Editors: Collins, Jannette; Stern, Eric J.
Title: Chest Radiology: The Essentials, 2nd Edition
> Table of Contents > Chapter 15 - Neoplasms of the Lung
Chapter 15
Neoplasms of the Lung
Bronchogenic carcinoma, a term referring to tumors originating from the bronchial epithelium, is the leading cause of death from cancer in men and women in the industrialized world. In 1987, bronchogenic cancer surpassed breast cancer as the most common fatal malignancy of U.S. women (1,2). Cigarette smoking is the most important causative factor in the development of bronchogenic carcinoma, and there is a direct link between cigarette smoking and development of bronchogenic cancer (Fig. 15-1), with approximately 85% of deaths directly attributable to tobacco use (2,3). This chapter will focus on the clinical presentation, histologic classification, and staging of bronchogenic carcinoma; this is followed by a brief discussion of postpneumonectomy complications and of carcinoid and salivary gland tumors of the trachea and bronchi.
FIGURE 15-1. Direct link between cigarette smoking and the development of bronchogenic carcinoma. Note the package of cigarettes within the patient's shirt pocket (straight arrows) adjacent to the peripheral adenocarcinoma within the left upper lobe (curved arrows).
Bronchogenic Carcinoma
Clinical Presentation
Bronchogenic carcinoma is relatively uncommon in patients under the age of 30 and typically occurs in 60- to 70-year-old men and women. Patients commonly present with symptoms produced by the primary tumor. Centrally located tumors can cause coughing, wheezing, hemoptysis, and postobstructive pneumonia. Tumors invading the chest wall, pleura, and mediastinal structures can cause pleuritic or local chest pain, dyspnea, cough, the Pancoast syndrome, the superior vena cava syndrome, or hoarseness (from involvement of the recurrent laryngeal nerve). Symptoms can also be related to local or distant metastases (Table 15-1) or paraneoplastic syndromes
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(systemic manifestations of the primary tumor unrelated to distant metastases). Paraneoplastic syndromes can cause cachexia of malignancy, digital clubbing and hypertrophic osteoarthropathy, nonbacterial thrombotic endocarditis, migratory thrombophlebitis, and various neurologic and cutaneous syndromes. Paraneoplastic syndromes may also be secondary to secretion of ectopic hormones by tumor cells, which can cause hypercalcemia, the syndrome of inappropriate secretion of antidiuretic hormone, Cushing syndrome from corticotropin secretion, gynecomastia, and acromegaly (4).
TABLE 15-1 COMMON EXTRATHORACIC SITES FOR METASTASES OF BRONCHOGENIC CARCINOMA
"LABB"
Liver
Adrenal
Bone
Brain
FIGURE 15-2. Poorly differentiated non–small cell lung cancer. A: Posteroanterior (PA) chest radiograph of a 68-year-old woman with emphysema shows a 6-cm mass in the right upper lobe. B: The mass is seen superiorly on the lateral view (arrows).
Histologic Classification
In 2004, the World Health Organization updated its classification of lung tumors based on histologic features (5). Four cell types account for more than 95% of all primary lung neoplasms: (i) adenocarcinoma (of which bronchioloalveolar carcinoma is a subset), (ii) squamous cell carcinoma, (iii) large cell carcinoma, and (iv) small cell carcinoma. Mixtures of these cell types may occur within the same primary neoplasm, and some tumors are too poorly differentiated to be further classified (Fig. 15-2). Rapid growth, early metastatic spread, and responsiveness to chemotherapy and radiation therapy distinguish small cell carcinoma from the others, which has led to the classification of "small cell" and "non–small cell" carcinoma. Features of the four histologic types are outlined in Table 15-2.
Adenocarcinoma
Adenocarcinoma accounts for 50% of all bronchogenic carcinomas (6), and it is the most common cell type seen in women and nonsmokers. There is a weak association with cigarette smoking and the development of adenocarcinoma. Microscopically, adenocarcinomas are characterized by the formation of glands and papillary structures. Adenocarcinomas can arise from pre-existent lung scars, or they can engulf pre-existing scars, giving rise to the term scar carcinoma. Like most bronchogenic carcinomas, adenocarcinomas occur most frequently in the upper lobes (Figs. 15-3 and 15-4). They are typically peripheral and subpleural in location, associated with
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retraction of the adjacent pleura, but can also occur centrally (Fig. 15-5). On chest radiography, adenocarcinomas manifest as a solitary pulmonary nodule or mass that can have well-marginated, lobulated, irregular, or spiculated margins. Peripheral adenocarcinomas may directly invade the pleura and grow circumferentially around the lung, mimicking diffuse malignant mesothelioma, metastatic adenocarcinoma of nonlung primary, or malignant thymoma. On computed tomography (CT), adenocarcinomas often have air bronchograms (Fig. 15-6).
TABLE 15-2 CLINICAL AND RADIOLOGIC FEATURES OF THE FOUR HISTOLOGIC TYPES OF BRONCHOGENIC CARCINOMA
Non–small cell carcinoma
   Adenocarcinoma
      Most common type
      Weak association with cigarette smoking
      Usually peripheral in location
      Most common type to have air bronchograms
      Bronchioloalveolar carcinoma is a subtype
   Squamous cell carcinoma
      Second most common type
      Strong association with cigarette smoking
      Usually central in location
      Most common type to cavitate
   Large cell carcinoma
      Least common type
      Usually >3 cm in size
      Usually in lung periphery
Small cell carcinoma
   Strong association with cigarette smoking
   Usually central in location
   Often presents with bulky mediastinal adenopathy
   Worst prognosis of all types
FIGURE 15-3. Adenocarcinoma. A: PA chest radiograph of a 75-year-old woman shows a mass in the right upper lobe abutting the mediastinum. B: CT shows the mass (arrow) compressing the superior vena cava (S). C: The mass (arrow) is seen on a shoulder radiograph obtained 3 months earlier. Incidental lung cancers can be detected on cervical spine and shoulder radiographs, and review of these studies should include a look at the visualized lungs.
FIGURE 15-4. Adenocarcinoma. PA chest radiograph of a 73-year-old woman with hoarseness and shortness of breath shows calcified pleural plaques (arrows) and a poorly defined mass in the left upper lobe (circle). The pleural plaques are related to previous asbestos exposure. The hoarseness and elevation (paralysis) of the left hemidiaphragm are related to tumor involvement of the left recurrent laryngeal nerve and left phrenic nerve, respectively, in the aortopulmonary window.
Bronchioloalveolar carcinoma (BAC) is a subtype of adenocarcinoma that has a "lepidic" pattern of growth, with cuboidal or columnar cells lining the walls of distal airspaces. The pulmonary interstitium serves as scaffolding for tumor growth. Neoplastic cells can detach from the primary tumor and attach to alveolar septa elsewhere in the lung, resulting in multifocal spread of tumor. The cells can produce abundant mucus, giving rise to "bronchorrhea," the expectoration of large amounts of mucus. The radiologic patterns of BAC are protean. The most common radiologic manifestation of BAC is a well-circumscribed peripheral solitary nodule or mass (7). Actual cavitation is uncommon, although "pseudocavitation" is a well-known feature. Air bronchograms are commonly seen (Figs. 15-6 and 15-7). The lepidic pattern of growth can look like airspace disease on chest radiography, an appearance similar to that of pneumonia (Fig. 15-8). Less common patterns include multiple nodules or extensive alveolar lung disease involving one or more lobes.
FIGURE 15-5. Adenocarcinoma. A: PA chest radiograph of a 48-year-old man shows an irregular mass in the right upper lobe abutting the mediastinum. B: CT shows the mass extending into the mediastinum. The center of the mass is of low attenuation, secondary to tumor necrosis. C: CT at a more inferior level shows tumor along the posterior wall of the right upper lobe bronchus. D: CT with lung windowing shows the spiculated mass and a background of paraseptal and centrilobular emphysema.
Radiologically, peripheral adenocarcinomas produce a spectrum of ground-glass to solid opacities and can have varying degrees of BAC histology (Fig. 15-9). The greater the solid component, the greater the likelihood of an invasive growth component. A common appearance of adenocarcinoma with a BAC component is a nodule with a central solid component and peripheral ground-glass opacity, the so-called "fried egg" sign (Fig. 15-10). Kodama et al (8) have shown that the radiologic ground-glass component correlates with noninvasive growth (BAC) in pathology specimens. The strict definition of BAC requires that the tumor be composed entirely of a lepidic pattern of growth without evidence of interstitial or stromal invasion (5). In one series, small (<3.0-cm) solitary tumors that comprised an entirely lepidic growth pattern had a 5-year survival rate of 100% (9). BAC can be indolent, growing slowly over many months or years, and should always be considered when serial chest radiographs show chronic alveolar lung disease. It can recur in multiple areas of the lung after resection (Figs. 15-9 and 15-11).
Squamous Cell Carcinoma
Squamous cell carcinoma is the second most common type of bronchogenic carcinoma, and it is strongly associated with
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cigarette smoking. It is the most common type to cavitate and to be associated with hypercalcemia. Microscopically, squamous cell carcinoma is characterized by the presence of intercellular bridges, individual cell keratinization, and formation of keratin pearls. These tumors are most commonly central in location (within the main, lobar, or segmental bronchi), although approximately 25% are peripheral (Figs. 15-12 and 15-13). The typical radiologic manifestations of central squamous cell carcinomas are postobstructive pneumonia and atelectasis because of the total or partial bronchial obstruction produced by these central tumors (Fig. 15-14). The central tumor mass, adjacent to a displaced fissure from obstructive atelectasis, gives rise to the radiographic Golden S sign (see Chapter 2).
FIGURE 15-6. Adenocarcinoma with bronchioloalveolar carcinoma component. A: PA chest radiograph of a 73-year-old woman with chronic cough and symptoms of pneumonia for 3 months shows airspace disease in the left lower lung. B: CT shows numerous air bronchograms within the left lower lobe airspace opacity. The patient was treated with antibiotics for presumed lobar pneumonia before the diagnosis of cancer was made. Adenocarcinoma, particularly bronchioloalveolar carcinoma, should be considered when chest radiographs show chronic airspace disease.
FIGURE 15-7. Bronchioloalveolar carcinoma. A: PA chest radiograph of a 79-year-old woman with a 50–pack-year history of cigarette smoking shows a subtle nodule superimposed on the shadow of the left sixth posterior rib (arrow). B: CT shows an ill-defined nodule (arrow) with air bronchograms in the posterior segment of the left upper lobe.
FIGURE 15-8. Bronchioloalveolar carcinoma. A: PA chest radiograph shows focal airspace disease in the left lower lobe, obscuring the medial left hemidiaphragm. B: Lateral view shows increased opacification over the lower thoracic spine (the so-called "spine sign"). The appearance is similar to that of left lower lobe pneumonia.
FIGURE 15-9. Bilateral bronchioloalveolar carcinomas. A: CT of a 71-year-old woman with a 30–pack-year history of cigarette smoking and resection of bronchioloalveolar carcinoma in the right upper lobe 4 years earlier shows a ground-glass nodule in the right lower lobe (arrow). B: CT at a more superior level shows a ground-glass nodule in the left upper lobe (arrow). Both nodules were proven to represent bronchioloalveolar cell carcinoma. Ground-glass nodules are very worrisome for bronchioloalveolar carcinoma, especially in a patient with a history of this type of cancer.
FIGURE 15-10. Bronchioloalveolar carcinoma. CT of a 52-year-old woman with an 11–pack-year history of cigarette smoking shows an incidental right lower lobe nodule (arrow). The nodule has a central dense component and a ground-glass peripheral component, giving rise to the "fried egg" appearance that is characteristic of bronchioloalveolar carcinoma. The patient underwent right lower lobectomy for a stage IA (T1N0M0) cancer.
FIGURE 15-11. Recurrent bronchioloalveolar carcinoma. A: CT scan of a 59-year-old woman shows a nodule in the left upper lobe (arrow) with a "fried egg" appearance. The patient underwent lingulectomy to remove a stage IA bronchioloalveolar carcinoma. B: CT image obtained 2 years later shows a ground-glass nodule with an air bronchogram in the medial right lung (arrow). Wedge resection of the right upper lobe and superior segment of the right lower lobe confirmed recurrence of bronchioloalveolar carcinoma.
FIGURE 15-12. Squamous cell carcinoma. A: PA chest radiograph of a 62-year-old woman with left chest pain shows an ill-defined mass with central lucency in the left middle lung. B: Lateral view confirms that this mass is in the superior segment of the left lower lobe (arrows). C: CT shows a subpleural mass in the superior segment of the left lower lobe, lacking the cavitation that was suggested by the chest radiograph. Approximately 25% of squamous cell lung cancers are peripheral in location.
Peripheral squamous cell carcinoma is the most common type of bronchogenic cancer to cause the Pancoast syndrome. In 1924, Henry Pancoast first described a clinical syndrome diagnostic of an apical lung tumor (10). This syndrome is characterized by pain or atrophy of muscles of the ipsilateral upper extremity, caused by involvement of the lower brachial plexus, and Horner syndrome, which results from involvement of the sympathetic chain and the stellate ganglion. Pancoast
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tumors can manifest as apical masses or asymmetric apical pleural thickening (Fig. 15-15) and can be associated with bone destruction and soft tissue invasion. Magnetic resonance imaging (MRI) is superior to CT in determining whether there is tumor involvement of the chest wall, brachial plexus, subclavian artery, vertebral bodies, and spinal canal.
FIGURE 15-13. Squamous cell carcinoma. A: PA chest radiograph of an 82-year-old woman with a history of cigarette smoking shows a mass in the right lower lung. B: Lateral view shows that the mass is anterior (arrows) in the right middle lobe. C: CT shows a lobulated mass in the right middle lobe abutting the major fissure posteriorly.
FIGURE 15-14. Squamous cell carcinoma. A: PA chest radiograph of a 63-year-old man with hemoptysis, cough, and dyspnea on exertion shows collapse of the right lung. The right main bronchus appears to be cut off (arrow). The right hemithorax is opaque and the mediastinum is shifted to the right. B: CT shows a mass that almost completely obliterates the lumen of the right main bronchus (arrow). The large, low-attenuation mass extends out into the right lung. C: CT at a more inferior level shows anterior compression of the left atrium (LA) by the mass. D: CT at a level inferior to (C) shows obliteration of the right inferior pulmonary vein by tumor (solid arrow). Note the normal left inferior pulmonary vein (dashed arrow). The appearance of a central tumor with postobstructive pneumonia and atelectasis secondary to total or partial bronchial obstruction is typical of squamous cell carcinoma.
FIGURE 15-15. Pancoast tumor. A: CT of a 54-year-old man with pain in the right suprascapular area radiating down the medial right forearm, a 60–pack-year history of cigarette smoking, and previous exposure to asbestos shows a right apical mass (M) involving the right posterior chest wall and rib. The mass is in close proximity to the right axillary artery (arrow), which is suspicious for brachial plexus involvement by tumor. B: CT with bone windowing confirms rib involvement by tumor (arrows). The patient underwent induction chemotherapy and radiation, followed by right upper lobectomy. At surgery, the tumor was found to be invading the second through the fifth ribs.
Large Cell Carcinoma
These tumors are the least common type of bronchogenic carcinoma. They grow rapidly, metastasize early, and are strongly associated with cigarette smoking. The histologic diagnosis is one of exclusion, given only to bronchogenic carcinomas that lack features of squamous, glandular, or small cell differentiation. Large cell carcinomas are appropriately named: they are usually bulky tumors greater than 3 cm in diameter. They are typically located in the lung periphery, but central lesions are not uncommon (Fig. 15-16). The typical radiologic appearance of these tumors is a large peripheral lung mass (11).
Small Cell Carcinoma
Small cell carcinoma is a rapidly growing neoplasm characterized by early and widespread metastases and by a strong association with cigarette smoking. Histologically, small cell carcinoma is characterized by small, uniform, oval cells with scant cytoplasm. Extensive crushing artifact is frequently seen in bronchial biopsy specimens, reflecting the tumor's scant tumor stroma and lack of desmoplastic reaction. Small cell carcinoma has been classified as a "neuroendocrine neoplasm" of the lung, and it is the most common cell type to cause a clinical hormone syndrome by secreting ectopic hormones. The majority of these tumors are located centrally within lobar and mainstem bronchi. They have extensive necrosis and hemorrhage, invade adjacent structures and lymph nodes, and disseminate along lymphatic routes.
The chest radiograph usually shows a hilar or perihilar mass associated with mediastinal widening; this can be caused by the primary tumor, metastases to hilar/mediastinal lymph nodes, or a combination of both (Fig. 15-17). The primary tumor may not be evident, and nodal enlargement may be the dominant abnormality. Rarely, small cell carcinoma may manifest as a solitary pulmonary nodule or mass (Fig. 15-18). CT usually shows extensive mediastinal lymph node involvement, with soft tissue "infiltration" of the mediastinum similar to that seen with lymphoma (Figs. 15-19 and 15-20). Small cell carcinoma is the most common primary lung cancer to cause superior vena cava obstruction, secondary to extrinsic vascular compression by the tumor, endoluminal thrombosis, or invasion (12). Surgical resection is considered in selected patients with small cell carcinoma only when the tumor manifests as a solitary pulmonary nodule in the absence of metastases. Most patients have disseminated disease at presentation and undergo chemotherapy
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and radiation therapy. The response to this treatment is usually dramatic, and the mass can disappear in a relatively short period of time, but most patients still die with rapidly recurrent small cell carcinoma (13).
FIGURE 15-16. Large cell carcinoma. A: CT of an 80-year-old woman with dyspnea, wheezing, cough, fatigue, 12-pound weight loss, and no history of cigarette smoking shows a mass partially obstructing the left main bronchus (arrow). B: CT at a higher level shows mediastinal lymphadenopathy causing leftward displacement of the trachea (arrow).
FIGURE 15-17. Small cell carcinoma. A: CT scout image of a 73-year-old woman with a 75–pack-year history of cigarette smoking shows a right hilar mass (arrows). B: CT shows tumor infiltrating the mediastinum.
FIGURE 15-18. Small cell carcinoma. A: PA chest radiograph of a patient with pulmonary fibrosis, obtained as part of a workup for lung transplantation, shows a nodule (arrows) in the right lung. B: CT shows a subpleural nodule in the right lower lobe. Note bilateral subpleural reticular interstitial lung disease. Wedge resection confirmed a stage IB cancer. This is a known but uncommon appearance of small cell lung cancer, which usually presents with extensive lymph node involvement and widespread metastases.
FIGURE 15-19. Small cell carcinoma. A: PA chest radiograph of a 56-year-old woman with weight loss and malaise shows widening of the left mediastinal contour (straight arrows), right hilar convexity, and collapse of the right upper lobe, with elevation of the minor fissure (curved arrows). The trachea is displaced to the right (arrowheads). B: CT shows abrupt tapering of the right upper lobe bronchus (arrowhead) and collapse of the right upper lobe against the mediastinum (arrows). The tumor infiltrates the mediastinum posterior to the ascending aorta (A) and superior vena cava (S). C: CT at a level inferior to (B) shows encasement and slitlike compression of the superior vena cava (arrowheads) and right pulmonary artery (P) by tumor. D: PA chest radiograph obtained 4 months later, after chemotherapy and radiation therapy, shows marked regression of tumor. A nipple shadow is incidentally projected over the right lung base (arrow).
Staging of Bronchogenic Carcinoma
Staging differs between small cell and non–small cell lung cancer. Small cell carcinoma is generally considered inoperable, except in rare cases of small, localized tumors. It is staged as limited or extensive, depending on whether disease is confined to a single radiation port (limited) (Fig. 15-21) or not (extensive) (Fig. 15-22). Patients with limited disease receive radiation therapy and chemotherapy, whereas patients with extensive disease receive only chemotherapy.
The primary goal of staging non–small cell lung cancer is to determine resectability. Revisions to the stage grouping of the TNM (tumor-node-metastases) subsets (Table 15-3) in the International System for Staging Lung Cancer were adopted in 1997 (14). Refinements in the staging system were made to better evaluate treatment strategies for carefully staged groups of patients. Stage grouping involves the concept of combining subsets of patients classified according to TNM descriptors into categories or stages, with each having generally similar treatment options and survival expectations (Table 15-4).
Tumor classification is the most complicated component of the TNM system. Tumors that are classified as anything other
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than T4 are potentially resectable. T4 tumors invade the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina; or they are associated with a malignant pleural or pericardial effusion or satellite tumor nodules within the ipsilateral primary tumor lobe of the lung. Satellite nodules outside the primary tumor lobe are considered M1 disease (Fig. 15-23). Most pleural effusions associated with lung cancer are malignant, but cytologic proof of malignancy cannot always be obtained. In these cases, the effusion should be excluded as a staging element.
FIGURE 15-20. Small cell carcinoma. A: CT of a 57-year-old woman with hoarseness shows tumor infiltrating the aortopulmonary window and invading the left recurrent laryngeal nerve. B: CT at a level inferior to (A) shows encasement of the left pulmonary artery (arrows) by tumor and extension of tumor posterior to the carina, obliterating the fat plane adjacent to the descending aorta (D). C: CT at a level inferior to (B) shows encasement of the left upper lobe bronchus by tumor (arrows).
FIGURE 15-21. Small cell carcinoma, limited stage. A: CT of a 64-year-old woman shows a lobulated mass in the right lower lobe. B: CT with mediastinal windowing shows calcification or contrast enhancement within the mass. Mediastinal lymphadenopathy was present in the right paratracheal area (not shown). CT and positron emission tomography showed no evidence of extrathoracic tumor. The patient received radiation therapy and chemotherapy.
FIGURE 15-22. Small cell carcinoma, extensive. A: PA chest radiograph of a 47-year-old man with abdominal pain and vomiting shows enlargement of the cardiac silhouette, right pleural effusion, and abnormal opacities in the right paratracheal area, right hilum, and both lung bases. B: CT shows bilateral pleural effusions, bulky subcarinal lymphadenopathy, and a large pleural mass anteriorly. C: CT at a more inferior level shows anterior displacement of the left atrium by bulky tumor. D: CT at a level inferior to (C) shows numerous pleural tumor deposits (arrows). E: CT of the upper abdomen shows bulky celiac lymphadenopathy (arrow). The patient received chemotherapy.
TABLE 15-3 TNM DESCRIPTORS FOR STAGING BRONCHOGENIC CARCINOMA
Primary tumor (T)
   TX Primary tumor cannot be assessed, or tumor proven, by the presence of malignant cells in sputum or bronchial washing but not visualized by imaging or bronchoscopy
   T0 No evidence of primary tumor
   Tis Carcinoma in situ
   T1 Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchusa (i.e., not in the main bronchus)
   T2 Tumor with any of the following features of size or extent:
      >3 cm in greatest dimension
      Involves main bronchus, ≥2 cm distal to the carina
      Invades the visceral pleura
      Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung
   T3 Tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus <2 cm distal to the carina, but without involvement of the carina or associated atelectasis or obstructive pneumonitis of the entire lung
   T4 Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or tumor with a malignant pleural or pericardial effusionb or with satellite tumor nodule(s) within the ipsilateral primary tumor lobe of the lung
Regional lymph nodes (N)
   NX Regional lymph nodes cannot be assessed
   N0 No regional lymph node metastasis
   N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes involved by direct extension of the primary tumor
   N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s)
   N3 Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)
Distant metastasis (M)
   MX Presence of distant metastasis cannot be assessed
   M0 No distant metastasis
   M1 Distant metastasis presentc
TNM, tumor-node-metastases.
a The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified T1.
b Most pleural effusions associated with lung cancer are caused by tumor. However, there are a few patients in whom multiple cytopathologic examinations of pleural fluid show no tumor. In these cases, the fluid is nonbloody and is not an exudate. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient's disease should be staged T1, T2, or T3. Pericardial effusion is classified according to the same rules.
c Separate metastatic tumor nodule(s) in the ipsilateral nonprimary tumor lobe(s) of the lung also are classified M1.
Reproduced with permission from Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–1717.
TABLE 15-4 STAGE GROUPING AND CORRESPONDING TNM SUBSETS
Stage TNM subset Stage TNM subset
0 Carcinoma in situ IIIB T4N0M0
IA T1N0M0 T4N1M0
IB T2N0M0 T4N2M0
IIA T1N1M0 T1N3M0
IIB T2N1M0 T2N3M0
T3N0M0 T3N3M0
IIIA T3N1M0 T4N3M0
T1N2M0 IV Any T Any N M1
T2N2M0
T3N2M0
TNM, tumor-node-metastases.
Staging is not relevant for occult carcinoma, which is designated TXN0M0.
Reproduced with permission from Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–1717.
Hilar node involvement is classified as N1. N2 nodes are ipsilateral mediastinal nodes, and N3 nodes are contralateral mediastinal or hilar nodes. N3 nodes also include any ipsilateral or contralateral scalene or supraclavicular lymph nodes. The distant metastases classification is simple. M0 indicates no distant metastases, and M1 is positive distant metastases.
The staging system is complicated and difficult to remember unless one routinely evaluates and stages lung cancer. Patients with T1N0M0 tumors (stage IA) have a significantly better outcome than patients in the other subsets (15,16) (Fig. 15-24). These patients have a tumor that is 3 cm or less in diameter, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus, and without nodal involvement or metastases. In other words,
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these are patients with a solitary pulmonary nodule and no spread of tumor. Stage IB tumors also have no nodal or distal metastases, but the primary tumor is either larger than 3 cm in diameter, involves the main bronchus, invades the visceral pleura, or is associated with atelectasis or obstructive pneumonitis. Sixty-one percent of patients with clinical stage IA disease and 38% of those with clinical stage IB tumors are expected to survive more than 5 years after treatment. IA and IB subsets have no evidence of lymph node or other metastases and therefore have the best prognosis.
FIGURE 15-23. Adenocarcinoma. A: PA chest radiograph of a 65-year-old man with a 100–pack-year history of cigarette smoking shows a nodule in the right medial lung (arrow). B: PA chest radiograph obtained 1 year later shows widespread parenchymal metastases. C: CT shows numerous circumscribed pulmonary metastases involving both lungs. Note a pathologic rib fracture on the right (arrow). Other images showed metastases to both adrenal glands, multiple lytic bone lesions, and extensive mediastinal lymphadenopathy.
FIGURE 15-24. Adenocarcinoma, stage IA. CT of a 66-year-old woman with pulmonary fibrosis shows a small subpleural nodule (arrow) in the left upper lobe, with no evidence of lymphadenopathy or metastatic disease. Nodes removed at surgery were negative.
Stage IIA, IIB, and IIIA tumors are potentially resectable, although the prognosis after treatment is poor, especially with IIIA tumors. Some surgeons opt not to resect IIIA tumors for this reason. IIIB staging involves either T4 tumors or N3 nodes, making such tumors unresectable. IIIB tumors are confined to the lung, however, which is an important consideration for radiotherapy. Stage IV tumors are defined by an M1 classification and are therefore unresectable and not confined to the lung. If treated, systemic therapy is required.
CT is commonly used for staging bronchogenic carcinoma prior to surgical resection. Patients with bulky N3 nodes are clearly not surgical candidates, and those patients without evidence of nodal involvement are considered surgical candidates (in the absence of T4 or M1 disease). CT is not perfect in detecting nodal involvement, however. In general, nodes greater than 1 cm in short-axis diameter are considered positive or suspicious, but many of these cases will turn out to be false-positive findings. In addition, nodes that are smaller than 1 cm or not visibly enlarged on CT can be positive histologically. Nodes can be sampled percutaneously, transbronchially, or via transcervical mediastinoscopy (requiring general anesthesia). The Chamberlain procedure involves an anterior thoracotomy, usually with removal of the second anterior rib to
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allow sampling of lymph nodes in the anterior mediastinum, the aorticopulmonary window, and the hilum. Other limitations of CT include the inability to determine mediastinal or chest wall invasion with certainty. MRI plays a role in evaluating these cases, as well as in evaluating for the presence of brachial plexus invasion.
Whole-body positron emission tomography (PET) imaging with [18]-fluoro-2-deoxy-D-glucose (FDG) has become an integral part of staging non–small cell lung cancer. PET improves the detection of nodal and distant metastases and frequently alters patient management (17). Integrated CT-PET scanners allow for the acquisition of coregistered, spatially matched functional and morphologic data. PET is sufficiently sensitive that a patient with negative mediastinal PET results may proceed directly to surgical resection of the primary tumor without a staging mediastinoscopy (18).
Postpneumonectomy Complications
In the United States, the most common indication for pneumonectomy is non–small cell carcinoma of the lung. Most pneumonectomies performed for bronchogenic carcinoma follow an interpleural plane of resection (meaning the parietal pleura is left intact). If there is extension of tumor into the pleural space or parietal pleura, or in the case of malignant mesothelioma, an extrapleural pneumonectomy is generally performed. In this case, the plane of resection is between the parietal pleura and the endothoracic fascia (19).
FIGURE 15-25. Postpneumonectomy bronchopleural fistula. A: AP upright chest radiograph of a 52-year-old man after right pneumonectomy shows shift of the mediastinum to the operative side and an air–fluid level within the right pneumonectomy space (arrows). There is "postpneumonectomy pulmonary edema" of the left lung. B: AP upright chest radiograph obtained 1 day later shows increased air within the right pneumonectomy space and shift of the mediastinum away from the operative side, consistent with a bronchial stump leak and bronchopleural fistula.
After pneumonectomy, pleural fluid accumulates in the pneumonectomy space, replacing the normal immediate postoperative air that is resorbed at a variable rate. It is not uncommon for multiple air–fluid levels to be present within the early pneumonectomy space, representing loculation of fluid, and this finding on chest radiography does not necessarily suggest a complication. Most of the air is resorbed by 2 weeks after pneumonectomy; residual air may persist for months, however, or, in a small population of patients, it may never be completely resorbed. Eventually, the pneumonectomy space will contract, with ipsilateral shift of the mediastinum and elevation of the diaphragm, and the space will fill with fluid and some degree of solid fibrothorax. Shift of the mediastinum away from the operated side indicates a buildup of air or fluid within the pneumonectomy space. Mediastinal displacement away from the operative side suggests one of five diagnoses, depending on the length of time after surgery (Table 15-5). If the air–fluid level has not continued to rise after surgery, the cause of the contralateral mediastinal shift is likely a bronchial stump air leak. If the air–fluid level has continued to rise, the shift can be a result of hemothorax, chylothorax, or empyema, with or without a bronchopleural fistula. A drop in the air–fluid level indicates that fluid is draining through a chest tube, by thoracentesis, through a dehiscence of the incision, through an opening in the bronchial stump (Fig. 15-25), or through a rent in the diaphragm (19). After the postoperative period, shift
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of the mediastinum away from the operative side is also suspicious for recurrent tumor (Fig. 15-26), which can be recognized on CT as a soft tissue mass at the site of surgical ligation and soft tissue deposits studding the periphery of the pneumonectomy space. Recurrence can also be seen in the remaining lung (Fig. 15-27). PET scanning can be very helpful in evaluating for recurrence.
TABLE 15-5 POSTPNEUMONECTOMY COMPLICATIONS
Early
   Bronchopleural fistula (stump leak)
   Empyema
   Hemothorax (blood within pneumonectomy space)a
   Chylothorax (chylous leak into pneumonectomy space)
Late
   Recurrent neoplasm
   Bronchopleural fistula
   Empyema
   Hemothorax
   Chylothorax
aThere is no true pleural space after pneumonectomy, and the resulting space is referred to as the pneumonectomy space.
FIGURE 15-26. Recurrence of bronchogenic carcinoma after pneumonectomy. A: PA chest radiograph of a 65-year-old man after left pneumonectomy for bronchogenic carcinoma shows an air–fluid level in the left pneumonectomy space (arrows), left skin staples (arrowheads), and shift of the mediastinum toward the operative side. B: PA chest radiograph obtained 8 months later shows abnormal shift of the mediastinum away from the operative side, an appearance that is consistent with hemothorax, chylothorax, or recurrence of tumor with malignant fluid in the pneumonectomy space. Empyema is less of a consideration in the absence of air within the pneumonectomy space. C: CT shows a soft tissue mass (M) between the surgical clips and soft tissue deposits studding the surface of the pneumonectomy space (arrows). There is malignant fluid within the left pneumonectomy space.
The mortality of pneumonectomy is approximately 6%, with the major causes of death being pneumonia, respiratory failure, pulmonary embolism, myocardial infarction, bronchopleural fistula, and empyema (20,21). The incidence of empyema is 2% to 5%, often with associated bronchopleural fistula (22). In the first postoperative week, empyema is caused by intraoperative soilage or preoperative pleural infection. Delayed onset of empyema is often associated with bronchopleural or esophagopleural fistula. New air within the pneumonectomy space, in a previously opacified hemithorax, with contralateral shift of the mediastinum, is suggestive of empyema or bronchopleural fistula and bronchial stump leak (Fig. 15-28).
A rare complication of right pneumonectomy is obstruction of the left main bronchus, a result of extreme rightward shift and counterclockwise rotation of the mediastinum, causing compression of the left bronchus between the aorta and the left pulmonary artery. This complication is termed the right pneumonectomy syndrome, and it can occur between 1 and 37 years after surgery (23). The diagnosis is suggested on chest radiography by marked mediastinal shift to the right and inversion of the left diaphragm, caused by the trapping of air from a narrowing of the left bronchus (19). There can also be recurrent left lower lobe pneumonia resulting from airway obstruction.
Carcinoid and Salivary Gland Tumors
The term bronchial adenoma refers to a group of tumors that includes bronchial carcinoid (most common), mucoepidermoid carcinoma, and adenoid cystic carcinoma. This term, however,
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is not accurate, as adenoma implies a benign tumor, and many of these tumors are not benign. Additionally, adeno- implies glandular elements, which are sometimes lacking in these tumors. Carcinoid tumors have a different cell of origin, and adenoid cystic and mucoepidermoid carcinomas are classified as salivary gland tumors. Because the term exists in the radiology literature and is still used by some clinicians, it is discussed in this chapter.
FIGURE 15-27. Metastases after pneumonectomy. PA chest radiograph of a 56-year-old man after right pneumonectomy for bronchogenic carcinoma shows pulmonary metastases within the left lower lobe (arrows). Note the normal shift of the mediastinum toward the operative side.
FIGURE 15-28. Bronchopleural fistula after pneumonectomy. A: AP chest radiograph after right pneumonectomy shows complete opacification of the right pneumonectomy space. The air within the pneumonectomy space has resorbed completely. The mediastinum is shifted toward the operative side. There is "postpneumonectomy pulmonary edema" of the left lung. B: AP chest radiograph taken 1 day later shows new air within the right pneumonectomy space, consistent with a bronchial stump leak and bronchopleural fistula. Note the subcutaneous air within the chest wall bilaterally.
There are two forms of bronchial carcinoid: typical carcinoid and atypical carcinoid. Atypical carcinoid has cellular and clinical features that are intermediate, between those of typical carcinoid and small cell carcinoma of the lung (24). All three of these tumors are of neuroendocrine origin. Only 15% of typical carcinoids metastasize (25), and the prognosis following surgical resection is excellent. Approximately half of atypical carcinoids metastasize. Most typical bronchial carcinoids arise centrally in the main, lobar, or segmental bronchi and can cause cough and wheezing (symptoms resembling asthma). Recurrent bouts of postobstructive pneumonia are common. Because of their vascularity, bronchial carcinoids can present with hemoptysis (25). "Carcinoid syndrome" is rare with bronchial carcinoids unless liver metastases are present (26).
A bronchial carcinoid tumor can appear on chest radiography as a hilar mass, often with associated atelectasis or postobstructive pneumonia, but when entirely intraluminal it can be very difficult to detect. On CT, the tumor can be seen within a central bronchus, often causing widening of the bronchus (Fig. 15-29). Small tumors in segmental or subsegmental bronchi may result in a bronchocele (mucoid impaction) on chest radiography or CT, resembling bronchial atresia (Fig. 15-30). Approximately 10% to 20% of bronchial carcinoids appear on chest radiography as a solitary pulmonary nodule, usually well defined, round, oval, or lobulated, with occasional calcification (27) (Fig. 15-31). The incidence of calcification is significantly greater in centrally located and larger tumors. It can manifest as multiple nodular and curvilinear configurations, complete calcification, or even ossification of the entire nodule. Contrast enhancement can be marked on CT because of the vascularity of these tumors.
Adenoid cystic carcinoma is the most common salivary gland tumor in the thorax, followed by mucoepidermoid carcinoma. Mucoepidermoid carcinoma is more frequent in the
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major bronchi than in the trachea, and adenoid cystic carcinomas most commonly involve the posterior wall of the lower two thirds of the trachea (Fig. 13-6). Both are seen on imaging studies as an intraluminal nodule, either polypoid in shape or circumferential. CT can show the extraluminal component, but it is poor at indicating whether mediastinal structures, such as the esophagus and aorta, are invaded (28).
FIGURE 15-29. Carcinoid tumor. A: CT of a 57-year-old man shows a soft-tissue filling defect within the bronchus intermedius (arrows). B: CT scan at the same level as (A), with lung windowing, shows slitlike narrowing of the bronchus intermedius (arrowhead) and postobstructive atelectasis of the right lower lobe (arrows). C: CT at a level inferior to (A) shows the mass compressing the right middle lobe (straight arrow) and right lower lobe (curved arrow) bronchi.
FIGURE 15-30. Carcinoid tumor. A: CT of a 58-year-old woman shows a mass with central calcification in the proximal left lower lobe bronchus (arrow). B: CT at a more inferior level shows low-attenuation material within the left lower lobe segmental bronchi. Small carcinoid tumors in segmental bronchi may result in mucoid impaction, as shown in this case.
FIGURE 15-31. Carcinoid tumor. A: PA chest radiograph of a 66-year-old woman shows a solitary pulmonary nodule in the right upper lung (arrow). B: CT shows the nodule in the right upper lobe (arrow), lateral to the proximal right upper lobe bronchus.
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