Diagnostic Challenges in Pleural Mesothelioma

Accurate diagnosis of PM and precise histologic subtyping are critical for optimal therapeutic decision-making, as treatment strategies—including chemotherapy, immunotherapy, or multimodality approaches—are largely subtype-dependent. Because of the several-decade latency between fiber inhalation and symptom onset, many cases are diagnosed at an advanced stage, when patients are already in poor clinical condition. As observed across multiple solid malignancies, earlier-stage diagnosis is associated with improved prognosis and expanded therapeutic options. However, the rarity of PM, the absence of validated screening strategies, and its nonspecific clinical and radiologic presentation—often mimicking both benign and metastatic pleural conditions, frequently result in diagnostic delay. Furthermore, the lack of pathognomonic histopathologic markers further complicates timely and definitive diagnosis. This review aims to delineate the epidemiologic, clinical, radiologic, and pathologic barriers that hinder accurate and early detection of PM. Current clinical evidence points to an urgent need to develop novel, validated biomarkers in PM, which will require a multidisciplinary approach.