Mesothelial tumors
Diffuse malignant mesothelioma

Topic Completed: 1 November 2013

Minor changes: 22 June 2020

Copyright: 2003-2019,, Inc.

PubMed Search: Diffuse malignant mesothelioma[TI]

See also: Clear cell variant, Deciduoid variant, Desmoplastic, Epithelioid, Mixed, Sarcomatoid

Vaidehi Avadhani, M.D.
Page views in 2020 to date: 34
Cite this page: Avadhani V. Diffuse malignant mesothelioma. website. Accessed September 26th, 2020.
Definition / general
  • Malignant mesothelioma arises from mesothelial lining of pleura, peritoneum, pericardium and tunica vaginalis - pleural mesothelioma is the most common of these
  • Smoking is not a risk factor
  • Risk factors include:
    1. Asbestos exposure:
      • Usually a prolonged latency period
      • Studies do not show a linear dose / response relationship between asbestos exposure and malignant mesothelioma
      • Role of amphibole (crocidolite) asbestos is well established
      • Crocidolite is a much more potent carcinogen than chrysotile (serpentine form); it accounts for 95% of asbestos used and so is the main cause of malignant mesothelioma
    2. Radiation
    3. Erionite: very carcinogenic mineral fiber used in gravel roads
    4. SV40 virus (association is not clear)
Clinical features
  • Current standard requires biopsy followed by immunohistochemistry using a large panel of markers to distinguish from other tumors
  • If available, or immunohistochemistry results are not clear, EM studies should be conducted
  • Soluble mesothelin related peptide (SMRP) levels may correlate with disease status
Radiology description
  • Strongly suggestive of malignancy: pleural effusion, pleural wall thickening, circumferential pleural thickening involving the mediastinal pleura, nodular pleural thickening (Tuberc Respir Dis (Seoul) 2013;74:74)
Prognostic factors
  • Epithelioid histology is favorable
  • Sarcomatoid histology and mixed tumors are unfavorable
Case reports
  • Stage I - III cases: induction chemotherapy with pemetrexed and cisplatin or surgical exploration
  • Surgical treatments include pleurectomy / decortication or extrapleural pneumonectomy (EPP)
  • Talc pleurodesis or pleural catheter, for management of pleural effusions
  • Both chemotherapy and radiotherapy improve long term survival
Gross description
  • Multifocal studding of lung or pleural surfaces
  • Circumferential or nodular pleural thickening
Gross images

Images hosted on other servers:

Tumor mass arises from visceral pleura

Microscopic (histologic) description
  • Three broad histopathological features (see below):
    • Epithelioid: includes tubulopapillary, deciduoid, clear cell and small cell types
    • Sarcomatoid: desmoplastic and lymphohistiocytoid types
    • Biphasic / mixed
  • Stromal or fat invasion is helpful in diagnosis
Microscopic (histologic) images

Contributed by Jijgee Munkhdelger, M.D., Ph.D. and Andrey Bychkov, M.D., Ph.D.
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Low power

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Infiltration through the membrane

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High power

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Epithelioid mesothelioma immunoprofile

Contributed by Andrey Bychkov, M.D., Ph.D., Kameda Medical Center

Strong membranous HBME-1 immunoreactivity

Strong HBME-1
with apical membrane

Images hosted on other servers:

Epithelioid cells with round nuclei

Mesothelioma cells infiltrating into adipose tissue

Enlarged nuclei with prominent nucleoli

Spindle cells or
plump rounded cells
forming gland-like

CK5 / 6

WT1 staining

D2-40, MOC31, TTF1

Cytology description
  • Disadvantage of cytology: cannot assess invasion
  • Most useful in diagnosis of epithelioid variant
  • Criteria for malignancy:
    • Profusion of mesothelial proliferation
    • Morular papillary structures comprising 50 cells or more
    • Cytological atypia
    • Macronucleoli
    • Frequent cytoplasmic vacuoles
    • Single population of atypical cells (helps to exclude secondary carcinoma)
Cytology images

Contributed by Andrey Bychkov, M.D., Ph.D., Kameda Medical Center

Brush border

Glycogen granules

Pleural effusion

Images hosted on other servers:

Parakeratotic-like cell

Positive stains
  • Histochemical stains:
    • Vacuoles contain hyaluronic acid which is positive for Alcian blue and digestible by hyaluronidase
    • Vacuoles are negative for PASD
    • Mucicarmine should NOT be used to distinguish mesothelioma and adenocarcinoma because it may stain hyaluronic acid (as well as mucin in adenocarcinoma)
  • Immunohistochemistry:
    • Calretinin: strong positivity, nuclear and cytoplasmic
    • Cytokeratin 5 or 5 / 6: expressed in 75 - 100% of mesotheliomas, 2 - 20% of lung adenocarcinomas are focally positive
    • WT1: 70 - 95% of mesotheliomas are positive with nuclear staining, lung adenocarcinomas are negative
    • D2-40: 90 - 100% mesotheliomas are positive with cell membranes positivity
Negative stains
Electron microscopy description
  • Long, slender microvilli (length > 15× diameter) with tonofilaments but without glycocalyx
  • No lamellar bodies (adenocarcinoma has short stubby microvilli)
  • Most useful in epithelioid variant and moderately well differentiated tumors
  • Sarcomatoid mesotheliomas do not show mesothelial features by EM
  • Limitations:
Molecular / cytogenetics description
  • BAP1 (BRCA associated protein 1) germline mutations may identify those at increased risk
  • Homozygous deletions of p16 / CDKN2A at 9p21
  • Inactivating mutations in NF2 gene
  • Mutations in LATS2 gene at 13q21 (identified in cell lines)
  • These findings may be useful for targeted therapy (Ann Cardiothorac Surg 2012;1:462)
Additional references
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