MALIGNANT PLEURAL MESOTHELIOMA
Malignant
pleural mesothelioma (MPM) is a tumor arising in the pleura from mesothelial
cells. It may also arise in the peritoneal cavity, pericardium, and tunica
vaginalis (rarely). Pleural mesothelioma may be restricted to a small area or
grow diffusely in a multifocal or continuous manner. The histologic types of
MPM are epithelioid, which is the most common; sarcomatoid; and biphasic or
mixed. Desmoplastic mesothelioma is considered a subtype of sarcomatoid
mesothelioma. Localized malignant mesothelioma presents as a nodular lesion
without diffuse pleural spread but is histologically identical to diffuse MPM.
Results of immunohistochemical staining with cytokeratin 5/6, calretinin, and
Wilms tumor-1 are positive in the vast majority of epithelioid mesothelioma but
are less often positive in sarcomatoid mesothelioma. These markers are
typically, but not always, negative in adenocarcinoma.
The etiologic agent of MPM is asbestos in a large
majority of the cases, but documentation requires a careful exposure history,
and the delay between exposure and disease is generally 30 to 50 years. The
frequency of MPM increases with increasing asbestos exposure, but there is no
documented lower limit or safe threshold level of asbestos exposure. Certain
individuals are believed to be genetically more susceptible, but the exact
genetics have not been delineated.
The most common presentations are pleural effusion or
pain. Dyspnea may be present if the pleural effusion is of significant size.
Pain is generally described as a dull ache or pulling sensation in the chest
wall. The chest radiograph may show pleural effusion or pleural thickening with
or without irregular thickening of the interlobar fissure. Calcified pleural
plaques may be present and are a sign of prior asbestos exposure. Computed
tomography (CT) of the chest usually demonstrates pleural thickening and
nodularity if it is not hidden by the pleural effusion that is present in most
cases. Thickening of the intralobar fissure is frequently present. With more
extensive involvement, contraction of the involved hemithorax may occur.
The diagnosis can be difficult. Pleural fluid cytology
results are positive for malignant cells in one-third of cases, but
pathologists have difficulty determining adenocarcinoma involving the pleura
versus MPM. Percutaneous or closed pleural biopsy often yields adequate tissue
for diagnosis. When these test results are nondiagnostic, then thoracoscopy
with biopsy under direct visualization is diagnostic in 90% of cases. The
typical description at visualization is that of multiple nodular densities of
the pleura. Because of the paucity of cases (~2000-3000 per year in the United
States), many pathologists see few cases of MPM. It is therefore very important
that biopsy samples be reviewed by a pathologist with particular expertise in
mesothelioma.
The treatment of patients with MPM is difficult and
somewhat controversial. For those with earlier stage tissue, aggressive
trimodality treatment has been advocated by some. This approach includes induction chemotherapy
followed by extrapleural pneumonectomy and postoperative hemithoracic
radiotherapy. Most patients with MPM are clinically or medically inoperable,
and these individuals should be considered for systemic chemotherapy or
supportive care only.
The natural history of this disease is that of initial
local progression in the pleura (with encasement of the lung), mediastinum,
pericardium, and diaphragm.
Intraabdominal spread, contralateral pleura, and
distant organs occur later in the disease process. The median survival in 9 to
12 months in most nonsurgical series and 16 to 18 months in surgical series
with earlier stage patients. Twenty percent or fewer patients survive beyond 2
years, but there are reports of 4- to 5-year survival in selected patients with
minimal treatment. Patients generally die of cardiorespiratory failure caused
by encasement of the heart and lungs by tumor.
