Elsevier

Lung Cancer

Volume 45, Supplement, August 2004, Pages S29-S33
Lung Cancer

Pathological anatomy and molecular pathology

https://doi.org/10.1016/j.lungcan.2004.04.005Get rights and content

Abstract

The incidence of malignant mesotheliomas in Germany has increased since about the mid 1980s, and a further increase is expected until about 2020 due to the peak in asbestos processing in Germany between 1965 and 1980. About 90% of the mesotheliomas recorded in the files of the German Mesothelioma Registry in Bochum are asbestos-related and therefore possibly due to an occupational exposure. In 2003, 717 mesotheliomas were newly diagnosed at the German Mesothelioma Registry. Mesotheliomas are very heterogeneous in terms of histological appearances and of prognosis. At present, the diagnostic gold standard is conventional histology in combination with additional immunohistochemical analysis. We were not able to confirm a promising report that described telomerase reverse transcriptase catalytic subunit (TERT) for the differentiation between reactive and neoplastic mesothelial lesions, which can be extremely difficult. DNA cytometric analysis may also help differentiate between reactive and neoplastic mesothelial lesions. There are some characteristic patterns of chromosomal imbalances as detectable by comparative genomic hybridization (CGH), but at present, specific chromosomal or genetic defects that give rise to a mesothelioma are not known. A reliable pathological diagnosis is the basis for therapeutic, prognostic, and medicolegal consequences. In general, it can be achieved by thoracoscopic inspection with specifically directed biopsy. Furthermore, a description of the peculiarities of each mesothelioma by the pathologist might be the key to a more individual therapy in the future.

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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