asbestos

WP

Images

 Asbestosis - Extensive fibrosis of pleura and lung parenchyma.
 Asbestosis - Fibrous pleural plaque.
 Asbestosis - Pleural fibrosis & calcification.
 Asbestosis - Asbestos bodies.
 Asbestosis - Asbestos body.
 Asbestosis and non-small cell lung carcinoma, NOS.

Pathology

 asbestos-associated diseases

• asbestos-associatedpulmonary diseases

 asbestos-associated cancers

• asbestos-associated mesothelioma

Localization

 pleural asbestosis
 pulmonary asbestosis

Tumorigenesis

Widespread asbestos exposure during the past century has been linked to the dramatic increased incidence of malignant mesothelioma (MM), a malignancy that was so rare until 1950–1960 that some pathologists questioned its existence.

Although asbestos has been clearly linked to MM pathogenesis, until recently the mechanisms of asbestos carcinogenesis in humans have remained obscure.

Recent results revealed that asbestos carcinogenesis in humans and in rodents is linked to the activation of the AP-1 pathway, which induces cell division, and to the secretion of TNF-α (and the expression of its receptor) by mesothelial cells and by nearby macrophages exposed to asbestos.

In mesothelial cells, TNF-α signaling through NF-κB activation prevents apoptosis and cell death, allowing mesothelial cells to survive the genetic damage induced by asbestos and divide.

In addition, mutagenic oxygen radicals released mainly by lung macrophages may contribute to asbestos carcinogenesis.

Very recent results indicate that mineral fiber carcinogenesis can be influenced by genetics and microbial infections.

Genetic susceptibility to the mineral fiber erionite has been demonstrated in some Turkish families and causes a MM epidemic in Cappadocia, Turkey. In these mesothelioma families, exposure to minimal amounts of erionite or asbestos appears sufficient to cause mesothelioma.

Recent results (Kroczynska B, et al: Proc Natl Acad Sci USA), demonstrate that SV40 and crocidolite asbestos are co-carcinogens and that, in the presence of SV40, significantly lower amounts of asbestos suffice to induce MM. These findings indicate that the risk varies among asbestos- and erionite-exposed individuals because of their genetic background or because of exposure to other carcinogens. Moreover, these data provide a rationale for the observation that only a fraction of heavily exposed asbestos workers developed mesothelioma, and novel targets for prevention and therapy.

Approximately 2500 people develop and die of mesothelioma each year in the US; this is about 0.7% of all cancer deaths. Although the exact percentage of malignant mesothelioma (MM) linked to asbestos exposure is unclear because of very different results reported by various investigators, there is a general consensus that most MM in the Western world are caused by asbestos.

References

 Wright JL, Churg A. Morphology of small-airway lesions in patients with asbestos exposure. Hum Pathol. 1984 Jan;15(1):68-74. PMID: 6693111