Pathological anatomy and molecular pathology
Introduction
The history of malignant mesothelioma is relatively short. The existence of primary tumours of the serous membranes was proven in the 20s and 30s of the 20th century. It was not before the 1960s that a considerable number of mesotheliomas were documented, especially in cohorts of workers with histories of heavy asbestos exposure. The reliability of the diagnoses at that time was not as high as it is today, because of the lack of immunohistochemical analyses, which were introduced in the mid-1980s and have been considerably improved since the mid-1990s.
Pleural mesotheliomas are much more common than peritoneal ones (pleura:peritoneum about 10:1). Primary pericardial localization accounts for about 1% of all mesotheliomas, and the tunica vaginalis testis is a very rare primary localization (own data). Secondary pleural tumours are about 100 times more frequent than primary [1]. Men are affected much more frequently than women, and the most common age of onset is the sixth decade.
Section snippets
Aetiology
The most important aetiologic agent is still asbestos. It was already known in the ancient world, but common industrial use did not start until after the Second World War. Industrial asbestos production and the use of asbestos products in Germany reached a peak between 1965 and about 1980. The latency period between exposure and the onset of mesothelioma symptoms is about 30 years on average, but can range between about 10 and more than 50 years in individual cases. All commercially used
Simian virus 40 (SV40)
In human mesotheliomas, SV40-like DNA sequences were detected in 1994 for the first time [5]. Positive results for the detection of viral segments in mesotheliomas have been published by some international working groups. The potential of the large T antigen of the SV40 genome to bind and functionally inactivate the P53 protein and the proteins of the retinoblastoma gene family is the basis for the carcinogenic potency of the SV40 [6]. A study on 118 German and US-American mesotheliomas and 13
Pathogenesis
The exact mechanisms of mesothelioma pathogenesis are unknown. As in other malignant tumours, many genetic alterations seem to be involved in mesothelioma initiation and progression. The first report on the cytogenetic findings in mesotheliomas dates from 1978 [8]. In follow up studies about 10 years later, an involvement of the oncogenes myc (myelocytomatosis virus family), ras (rat sarcoma virus), raf (RAS activated fragment), and met (N-methyl-N′-nitroso-guanidin treated human osteosarcoma
Macroscopic findings
The typical macroscopic findings in late stages with complete obliteration of the pleural space and the interlobular septa are widely known. Pleural carcinoses may mimic mesotheliomas in early and late stages. One has to be aware that rare cases of local malignant mesotheliomas do exist which do not show the typical mesothelioma growth pattern. Epithelioid mesotheliomas are stickier, whereas the firm-to-hard section of predominantly sarcomatoid mesotheliomas is reminiscent of pleural scars. In
Additional analyses
Any mesothelioma diagnosis should be confirmed by a panel of histo- and immunohistochemical stainings. It is often impossible to decide reliably, by means of conventional histological analysis alone, whether an epithelial tumour is a pleural or peritoneal carcinosis or a mesothelioma, or if a sarcomatous tumour is a mesothelioma or a sarcoma. In the differential diagnosis of epithelial lesions, calretinin has proven to be the most important, but not the only, antibody. In our laboratory, we use
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