Lung carcinoma.
• Malignant mesothelioma.

Possible association with asbestos exposure:

• Gestational trophoblastic disease.

Microscopic

Features:

• Infiltrative atypical cells - key feature.
  • Infiltration into fat - diagnostic.
  • +/-Epithelioid cells - may be cytologically bland, i.e. benign appearing.
    • Variable architecture: sheets, microglandular, tubulopapillary.
    • +/-Psammoma bodies.
  • +/-Spindle cells.
• +/-Ferruginous body - strongly supportive.
  • Looks like a (twirling) baton - segemented appearance, brown colour.
  • Thin (asbestos) fiber in the core.

Notes:

• Asbestos body is not strictly speaking a synonym for ferruginous body.
• Don't diagnose mesothelioma in situ.^{[citation needed]}

DDx:

• Fibrosing pleuritis - should not have nodules, more cellular on the aspect adjacent to the effusion.
• Reactive mesothelial cells - may be atypical.
• Mesothelial hyperplasia.
• Adenocarcinoma - esp. lung adenocarcinoma.
• Serous carcinoma.
• Synovial sarcoma.

Images

• 

  Ferruginous body. (WC)

• 

  MM - low mag.

• 

  MM - intermed. mag.

• 

  MM - high mag.

• 

  MM - very high mag.

• 

  MM - calretinin - intermed. mag.

• 

  MM - calretinin - high mag.

www

• Mesothelioma (rosaicollection.org/index.cfm).

Subtypes

List of subtypes - mnemonic BEDS:

• Biphasic mesothelioma.
  • 10%+ of epithelioid & 10%+ sarcomatoid.
• Epithelioid mesothelioma.
• Desmoplastic mesothelioma.
  • Should be 50%+ dense tissue with storiform pattern & atypical cells.
• Sarcomatoid mesothelioma.

Other:

• Small cell mesothelioma.

Stains

• PASD -ve.
• Mucicarmine -ve.
  • Typically +ve in adenocarcinoma.

IHC

Mesothelioma versus mesothelial hyperplasia

Features:

• EMA +ve ~100% (vs. ~10%).
• Desmin -ve ~5% (vs. ~85%).
• GLUT1 +ve ~50% (vs. ~10%).
• p53 +ve ~50% (vs. ~2%).
• BAP1 -ve ~57%.

Note:

• The above are not very useful in individual cases.
• A simple pankeratin is useful for seening where epithelial cells are.

Others:

• MTAP -ve.
  • May not be sensitive and specific for peritoneal mesothelioma.^{[citation needed]}

Mesothelioma versus adenocarcinoma

• Several panel exists - no agreed upon best panel.
  • Usually two carcinoma markers + two mesothelial markers.

Panel:

• Mesothelial markers:
  • Calretinin.
  • WT-1.
  • D2-40.
  • CK5/6.
  • CA-125.
• Carcinoma markers:
  • CEA (monoclonal and polyclonal).
  • TTF-1.
  • Ber-EP4.
    • 100% of lung adenocarcinoma versus ~25% of mesotheliomas.
  • MOC-31.
  • CD15.
  • B72.3.

Other carcinoma markers

• PAX8 -ve.
• Claudin-4.
  • Mesothelioma may be focally positive.
• p63 -ve.
• CD138 +ve.
  • Usually -ve in mesothelioma.

Molecular

• p16 deletion by FISH.

Notes:

• p16 IHC does not give the same result.
• Sensitivity of p16 deletion is low.

Sign out

Pleural Tissue of Right Lung, Removal:
- MALIGNANT MESOTHELIOMA, epithelioid type.

Comment:
IHC confirms the morphologic impression. 

The tumour stains as follows:
POSITIVE: calretinin (very strong), CK5/6.
NEGATIVE: TTF-1.

See also

• Lung tumours.
• Omentum.
• Empyema peel.