Mesothelioma-Online

Mesothelioma - Aetiology and Pathogenesis

Dr Sampurna Roy MD

 

                                                                                                                      

 

 

The term Mesothelioma refers to a malignant tumour arising from the mesothelium of the serous cavities of the body.

Diagram of pleural mesothelioma

 

Link between mesothelioma and asbestos was first reported in 1960 by Wagner et al. who demonstrated a high incidence of the tumour among asbestos workers in Cape Province of South Africa. (Diffuse pleural mesotheliomas and asbestos exposure in the north western Cape Province. Br J Ind Med 1960; 17:260-271 ; The discovery of the association between blue asbestos and mesotheliomas and the aftermath. Br J Ind Med 1991; 48:399-403.)

Since then several publications have reported mesothelioma in various occupational  groups ( Example-  Shipyard workers ; insulation workers ; asbestos cement workers and gas mask manufacturers ).

 

The main sources of environmental, non-occupational exposure to asbestos or asbestiform fibres are:

a) industrial plants in which asbestos was used in the production process;

b) asbestos "in place" (mainly in buildings);

c) contaminated soils.

Site: The pleura is most frequently involved, then the peritoneum, the pericardial sac and the lining of a hydrocele sac (the tunica vaginalis of the testes) in order of decreasing frequency. 

Age and Sex:  Mesothelioma is a tumour of adult life that mainly affects persons older than 50 and occurs more commonly in men than in women.

Clinical features : General malaise ; weight loss ; pain chest ; shortness of breath ; a haemorrhagic effusion ; usually unilateral ; on enquiry, a history of asbestos exposure.

Aetiology and pathogenesis:

(i) Asbestos induced mesothelioma ;  (ii) Non asbestos associated mesothelioma.

(i) Asbestos induced mesothelioma ;

Asbestos fibres - Physical properties:

Asbestos includes heterogeneous group of hydrated fibrous silicates.

The two main varieties are Serpentine and Amphibole.

Serpentine:  Crysotile or white asbestos belongs to Serpentine family.

Amphibole:  Crocidolite or blue asbestosis ; amosite ; anthropylite; tremolite ; actinolite. 

All forms are fire resistant and insulating. 

Asbestos is used in the following products: Paints ; plastics ; textile; brakes; clutch lining ; pipes ; sheet; vinyl-asbestos tiles.

Asbestos fibres:

Serpentine (crysotile) fibres: Curved large fibres which tend to be deposited in the upper airways.

Amphibole (crocidolite ) fibres:  Smaller straight fibres which penetrate into the lower respiratory tract. The fibres are up to 30 micron in length and 0.5 micron in diameter.

Ferruginous bodies: Coated fibres with protein and iron precipated on the surface. They appear golden brown, drumstick shaped, up to 30 micron in length and 6 micron in diameter.

Asbestos bodies (curious bodies) were first reported in 1924 in African asbestos miners.

Effects of Asbestos on the Respiratory Tract:

 

1. Asbestosis : Interstitial Pulmonary Fibrosis - This is a type of pneumoconiosis and is subject to industrial compensation.

2. Pleural plaques : These are benign asymptomatic fibrotic plaques but may cause diagnostic confusion radiographically.

3. Mesothelioma: Pleural, peritoneal or pericardial spreading into the pleura.

4. Carcinoma of lung: This is usually adenocarcinoma, but also other types of malignant tumours may occur.

Carcinoma usually develops in smokers with a multiplicative increase in risk rather than merely additive.

Other tumours:  Example. Upper Gastrointestinal Tract and Larynx are also more common with asbestos exposure.

Asbestos related mesotheliomas usually have long latency periods (time calculated from first exposure to asbestos, to death from the disease).

Studies have indicated that mesothelioma risk increases with dose and exposure to amphibole asbestos fibres.

Fibre dimension may be related to the risk of mesothelioma formation.

Chrysotile and amphibole fibres have been identified in the visceral and parietal pleura.

Greater the biopersistence of the asbestos fibre, greater the time it has to cause damaging changes in the body.

Amphibole may persist for many years after exposure and play an important role in causing mesothelioma.

Active oxygen free- radicals are considered to play an important role in both asbestos-induced lung disease and formation of mesothelioma.

Crocidolite has greater surface area and higher ferrous iron content compared to Chrysotile.

It is biologically more active in the generation of oxygen free radicals.

 

Factors related to asbestos fibres that may determine the risk of mesothelioma :

1. Fibre type; 

2. Time of exposure; 

3. Cumulative exposure; 

4. Fibre dimension; 

5. Fibre biopersistence;  

6. Fibre surface properties.

 

Pathogenesis of asbestos related mesothelioma:

 

Asbestos appears to act as a complete carcinogen. 

Oxygen free-radicals are regarded as important mediators in asbestos induced neoplasia and may cause genotoxic or cytotoxic change within the mesothelial cells.

These radicals are generated by direct or indirect mechanism.

Direct mechanism:  Involves iron-catalyzed reaction on the surface of the fibre.

Indirect mechanism:  There is physical interaction with phagocytic cells. Oxygen-free radicals are released by macrophages and neutrophils. Active oxygen radicals may interact with chromosomal material causing mutational change.

Some authors have suggested that autocrine growth factors (platelet growth factor, epidermal growth factor and insulin like growth factors) may act as a stimulus for mesothelial cells.

CD44H is considered to play a role in tumour cell invasion and metastasis.

 

(ii) Non-asbestos associated mesothelioma:

Causes:

1. Non-asbestiform fibres - Eronite ; Organic fibres- mesothelioma has been recorded in sugar cane workers.

2. Radiation - It has been suggested that combined exposure to atomic radiation and asbestos is associated with an increased incidence of malignant mesothelioma. 

3. Viruses - Association of simian virus 40 (SV40) with malignant mesothelioma has been reported, suggesting that SV40 plays an important role in the origin of a subset of these tumors.

4. Chronic inflammation-

5. Heavy metals -nickel and beryllium ;

6. Chemical agents - Diethylstilboestrol.

 

Further reading:

Infrequent existence of simian virus 40 large T antigen DNA in malignant mesothelioma in Japan.

Prospective study of mesothelioma mortality in Turkish villages with exposure to fibrous zeolite.  

The role of analytical SEM in the determination of causation in malignant mesothelioma.

Biologic, cytogenetic, and molecular factors in mesothelial proliferations.

Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients.

Mesothelioma associated with environmental exposures.

Mortality from malignant neoplasms among workers of an asbestos processing plant in Poland: results of prolonged observation.

Descriptive epidemiology of malignant mesothelioma.

Pleural mesothelioma in women is associated with environmental exposure to asbestos.

Non-asbestos related diffuse malignant mesothelioma.

Asbestos-related carcinogenic risk.

Malignant mesothelioma of the pleura, pericardium and peritoneum. 1: Etiology, pathogenesis, pathology.

Health effects of asbestos exposure in humans: a quantitative assessment.

The epidemiology of mesothelioma in historical context.

Pleural mesothelioma and asbestos exposure among Italian oil refinery workers.

Malignant mesothelioma: attributable risk of asbestos exposure.

Malignant peritoneal mesothelioma in a 17-year-old boy with evidence of previous exposure to chrysotile and tremolite asbestos.

Malignant mesothelioma in a clerk working in an asbestos factory.

Occupational asbestos exposure, lung-fiber concentration and latency time in malignant mesothelioma.

 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

 

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