Malignant mesothelioma is a rare but highly aggressive cancer primarily associated with asbestos exposure, both occupational and environmental.1,2 It originates from the mesothelial cells lining the pleura, the peritoneum, pericardium, and tunica vaginalis. Malignant pleural mesothelioma (MPM) accounts for around 85% of all mesothelioma cases and is the predominant form of primary malignancy of the pleura.3

Historically, the use of asbestos, a fibrous silicate mineral known for its heat resistant properties, has been extensive in construction and manufacturing. When inhaled, asbestos fibers lodge in the mesothelial linings, initially causing no symptoms. Overtime, these fibers trigger chronic inflammation that leads to genetic and cellular disruptions, eventually manifesting as mesothelioma​​​.2,4 In the 1960s, Wagner et al. first documented the connection between mesothelioma and asbestos exposure in the Northwestern Cape Province, marking a significant milestone in our understanding of this disease.5 Since then, accumulating evidence has confirmed this link, leading to the World Health Organization's (WHO) declaration that all types of asbestos cause cancer in humans.6 Subsequently, since the 1970′s many countries have implemented bans on asbestos use to varying degrees, with some completely prohibiting asbestos containing products, demonstrating a global commitment to reducing the risk of mesothelioma.7 Simian virus 40 (SV40), that can infect and transform human mesothelial cells, has been suggested to increase mesothelioma incidence with a synergistic effect identified between SV40 and asbestos exposure in regions affected by SV40 contaminated polio vaccines.8, 9, 10, 11 Although most mesothelioma cases are linked to asbestos exposure, reports suggest that ionizing radiation may also cause mesothelioma, such as in patients previously treated with radiation for Hodgkin lymphoma, lung cancer, or breast cancer.12, 13, 14, 15 Other risk factors such as exposure to minerals like zeolite or tremolite, diethylstilbestrol, and genetic predisposition also contribute to the occurrence of MPM.1,4,16,17

MPM shows a significant male predominance and is rare in young individuals, with incidence sharply increasing after the age of 50.1,7,18 Developed countries report higher incidence of mesothelioma, partially due to differences in industrialization levels, asbestos usage and regulation, and the effectiveness of reporting systems in tracking disease prevalence.1,18

The latency period of mesothelioma can range from 10 to 50 years after initial asbestos exposure19 and symptoms may not appear for decades. Common initial symptoms include chest discomfort and respiratory distress, often due to pleural effusion, other nonspecific symptoms can include weight loss, reduced appetite, persistent cough, and fatigue, with some patients noticing a chest wall lump.19,20

Due to its long latency and nonspecific symptoms, detection often comes late, and the prognosis remains poor, with a median survival of 9 to 12 months. Research indicates that females generally have better overall survival, possibly due to lower exposure levels and duration to asbestos, more favorable clinical characteristics, and protective effects of estrogen.7,21,22

Histologically, mesothelioma manifests in three types: the more favorable epithelioid type (50%-60%), sarcomatoid (10%−20%) which is more aggressive, and mixed/biphasic (20%-40%) that has both epithelioid and sarcomatoid features.17,23 Diagnosis requires biopsy, where cellular morphology and immunohistochemistry are critical for choosing the appropriate treatment.24,25

Patients with MPM should be managed by an experienced multidisciplinary team, which typically includes oncologists, pulmonologists, radiologists, and pathologists. This team approach is crucial for comprehensive care and ensuring that all aspects of the disease are addressed. Treatment options include surgery, radiation therapy, and systemic therapies.17 Most patients have advanced disease at presentation, and surgery is not recommended for them. The NCCN guidelines15 recommend assessment of patients with operable MPM for a trimodality therapy approach –using chemotherapy either preoperative or postoperative, surgery, and hemi-thoracic radiation therapy- which was found to prolong survival.15,26, 27, 28, 29

Systemic therapy alone is recommended for patients with inoperable MPM due to advanced disease stage, patients related reasons or sarcomatoid or biphasic histology regardless of stage.15 First line therapy for unresectable MPM rely on chemotherapy and immunotherapy. Platinum based chemotherapeutic drugs are used in conjunction with Pemetrexed with or without the addition of Bevacizumab.15,19,20,30

The CheckMate7433 trial led to the approval of a double immunotherapy regime the treatment of unresectable MPM. This regime uses human immune checkpoint inhibitor antibodies: Nivolumab and Ipilimumab.31 Immunotherapy works by enhancing the body's immune response against cancer cells, and this double immunotherapy approach has shown promising results in improving survival rates for patients with MPM.

While radiation therapy is not recommended as a sole treatment option for MPM, it can be a valuable part of a multimodality regimen.15 In addition, radiation therapy can be used as palliation for relief of chest pain, bronchial or esophageal obstruction, or other symptomatic sites associated with MPM, such as metastases to bone or brain.19,32

Pleural effusion can be managed through various approaches, depending on the patient's condition and treatment goals. Options include thoracoscopic talc pleurodesis, which involves the application of talc to the pleural space to induce fibrosis and prevent further fluid accumulation. Alternatively, a drainage catheter can be placed to continuously remove fluid. For immediate relief, therapeutic or palliative thoracentesis can be performed to extract pleural fluid, thereby reducing dyspnea. This procedure is particularly beneficial either before starting other treatments or for patients who are not suitable for more invasive interventions.15