Preface

Mesothelioma is a peculiar malignant tumour that develops from the mesothelial lining of serosal cavities, including pleura (more than 80% of cases), peritoneum, pericardium and tunica vaginalis. It is well known for its classic association with asbestos exposure and unusual gross growth pattern. However, as a difficult diagnosis with limited treatment efficacy and thus adverse survival, mesothelioma also represents an unmet need for the healthcare system. Despite its rarity, mesothelioma remains an intriguing clinical and scientific challenge. As regards basic research, the dominant yet incomplete association with asbestos provides a stable background for pathogenetic studies and search for other causes. Clinically, the possibilities of surgical treatment are limited because of the anatomic fragility of serous membranes and extensive tumour spread; the response to current chemotherapeutic options is unsatisfactory and even the definitive confirmation of diagnosis can be complicated.

*Mesothelioma - Diagnostics, Treatment and Basic Research* is intended as a summary of classic views and recent advances in pathogenetic concepts, diagnostics, treatment and scientific studies of mesothelioma. It contains a collection of review articles, grouped into three sections: "Etiology and Pathogenesis of Mesothelioma", "Diagnostic Aspects of Mesothelioma" and "Treatment of Mesothelioma".

In the first section, Chapter 1 is devoted to the causes and pathogenesis of malignant mesothelioma, and provides a complete and clear analysis of different etiological agents comprising not only asbestos but also erionite, fluoroedenite, balangeroite and carbon nanotubes, as well as genetic factors, including BAP1 and other genes linked to the pathogenesis of malignant mesothelioma. The authors also discuss the role of simian virus SV 40, ionising radiation and inflammation in the development of mesothelioma. The pathogenesis is further detailed in Chapter 2 on epigenetic events in pleural mesothelioma.

Although the ultimate "gold standard" of mesothelioma diagnostics is verification of the diagnosis in tissue material, this is an invasive approach, hence the search for new technologies. The second section, "Diagnostic Aspects of Mesothelioma", begins with an introduction to the cytological, histological and immuno-phenotypical diagnostics of mesothelioma, covered in Chapter 3. The comprehensive analysis of a complex morphological diagnosis is adapted both for pathologists and clinicians. Recent (2021) changes in WHO classification, as well as morphological features of mesothelioma and relevant immunohistochemical stains, are also discussed. The general mesothelial markers, markers for differential diagnosis between benign versus malignant mesothelial cells, as well as carcinoma markers, are presented. The basic technical requirements and laboratory procedures used for the preparation of cytological and histological samples are also discussed. These aspects are among the major strengths of this chapter because they have been less extensively discussed in previous scientific literature, but can influence the diagnostic outcome significantly.

Chapter 4, by a world-renowned group of scientists who have significantly contributed to current mesothelioma research, looks at diagnostic advances, with an examination of a patient-friendly, innovative approach in the early diagnostics of pleural mesothelioma by assessment of a novel marker, fibulin-3. The gene expression of fibulin-3 is described, followed by an explanation of its biological action and a description of laboratory methods used to detect this molecule in tissues and in biological liquids. Findings in tissue samples, pleural fluid and peripheral blood are reported, and the informativity of fibulin-3 is compared with other biomarkers.

The third section concentrates on surgical and non-surgical treatment of mesothelioma. Surgical approaches to pleural mesothelioma are highlighted in Chapter 5 by a team of experts in this challenging and highly controversial area. The crucial types of operations for mesothelioma ‒ extrapleural pneumonectomy and pleurectomy/decortication ‒ are described and critically analysed, with their indications and outcomes. The role of surgery is discussed within the frameworks of pre-operative diagnostic evaluation and multimodality oncological treatment.

However, mesothelioma is rarely amenable to surgery, leaving systemic therapy as the main treatment approach. Chapter 6 is devoted to developments in systemic cytotoxic treatment, inhibitors of angiogenesis and immune checkpoint inhibitors for the therapy of malignant pleural mesothelioma. Recent mesothelioma trials are summarised in a clear, reader-friendly review. In view of the dismal prognosis of mesothelioma and the limited response to current therapeutic options, the topic is clinically and scientifically important.

The book has been created by a truly global team of doctors and scientists from Italy, Japan, Mexico, Greece and Estonia. We would like to sincerely thank all the authors for their excellent contributions, clinical experience and sharp minds.

This work would not have been possible without the editorial help of my distinguished colleagues, Dr. Romans Uljanovs and Boriss Strumfs, MSc, Ph.D.

Last but not least, we express our sincere gratitude to the IntechOpen editorial team for their continuous support and professional help throughout all stages of book production.

> **Ilze Strumfa, MD, Ph.D.** Department of Pathology, Riga Stradiņš University, Riga, Latvia

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Section 1

Etiology and Pathogenesis

of Mesothelioma

Section 1
