Any T any N M1
Source: Adapted from Mountain,40 by permission of Chest.
Source: Adapted from Mountain,40 by permission of Chest.
bronchial tumors within 2 cm of the carina, but without involvement of the carina, are also classified as T3 tumors. Invasion of the chest wall can be evaluated with CT or MR imaging, although the patient's description of chest wall pain may be just as accurate as an indicator of chest wall invasion.36,37 CT criteria for chest wall invasion include rib destruction, contact of 5cm or more with the chest wall, obtuse (greater than 90°) angle of the mass with the chest wall, increase in attenuation of the subpleural fat plane, and visualization of tumor in the intercostal space or deeper chest wall tissue.36,38-41 When chest wall invasion is suggested on CT images, thin-section CT or MR imaging may be helpful. Uhrmeister et al. acquired 1-mm collimation CT images to evaluate 39 patients who had tumor contact with the chest wall and who underwent surgical exploration. Soft tissue invasion and abnormalities in the fat plane were more accurately identified on 1-mm CT images reconstructed by means of a standard soft tissue algorithm than with 10-mm collimation.42
On MR images, the most accurate indicator of parietal pleura invasion is signal intensity within the parietal pleura that is identical to that of tumor on Trweighted images.37 This sign was present in 17 of 20 patients with chest wall invasion, with no false-positive errors, for an overall accuracy of 91%. In this series, Padovani et al. found that T2-weighted images and gadolinium-enhanced Trweighted images provided no additional information.37 Shiotani et al. recommended breathing dynamic echoplanar MR imaging of the thorax to look for movement of the tumor against the pleura or fixation of the tumor to the chest wall.43 Sakai et al. pointed out, however, that benign pleural adhesions cannot be distinguished from chest wall invasion on MR images.44
T4 tumors are the most extensive, invading the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina. The presence of a malignant pleural effusion indicates a T4 tumor. Satellite tumor nodules within the same lobe as the primary lesion are also categorized as T4
disease. Surgical treatment is not appropriate for T4 tumors, which are considered stage IIIB or stage IV disease, depending on the presence or absence of distant metastases.
Nodal Involvement (N) The most widely used CT criterion for the evaluation of hilar and mediastinal lymph nodes is the short-axis diameter. Lymph nodes larger than 1 cm in the short axis on axial CT images are considered abnormal; lymph nodes with diameters up to and including 1 cm are considered normal (Figure 29.5). Because normal-sized lymph nodes can harbor microscopic metastases, CT results can be falsely negative. Conversely, lymph nodes that are enlarged because of inflammatory disease can lead to a false-positive interpretation. In 2003, Toloza et al. published a meta-analysis of 20 studies comparing CT with mediastinoscopy in the staging of lung cancer. The data pooled from a total of 3,438 patients suggest that CT for staging mediastinal disease has a sensitivity of 57%, specificity of 82%, positive predictive value of 56%, and negative predictive value of 83%.45 These investigators concluded that, despite a decade of advances in CT technology, the accuracy of CT scanning for staging mediastinal disease was not significantly better than results reported in a metaanalysis by Dales et al. in 1990.45,46 These limitations notwithstanding, CT remains valuable in that it can guide the selection of nodes for mediastinoscopy or transbronchial needle aspiration.
In 2003, Gould et al. published a meta-analysis of 39 studies that were reported between 1994 and 2003, evaluating FDG-PET for mediastinal lymph node staging in patients with known or suspected non-small cell lung cancer. They determined that PET with 18-FDG was more accurate than CT for mediastinal staging.47 The median sensitivity and specificity of CT for identifying mediastinal nodal (N2 and
N3) disease were 61% and 79%, respectively, whereas median sensitivity and specificity were 85% and 90%, respectively, for PET. When CT showed enlarged lymph nodes, PET was more likely to yield both true positives and false positives. False-positive PET interpretations most commonly occur when acute inflammation is present within lymph nodes, particularly in patients with sarcoidosis, silicosis, and tubercu-losis.48-50 False-positive PET results can also occur when there is direct extension of the primary tumor into the mediastinum, as nodal glucose uptake contiguous with the primary lesion may not be distinguishable from direct tumor extension into the node.51 False-negative interpretations of PET scans can occur as a result of misalignment of the PET findings to the American Thoracic Society (ATS) nodal map, so that FDG uptake is not localized correctly.49,52 Other false negatives with PET scan interpretation are due to small malignant lymph nodes that are below the spatial resolution limits of the scanner or enlarged lymph nodes with subtotal tumor replacement.49,51 Cerfolio et al. reported that false-negative FDG-PET results were most common in evaluating the subcarinal (ATS station 7) and aortopulmonary window (ATS stations 5 and 6) nodal stations.53
Positive findings on PET studies should be confirmed by biopsy. Some authors believe that negative findings on PET studies should be considered in light of the patient's pretest probability of mediastinal metastasis and whether enlarged mediastinal nodes are demonstrated by CT.47 Graeter et al. reported a negative predictive value of 98.4% in their series and suggested that the negative predictive value of PET is sufficient to omit mediastinoscopy.48 The American Society of Clinical Oncology (ASCO) recommends biopsy of lymph nodes that are either greater than 1.0 cm in short axis on CT or positive on PET scanning (Figure 29.6). Their 2003 recom-
mendations are that a lymph node that is enlarged on CT should still undergo biopsy even if the FDG-PET scan is negative.54
Staging is also more accurate with PET than with CT for predicting the likelihood of long-term survival.55,56 Dunagan et al. suggested that staging with PET may prove especially worthwhile in patients with comorbid illnesses or poor functional status, in whom the risk from invasive diagnostic procedures or surgery is accelerated.55
Some of the errors encountered in visual correlation of PET and CT images can be altered with coregistration of CT and PET data sets.32,57,58 A dual PET/CT scanner allows precise coregistration of the functional images of PET with the anatomic images of CT.59 Antoch et al. reported a slight, but not statistically significant, improvement in the assessment of lymph node involvement with dual PET/CT when compared with PET.60 The positive and negative predictive values were 89% and 94%, respectively, for dual PET/CT, 80% and 94% for PET, and 50% and 77% for CT. Lardinois et al. found that nodal staging with integrated PET/CT was significantly more accurate than with PET alone. Integrated CT-PET provided additional information in 20 (41%) of 49 patients with non-small cell bronchogenic carcinoma beyond that provided by conventional visual correlation of PET and CT.32
Because of its rapid growth and early metastatic spread, small cell lung carcinoma is considered separately from non-small cell carcinoma. One in seven patients with lung cancer has small cell lung cancer. In 2000, the age-adjusted incidence of small cell lung cancer in the United States was 8.6 cases per 100,000 population, whereas the incidence of non-small cell lung cancer was 53.8 cases per 100,000.61 The typical radiographic appearance of small cell lung cancer is that of a hilar or perihilar mass, which may represent a combination of the primary tumor and lymphadenopathy, and bulky mediastinal lymphadenopathy. Tracheobronchial and vascular compression are often present. Bronchial compression is frequently associated with obstructive atelectasis, which is demonstrated radiographically in 22% of patients.62 Although chest radiography and CT suggest complete compression of the bronchus, bronchoscopy usually demonstrates a detectable lumen.62 Small cell lung cancer is the most common primary tumor to cause superior vena cava syndrome, which results from mass effect on the superior vena cava, brachiocephalic veins, or both. The enlarged lymph nodes may also compress the pulmonary artery, producing oligemia in the involved lung.
The Veterans Administration Lung Cancer Study Group recommended a two-stage system for lung cancer: limited stage, which includes tumor that is confined to the thorax and can be encompassed in a tolerable radiation field, and extensive stage, which extends beyond those confines. A majority of patients (65% to 90%) have extensive-stage disease at presentation. Use of the TNM system has been recommended for those few patients with small cell lung cancer that is potentially surgically resectable. The clinical staging of small cell lung cancer focuses on the most common sites of metastatic disease: the liver, adrenal glands, retroperitoneal lymph nodes, brain, skeleton, and bone marrow. Staging with MR imaging or CT of the brain and abdomen, radionuclide bone scan, and bone marrow aspiration is routine, as patients may have distant metastases without clinical signs or symptoms. PET scanning may prove to be a worthwhile replacement for this combination of studies. FDG-PET imaging was compared with the sum of other staging procedures in 30 patients with histologically proven small cell lung cancer.63 FDG-PET and the conventional staging system showed identical results in 23 of 36 examinations. Discordant results were observed in the examinations of 5 patients, but the overall staging of limited versus extensive disease was not affected. A retrospective analysis of PET in 46 patients with both treated and untreated small cell lung cancer demonstrated that PET had prognostic value.64 Overall survival rates were significantly lower in patients with positive PET results than in those with negative PET results. Survival also showed a significant negative correlation with the maximum standardized uptake value (SUV).
Small cell lung cancer is somewhat unusual in its rapid response to therapy. Within 1 month of initiation of therapy, follow-up chest radiographs show a decrease in mediastinal and hilar lymphadenopathy and often return to their normal baseline appearance. In patients with obstructive atelectasis at presentation, partial or complete reexpansion of the lung is evident radiographically in 85% of patients within 1 month of initiation of therapy.62 Contrast enhancement of the medi-astinal lymph nodes on CT images has been suggested as predictive of response to chemotherapy. Enhancement of the nodes by 30 Hounsfield units (HU) or more predicted a reduction of at least 80% in tumor volume.65 PET may also provide prognostic information in follow-up of treated patients with small cell lung cancer.64 Routine radiographic follow-up is not currently recommended, however, to detect recurrence in these patients. Recurrences are signaled by clinical histories in 71% of patients and by chest radiographs in only 12%.66
Bronchial carcinoid is a neuroendocrine neoplasm with behavior that can vary from that of a low-grade typical carci-noid to a more aggressive atypical carcinoid. Pulmonary car-cinoid tumors account for 1% to 2% of all lung neoplasms. The patient with carcinoid tumor is usually symptomatic, typically in the fifth decade of life, and likely to describe symptoms related to bronchial obstruction such as cough, hemoptysis, dyspnea, or recurrent pneumonia.67,68 Chest radiographs may show signs related to the bronchial obstruction, including lobar atelectasis, or postobstructive pneu-monitis.69,70 Bronchial obstruction may also produce hypoxic vasoconstriction of the affected lung, resulting in a hyper-lucent, oligemic appearance.69 A hilar or perihilar mass may also be visible radiographically. With CT, the tumor can be localized within a lobar, segmental, or large subsegmental bronchus. Volume loss of the lobe or lung segment is characterized by displacement of fissures and crowding of the bronchi and pulmonary vessels. In many patients, post-obstructive pneumonitis predominates, with consolidation of the lung and little evidence of volume loss. The presence of air-trapping can facilitate recognition of an endobronchial lesion. Air-trapping is usually visible on inspiratory images but is more marked on images obtained in expiration. Mucoid impaction may also be seen distal to the endobronchial obstruction, signaled by the gloved-finger appearance of mucus-filled bronchi. On noncontrast-enhanced CT images, calcification may be seen within the carcinoid tumor. CT
imaging of thoracic malignancies
demonstrates calcification in 43% of central carcinoids but in only 10% of peripheral carcinoids.71,72 Because of their vascular nature, carcinoid tumors often enhance intensely after the intravenous administration of contrast material. The enhancement can be so intense that the tumor is mistaken for a vascular abnormality, such as a pulmonary varix or an arteriovenous malformation (Figure 29.7).73
One third of patients with carcinoid tumors are asymptomatic, and a solitary peripheral pulmonary nodule or mass is discovered incidentally on a chest radiograph. These patients are typically a decade older than symptomatic patients with a central carcinoid tumor. Peripheral carcinoids are usually round or ovoid, with smooth, lobulated margins. The size of these tumors ranges from 1 to 10 cm.74 Peripheral carcinoids are occasionally multiple; a larger tumor may be accompanied by one or more tumorlets. The peripheral car-cinoid is likely to be found in the right upper lobe, right middle lobe, or lingula. On CT images, the peripheral carci-noid is of homogeneous attenuation. On MR images, bronchial carcinoids have high signal intensity on T2-weighted images and short-inversion-time inversion recovery images.75
Erasmus et al. reported PET imaging of seven carcinoid tumors, including three central endobronchial lesions, three peripheral pulmonary nodules (1.5-3.0cm), and one 10-cm lung mass.76 The endobronchial lesions had SUV measurements of 1.6 to 2.3 and were indistinguishable from medi-astinal activity. SUVs were 2.2 to 2.4 in the peripheral nodules and 6.6 in the large lung mass. Currently, PET imaging is not useful in distinguishing carcinoid tumors from benign nodules.
Although the histologic distinction between typical and atypical carcinoid is important for therapeutic decisions and prognosis, no radiographic features distinguish the two.77 Both typical and atypical carcinoid tumors can metastasize to regional lymph nodes or to distant sites, including liver, bone, and skin. Hilar and mediastinal lymph node enlargement can be readily identified with CT. CT is also superior to imaging with radiolabeled somatostatin analogues (123I-Tyr-3-octreotide) in the detection of metastases from carcinoid tumors.78
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