PERSPECTIVE, PATTERNS OF SPREAD, AND PATHOLOGY
Mesotheliomas render the invisible pleural space visible by developing nodular lesions on its visceral and parietal surfaces, extending in a corkscrew fashion into fissure surfaces.
PERSPECTIVE AND PATTERNS OF SPREAD
Malignant mesotheliomas are extremely aggressive, but uncommon thoracic neoplasms, accounting for 2% of chest tumors. The bioassociation with asbestos exposure is well recognized, with long latency periods of 20 to 25 years. Routine chest radiographs are inadequate to detect fibers, the amphiboles, particularly crocidolite, which gradually wiggles into the pulmonary lymphatics reaching the visceral pleura and irritating the smooth surface lining of mesothelial cells (Fig 19.1). With time, nodular lesions develop on visceral and parietal surfaces, extending in a corkscrew fashion into fissure surfaces. Although slow growing, their insidious onset obscures early detection. Recent data suggest early stage diagnosis and multimodal treatment can yield long-term survival (Fig. 19.2; Table 19.2).
Mesothelioma can present as pleural effusions and is also characteristic of carcinomas. Pleural effusions were T4 in the American Joint Committee on Cancer (AJCC) sixth edition and the seventh edition as well. There are a variety of causes of pleural effusion and these require positive cytology for diagnosis. Pleural effusions can occur due to pulmonary vein compression, more often left side than right, since the left pulmonary vein is longer. Negative cytology suggests compression by tumor, often hilar nodes.
Chyliform effusions tend to be right sided and are often due to posterior mediastinal invasion entrapping the thoracic duct as it crosses the midline from right to left at the T3-4 level prior to its exit in the left supraclavicular fossa. True chyle have globules that can be stained for fatty acids. Pseudochylous effusions can be milky in appearance but are due to tumor cell breakdown releasing lecithin.
PATHOLOGY
Pathologically, these tumors are divided into four types: epithelioid, mesenchymal (sarcomatous), desmoplastic, and mixed or by basic (at least 10% of both epithelioid and sarcomatoid) elements. Pure epithelioid carry a better prognosis than the sarcomatous and, although desmoplastic reactions appear benign, these tumors have the poorest survival rate (Table 19.1; Fig. 19.1).
Figure 19.1| Pleural malignant mesothelioma. A. The lung is encased by a dense pleural tumor that extends along the interlobar fissures but does not involve the underlying lung parenchyma. B. This mesothelioma is composed of a biphasic pattern of epithelial and sarcomatous elements.
Figure 19.2 | Patterns of spread. The primary cancer (mesothelioma) invades in various directions, which are color-coded vectors (arrows) representing stage of progression: T0, yellow; T1, green; T2, blue; T3, purple; T4, red; and when metastatic, black. The concept of visualizing patterns of spread to appreciate the surrounding anatomy is well demonstrated by the six-directional pattern i.e SIMLAP Table 19.2
TNM STAGING CRITERIA
TNM STAGING CRITERIA
The AJCC has adopted the staging system of the International Mesothelioma Interest Group (IMIG) and is based on patterns of spread of this aggressive thoracic malignancy. The pleura is like the peritoneum; although it consists of only a single layer of cells, it acts as a barrier to cancer spread. Thus, T1 tumors are focal nodular lesions of parietal pleura; T2 indicates spread to visceral pleura and lung; and T3 is deeper invasion of the chest wall and mediastinum, but potentially resectable. The major feature of unresectability are T4 criteria and include destruction of the chest wall ribs or vertebra or mediastinal, visceral infiltration, and extension through the diaphragm into the peritoneal cavity, the contralateral pleural space, or the brachial plexus in the neck.
SUMMARY OF CHANGES SEVENTH EDITION AJCC
• Peridiaphragmatic lymph nodes have been added to the N2 category (Fig. 19.3).
The TNM staging matrix is color coded for identification of stage group once T and N stages are determined (Table 19.3).
MESOTHELIOMA
Figure 19.3 | TNM staging diagram. Mesotheliomas arise in the pleural spaces, first on the parietal, then the visceral pleura, and continue invading into fissures. Then the aggressive malignancy spreads into the parietal pleura, chest wall and mediastinal pleura, and mediastinal structures. Unlike lung cancers, stage IVA is T4N3M0 and stage IVB M1 is metastatic. Vertical presentations of stage groupings, which follow the same color code for cancer stage advancement, are organized in horizontal lanes: Stage 0, yellow; I, green; II, blue; III, purple; IVA, red; and metastatic stage IVB, black. Definitions of TN are on the left and stage groupings are on the right.
T-ONCOANATOMY
ORIENTATION OF THREE-PLANAR ONCOANATOMY
The pleural space is coated by the visceral and parietal pleura of the chest wall and mediastinal pleura. This is presented at the thoracic T7-8 level (Fig. 19.4).
T-Oncoanatomy
The T-oncoanatomy is displayed in 3 planar views. A. Coronal, B. Sagittal, C. Transverse Axial. (Figure 19.5).
The pleural space is readily recognized during pathologic states as a pleural effusion or pneumothorax; in its normal state, it is invisible but shown in reference to the lung in expiration (Fig. 19.4).
• Coronal: Anterior and posterior views, the pleura extends into the neck and enters the costadiaphragmatic recess. The visceral pulmonary pleura faces the parietal pleural on the chest wall and medially the mediastinal pleura. The horizontal and oblique fissures are due to visceral pleural invagination on the right side and, similarly, the oblique fissure of the left lung as constituted by visceral pleura.
• Sagittal: The pleura invaginates its layers to form fissures. In the lateral view, pleural recesses are more shallow.
• Transverse: The diaphragmatic surface can be viewed as separating the pleural and peritoneal cavities.
Figure 19.4 | Orientation of T-oncoanatomy. The isocenter for three-planar oncoanatomy in the coronal view is at the T7-8 level. A. Coronal. B. Sagittal.
Figure 19.5 | T-oncoanatomy. The color code for the stage group (Fig. 19.3) and the patterns of spread (Fig. 19.2) and SIMLAP table (Table 19.2). Connecting the dots in similar colors will provide an appreciation for the 3D oncoanatomy.
N-ONCOANATOMY AND M-ONCOANATOMY
N-ONCOANATOMY
The regional lymph nodes are dependent on invasion patterns. Generally, they are mediastinal nodes, but with lung invasion, pulmonary and hilar nodes are at risk, and with chest wall invasion, costal nodes and internal thoracic nodes are at risk. The AJCC notes regional nodes are similar to lymph node map, nomenclature, and numbering for lung cancers (Fig. 19.6A; Table 19.4).
REGIONAL LYMPH NODES
The regional lymph nodes include:
• Intrathoracic
• Scalene
• Supraclavicular
• Internal mammary
• Peridiaphragmatic
The regional lymph node map and nomenclature adopted for the mesothelioma staging system is identical to that used for lung cancer. A detailed list of intrathoracic lymph nodes can be found in AJCC Cancer Staging Manual, 7th edition (Chapter 25). 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. In addition, mesotheliomas often metastasize to lymph nodes not involved by lung cancers, most commonly the internal mammary and peridiaphragmetic nodes. These latter two regions also are classified as N2 nodal stations. Contralateral mediastinal and supraclavicular nodes may be available if a mediastinoscopy or node biopsy is also performed. If involved by metastatic disease these would be staged as N3 (Fig. 19.6B).*
M-ONCOANATOMY
The chest wall has a rich venous network of intercostals veins, azygos and hemiazygos veins interdigitating with intervertebral veins. Metastases to spinal cord and brain, contralateral spread to opposite chest, and lung can occur. Most common metastatic sites are on the mesothelial surfaces as opposed to pleura, pericardial, and peritoneal cavity. With dissemination, uncommon sites such as thyroid and prostate have been noted (Fig. 19.7).
*Preceding passage from Edge SB, Byrd DR, and Compton CC, et al. AJCC Cancer Staging Manual, 7th edition. New York, Springer, 2010, pp. 271.
Figure 19.6 | A. N-oncoanatomy. With pulmonary invasion, intrapulmonary and interbronchial nodes are involved. With extension to mediastinal pleura, the mediastinal nodes are at risk. B. M-oncoanatomy. International Association for the Study of Lung Cancer (IASLC). Labels correlate with Table 19.4.
Figure 19.7 | Orientation of M-oncoanatomy. Pulmonary anterior views are related to metastatic spread to and from lung, respectively.
STAGING WORKUP
RULES FOR CLASSIFICATION AND STAGING
Clinical Staging and Imaging
The TNM classification system is primarily for staging non–small cell lung cancers. The most important change dates back to the fourth edition of the AJCC where T3, resectable disease, was distinguished from T4, unresectable disease. Simultaneously, a greater reliance on more sophisticated imaging has occurred. It is with the sixth edition that computed tomography (CT) and positron emission tomography (PET) are allowed. The imaging modalities for detection and diagnosis apply to staging (see Table 19.5). Chest films and CT (preferably spiral) are essential steps in both diagnosis and staging. PET combined with CT is utilized to overcome motion artifacts. Magnetic resonance imaging (MRI) is useful for mediastinal evaluation. Another advantage of CT over MRI for staging is that it allows for metastatic workup of lung, liver, adrenal, ribs, and vertebrae (Fig. 19.8).
Pathologic Staging
All pathologic specimens from clinical invasive procedures—bronchoscopy, mediastinoscopy, mediastinotomy, thoracentesis, and thorascopy—are applicable to pathologic stage. Thoracotomy and resection of primary and lymph nodes are the mainstay of pathologic staging. Margin status and any residual cancer need to be noted. Preferably, six nodes are examined.
Oncoimaging Annotations
• Chest radiographs seldom detect primary mesotheliomas in their early stages.
• Spiral CT is useful in high-risk patients to detect nodule and infiltrates.
• PET imaging with18 FDG (fluorodeoxyglucose) appears to be of value in discriminating malignant versus benign nodules.
• CT can detect mediastinal adenopathy, but histologic verification is essential to ascertain if it is malignant.
• Determining N2 versus N3 mediastinal nodes is important; it establishes resectability.
• MRI can be of value in assessing mediastinal invasion, chest wall and rib erosion, and compromised large vein involvement.
• Small pleural plaques and subpleural spread can be compatible with asbestosis inhalation.
• Extension along diaphragmatic curare can lead to peritoneal invasion across the diaphragm.
PROGNOSIS AND CANCER SURVIVAL
CANCER STATISTICS AND SURVIVAL
It is difficult to find a malignancy more lethal than lung cancer, especially small cell cancers, which comprise overall about 5% of cases. However, mesotheliomas have virtually no 5-year survivors. Most reports with radical extrapleural pneumonectomy with chemoradiation are yielding median survival of less than 1 year (9 months) with high complication rates with mortality rates down to 10% or less. Elegant radiation using three-dimensional conformal techniques with intensity modulation has not been able to alter the dismal course of this disease.
PROGNOSIS
Prognostic factors are mainly related to histopathology sub-types (Table 19.6).
Figure 19.8 | Axial CTs of T7 and T8 level correlate with the T-oncoanatomy transverse section (Fig. 19.5C). Oncoimaging with CT is commonly applied to staging cancers, often combined with PET to determine true extent of primary cancer and involved lymph nodes. A. Mediastinal window. 1, ascending aorta; 2, descending aorta; 3, right ventricular outflow tract; 4, right atrium; 5, right atrial appendage; 6, left atrium; 7, left atrial appendage; 8, basal lower lobe artery; 9, esophagus; 10, left coronary artery. B. Lung window. 1, basal trunk lower lobe bronchus; 2, basal lower lobe artery; 3, RML vein; 4, medial segment RML artery.