Mesothelioma Diagnosis

Mesothelioma is often discovered by an X-ray or other imaging test (CT, MRI, PET) followed by blood marker tests and confirmed with a biopsy for diagnosis. Diagnosing mesothelioma is difficult and usually requires a biopsy to verify the results. Learn about the tests doctors use to diagnose mesothelioma.

Diagnosing mesothelioma is challenging because of delayed symptoms and the rarity of this type of cancer, but getting diagnosed is important for treatment.

Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers. Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.

Micrographs showing conventionally-stained mesothelioma in a core biopsy (higher magnifications on right).

Imaging

Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient’s medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe. For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis, heart failure). However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis. Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology.

Biopsy

Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary.

Immunochemistry

Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer.

Typical immunohistochemistry results
Positive Negative
EMA (epithelial membrane antigen) in a membranous distribution CEA (carcinoembryonic antigen)
WT1 (Wilms’ tumour 1) B72.3
Calretinin MOC-3 1
Mesothelin CD15
Cytokeratin 5 Ber-EP4
HBME-1 (human mesothelial cell 1) TTF-1 (thyroid transcription factor-1)
Podoplanin (PDPN) Claudin-4
Osteopontin Epithelial cell adhesion molecule (EpCAM)
Estrogen receptor alpha
Mammaglobin

Subtypes

There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas sarcomatous mesothelioma has not been studied extensively. Most mesotheliomas express high levels of cytokeratin 5 regardless of subtype.

Epithelioid mesothelioma is characterized by high levels of calretinin.

Sarcomatous mesothelioma does not express high levels of calretinin.

Other morphological subtypes have been described:

  • Desmoplastic
  • Clear cell
  • Deciduoid
  • Adenomatoid
  • Glandular
  • Mucohyaline
  • Cartilaginous and osseous metaplasia
  • Lymphohistiocytic

Differential diagnosis

  • Metastatic adenocarcinoma
  • Pleural sarcoma
  • Synovial sarcoma
  • Thymoma
  • Metastatic clear cell renal cell carcinoma
  • Metastatic osteosarcoma

Staging

Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group. TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.

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