Mesothelioma Workup

  • Author: Winston W Tan, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Dec 6, 2011
 

Laboratory Studies

  • Hollevoet et al found that megakaryocyte potentiating factor (MPF) can be used as a serum biomarker of malignant mesothelioma. MPF originates from the same precursor protein as soluble mesothelin (SM), which is currently the reference serum biomarker for malignant mesothelioma. At 95% specificity, SM had a sensitivity of 64% (cutoff = 2.00 nmol/L) and MPF had a sensitivity of 68% (cutoff = 12.38 ng/mL). Combining both markers did not improve the diagnostic performance.[5]
  • Pleural fluid findings in patients with mesothelioma are typically not diagnostic. The specific gravity of the pleural fluid is nondiagnostic.
  • Typically, the pleural fluid has less than 1000 leukocytes per microliter, few erythrocytes, elevated protein levels, and normal lactate dehydrogenase levels.
  • Results of cytologic examination are occasionally positive for malignant mesothelial cells; however, most often the pleural fluid cytology results are not diagnostic.[6]
  • Diagnosis is made based on the following:
    • More than 90% of patients present with pleural effusion that decreases after thoracentesis. Cytologic examination findings are diagnostic in only 32% of patients and are suggestive in 56% of patients. Thoracoscopically guided biopsy should be performed if mesothelioma is suggested, and results are diagnostic in 98% of cases.
    • Careful scrutiny of routinely stained biopsy preparations is the most valuable diagnostic tool for making a diagnosis. A battery of commercial immunohistochemistry stains (eg, for cytokeratins, vimentin, human milk fat globulin 2, anti-Leu M1, BerEP4, and carcinoembryonic antigen) can be used.[7]
    • Diagnostic features distinguishing malignant mesothelioma from adenocarcinoma include negative test results for periodic acid-Schiff stain, mucicarmine stain, carcinoembryonic antigen, and Leu M1 and positive test results for calretinin, vimentin, and cytokeratin. Electron microscopy reveals that cells have long microvilli, in contrast to adenocarcinomas, which have short microvilli. One of the new most intriguing markers is serum mesothelin-related protein (SMRP) measured in fluid or serum. The circulating SMRP level was reported to be elevated in 84% of patients with malignant mesothelioma and in 2% of patients with lung cancer.
    • Recently, 4 new mesothelioma cell lines have been characterized based on ultrastructural and immunophenotypic analysis.[8] Cell lines express vimentin, cytokeratins 8 and 18, and mesothelial antigen recognized by HBME-1 monoclonal antibody. Surface HLA class I and intercellular adhesion molecule I are present in all lines.
    • While HLA class II and CD 86 are undetectable, HLA class II is present after interferon gamma stimulation. All cell lines display abnormal karyotypes with chromosome 6 abnormalities. The persistence of large T antigen with HLA class I and intercellular adhesion molecule I suggests large T antigen as a target for cytotoxic-based immunotherapy.
  • Savic et al used fluorescence in situ hybridization (FISH) to distinguish malignant mesothelioma from reactive mesothelial cells in effusions. Diagnosis of mesothelioma by detection of chromosomal aberrations with FISH had 79% sensitivity; positive and negative predictive values for detection of mesothelioma were 100% and 72%, respectively.[9]
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Imaging Studies

  • Imaging studies may include a chest radiograph (see History), CT scan of the chest, MRI of the chest, and positron emission tomography (PET) scan.[10] The latter is still considered investigational for helping differentiate between benign and malignant mesothelioma. The value of fluorodeoxyglucose positron emission tomography (FDG-PET) was evaluated in 17 patients. The survival distribution in the group with high FDG uptake showed shorter survival compared with the low FDG group.[11]
  • The optimal preoperative staging procedures are debatable. In 1996, Sugarbaker et al recommend MRI as a standard part of staging.[12] Others argue that laparoscopic thoracoscopy is the best way to determine the extent of the disease. Some argue that PET scans may be helpful, but their role in staging needs to be defined. MRI performed with different pulse sequences and gadolinium-based contrast material can improve detection of tumor extension, especially to the chest wall and diaphragm. PET scans can provide metabolic and anatomic information, especially for those with extrathoracic or mediastinal metastasis. The appropriate role of PET scans in the management of this disease is still undefined.
  • Determining the extent of disease by performing a laparoscopy or MRI and a cardiopulmonary evaluation is important, if the patient is amenable.
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Other Tests

  • Measuring the diffusion capacity of the lung preoperatively is important because most patients have poor pulmonary reserve secondary to interstitial lung disease.
  • A cardiopulmonary stress test with pharmacologic agents is a reasonable choice to eliminate the possibility of evidence of silent myocardial ischemia.
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Procedures

  • See Lab Studies.
  • Thoracoscopy or pleuroscopy should be performed to confirm the diagnosis.
  • Laparoscopy is important for staging but is still investigational to evaluate for transdiaphragmatic involvement.
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Histologic Findings

See Lab Studies. Gross pathology reveals that the pleural surfaces are seeded with malignant mesothelioma cells, which form grouped nodules. As the disease progresses, it covers the entire pleural space and invades the chest wall, mediastinum, and diaphragm. Microscopically, the 3 histologic types are epithelial, sarcomatous, and mixed. The epithelial type correlates with a better prognosis.[13]

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Staging

Six staging categories have been proposed for mesothelioma. In 1996, Sugarbaker and associates proposed the Brigham staging system based on tumor resectability and nodal status, a system validated in a clinical trial.[12] To date, the accepted system is the TNM classification accepted by the International Mesothelioma Interest Group (IMIG).

  • Stage I - Completely resected within the capsule of the parietal pleura without adenopathy (ie, ipsilateral pleura, lung, pericardium, diaphragm, or chest wall disease limited to previous biopsy sites)
  • Stage II - All stage I characteristics, with positive resection margins, intrapleural adenopathy, or a combination
  • Stage III - Local extension of disease into the chest wall or mediastinum, into the heart, through the diaphragm or peritoneum, or extrapleurally to involve the lymph nodes
  • Stage IV - Distant metastatic disease

Based on many clinical factors, 2 separate groups, the Cancer and Leukemia Group B and the European Organization for Research and Treatment of Cancer, had identified the following poor prognostic factors:[14, 13]

  • Performance status of 2 or greater
  • Nonepithelial histology
  • Chest pain
  • Age older than 75 years
  • Male sex
  • High platelet count
  • Lactate dehydrogenase greater than 500 IU/L
  • Low hemoglobin
  • High white count
  • Weight loss

The pattern of nodal metastasis is different from that of lung cancer. The mechanism of spread of the disease to the hilar nodes may be through lung invasion and not due to spread directly from the pleura. In a study of 53 patients, of the 49 patients operated on only 7 had no lung invasion and none had positive hilar nodes. In the postpneumonectomy patients, 6 of 14 had positive hilar node and mediastinal nodes.

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Contributor Information and Disclosures
Author

Winston W Tan, MD  Assistant Professor of Medicine, Mayo Medical School; Consulting Staff, Mayo Group Practices

Winston W Tan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, and Texas Medical Association

Disclosure: Medivation Grant/research funds Other; Oncogenix Grant/research funds Other; Genentech Grant/research funds Other

Specialty Editor Board

Michael Perry, MD, MS, MACP  Nellie B Smith Chair of Oncology Emeritus, Director, Division of Hematology and Medical Oncology, Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Benjamin Movsas, MD  Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine; Consulting Staff, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

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