Background/Objectives: Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis and complex diagnostic pathways. Pulmonologists often play a central role in its initial recognition and investigation. This narrative review synthesizes the current evidence on the diagnostic approach to [malignant pleural mesothelioma (MPM)], with emphasis on imaging, tissue sampling, histopathology, and emerging diagnostic innovations relevant to clinical pulmonology.
Methods: English-language studies published between January 2005 and June 2025 were identified from PubMed and Scopus. International guidelines and consensus documents were also reviewed to provide an updated overview of diagnostic strategies.
Results: Diagnosis of [malignant pleural mesothelioma (MPM)] relies on a stepwise integration of clinical, radiological, and pathological information. Thoracic ultrasound, computed tomography, positron emission computed tomography and magnetic resonance imaging complement each other across different stages of the diagnostic pathway. Image-guided pleural biopsy and medical thoracoscopy remain the gold standard for tissue confirmation, supported by immunohistochemistry and molecular testing. The 2021 World Health Organization classification of pleural tumors and the International Association Study of Lung Cancer 9th Edition Tumour-Node-Mestastatis system have refined histologic and staging criteria, thereby improving reproducibility and prognostic accuracy. Emerging tools, including liquid biopsy, novel serum and molecular biomarkers, artificial-intelligence-based radiomics, and breathomics, offer promise for earlier and less invasive diagnosis but require prospective validation.
Conclusions: Current advances are redefining [malignant pleural mesothelioma (MPM)] diagnosis toward integrated, multidisciplinary, and precision-based models. Future priorities include standardizing diagnostic algorithms, validating minimally invasive biomarkers, and integrating AI and molecular profiling into clinical workflows to enhance patient stratification.
1. Introduction
1.1. Background and Rationale
Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm that arises from the mesothelial cells lining the pleural cavity. Despite advances in oncological care, prognosis remains poor, with median survival rarely exceeding one year after diagnosis [1].
Early and accurate diagnosis of [malignant pleural mesothelioma (MPM)] is crucial, as it influences therapeutic decision-making, eligibility for multimodal treatment, and ultimately patient outcomes [2]. However, the diagnostic pathway is frequently challenging due to the non-specificity of symptoms [3], which overlap with a variety of benign and malignant conditions, or the absence of known occupational exposure to risk factors [4]. In addition, non-invasive diagnostic tools, such as imaging modalities, are often limited by constraints on sensitivity and specificity.
In recent years, progress has been made in refining diagnostic strategies through improved imaging protocols, advances in endoscopic techniques, the application of immunohistochemistry panels, and the investigation of novel molecular and circulating biomarkers [5]. Furthermore, international guidelines have sought to standardize diagnostic approaches [6], although variations in clinical practice and access to resources persist.
Given the complexity and heterogeneity of diagnostic options, there is a pressing need to synthesize available evidence and provide a comprehensive overview tailored to pulmonologists, who are frequently the first specialists to encounter suspected cases.
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