Mesothelioma

Basics

  • very aggressive
  • local progression is the main cause of mortality
    • direct extension and seeding throughout the pleural space, including fissures, diaphragmatic and pericardial surfaces, through the chest wall, and into the mediastinum peritoneum, and lymph nodes.
  • disseminated disease —> very late
  • The major problem
  • Surgery alone even in selected cases has not improved survival
    • 2year survival —> 10%-33%

Etiology and Epidemiology

  • very rare
  • 1000-2000 per year
  • Asbestos
    • most cases occur over 20years after exposure
    • asbestose history in 80-90% of cases
    • Ocupational (e.g., construction work, automotive brake repair, boiler work, shipbuilding)
    • ==> 90% male predominance.
    • Endogenous environmental asbestos exposure
      • Central Turkey
      • Western Australia
  • Radiation
  • Mdian age —> years.
  • No direct association between mesothelioma and smoking
    • BUT smoking greatly increases the risk when there is also asbestos exposure

Clinical Evaluation and Staging

  • Dyspnea
  • Chest pain
    • involvement of the endothoracic fascia
  • Cough
  • Weight loss
  • Pulmonary function tests —> restrictive pattern <== “trapping” of the lung or chest wall involvement
  • transthoracic involvement from instrumentation ==> axillary and supraclavicular lymph nodes involvement
  • Miliary disease under surface of peritoneum and diaphragm
    • hard to detect with imaging

Imaging

  • CXR
    • pleural effusion
    • calcified pleural plaques
  • CT-scan with contrast
    • Mainstay of imaging
    • Circumferential pleural thickening
    • Irregular pleural contour
    • Contraction of the ipsilateral hemithorax
    • Invasions of the diaphragm and/or chest wall are difficult to detect in early cases
    • The interlobar fissures are often involved.
    • Invasion of adjacent structures
      • chest wall
      • mediastinum
      • great vessels
      • vertebral body
      • heart
    • Mediastinal and hilar lymph nodes involvement
      • Lower paraesophageal nodes (level 8), pulmonary ligament nodes (level 9), and diaphragmatic nodes much more commonly than lung cancers.
    • Pericardial effusions
    • Ascites
  • PET-CT
    • may be useful in avoiding unnecessary surgery in patients with more advanced disease

Invasive Staging

The diagnosis of mesothelioma can be difficult because of the
relative rarity of the disease and the cytologic similarity to
more common metastatic neoplasms, such as adenocarcinoma.
Thoracentesis is often the first procedure performed to obtain
diagnosis, but it has a diagnostic sensitivity of only 32%.394
Percutaneous fine-needle aspiration biopsy similarly has low
diagnostic sensitivity, although ultrasound-guided coreneedle
biopsy has been reported to improve accuracy.395 Before
beginning multimodality treatment, accurate preoperative
staging is necessary. An open pleural biopsy is the gold standard.
386 Surgical intervention with open thoracotomy or videoassisted
thoracoscopic surgery can also be done. Diagnostic
thoracentesis is an alternative, though it has a lower yield than
video-assisted thoracoscopic surgery.387
Mesothelioma has a tendency to track along sites of chest
wall violation, and tumor may recur at previously placed thoracoscopy
port sites if they are not excised at the time of
definitive surgery. Limiting the number of port sites at the
time of video-assisted thoracoscopic surgery and placing the
port sites where they are easily excised help to reduce local
chest wall recurrence. When it is difficult to establish entrance
into the pleural space, it is preferable to perform a limited
open biopsy of the parietal pleura by extending the port site
incision slightly, rather than to perform a formal thoracotomy.
A thoracotomy performed for diagnosis significantly compromises
potentially curative surgery.
Unfortunately, preoperative assessment of mesothelioma
tumor stage is less than ideal. Although CT, PET, and MRI are
reasonably accurate in defining tumor volume within the
thorax and chest wall and in identifying sites of distant disease,
they are less successful in determining tumor involvement at
two critical sites: contralateral mediastinal nodal involvement
and tumor invasion through the diaphragm. Tumor involvement
at either site negates resection, and we therefore think
that an accurate assessment of these areas is necessary before
performing EPP. All patients at our institution undergo pretreatment
laparoscopy with peritoneal lavage and cervical
mediastinoscopy. At the M.D. Anderson Cancer Center, of
118 patients with MPM who were clinically and radiographically
determined to have resectable disease, laparoscopy
and peritoneal lavage revealed transdiaphragmatic or peritoneal
involvement in 12 (11%) of 109 patients and mediastinoscopy
identified positive contralateral nodes in 4 (4%) of
111 patients. Overall, 15 (13%) patients were identified with
occult advanced disease and spared unnecessary EPP.
Staging
The AJCC seventh edition staging system for mesothelioma is
shown in Box 44-4 and is based on the International Mesothelioma
Interest Group (IMIG) staging system. The staging
systems are useful only after surgical staging, and no clinical
staging system has been developed or validated.
Several important prognostic markers have been identified
for MPM. Metastases to any nodal station predict a worse
outcome. However, unlike non-small cell lung cancer, it is not
clear that mediastinal metastases reflect a worse prognosis
than hilar or intrapulmonary nodal metastases. The completeness
of resection is also prognostic. Patients with R1 or R2
resections have been reported to have a worse outcome in
some series.388
Another poor prognostic marker is nonepithelioid histologic
findings. Epithelioid histologic characteristics are found
in 50% of cases. Pure epithelioid mesothelioma may be difficult
to distinguish from metastatic adenocarcinoma of the
lung, so immunohistochemistry or electron microscopy is