Mesotelioma Pleural

2/6/2019 Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma - UpToDate
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Presentación, evaluación inicial y pronóstico del

mesotelioma pleural maligno
Autores: Daniel H Sterman, MD, Leslie A Litzky, MD, Larry R Kaiser, MD
Editores de secciones: Rogerio C Lilenbaum, MD, FACP, Eric Vallières, MD, FRCSC
Deputy Editor: Sadhna R Vora, MD
Todos los temas se actualizan a medida que se dispone de nueva evidencia y se completa nuestro proceso de revisión
por pares .
Revisión de literatura vigente hasta mayo de 2019. | Este tema se actualizó por última vez: 24 de enero de 2018.
INTRODUCCIÓN
El mesotelioma maligno es una neoplasia rara e insidiosa con un mal pronóstico. Se origina en las
superficies mesoteliales de la cavidad pleural, cavidad peritoneal, túnica vaginal o pericardio. El
mesotelioma pleural maligno (MPM) es el tipo más común y puede ser difícil de tratar porque la
mayoría de los pacientes tienen una enfermedad avanzada en el momento de la presentación.
La presentación clínica, la evaluación, la estadificación y el pronóstico de la MPM se revisarán aquí.

La epidemiología y el tratamiento del mesotelioma pleural, así como los problemas relacionados con
el mesotelioma peritoneal, están cubiertos en otros lugares:
● (Consulte "Epidemiología del mesotelioma pleural maligno" .)
● (Ver "Patología del mesotelioma pleural maligno" .)
● (Consulte "Manejo inicial del mesotelioma pleural maligno" .)
● (Consulte "Tratamiento sistémico para el mesotelioma pleural maligno no resecable" .)
● (Consulte "Mesotelioma peritoneal maligno: epidemiología, factores de riesgo, presentación

clínica, diagnóstico y estadificación" .)
● (Ver "Mesotelioma peritoneal maligno: Tratamiento" .)
https://www.uptodate.com/contents/presentation-initial-evaluation-and-prognosis-of-malignant-pleural-mesothelioma/print?search=mesotelioma&sour… 1/31
MANIFESTACIONES CLÍNICAS
La gran mayoría de las MPM se presentan en pacientes de 60 años o más, que suelen presentarse
décadas después de una exposición al asbesto con síntomas pulmonares no específicos que
empeoran gradualmente. La epidemiología de MPM se discute en otra parte. (Ver "Epidemiología del
mesotelioma pleural maligno" .)
Los síntomas, signos y hallazgos en las imágenes se discuten en las secciones a continuación.
Síntomas : la mayoría de los pacientes con MPM se presentan con el inicio gradual de síntomas
inespecíficos, como dolor en el pecho, disnea, tos, ronquera, sudores nocturnos o disfagia, que se
producen en el contexto de una enfermedad intratorácica extensa. La diseminación metastásica a
distancia es menos común, pero rara vez puede afectar el hueso, el hígado o el sistema nervioso
central (SNC). También pueden presentarse síntomas sistémicos, como fatiga y pérdida de peso,
especialmente en pacientes con enfermedad avanzada. Los síntomas pueden estar presentes
durante meses o más antes del diagnóstico.
En casos muy raros, los pacientes con mesotelioma presentarán síntomas agudos de invasión local
de estructuras vitales. Por ejemplo, la participación del plexo braquial o la compresión de la médula
espinal puede conducir a déficits neurológicos focales. El crecimiento a través del diafragma puede
llevar a una obstrucción intestinal, lo que ocasiona dolor abdominal, distensión y vómitos. El
pinzamiento en la vena cava superior puede causar síntomas de plenitud en la cabeza o hinchazón
facial. La afectación cardíaca puede provocar arritmias o insuficiencia cardíaca. Otras
presentaciones raras de MPM incluyen síndromes paraneoplásicos [ 1-5], aunque estos se ven
generalmente en el contexto de la enfermedad avanzada que se presentó anteriormente con
síntomas más típicos. Las afecciones paraneoplásicas informadas incluyen coagulación intravascular
diseminada, tromboflebitis migratoria, trombocitosis, hipoglucemia, diversos trastornos neurológicos,
enfermedad renal e hipercalcemia.
Los hallazgos del examen - hallazgos físicos comunes en el momento del diagnóstico
generalmente se deben a un derrame pleural, que casi siempre está presente, e incluyen
embotamiento unilateral a la percusión en la base pulmonar, disminución de movimiento de aire en el
lado de la participación, y la pared torácica asimétrica Expansión durante la respiración. Las masas
palpables de la pared torácica, así como los nódulos tumorales en la incisión previa o los sitios de
punción de toracocentesis, y la escoliosis hacia el lado de la neoplasia maligna pueden observarse
en la enfermedad avanzada.
Hallazgos en las imágenes : la imagen del tórax generalmente se realiza como parte de la
evaluación inicial de los síntomas. Por lo general, la radiografía de tórax (CXR) es el examen inicial,
aunque a menudo se realiza una tomografía computarizada (TC) de tórax posteriormente, dada una
sensibilidad y especificidad limitadas con el CXR. Los hallazgos radiográficos comunes para los
pacientes con mesotelioma pleural incluyen los siguientes:
● Una anomalía pleural unilateral con un derrame pleural unilateral grande ( imagen 1A ).
● Una masa o cáscara pleural o engrosamiento pleural difuso en ausencia de derrame pleural (
imagen 1A-B ).
● Placas y / o calcificaciones pleurales .
● Desplazamiento mediastínico ipsilateral debido al encapsulamiento del pulmón por una espesa
corteza del tumor y la pérdida relativa de volumen del pulmón ipsilateral.
Otras características radiográficas relacionadas con la malignidad, aunque menos específicas para el
mesotelioma, incluyen la pérdida unilateral del volumen pulmonar, la pérdida de los planos de grasa
normal y la extensión bruta de una masa a la grasa mediastínica [ 6 ]. Solo el 20 por ciento de los
pacientes con mesotelioma pleural tienen signos radiográficos de asbestosis (como la fibrosis
intersticial bibasilar).
En los pacientes con tomografía por emisión de positrones (PET), se observa una mayor captación
de fluorodeoxiglucosa (FDG). (Consulte 'Imágenes avanzadas' a continuación.)
DIAGNOSIS
Clinical suspicion for MPM may arise in the setting of respiratory symptoms in the context of pleural
thickening or an effusion on chest imaging and a history of asbestos exposure. Although these
features may raise the suspicion of MPM, a biopsy is necessary to confirm the diagnosis [7].
Evaluation — Initial evaluation of patients with suspected MPM includes contrast-enhanced

computed tomography (CT) of the chest to identify pleural abnormalities and extent of disease,
thoracentesis of any existing pleural effusion, and closed pleural biopsy. Further imaging for
diagnosed cases of MPM, including positron emission tomography (PET), is discussed below. (See
'Advanced imaging' below.)
However, frequently this initial approach does not provide sufficient tissue to definitively establish a
diagnosis of MPM and, specifically, to differentiate it from adenocarcinoma. In such instances,
surgical intervention via video-assisted thoracoscopic (VATS) biopsy or open thoracotomy should be
pursued. Additionally, we evaluate with concurrent bronchoscopy at the time of surgery, as
endobronchial lesions are typically not seen in mesothelioma, and their presence argues against this
diagnosis. This also allows for the performance of endobronchial ultrasound (EBUS)-guided biopsies
of mediastinal pleural lesions, tumor masses in the subcarinal space, and mediastinal and hilar lymph
nodes ipsilateral and contralateral to the primary process, which provides staging information if MPM
is diagnosed. (See 'Surgical staging' below.)
The difficulties in establishing a diagnosis of mesothelioma are illustrated by a study of 188

consecutive patients evaluated between 1973 and 1990 [8]. Thoracentesis and pleural fluid cytology
yielded a diagnosis in 26 percent of cases, and thoracentesis plus closed pleural biopsy was
diagnostic in 39 percent of cases. By contrast, VATS was diagnostic in 98 percent of cases. (See
"Medical thoracoscopy (pleuroscopy): Equipment, procedure, and complications".)
Approximately 10 percent of patients who undergo an invasive diagnostic procedure for

mesothelioma seed the biopsy site with tumor cells and later develop a chest wall recurrence. The
role of prophylactic radiation therapy to prevent this complication is discussed separately. (See "Initial
management of malignant pleural mesothelioma", section on 'Tumor seeding at the instrumented
site'.)
Tissue diagnosis — The diagnosis of pleural mesothelioma is established by morphologic and

immunohistochemical features of a cytologic or surgical specimen [7].
Most malignant mesothelioma appear as one of three histologic subtypes: epithelioid, sarcomatoid, or
biphasic (mixed). Within each subgroup, a broad range of morphologic features may be present or
absent, making morphology alone insufficient to establish the diagnosis in most cases. However,
based on morphology and the degree of differentiation of the tumor, specific immunohistochemical
markers are chosen to evaluate the specimen further. Because no single immunohistochemical
marker exhibits high sensitivity or specificity, the International Mesothelioma Interest Group (IMIG)
recommends using a panel of at least two immunoreactive and two nonimmunoreactive markers to
establish the diagnosis of mesothelioma [9]. The immunohistochemistry as well as other features of
pathology are discussed in more detail elsewhere. (See "Pathology of malignant pleural
mesothelioma", section on 'Histology'.)
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of MPM includes both benign and malignant processes:
● Benign conditions – Inflammatory reactions, such as chronic organized empyema, can often
mimic the dense parietal and visceral pleural thickening along with a large pleural effusion that is
characteristic of mesothelioma. However, on pathologic examination, stromal invasion is present
in the case of MPM but absent with benign disease. (See "Pathology of malignant pleural
mesothelioma", section on 'Histology'.)
● Malignant conditions – Other malignant conditions can present in a similar clinical and
radiographic pattern as mesothelioma and may share similar morphologic characteristics under
microscopy. For example, certain sarcomas can present in similar fashion and infiltrate like
sarcomatoid mesotheliomas and may even appear histologically similar to sarcomatoid
mesothelioma. As further examples, pleural metastases of peripheral lung adenocarcinomas, as
well as metastases to the pleura from a number of solid tumors (including but not limited to the
lung, breast, stomach, kidney, ovary, thymus, and prostate), may grossly and histologically
resemble epithelioid mesothelioma. Immunohistochemical patterns of staining can distinguish
mesothelioma from these entities. (See "Pathology of malignant pleural mesothelioma", section
on 'Immunohistochemistry'.)
STAGING AND PRETREATMENT EVALUATION
While virtually all patients with MPM will receive chemotherapy, one goal of staging is to identify
patients who may benefit from surgical resection as well. Staging and pretreatment evaluation also
establishes baseline disease burden and organ function before beginning chemotherapy [10].
Clinical staging with imaging is the initial staging evaluation for patients with MPM. However, clinical
staging often underestimates the extent of disease, and pathologic staging provides a more reliable
assessment of whether or not the patient is a candidate for surgical resection. (figure 1).
Staging systems — The most widely used staging system is the Tumor, Node, Metastasis (TNM)
staging system that has been adopted by both the International Union Against Cancer (UICC) and the
American Joint Committee on Cancer (AJCC). Both the seventh edition (table 1) and the eighth
edition (table 2), which went into effect on January 1, 2018, are shown [11]. In both of these editions,
stage I and II disease have pleural involvement and may involve diaphragmatic muscle or pulmonary
parenchyma, but lack lymph node involvement or distant metastases. In the seventh edition, stage III
mesothelioma includes locally advanced disease, including cases with regional lymph node
involvement; and stage IV disease includes those with locally advanced unresectable disease,
contralateral lymph node involvement, supraclavicular lymph node involvement, or distant
metastases. In the eighth edition of the TNM staging system, however, stage IV disease includes only
those with distant metastases; other tumors previously considered stage IV, including locally
advanced unresectable disease, will be considered as a subset of stage III disease.
To develop the eighth edition of the TNM system, the International Association for the Study of Lung
Cancer (IASLC) and the International Mesothelioma Interest Group (IMIG) used a database with
information on 3101 patients with mesothelioma diagnosed in 15 centers between 1995 and 2009
[10]. The information in this database was correlated with various prognostic factors (see 'Prognostic
factors' below). A second database including 3519 patients diagnosed between 2000 and 2013 in 29
centers worldwide was developed to acquire more detailed TNM information to further refine the
staging system.
Other staging systems have been developed and are used at some centers. As an example, the
Brigham staging system is a modification of the older Butchart system [12]. Involvement of hilar,
ipsilateral, and midline mediastinal lymph nodes categorizes a patient as stage II. In addition, the
presence of positive surgical margins also qualifies for classification as stage II. Invasion of chest
wall, mediastinum, heart, esophagus, or contralateral structures upstages a patient to stage III, as
does extrapleural nodal involvement.
A major limitation of all of the staging systems is the difficulty in assessing the extent of disease prior
to treatment. In a database study including 1056 cases in which both clinical and pathologic staging
were available, clinical staging was unreliable, with approximately 80 percent of clinical stage I
patients and 70 percent of stage II patients being upstaged following pathologic evaluation based
upon surgery (figure 1).
Staging evaluation — The initial staging evaluation for MPM is through imaging, followed by surgical
staging for those in whom surgical resection is being considered. (See "Initial management of
malignant pleural mesothelioma", section on 'Patient selection'.)
Advanced imaging — For diagnosed cases of pleural mesothelioma, we obtain integrated

positron emission tomography with computed tomography (PET-CT) as part of the staging
assessment [7]. The use of PET aids in assessment of the mediastinal lymph nodes, for which CT
has only limited sensitivity [13,14]. For patients in whom resection is being considered, additional
imaging with magnetic resonance imaging (MRI) may help define the local extent of disease. MRI is
particularly useful for those in whom there is a concern based on previous imaging for involvement of
the brachiocephalic vessels, chest wall, central mediastinal structures, or diaphragm. For example, in
the latter instance, coronal MRI images may identify extension of pleural mesothelioma through the
diaphragm into the peritoneal cavity, which would preclude surgical intervention (image 2A-B) [15].
Several series have suggested that PET-CT imaging is the most reliable imaging modality for initial
assessment, particularly in determining whether a tumor is resectable [16-18]. For example, in one
series, 42 consecutive patients with potentially resectable disease based upon CT were assessed
with PET-CT [16]. In 12 cases (29 percent), patients were reclassified as inoperable based upon the
presence of a T4 lesion or distant metastasis (29 and 14 percent, respectively). In another series of
54 patients who underwent imaging followed by surgical staging, PET-CT was more accurate than CT
or PET alone or MRI in assessing stage and extent of disease [17].
Early studies suggest that staging determined by volumetric CT, in which tumor volumes are
calculated semiautomatically from CT measurements, may correlate with overall survival. In a study
of 164 patients, volume correlated with pathologic TNM staging and overall survival, best defined by
three groups with average volumes of 91, 245, and 511 cm3, associated with median overall survival
of 37, 18, and 8 months, respectively [19]. Further study is indicated before incorporation into routine
practice.
Surgical staging — For patients in whom imaging suggests resectable disease, we pursue
extended surgical staging prior to definitive surgery. Specifically, this includes mediastinoscopy or
endobronchial ultrasound (EBUS)-mediated staging of mediastinal lymph nodes. It typically also
includes laparoscopy with peritoneal lavage to detect subdiaphragmatic involvement, which is most
useful when there is concern for invasion of the diaphragm. Patient selection for surgical intervention
is discussed elsewhere. (See "Initial management of malignant pleural mesothelioma", section on
'Patient selection'.)
Extended surgical staging has prognostic utility, but also may guide management [20,21]. For
example, in a series of 118 consecutive patients, surgical staging with laparoscopy with peritoneal
lavage followed by mediastinoscopy allowed 14 percent of patients to avoid an inappropriate
intervention [20].
Pretreatment evaluation — For patients with MPM, we obtain routine prechemotherapy laboratory
tests, including a complete blood count with platelets, liver function tests, and serum alkaline
phosphatase. We also obtain lactate dehydrogenase (LDH) for its prognostic utility [22-24] (see
'Prognostic scoring systems' below). For patients in whom surgical resection is being considered, we
obtain pulmonary function tests (PFTs) prior to surgery to determine whether residual lung function
after surgery will be sufficient.
Several biomarkers are selectively elevated in patients with mesothelioma. Some UpToDate experts
follow soluble mesothelin-related peptides (SMRPs) for patients on treatment, although this is not
uniform. This and other biomarkers are discussed below. (See 'Biomarkers under investigation'
below.)
PROGNOSIS
The prognosis of patients with MPM is poor, with overall survival being on the order of 9 to 17 months
after diagnosis [25-27]. Few patients are cured [28,29]. The majority of affected patients die from local
extension and respiratory failure. In some cases, tumor extension below the diaphragm may result in
death from small bowel obstruction. Patients may also die from arrhythmias, heart failure, or stroke
caused by tumor invasion of the heart or pericardium.
Prognostic factors — Stage and histology are the strongest prognostic factors among patients with
mesothelioma, with sarcomatoid and biphasic histologic subtypes having worse outcomes compared
with epithelioid mesothelioma (figure 2 and figure 3). The pure epithelioid variant is associated with
the best prognosis especially if the disease can be completely resected. Other poor prognostic
features include poor performance status, age >75 years, elevated lactate dehydrogenase (LDH), and
hematologic abnormalities [22,30,31]. These factors are included in scoring systems discussed
below. (See 'Prognostic scoring systems' below.)
Information from a database of approximately 3100 patients, developed to refine the Tumor, Node,
Metastasis (TNM) staging system, suggests the prognostic importance of histology and stage. In this
database, median survivals for those with epithelial, biphasic, and sarcomatoid histology were 19, 13,
and 8 months (figure 4) [10]. Based upon surgical staging when available (and clinical staging for
those without surgical staging) (table 1), patients with stage I, II, III, and IV disease had median
survivals of 20, 19, 16, and 11 months, respectively (figure 5).
Prognostic scoring systems — Prognostic scoring systems that incorporate both the extent of
disease as well as systemic factors have been developed by the European Organisation for Research
and Treatment of Cancer (EORTC) and the Cancer and Leukemia Group B (CALGB). While these
scoring systems were developed prior to the use of pemetrexed, which has subsequently become a
standard treatment option for mesothelioma, subsequent study has supported the prognostic value of
the EORTC index [32].
The EORTC reviewed data from 204 adults with MPM who were entered into five consecutive phase
II trials over nine years [30]. Patients with all stages of disease were permitted. When five factors
were taken into consideration (poor performance status, high white blood cell [WBC] count, male
gender, sarcomatous subtype, and the certainty of the diagnosis), a good and bad prognostic group
could be discerned, with one-year survival rates of 40 and 12 percent, respectively (table 3). Median
survival from the date of study entry was 8.4 months. The prognostic significance of the EORTC
index has subsequently been confirmed in a multivariate analysis of a phase III trial assessing
cisplatin plus raltitrexed [32]. (See "Systemic treatment for unresectable malignant pleural
mesothelioma", section on 'Raltitrexed plus cisplatin'.)
Similarly, the CALGB evaluated the impact of clinical characteristics on the survival of 337 patients
with malignant mesothelioma (of any stage and arising from any anatomic site) who were enrolled in
phase II treatment studies [22]. In multivariate analysis, pleural (as compared with peritoneal or
pericardial) involvement, serum LDH greater than 500 international units/L, poor performance status,
chest pain, platelet count over 400,000/microL, nonepithelial histology, and age older than 75 years
jointly predicted poor survival. Six distinct prognostic subgroups were generated with median survival
times ranging from 1.4 to 13.9 months (table 4). The median survival overall was seven months. This
prognostic schema was subsequently validated in an American phase II trial evaluating the
investigational agent ranpirnase and in an independent European data set [23,24].
The small number of mesothelioma patients enrolled in clinical trials and the heterogeneity of study
populations has limited the identification of molecular biomarkers for prognosis. New molecular
technologies, such as gene expression profiling, may eventually classify patients into distinct
prognostic subgroups [33,34].
BIOMARKERS UNDER INVESTIGATION
Several biomarkers are selectively elevated in patients with mesothelioma. However, further study
and validation is required before these are recommended for diagnosis of mesothelioma. Some
UpToDate experts follow serial measurements of soluble mesothelin-related peptides (SMRPs) as an
adjunct to imaging in monitoring treatment response in those found to have elevations at the time of
diagnosis of mesothelioma.
SMRPs are found in serum or pleural fluid and are believed to be peptide fragments of mesothelin, a
glycoprotein present on normal mesothelial cells and overexpressed on mesothelioma cells [35,36].
However, SMRPs are not elevated in sarcomatoid lesions, have limited sensitivity in other histologic
subtypes, and are also elevated in other malignancies, and therefore are of limited diagnostic utility. A
meta-analysis of 16 diagnostic studies found that the sensitivity of serum SMRPs ranged from 19 to
68 percent, depending upon the specific criterion for positivity [37]. In patients with stage I or II
disease, the sensitivity was only 32 percent when a specificity criterion of 95 percent was used.
SMRPs have also been measured in pleural fluid [38-40], with one retrospective study suggesting
sensitivity of 67 percent and specificity of 98 percent [39].
Other biomarkers of interest include fibulin-3 and osteopontin [41-45], although more study is needed
before routine clinical use.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Diagnosis and management of lung
cancer".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The
Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-
mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Pleural mesothelioma (The Basics)" and "Patient
education: Asbestos exposure (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Malignant pleural mesothelioma (MPM) is a rare insidious neoplasm that typically presents with
advanced disease. (See 'Introduction' above.)
● Most patients with MPM present with the gradual onset of nonspecific symptoms such as chest
pain, dyspnea, cough, hoarseness, or dysphagia, which occur in the setting of extensive
intrathoracic disease. (See 'Symptoms' above.)
● Chest imaging typically shows unilateral pleural thickening and pleural effusion. (See 'Findings
on imaging' above.)
● Initial evaluation of patients with suspected MPM includes computed tomography (CT) of the
chest with contrast, thoracentesis of any existing pleural effusion, and closed pleural biopsy.
However, if insufficient tissue is acquired to make a diagnosis, surgical intervention via video-
assisted thoracoscopic (VATS) biopsy or open thoracotomy should be pursued. (See 'Evaluation'
above.)
● The diagnosis of pleural mesothelioma is established by morphologic and immunohistochemical

features of a cytologic or surgical specimen. (See 'Tissue diagnosis' above and "Pathology of
malignant pleural mesothelioma".)
https://www.uptodate.com/contents/presentation-initial-evaluation-and-prognosis-of-malignant-pleural-mesothelioma/print?search=mesotelioma&so… 10/31
● The differential diagnosis of MPM includes benign processes such as inflammatory reactions, as
well as malignant processes, including metastases from other solid tumors. Evidence of stromal
invasion on biopsy distinguishes mesothelioma from benign etiologies, while
immunohistochemistry can distinguish mesothelioma from other malignancies. (See 'Differential
diagnosis' above.)
● For diagnosed cases of pleural mesothelioma, we obtain integrated positron emission

tomography with computed tomography (PET-CT) as the initial staging assessment. For patients
in whom imaging suggests resectable disease, we pursue extended surgical staging prior to
definitive surgery. Specifically, this includes laparoscopy with peritoneal lavage to detect
subdiaphragmatic involvement, followed by mediastinoscopy. (See 'Staging evaluation' above.)
● The prognosis of patients with MPM is poor, with overall survival being on the order of 9 to 17
months after diagnosis. Few patients are cured. (See 'Prognosis' above.)
● Several biomarkers are selectively elevated in patients with mesothelioma, including soluble
mesothelin-related peptides (SMRPs), fibulin-3, and osteopontin, although they are not routinely
used in the diagnosis of mesothelioma. (See 'Biomarkers under investigation' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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not with lung adenocarcinoma. Am J Surg Pathol 1992; 16:259.
36. Ordóñez NG. Value of mesothelin immunostaining in the diagnosis of mesothelioma. Mod
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45. Grigoriu BD, Scherpereel A, Devos P, et al. Utility of osteopontin and serum mesothelin in
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Topic 4627 Version 25.0
GRAPHICS
Malignant mesothelioma
CT scan shows right-sided nodular circumferential pleural thickening exceeding

1 cm in thickness, typical of a malignant process (arrows). No clear cut invasion
of the chest wall is present. A slightly enlarged pretracheal lymph node proved
to be reactive in nature.
CT: computed tomography.
Courtesy of Paul Stark, MD.
Graphic 52053 Version 3.0
Malignant mesothelioma
CT scan shows right-sided circumferential pleural thickening with thickening of

the major fissure; there is extension into azygo-esophageal recess and into the
anterior mediastinal, pericardial fat.
CT: computed tomography.
Correlation of clinical and pathological staging in pleural

mesothelioma
Reproduced with permission from: Rusch VW, Giroux D, Kennedy C, et al. Initial
Analysis of the International Association For the Study of Lung Cancer Mesothelioma
Database. J Thorac Oncol 2012; 7:1631. Copyright © 2012 Lippincott Williams &
Wilkins.
TNM staging system for diffuse malignant pleural mesothelioma
Primary tumor (T)

TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor limited to the ipsilateral parietal pleura with or without mediastinal pleura and with or without
diaphragmatic pleural involvement
T1a No involvement of the visceral pleura
T1b Tumor also involving the visceral pleura
T2 Tumor involving each of the ipsilateral pleural surface (parietal, mediastinal, diaphragmatic, and visceral
pleura) with at least one of the following:
Involvement of diaphragmatic muscle
Extension of tumor from visceral pleura into the underlying pulmonary parenchyma
T3 Locally advanced but potentially resectable tumor
Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura)
with at least one of the following:
Involvement of the endothoracic fascia
Extension into the mediastinal fat
Solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall
Nontransmural involvement of the pericardium
T4 Locally advanced technically unresectable tumor
Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura)
with at least one of the following:
Diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction
Direct transdiaphragmatic extension of tumor to the peritoneum
Direct extension of tumor to the contralateral pleura
Direct extension of tumor to mediastinal organs
Direct extension of tumor into the spine
Tumor extending through to the internal surface of the pericardium with or without a pericardial effusion or tumor
involving the myocardium
Regional lymph nodes (N)

NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
N1 Metastases in the ipsilateral bronchopulmonary or hilar lymph nodes
N2 Metastases in the subcarinal or the ipsilateral mediastinal lymph nodes including the ipsilateral internal
mammary and peridiaphragmatic nodes
N3 Metastases in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral

supraclavicular lymph nodes
Distant metastasis (M)

M0 No distant metastasis
MI Distant metastasis present
Anatomic stage/prognostic groups

Stage T1 N0 M0
I
Stage T1a N0 M0
IA
Stage T1b N0 M0
IB
Stage T2 N0 M0
II
Stage T1, T2 N1 M0
III
T1, T2 N2 M0
T3 N0, N1, N2 M0
Stage T4 Any N M0
IV
Any T N3 M0
Any T Any N M1
Note: cTNM is the clinical classification, pTNM is the pathologic classification.
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this
material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer New York, Inc.
Malignant pleural mesothelioma TNM staging AJCC 8th edition
Primary tumor (T)

T category T criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor limited to the ipsilateral parietal pleura with or without involvement of:
Visceral pleura
Mediastinal pleura
Diaphragmatic pleura
T2 Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal,

diaphragmatic, and visceral pleura) with at least one of the following features:
Involvement of diaphragmatic muscle
Extension of tumor from visceral pleura into the underlying pulmonary parenchyma
T3 Describes locally advanced but potentially resectable tumor.

Tumor involving all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic,
and visceral pleura) with at least one of the following features:
Involvement of the endothoracic fascia
Extension into the mediastinal fat
Solitary, completely resectable focus of tumor extending into the soft tissues of the
chest wall
Nontransmural involvement of the pericardium
T4 Describes locally advanced technically unresectable tumor.

Tumor involving all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic,
and visceral pleura) with at least one of the following features:
Diffuse extension or multifocal masses of tumor in the chest wall, with or without
associated rib destruction
Direct transdiaphragmatic extension of tumor to the peritoneum
Direct extension of tumor to the contralateral pleura
Direct extension of tumor to mediastinal organs
Direct extension of tumor into the spine
Tumor extending through to the internal surface of the pericardium with or without
a pericardial effusion, or tumor involving the myocardium
Regional lymph nodes (N)

N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
N1 Metastases in the ipsilateral bronchopulmonary, hilar, or mediastinal (including the

internal mammary, peridiaphragmatic, pericardial fat pad, or intercostal) lymph nodes
N2 Metastases in the contralateral mediastinal, ipsilateral, or contralateral supraclavicular

lymph nodes
Distant metastasis (M)

M category M criteria
M0 No distant metastasis
M1 Distant metastasis present
Prognostic stage groups

When T is... And N is... And M is... Then the stage group
is...
T1 N0 M0 IA
T2 or T3 N0 M0 IB
T1 N1 M0 II
T2 N1 M0 II
T3 N1 M0 IIIA
T1-3 N2 M0 IIIB
T4 Any N M0 IIIB
Any T Any N M1 IV
TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the
AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Corrected at 4th printing,
2018.
Mesothelioma on MRI
A coronal T1-weighted image shows a multilobular mass in the right

paravertebral sulcus (arrow) extending into the minor fissure and along the
diaphragm.
MRI: magnetic resonance imaging.
Mesothelioma with thickened fissures
Sagittal T2-weighted image shows high signal caused by tumor extending from
the diaphragmatic pleura into the thickened major and minor fissures.
Malignant pleural mesothelioma overall survival by stage TNM AJCC 8th

edition
Overall survival according to "best" overall stage, AJCC 8th edition. Included cases: All classifiable cases.
Best stage is defined as pathological stage where available, clinical stage otherwise. Statistical method:
Kaplan-Meier.
MST: median survival time.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this
information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International
Publishing.
Malignant pleural mesothelioma overall survival by stage and histology TNM

AJCC 8th edition
Overall survival according to "best" overall stage, AJCC 8th edition, for (A) cases with epithelioid histology,
and (B) cases with non-epithelioid histology. Included cases: All classifiable cases. Best stage is defined as
pathological stage where available, clinical stage otherwise. Statistical method: Kaplan-Meier.
MST: median survival time.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this
information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International
Publishing.
Pleural mesothelioma survival based upon histology
Reproduced with permission from: Rusch VW, Giroux D, Kennedy C, et al. Initial Analysis of the
International Association For the Study of Lung Cancer Mesothelioma Database. J Thorac Oncol
2012; 7:1631. Copyright © 2012 Lippincott Williams & Wilkins.
Survival following surgery for pleural mesothelioma
Staging was based upon most accurate available clinical and/or pathologic data.
Reproduced with permission from: Rusch VW, Giroux D, Kennedy C, et al. Initial Analysis of the
International Association For the Study of Lung Cancer Mesothelioma Database. J Thorac Oncol 2012;
7:1631. Copyright © 2012 Lippincott Williams & Wilkins.
Prognostic indices of survival for advanced mesothelioma in EORTC studies
EORTC studies
Study Response (percent) MST (months)
Mitoxantrone 2.4 7.5
Epidoxorubicin 13.5 8.9
Etoposide (IV) 4.2 6.7
Etoposide (PO) 7.3 8.7
Paclitaxel 0 9.3
Poor prognostic factors in multivariate analysis

Variable MST (months)
Performance status (PS) Good (0) 10.7
Poor (1-2) 7.2
WBC count High (>8.3) 6
Low (<8.3) 10.4
Hemoglobin difference* High (>1 g/dL) 7.3
Low (<1 g/dL) 9.6
Histologic diagnosis Definite 9.8
Possible 6
Sarcomatous subtype Present 5
Other subtype 8.4-9.1
EORTC prognostic groups

Group characteristics MST (months) 1 yr OS 2 yr OS
Low risk (prognostic score <1.27) 10.8 40 percent 14 percent

Equivalent to having 0-2 poor prognostic factors
High risk (prognostic score >1.27) 5.5 12 percent 0 percent

Equivalent to having three or more poor prognostic factors
EORTC: European Organization for Research and Treatment of Cancer; MST: median survival time; WBC: white blood cell
count, X 1000/microL.
* The difference relative to 16 g/dL in males and 14 g/dL in females.
Prognostic indices of survival for advanced mesothelioma in CALGB* studies
CALGB studies
Study Dates Response, % MST, months
#8435 (Mitomycin/cisplatin) 6/84-10/86 26 8.1
14 8.8
#8638 (Carboplatin) 2/87-2/88 7 7.1
#8833 (DHAC) 6/88-6/89 17 6.7
#8933 (Trimetrexate) 7/89-8/91 12 3.9
12 9.8
#9031 (DHAC/cisplatin) 7/90-7/93 14 6.4
#9131 (Edatrexate) 5/92-9/94 25 9.6
18 6.9
#9234 (Paclitaxel) 3/93-9/94 9 5
Poor prognostic factors in multivariate analysis

Variable Relative risk
Pleural disease Present 2.64
Lactic dehydrogenase (LDH) >500 IU/L 1.91
Poor performance status (PS) PS1 1.65
PS2 2.71
Platelet count >400,000/microL 1.57
Epithelial histology Absent 1.33
Age Each year over 75 yo 1.34
CALGB prognostic groups

Group Characteristics MST, months
Group I PS, 0; age <49 years 12.5
PS, 0; age ≥49 years; HGB* ≥14.6 14.5
Group II PS, 1 or 2; WBC* < 8.7; no chest pain 9.5
Group III PS, 0; age >49 years; HGB <14.6 9.3
PS, 1 or 2; WBC < 15.6; chest pain; weight loss; HGB ≥ 12.3 9.3
PS, 1 or 2; 9.8 ≤ WBC < 15.6; chest pain; weight loss; HGB ≥ 11.2 9.6
Group IV PS, 1 or 2; 8.7 ≤ WBC <15.6; no chest pain 6.6
Group V PS, 1 or 2; WBC <15.6; chest pain; no weight loss; HGB <12.3 3.9
PS, 1 or 2; 9.8 ≤ WBC <15.6; chest pain; weight loss; HGB <11.2 4.9
PS, 1 or 2; WBC < 9.8; chest pain; weight loss 3.9
Group VI PS, 1 or 2; WBC ≥ 15.6 1.4
CALGB: cancer and leukemia Group B; MST: median survival time; Mos: months; DHAC: dihydro-5-azacytidine; WBC: white
blood cell count, X 1000/microL; HGB: hemoglobin (HGB is given in g/percent; WBC, x 1000/microL).
Contributor Disclosures
Daniel H Sterman, MD Nada que divulgar Leslie A Litzky, MD Nada que divulgar Larry R Kaiser, MD
Nada que divulgar Rogerio C Lilenbaum, MD, Consultor de FACP / Juntas Consultivas: AstraZeneca
[cáncer de pulmón de células no pequeñas (Osimertinib)]. Eric Vallières, MD, FRCSC Oficina del orador:
AstraZeneca [cáncer de pulmón]; Consultor / Consejo Asesor: AstraZenca [cáncer de pulmón]; Espiración
[cáncer de pulmón]; Captación médica [cáncer de pulmón]. Sadhna R Vora, MD Nada que revelar
Las revelaciones de los contribuyentes son revisadas para los conflictos de interés por el grupo editorial.
Cuando se encuentran, estos se abordan examinando un proceso de revisión multinivel y los requisitos para que
se proporcionen referencias que respalden el contenido. El contenido referenciado adecuadamente es requerido
por todos los autores y debe cumplir con los estándares de evidencia UpToDate.
Política de conflicto de intereses.

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2/6/2019 Presentation, initial evaluation, and prognosis of malignant pleural mesothelioma - UpToDate

Reimpresión oficial de UpToDate ®

Presentación, evaluación inicial y pronóstico del

La presentación clínica, la evaluación, la estadificación y el pronóstico de la MPM se revisarán aquí.

● (Consulte "Epidemiología del mesotelioma pleural maligno" .)

● (Ver "Patología del mesotelioma pleural maligno" .)

● (Consulte "Manejo inicial del mesotelioma pleural maligno" .)

● (Consulte "Tratamiento sistémico para el mesotelioma pleural maligno no resecable" .)

● (Consulte "Mesotelioma peritoneal maligno: epidemiología, factores de riesgo, presentación

● (Ver "Mesotelioma peritoneal maligno: Tratamiento" .)

● Placas y / o calcificaciones pleurales .

Evaluation — Initial evaluation of patients with suspected MPM includes contrast-enhanced

The difficulties in establishing a diagnosis of mesothelioma are illustrated by a study of 188

Approximately 10 percent of patients who undergo an invasive diagnostic procedure for

Tissue diagnosis — The diagnosis of pleural mesothelioma is established by morphologic and

STAGING AND PRETREATMENT EVALUATION

Advanced imaging — For diagnosed cases of pleural mesothelioma, we obtain integrated

BIOMARKERS UNDER INVESTIGATION

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

● The diagnosis of pleural mesothelioma is established by morphologic and immunohistochemical

● For diagnosed cases of pleural mesothelioma, we obtain integrated positron emission

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1. Socola F, Loaiza-Bonilla A, Bustinza-Linares E, et al. Recurrent thrombotic thrombocytopenic

4. Bech C, Sørensen JB. Polyneuropathy in a patient with malignant pleural mesothelioma: a

5. Tanriverdi O, Meydan N, Barutca S, et al. Anti-Yo antibody-mediated paraneoplastic cerebellar

8. Boutin C, Rey F, Gouvernet J, et al. Thoracoscopy in pleural malignant mesothelioma: a

Topic 4627 Version 25.0

CT scan shows right-sided nodular circumferential pleural thickening exceeding

CT: computed tomography.

Courtesy of Paul Stark, MD.

Graphic 52053 Version 3.0

CT scan shows right-sided circumferential pleural thickening with thickening of

CT: computed tomography.

Courtesy of Paul Stark, MD.

Graphic 70651 Version 3.0

Correlation of clinical and pathological staging in pleural

Graphic 87269 Version 4.0

TNM staging system for diffuse malignant pleural mesothelioma

Primary tumor (T)

T0 No evidence of primary tumor

T3 Locally advanced but potentially resectable tumor

T4 Locally advanced technically unresectable tumor

Regional lymph nodes (N)

N0 No regional lymph node metastases

N1 Metastases in the ipsilateral bronchopulmonary or hilar lymph nodes

N3 Metastases in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral

Distant metastasis (M)

MI Distant metastasis present

Anatomic stage/prognostic groups

Note: cTNM is the clinical classification, pTNM is the pathologic classification.

Graphic 81665 Version 13.0

Malignant pleural mesothelioma TNM staging AJCC 8th edition

Primary tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T2 Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal,

T3 Describes locally advanced but potentially resectable tumor.

T4 Describes locally advanced technically unresectable tumor.

Regional lymph nodes (N)

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastases

N1 Metastases in the ipsilateral bronchopulmonary, hilar, or mediastinal (including the