Malignant mesothelioma: current status of histopathologic diagnosis and molecular profile

Malignant mesothelioma of the pleura is a relatively rare neoplasm that has been estimated to account for 20 deaths per million males per year in North America and Europe. A causative association has been well established with asbestos exposure. Paradoxically, the incidence of this tumor continues to rise despite public efforts to reduce, contain or eliminate exposure to asbestos fibers over the past few decades. Another paradoxical feature of the disease is that the majority of malignant mesotheliomas represent morphologically low-grade, well-differentiated neoplasms, yet they follow a relentlessly aggressive and virtually uniformly fatal outcome. For this reason, identification of clinical, morphologic, immunohistochemical or molecular genetic parameters is of extremely limited value for prognostication. Surprisingly, for a disease that currently has no known cure, one of the major problems still lies in establishing the correct diagnosis. Diagnosis acquires a particular relevance in light of the medicolegal ramifications of this disease, and diagnosis of malignant mesothelioma is still fraught with difficulties. Despite the advances in modern diagnostic techniques, no specific markers or morphologic features exist that are exclusive to these tumors. Herein, the current status of malignant mesothelioma diagnosis is reviewed, including the possible contributions of modern molecular techniques for their diagnosis.