Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. The late stage of MPM diagnosis and the long latency that exist between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects.

Methods: This manuscript is a review of current literature about the pathogenesis of malignant mesothelioma. In this overview, current published studies concerning pathogenesis of malignant mesothelioma are reviewed, with insights into its etiology and pathogenesis. We searched pubmed using the following subjects: mesothelioma, radiation, genetics, pediatric malignant mesothelioma, SV40 virus, and growth factors. We selected 350 valuable articles of which 152 sources were used to complete this review.

Conclusion: Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. In this review, we discuss the current molecular and genetic contributors to MPM pathogenesis and the risk factors associated with these carcinogenic processes.

Fig. 1

Gross specimen of malignant pleural mesothelioma. Presented here is an advanced case of malignant pleural mesothelioma encasing the lung and limiting lung compliance. Diffuse growth into the lung parenchyma is also present. (Personal photo of Neragi-Mianoab)

Fig. 2

Malignant pleural mesothelioma of epithelial type. Epithelial MPM derives from the mesothelial cells and consists of glands and tubules that resemble adenocarcinoma. Large spherical cells are arranged in solid masses and columns mostly within lymphatics. There may also be glandular formation as demonstrated in this photograph. (Personal photo of Neragi-Mianoab)

Fig. 3

Malignant pleural mesothelioma of sarcomatous type. Sarcomatous MPM originates from the deep connective tissue of the mesothelial surface and resembles fibrosarcoma. (Personal photo of Neragi-Mianoab)