Mesothelioma represents a fatal malignancy developing in the pleural and other serous cavities, linked to asbestos exposure. The combination of accurate medical history, physical examination, imaging studies and the acquisition of pathology is essential in the diagnosis of mesothelioma.

Direct exploration of the serous membranes (thoracoscopy for the pleural cavity and laparoscopy for the peritoneal cavity) is often a key step in the diagnostic process. In addition to facilitating the identification, multiple biopsies that are essential for correct diagnosis can be performed.

Imaging studies

Non-invasive imaging studies play an essential role in diagnosing and staging of patients with mesothelioma. Chest radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography have all been employed in evaluating the disease.

Initial detection of pleural mesothelioma usually stems from a radiographic chest examination. Primary radiographic signs include unilateral pleural abnormality with an associated pleural effusion, shift of the mediastinum on that side and lung volume loss. Still, this technique does not provide specific diagnosis; therefore a follow-up study with another imaging modality is usually indicated.

Intravenous contrast-enhanced CT currently represents the primary imaging modality for suspected pleural malignant disease. Mesothelioma is seen as a lobulated, circumferential soft tissue mass that often involves the interlobar fissures and the mediastinal pleura. On the other hand, CT findings of peritoneal mesothelioma are nonspecific and usually not sufficient to establish a proper diagnosis.

Magnetic resonance imaging adds significant information to the clinical evaluation of patients with pleural mesothelioma and can provide additional staging information, although it is not used routinely. The technique allows the acquisition of images in arbitrary planes, and the use of gadolinium enhancement can improve the identification of tumors that invaded the chest wall and the diaphragm.

PET provides different information than the other techniques due to the functional images of metabolic activity, thus in recent years it has gained recognition for the assessment of mesothelioma. The use of this type of tomography improves the accuracy of diagnosing mediastinal nodal metastases, helps in staging and preoperative evaluation of mesothelioma, and it is also used as a guide to the optimal site for guided pleural biopsy.

Morphological diagnosis

Histologically, malignant mesothelioma can show epithelial morphology (50-70% of all cases), sarcomatoid morphology (7-20% of cases) or biphasic morphology, i.e. a combination of both (20-35% of cases). The experienced pathologist will recognize those tumors as mesothelial, although atypical histology can resemble a metastatic carcinoma.

Immunohistochemical staining has a central role in the diagnosis of mesothelioma. This diagnostic procedure looks for different proteins on the surface of the cells or inside them. It is often used to assess whether the malignancy in question is a mesothelioma or a lung cancer, which can sometimes appear to start in the inner lining of the chest.

Also, it is important to distinguish a malignant pleural process from an inflammatory process and immunohistochemistry has demonstrated immunoreactivity for keratin, p53 and epithelial membrane antigen (otherwise unusual for benign pleural disease) can be found in mesothelioma.

Immunohistochemistry is important in the differentiation of mesothelioma from other malignant diseases via markers such as mesothelin, cytokeratin 5, thrombomodulin and calretinin. The latter is the most commonly used antibody for detecting mesothelioma, with a reported sensitivity of 95% and specificity of 87%.