20 Pleural Mesothelioma 20

20 Pleural Mesothelioma

(Tumors metastatic to the pleura and lung tumors that have extended to the pleural surfaces are not included.)

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SUMMARY OF CHANGES

• The AJCC has adopted the staging system proposed by the International Mesothelioma Working Group (IMIG) in 1995. It is based on updated informa- tion about the relationships between tumor (T) and N status and overall sur- vival. This staging system applies only to tumors arising in the pleura.

• T categories have been redefined

• T1 lesions have been divided into T1a and T1b, leading to the division of Stage I into Stage IA and Stage IB.

• T3 is defined as locally advanced but potentially resectable tumor.

• T4 is defined as locally advanced, technically unresectable tumor.

• Stage II no longer involves tumors with nodal metastasis; all nodal metastasis is categorized in Stage III or Stage IV.

C38.4 Pleura NOS

INTRODUCTION

Malignant mesotheliomas are relatively rare tumors that arise from the mesothe- lium lining the pleural, pericardial, and peritoneal cavities. They represent less than 2% of all malignant tumors. The most common risk factor for malignant mesotheliomas is previous exposure to asbestos. The latency period between asbestos exposure and the development of malignant mesothelioma is generally 20 years or more. Although peritoneal mesotheliomas are thought to occur in individuals who have had heavier exposure than those with pleural mesothe- lioma, there is no clearly documented relationship between the amount of asbestos exposure and the subsequent development of this neoplasm. Malignant mesotheliomas were previously thought to be virulent tumors. However, this impression was probably related to the fact that most mesotheliomas are diag- nosed when they are already at an advanced stage. Recent data indicate that the clinical and biological behavior of mesotheliomas is variable and that most mesotheliomas grow relatively slowly.

All mesotheliomas are fundamentally epithelial tumors. However, their morphology ranges from a pure epithelial appearance to an entirely sarco- matoid or even desmoplastic appearance. Distinguishing the pleiomorphic his- tology of mesotheliomas from that of other neoplasms can be difficult, especially for the pure epithelial mesotheliomas, which may closely resemble metastatic adenocarcinoma. Therefore, confirmation of the histologic diagnosis by immunohistochemistry and/or electron microscopy is essential.

During the past 30 years, many staging systems have been proposed for

malignant pleural mesothelioma. The first staging system for this disease

published by the American Joint Committee on Cancer (AJCC), and simulta- neously accepted by the International Union Against Cancer, appeared in the fifth edition of the AJCC Cancer Staging Manual. The staging system described here represents adoption of the one proposed in 1995 by the International Mesothelioma Interest Group (IMIG), which is based on updated information about the relationships between tumor (T) and N status and overall survival.

Although this system has been validated by several surgical reports, it will prob- ably require revision in the future as further data in larger numbers of patients become available. This staging system applies only to tumors arising in the pleura. Peritoneal and pericardial mesotheliomas are rare and do not lend them- selves easily to a TNM staging system.

ANATOMY

Primary Site. The mesothelium covers the external surface of the lungs and the inside of the chest wall. It is usually composed of flat, tightly connected cells no more than one layer thick.

Regional Lymph Nodes. The regional lymph nodes include internal mammary, intrathoracic, scalene, and supraclavicular. The regional lymph node map and nomenclature adopted for the mesothelioma staging system is identi- cal to that used for lung cancer. See Chapter 19 and Figure 19.2 for a detailed list and diagram of intrathoracic lymph nodes. For pN, histologic examination of a mediastinal lymphadenectomy or lymph node sampling specimen will ordinarily include regional nodes taken from the ipsilateral N1 and N2 nodal stations. Contralateral and supraclavicular nodes may be available if a mediastinoscopy or node biopsy is also performed.

Distant Metastatic Sites. Advanced malignant pleural mesotheliomas often metastasize widely to uncommon sites, including retroperitoneal lymph nodes, the brain and spine, or even organs such as the thyroid or prostate. However, the most frequent sites of metastatic disease are the peritoneum, contralateral pleura, and lung.

DEFINITIONS OF TNM

IMIG Staging System for Diffuse Malignant Pleural Mesothelioma Primary Tumor (T)

TX Primary tumor cannot be assessed T0 No evidence of primary tumor

T1 Tumor involves ipsilateral parietal pleura, with or without focal involve- ment of visceral pleura

T1a Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura;

no involvement of the visceral pleura (Figure 20.1)

T1b Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura, with focal involvement of the visceral pleura (Figure 20.1)

T2 Tumor involves any of the ipsilateral pleural surfaces with at least one of

the following (Figure 20.2):

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T1a T1b

Visceral pleura Parietal pleura

FIGURE 20.1. T1a (left) shows no involvement of the visceral pleura. T1b (right) involves ipsilateral parietal pleura, with focal involvement of the visceral pleura.

T2

Lung parenchyma

Diaphragm

FIGURE 20.2. T2 involves any of the ipsilateral pleural surfaces with at least one of

the following: confluent visceral pleural tumor (including fissure); invasion of

diaphragmatic muscle (as illustrated); and/or invasion of lung parenchyma (as

illustrated).

• Confluent visceral pleural tumor (including fissure)

• Invasion of diaphragmatic muscle

• Invasion of lung parenchyma

T3

Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following (Figure 20.3):

• Invasion of the endothoracic fascia

• Invasion into mediastinal fat

• Solitary focus of tumor invading the soft tissues of the chest wall

• Non-transmural involvement of the pericardium

T4

Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following (Figure 20.4):

• Diffuse or multifocal invasion of soft tissues of the chest wall

• Any involvement of rib

• Invasion through the diaphragm to the peritoneum

• Invasion of any mediastinal organ(s)

• Direct extension to the contralateral pleura

• Invasion into the spine

• Extension to the internal surface of the pericardium

• Pericardial effusion with positive cytology

• Invasion of the myocardium

• Invasion of the brachial plexus

T3

Chest wall

FIGURE 20.3. T3 involves any of the ipsilateral pleural surfaces, with at least one of the following: invasion of the endothoracic fascia; invasion into mediastinal fat;

solitary focus of tumor invading the soft tissues of the chest wall (as illustrated);

and/or non-transmural involvement of the pericardium.

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastases

N1 Metastases in the ipsilateral bronchopulmonary and/or hilar lymph node(s)

N2 Metastases in the subcarinal lymph node(s) and/or the ipsilateral internal mammary or mediastinal lymph node(s)

N3 Metastases in the contralateral mediastinal, internal mammary, or hilar lymph node(s), and/or the ipsilateral or contralateral supraclavicular or scalene lymph node(s)

Distant Metastasis (M)

MX Distant metastasis cannot be assessed M0 No distant metastasis

M1 Distant metastasis

STAGE GROUPING

I T1 N0 M0

IA T1a N0 M0

IB T1b N0 M0

II T2 N0 M0

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T4

Aorta

FIGURE 20.4. T4 involves any of the ipsilateral pleural surfaces with at least one

additional parameter, such as extension to the internal surface of the pericardium

as illustrated here. (The full list of additional parameters is provided under

Definitions of TNM.)

III T1, T2 N1 M0

T1, T2 N2 M0

T3 N0, N1, N2 M0

IV T4 Any N M0

Any T N3 M0

Any T Any N M1

NOTES

1. T3 describes locally advanced but potentially resectable tumor.

2. T4 describes locally advanced, technically unresectable tumor.