Review

Genetic factors in the aetiology of malignant mesothelioma

This chapter considers the clinicopathologic features of borderline and malignant mesothelial pleural neoplasms. They include “well-differentiated papillary mesothelioma,” multicystic mesothelial tumors of borderline biological potential, and malignant mesotheliomas. The specialized morphological features of those lesions are discussed, with emphasis on differential diagnosis with other tumors.

We aimed at investigating risk of specific second primary cancers (SPCs) after malignant mesothelioma (MM) and vice versa, which has not been reported. Among survivors of 3672 pleural MM and 895 peritoneal MM, overall 113 and 28 SPCs were recorded, respectively, while reverse analyses included overall 431 pleural and 88 peritoneal MMs after any first cancers. We found a bidirectional association of pleural MM with kidney cancer for overall [for second kidney cancer after pleural MM: standardized incidence ratios (SIRs) = 4.4, 95% confidence intervals (CIs): 2.0–8.3; for second pleural MM after kidney cancer: 2.3 (1.3–3.9)] and for <1 year follow-up [5.4 (2.0–12) and 4.9 (2.0–10), respectively, according to the 2-way analyses]. In contrast, a bidirectional association of pleural MM with unknown primary cancer was found only for follow-up ≥1 year [3.9 (1.1–10) and 2.8 (1.3–5.1), respectively]. We found a bidirectional association of pleural MM with kidney cancer for overall and for <1 year follow-up, suggesting the involvement of germline BAP1 mutations and increased medical surveillance, while the bidirectional association of pleural MM with unknown primary cancer suggests shared genetic or environmental risk factors.

Malignant mesothelioma of the tunica vaginalis testis is a rare but often fatal malignancy. Here, we report one patient with locally advanced disease who has a history of asbestos exposure. We review the literature concerning current management strategies of the disease. Radical surgery plus adjuvant radiotherapy seems to provide the best results.

Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events, especially deletions, which lead to the inactivation of multiple onco-suppressor genes in a multistep cascade mechanism. Past asbestos exposure represents the major risk factor for MM, and the link between asbestos fibers and MM has been largely proved by several epidemiologic and experimental studies. Asbestos fibers induce DNA and chromosomal damage. Most MM cases have shown multiple chromosomal abnormalities. Chromosomal losses are more common than gains. The most common cytogenetic abnormality in MM is a deletion in 9p21, the locus of CDKN2A, a tumor suppressor gene (TSG). The deletion of CDKN2A is a negative prognostic factor in MM. Loss of TSG CDKN2A/p14^ARF is also common in MM and mutations in NF2 occur in approximately half of the cases. Despite the ban on asbestos use in Western countries, the incidence of MM is increasing, and asbestos is still used in developing countries. This epidemiologic situation calls for further research. Ongoing studies are already applying high-throughput genomic profiling methods in MM. Genetic alterations observed in MM may be useful in differential diagnosis between lung cancer and MM, as diagnostic markers or therapeutic targets, and as indicators of premalignancy for primary prevention and health surveillance.