Pathology Outlines – Mesothelioma – general

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Cite this page: Avadhani, V. Mesothelioma – general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pleuramesothelioma.html. Accessed December 8th, 2018.

Definition / general

  • Malignant mesothelioma arises from mesothelial lining of pleura, peritoneum, pericardium and tunica vaginalis – pleural mesothelioma is the most common of these

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
      • 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)

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

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 other servers

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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

Images hosted on PathOut server

:

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


Strong membranous HBME-1 immunoreactivity


Strong HBME-1
immunoreactivity
with apical membrane
accentuation

Images hosted on other servers

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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 PathOut server

:

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

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)

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