Malignant mesothelioma: Facts, Myths, and Hypotheses

Abstract

Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM.

Mesothelioma: recent highlights

“…Mesothelial cells are the last remnant of mesoderm, so they are quite undifferentiated cells and maintain the ability to differentiate into different cell lines. Accordingly, some mesotheliomas have an epithelial morphology, others have a spindle cell morphology (often called sarcomatoid or fibrous mesothelioma) and others show a mixture of the two morphologies (called biphasic mesotheliomas) (1). More rare variants exist, but they are mostly a curiosity for the pathologist and have little clinical significance except that they are often misdiagnosed because they are rare and pathologists are not familiar with them.…”

“…More rare variants exist, but they are mostly a curiosity for the pathologist and have little clinical significance except that they are often misdiagnosed because they are rare and pathologists are not familiar with them. Histologically, the epithelial variants are less aggressive than the spindle cell variants (1). Biphasic malignancies tend to behave according to the prevalent histological composition: the more fibrous they are, the more malignant they are (1).…”

“…The incidence of mesothelioma has also increased worldwide over the past 50 years (23). A growing number of mesotheliomas, estimated at 20-50%, develop in individuals with no history of asbestos exposure suggesting that other factors cause mesothelioma or that some individuals may be very susceptible to even minimal amounts of asbestos (1,12). Fortunately, only a fraction of people exposed to asbestos developed mesothelioma.…”

Second line therapy in malignant pleural mesothelioma: A systematic review

“…The average latency of 40-45 years or more since the start of the exposure as found in studies with adequately long follow-up time explains the pattern of the observed mesothelioma incidence increases over the last decades with an estimated 43,000 annual deaths worldwide and why substantial decreases are not expected before 2020 [2]. Time trends indicate a slow shift of disease burden to countries consuming asbestos most recently [3], while incidence has peaked in most western industrialized countries after the ban of asbestos import and use in the eighties and nineties of last century [4]. Other possible causes are ionizing radiation, endemic erionite exposure and chronic inflammation of the pleura [3].…”

miR‐30d is related to asbestos exposure and inhibits migration and invasion in NCI‐H2452 cells

“…The median survival time commonly does not exceed 12–18 months after diagnosis 1. Therefore, biomarkers for early detection are imperative even for experienced pathologists.…”