Figure 1.
Figure 2.
The association between malignant mesothelioma and prior exposure to asbestos has been demonstrated repeatedly in epidemiologic, experimental animal, and pathologic studies [1]. Most investigators are of the opinion that all of the commercially valuable forms of asbestos, that is, crocidolite, amosite, and chrysotile (with its contaminant tremolite) are capable of causing pleural mesothelioma in humans. However, there appears to be a fiber gradient with respect to the disease mesothelioma, with crocidolite being a more potent inducer of the disease than amosite, which is in turn more potent than chrysotile, assuming equal amounts of exposure to each fiber type.
Some investigators have claimed that crocidolite is the cause
of the great majority of mesotheliomas in the world, including
most cases from the United States [2,3]. Since crocidolite was
rarely used in shipyards and in insulation products in this country
(the source of a large proportion of mesotheliomas in the U.S.),
we investigated our files for the proportion of the various asbestos
fiber types found in the lungs of patients with mesothelioma.
The data summarized below include analyses from more than 1500
fibers from 94 patients with mesothelioma [4].
Asbestos bodies may be observed in H&E stained sections of
lung parenchyma in just under half of patients with mesothelioma,
and are found after careful examination of iron stained sections
in somewhat more than half of all cases [5]. This finding is indicative
of an elevated tissue asbestos content [6]. When more sensitive
digestion procedures are employed, about 83% of mesothelioma patients
have a tissue asbestos body content which exceeds background values.
In an additional 6% of mesothelioma cases, an abnormal asbestos
fiber concentration can be detected by scanning electron microscopy
in the presence of an asbestos body content within the normal
range [7]. Thus at least 89% of mesotheliomas appear to be asbestos
related based on analysis of lung tissue burdens. This finding
is similar to the rate of asbestos related cases assuming a background
rate of 1 mesothelioma per million population per year and the
actual observed number of about 2200 cases per year in the United
States [8]. It should be noted that asbestos bodies are not observed
in histologic sections of mesothelioma (except when there is invasion
of underlying lung parenchyma), and that the asbestos content
of mesothelial tumor tissue is very low (if detectable at all)
in comparison to the underlying lung.
Figure 1.
Figure 2.
Studies of the mineral fiber content of lung in U.S. patients with mesothelioma have shown that amosite is the most common fiber type, accounting for nearly 60% of all fibers 5µ or greater in length among more than 1500 fibers analyzed from 94 cases [4]. Ten percent of the fibers analyzed were tremolite, and 3% were chrysotile. (Chrysotile tends to break down in the lungs over time so that there is a relative enrichment of the more stable tremolite contaminant). Crocidolite accounted for only 3% of fibers. Studies have shown that fibers in this size range are capable of reaching the visceral and parietal pleura [9-11].
Studies from Canada have shown an increased rate of mesothelioma
in workers at the Thetford mines, analyses of whose lung tissues
have demonstrated chrysotile and tremolite fibers only [12]. These
findings as well as earlier such studies demonstrate unequivocally
that chrysotile ore dust can cause mesothelioma in humans. It
remains unclear whether it is the chrysotile fiber itself or the
contaminating tremolite (or both) which is the offending agent.
Churg's studies have suggested that mesotheliomas only occur in
these miners at a high fiber burden (equivalent to levels seen
with asbestosis) [13]. Our own findings on end-product users suggest
that this is not necessarily the case [14]. However, mesothelioma
cases in which tremolite is the only fiber type identified in
increased amounts account for only a small percentage of the total
number of mesothelioma cases that we have studied (about 3%).
All the commercially valuable forms of asbestos cause mesotheliomas
in humans. Amosite, a commercial amphibole commonly used in the
past in insulation products and in shipbuilding in this country,
appears to be the primary culprit. Tremolite, a common contaminant
of chrysotile asbestos, appears to be next in importance. Crocidolite
is the least important and was uncommonly found in U.S. shipyards
and insulation products. Most exposures resulting in mesothelioma
were to mixtures of amosite and chrysotile. Exposure to chrysotile
dust alone can cause mesothelioma in humans, but does so uncommonly.