Pleural Mesothelioma - Cause of Mesothelioma, Chrysotile
Asbestos and Malignant Mesothelioma
Malignant mesothelioma related to asbestos
Malignant mesothelioma is a rare tumour of the lining of the cavity of the chest or of the abdomen and occasionally of the pericardium. It presents with pain and effusion of fluid into the cavity, grows mainly locally and, being highly malignant, leads to death, within months rather than years. No effective therapy has yet been found, although surgical intervention, radiotherapy and chemotherapy seems to prolong life in some cases. Smoking plays no role in mesothelioma. There is no convincing evidence that calcified pleural plaques (see the article on &ASBESTOSIS&) are precursors and lead to pleural mesothelioma. Pulmonary fibrosis (asbestosis) is not necessarily present in mesothelioma.
Diagnosis
The diagnosis is not as simple as it would appear. During life pleural mesothelioma may be difficult to distinguish from subpleural pulmonary cancer, or from chest metastases of cancers originating elsewhere. In the abdominal cavity cancers of all local organs may occasionally clinically appear like mesothelioma, for example ovarial tumours. The finding of hyaluronic acid and of the tumour cells in the pleural or abdominal fluid helps in clinical diagnosis. However, the only really decisive diagnosis is by autopsy, and even then mainly by excluding other primary cancers causing pleural or abdominal metastases which may mimic the mesothelioma. The pathological picture of mesothelioma differs from one case to another: epithelial, fibrous, and mixed forms have little specificity, and so even a histological diagnosis at autopsy (or at biopsy) requires a great deal of experience. This is the reason why in some countries the definite decision on the final diagnosis of primary mesothelioma is reserved to special "mesothelioma panels" of experienced pathologists.
The difficulty of diagnosis, particularly in cases with no autopsy, may have led to underdiagnosing in the past, and so it is hard to know whether in the past the primary mesothelioma, not unknown to pathologists, really was or only appeared to be extremely rare. Following the Wagner report of the link between mesothelioma and exposure to asbestos, this disease is being found more frequently where asbestos is used. Some underdiagnosing still may exist, e.g. due to insufficient rate of autopsy and/or lack of laboratory facilities and expertise in the developing countries. However, there is also overdiagnosing owing to active searching for mesothelioma wherever there is known to have been exposure to asbestos: in the Canadian province of Quebec, where chrysotile asbestos is mined, the frequency of reported mesothelioma was twice as high as in the other Canadian provinces, but the consequent revision by the Canadian mesothelioma panel of pathologists rejected this diagnosis in half of the reported cases.
Aetiology
Following the Wagner report and further studies a belief has spread, particularly among laymen, that every case of mesothelioma had been caused by asbestos and in every case of mesothelioma an asbestos cause was automatically anticipated. This generalisation is not supported by facts. Mesothelioma was known to pathologists long before any substantial quantity of asbestos was ever mined or used. It has occurred in children; human mesotheliomas were reported to result from exposures to ionising radiation, to farming sugar cane in India, to previous pleuropulmonary disease and previous pneumothorax; and there has been a striking endemic accumulation of cases of mesothelioma in persons exposed to a non-asbestos mineral, erionite, in Turkey. In the classical animal experiments Stanton produced pleural mesothelioma also by non-asbestos fibres, including glass fibre, and mesothelioma was produced in animals by as disparate causes as avian leucosis virus and ethylene oxide. Finally, in all epidemiological studies investigating mesothelioma as related to asbestos exposure there has always been a certain proportion of cases in whom no previous exposure to asbestos was traced even if the study had been specifically designed to search for such exposures. The mesothelial tissue obviously reacts to a wide variety of stimuli and causes by formation of a tumour.
Yet asbestos, although not the only cause of mesothelioma, appears to be its most important cause in modern times. Strong evidence for this comes from epidemiological studies.
These studies are, however, complicated by several circumstances. Mesothelioma is a rare tumour. In the general population of Canada and of the United States the frequency of about 2 cases per million inhabitants per year has been established, as a background for comparison. Occupational exposures have led to higher incidence of mesothelioma, but the excess of cases varies widely. Exposure to anthophyllite, even occupational, has not been shown to cause any cases at all. Also surprisingly, mining chrysotile in Canada, in Italy, in the USSR and in Cyprus has led to very few if any cases of mesothelioma, although with chrysotile mesothelioma was produced in animals. Textile and other asbestos manufacturing is linked with much higher incidence of mesothelioma, and the use of asbestos, particularly for insulation, now virtually abandoned, has led to a still higher incidence. In the last instances chrysotile has mostly been used together with amphiboles, crocidolite and/or amosite. The difference in incidence is well illustrated in table 3.
Table 3. Employment in occupational groups ten or more years before death for 344 male cases and their matched controls (Canada, 1960-1972; United States, 1972)
| Occupational group | Jobs | Men | Relative Risk | ||||
| Cases | Control | Cases | Control | ||||
| A. | Insulation | 27 | 1 | 27 | 1 | 46.0 | |
| B. | Asbestos production and manufacture | 25 | 7 | 6.1 | |||
| Mining and milling (chrysotile) | 4 | 2 | |||||
| Manufacture | 12 | 2 | |||||
| Asbestos cement products | 3 | 2 | |||||
Strikingly high accumulations of cases of mesothelioma were repeatedly reported in exposures to crocidolite: in the areas of crocidolite mining in South Africa and in Australia, in the war-time manufacture of gas-mask filters in the United Kingdom and Canada, and also in asbestos factories in England where crocidolite was used, or in shipyards where it was sprayed for insulation. The above epidemiological evidence has led to the widely accepted belief that crocidolite is more dangerous than the other kinds of asbestos. This belief has led to much stricter standards of permissible exposure to crocidolite in several countries and to outright ban of crocidolite in some. It must be admitted, however, that in the situations leading to the above accumulations of cases of mesothelioma linked with crocidolite the past exposure levels are not known and may have been exceptionally high because of exceptional circumstances, or other confounding factors unknown today.
Equally unclear is the level of risk of exposure to
amosite. In the South African Transvaal areas of amosite mining, in contrast with crocidolite mining areas of the Cape Province, extremely few cases of mesothelioma were detected. However, amosite is claimed to be the only material used in Selikoff's study of a cohort of former workers in an asbestos factory in Patterson, New Jersey, and amosite was used along with other materials, but with no crocidolite, in Selikoff's other cohort of insulation workers, in which the incidence of mesothelioma and mortality from cancers were among the highest on record. According to the Report of ILO Meeting of Experts on the Safe Use of Asbestos, 1973, "Evidence indicates that the risk was highest in insulation workers heavily exposed in the past. In this special section of the industry the proportion of mesothelioma may have been in the order of 10%. This compares with over 80% in the case of some potent chemical carcinogens such as beta-naphthylamine." This part was re-adopted by the ILO Meeting of Experts on the Safe Use of Asbestos, Geneva, October 1981. We have no exact measurements of dustiness in the years long past and we only have sketchy information on what levels of exposures may have been during wartime in the factory, and at construction sites with notoriously bad housekeeping or in shipyards under pressure of wartime conditions, where the insulation workers operated. Again, in some countries stricter standards are applied to amosite than to chrysotile, but less strict than to crocidolite.