Pleura
Mesothelial tumors
Mesothelioma - General

Author: Vaidehi Avadhani, M.D. (see Authors page)

Revised: 15 February 2017, last major update November 2013

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: pleural mesothelioma

Related Topics: Clear cell variant, Deciduoid variant, Desmoplastic, Epithelioid, Mixed, Sarcomatoid
Cite this page: Mesothelioma - General. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pleuramesothelioma.html. Accessed March 27th, 2017.
Definition / General
  • Malignant mesothelioma arises from mesothelial lining of pleura, peritoneum, pericardium and tunica vaginalis - pleural mesothelioma is the most common of these
Epidemiology
Etiology
  • 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
      • The 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
  • Progressive shortness of breath
  • Chest pain, possibly unilateral
  • Cough, fever, malaise, myalgia and weight loss (American Cancer Society)
Diagnosis
  • 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
Laboratory
  • 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
Treatment
  • 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 PathOut server:

Tumor mass arises from visceral pleura

Micro 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
Micro Images

Images hosted on PathOut server:

Contributed by Andrey Bychkov, M.D., Ph.D.:

Strong membranous HBME-1 immunoreactivity

Strong HBME-1 immunoreactivity with apical membrane accentuation



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
configurations


Calretinin, 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

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